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Alzheimer’s disease: Alternative mechanisms make clinical progress
SAN DIEGO – In 1906, a neuroanatomist and psychiatrist named Alois Alzheimer examined the brain of a 50-year-old woman whom he had treated for paranoia, sleep and memory problems, aggression, and confusion. His autopsy revealed plaques and tangles in her brain. The most common components of these tangles are beta-amyloid peptide (A-beta) and the microtubule binding protein tau. Over the past few decades, that finding has launched many clinical development programs and dozens of clinical trials.
To date, all but one program has failed. In 2021, amidst much controversy, FDA granted accelerated approval to Biogen’s Aduhelm, which effectively clears A-beta and tau deposits from patients’ brains. The problem is that the clinical benefit is small, and uptake has been so low that the company was forced to abandon a planned postmarketing observational trial.
Chasing the wrong target?
At a session at the 2022 Alzheimer’s Association International Conference, Raymond J. Tesi, MD, rather forcefully refuted that approach. “Amyloid and tau therapies have had 20 years to prove themselves. We have multiple cases where we’ve been able to decrease amyloid, maybe not so much tau, but certainly amyloid, and the benefits are mild at best. So I think that the Alzheimer’s drug development community, whether you look at the NIH, whether you look at academia, whether you look at biopharma, has focused on a target that has not proven itself, and it’s time to move on,” said Dr. Tesi, who is president, CEO, and chief medical officer at INmune Bio.
Later in the session,
One audience member defended the potential importance of A-beta and tau, especially in astrogliosis, which is a reaction to stress by astrocytes that attempts to limit tissue damage. The questioner suggested that it was still important to measure the effect of a novel drug on A-beta and tau. “What would be the cause of the reactive astrogliosis and microglia activation, if we are not giving a damn about amyloid and tau?” he asked.
After a bit of back and forth, Dr. Tesi replied: “We both have a religious belief here, and sooner or later we’ll get the answer.”
A diverse clinical pipeline
The session itself focused on four companies, including Dr. Tesi’s INmune Bio, which have drugs with alternative mechanisms entering the advanced stages of clinical development. That’s good news, according to Heather Snyder, PhD, who is vice president of Medical & Scientific Relations at the Alzheimer’s Association. “One of the things that I think is really important is the diversity of what’s in the clinical pipeline, and it’s not just in the very beginning anymore. We’re seeing [companies] now reporting phase 2 [studies] and planning their next stage. That’s something that as a field we should be excited about. As we understand more and more about the biology, we’re now seeing that translating into clinical trials and we’re seeing that translate through the clinical pipeline of development,” said Dr. Snyder in an interview.
Targeting neuroinflammation
Dr. Tesi kicked off the session describing INmune Bio’s focus on neuroinflammation. The company’s drug candidate targets soluble tumor necrosis factor (TNF), which the company believes is a direct cause of Alzheimer’s disease through promotion of inflammation. He noted that TNF is a primary mediator of inflammation in rheumatoid arthritis, and patients with RA have an eightfold increased risk of developing Alzheimer’s disease, compared with the general population, while patients with RA who are taking anti-TNF medication have a 60% lower risk than the general population.
The company’s TNF inhibitor XPro is also unique in that it induces remyelination in mice, while other TNF inhibitors potentially “abuse” the brain by causing demyelination. Earlier research showed that it reduces neuroinflammation, improves nerve cell survival, and improves synaptic function. The company is conducting two phase 2 clinical trials, one in patients with mild cognitive impairment (MCI) and one in mild Alzheimer’s disease. They also use the MCI Alzheimer’s Cognitive Composite (EMACC) tool for assessing outcomes rather than the more commonly used Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). “ADAS-Cog is like trying to make sushi with an axe. It is designed for moderate to severe disease, and trying to use it for mild (Alzheimer’s disease) or MCI is a mistake. EMACC is purpose built for mild [AD] and MCI patients,” said Dr. Tesi.
Maintaining homeostatis
Next, Hans Moebius, MD, PhD, chief medical officer of Athira Pharma, described his company’s focus on the hepatocyte growth factor (HGF) receptor, also known as tyrosine kinase MET (HGF/MET). It plays an important role in brain development and homeostasis, and it is expressed at lower levels in the frontal cortex and hippocampus of patients with Alzheimer’s disease. The company’s small-molecule drug candidate boosts the HGF/MET pathway, leading to downstream neuroprotection and neurotrophic effects. It also promotes formation of new synapses.
Dr. Moebius presented the results of a phase 2 trial showing that the drug, called fosgonimeton, led to significant cognitive improvement compared with placebo. The company is conducting a phase 3 clinical trial.
Type 3 diabetes?
In his talk, John Didsbury, PhD, founder and CEO of T3D Therapeutics, framed Alzheimer’s disease as a disease of metabolic dysfunction. He believes alterations to glucose and lipids in the brain cause structural changes that lead to symptoms. He pointed out that the strongest genetic Alzheimer’s disease risk factor is a mutant form of the lipid transport protein APOE4.
“What we have is dysregulated glucose energy metabolism and lipid metabolism that really cause, in our mind, the structural event changes and the stress event changes – plaques, tangles, inflammation, etc. – but these events perpetuate the dysregulated metabolism. It’s a massive positive feedback loop that many have called type 3 diabetes – a brain-specific form of diabetes,” said Dr. Didsbury.
The company’s approach is to use systems biology to identify a drug target that can bypass multiple aberrant insulin signaling pathways. Its drug candidate regulates the expression of multiple genes involved in glucose metabolism. Dr. Didsbury presented interim results from a phase 2 study showing improvement over placebo.
Focusing on neurotoxic proteins
The final presentation of the session was by Maria Maccecchini, PhD, founder, president, and CEO of Annovis Bio. The company’s drug, buntanetap, reduces expression of a range of neurotoxic proteins. The downstream effects include restoration of axonal transport, reduction of inflammation, and protection of nerve cells. The company believes that Alzheimer’s disease results from acute and chronic stress events that lead to high levels of neurotoxic proteins, which include A-beta, tau, alpha-synuclein, and TDP43. The proteins aren’t just players in Alzheimer’s disease – they are present in abnormal levels in Parkinson’s disease and a range of other brain pathologies.
“In the brain of an Alzheimer’s and of a Parkinson’s [patient], you’re going to find all four proteins. You’ll find them in different concentrations, at different time points, in different brain areas. If you just remove one, you still have the other three that cause impairment in axonal transport, and that leads to inflammation that leads to neurodegeneration,” said Dr. Maccecchini.
The company’s drug manages to reduce levels of all four proteins by binding to a segment of messenger RNA (mRNA) shared by all of them. mRNA serves as a template for protein synthesis. Under normal conditions, the neurotoxic protein concentrations are kept low because the mRNA segment remains bound to a regulatory protein that prevents synthesis from occurring. However, when stress leads to high levels of iron, this regulatory binding protein releases the mRNA segment (along with the rest of the mRNA). The freed mRNA becomes available to the cell’s protein synthesis machinery, which starts producing high levels of neurotoxic proteins. Annovis Bio’s drug improves the ability of the regulatory protein to bind to the mRNA segment, preventing protein expression even in high-iron conditions. It works on all four neurotoxic proteins because they all have the regulatory segment in their mRNA.
The drug led to improvements in phase 2 studies of Alzheimer’s disease and Parkinson’s disease, and the company is currently recruiting for a phase 3 study in Parkinson’s disease and a phase 2/3 dose-response study in Alzheimer’s disease.
Combination treatments for a complex disease
Taken together, the presentations provided a snapshot of the post–A-beta/tau Alzheimer’s development world, and the future could be messy. Alzheimer’s disease and other dementias are likely to require combination treatments, according to Dr. Snyder. “This is a complex disease, not just Alzheimer’s but other dementias. It’s not going to be a single drug, a single target. It’s going to require some type of combinatorial approach, whether that be with medication and lifestyle interventions, or risk reduction, and different medications,” she said.
The latest results are good news for that approach: “We’re seeing that maturation of the science in these trials,” said Dr. Snyder.
Cheng Fang, PhD, senior vice president of research and development at Annovis Bio, agreed with that sentiment. “I believe [Alzheimer’s disease and dementia] is a very complicated disease. I always call them diseases instead of a disease because it’s a spectrum. I don’t believe one drug can cure them all, as much as I am confident in our drug. I think it’s extremely important to encourage this kind of diverse thinking,” said Dr. Fang.
Dr. Snyder has no relevant financial disclosures. Dr. Tesi, Dr. Moebius, Dr. Didsbury, Dr. Maccecchini, and Dr. Fang are employees and in some cases stockholders of their respective companies.
SAN DIEGO – In 1906, a neuroanatomist and psychiatrist named Alois Alzheimer examined the brain of a 50-year-old woman whom he had treated for paranoia, sleep and memory problems, aggression, and confusion. His autopsy revealed plaques and tangles in her brain. The most common components of these tangles are beta-amyloid peptide (A-beta) and the microtubule binding protein tau. Over the past few decades, that finding has launched many clinical development programs and dozens of clinical trials.
To date, all but one program has failed. In 2021, amidst much controversy, FDA granted accelerated approval to Biogen’s Aduhelm, which effectively clears A-beta and tau deposits from patients’ brains. The problem is that the clinical benefit is small, and uptake has been so low that the company was forced to abandon a planned postmarketing observational trial.
Chasing the wrong target?
At a session at the 2022 Alzheimer’s Association International Conference, Raymond J. Tesi, MD, rather forcefully refuted that approach. “Amyloid and tau therapies have had 20 years to prove themselves. We have multiple cases where we’ve been able to decrease amyloid, maybe not so much tau, but certainly amyloid, and the benefits are mild at best. So I think that the Alzheimer’s drug development community, whether you look at the NIH, whether you look at academia, whether you look at biopharma, has focused on a target that has not proven itself, and it’s time to move on,” said Dr. Tesi, who is president, CEO, and chief medical officer at INmune Bio.
Later in the session,
One audience member defended the potential importance of A-beta and tau, especially in astrogliosis, which is a reaction to stress by astrocytes that attempts to limit tissue damage. The questioner suggested that it was still important to measure the effect of a novel drug on A-beta and tau. “What would be the cause of the reactive astrogliosis and microglia activation, if we are not giving a damn about amyloid and tau?” he asked.
After a bit of back and forth, Dr. Tesi replied: “We both have a religious belief here, and sooner or later we’ll get the answer.”
A diverse clinical pipeline
The session itself focused on four companies, including Dr. Tesi’s INmune Bio, which have drugs with alternative mechanisms entering the advanced stages of clinical development. That’s good news, according to Heather Snyder, PhD, who is vice president of Medical & Scientific Relations at the Alzheimer’s Association. “One of the things that I think is really important is the diversity of what’s in the clinical pipeline, and it’s not just in the very beginning anymore. We’re seeing [companies] now reporting phase 2 [studies] and planning their next stage. That’s something that as a field we should be excited about. As we understand more and more about the biology, we’re now seeing that translating into clinical trials and we’re seeing that translate through the clinical pipeline of development,” said Dr. Snyder in an interview.
Targeting neuroinflammation
Dr. Tesi kicked off the session describing INmune Bio’s focus on neuroinflammation. The company’s drug candidate targets soluble tumor necrosis factor (TNF), which the company believes is a direct cause of Alzheimer’s disease through promotion of inflammation. He noted that TNF is a primary mediator of inflammation in rheumatoid arthritis, and patients with RA have an eightfold increased risk of developing Alzheimer’s disease, compared with the general population, while patients with RA who are taking anti-TNF medication have a 60% lower risk than the general population.
The company’s TNF inhibitor XPro is also unique in that it induces remyelination in mice, while other TNF inhibitors potentially “abuse” the brain by causing demyelination. Earlier research showed that it reduces neuroinflammation, improves nerve cell survival, and improves synaptic function. The company is conducting two phase 2 clinical trials, one in patients with mild cognitive impairment (MCI) and one in mild Alzheimer’s disease. They also use the MCI Alzheimer’s Cognitive Composite (EMACC) tool for assessing outcomes rather than the more commonly used Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). “ADAS-Cog is like trying to make sushi with an axe. It is designed for moderate to severe disease, and trying to use it for mild (Alzheimer’s disease) or MCI is a mistake. EMACC is purpose built for mild [AD] and MCI patients,” said Dr. Tesi.
Maintaining homeostatis
Next, Hans Moebius, MD, PhD, chief medical officer of Athira Pharma, described his company’s focus on the hepatocyte growth factor (HGF) receptor, also known as tyrosine kinase MET (HGF/MET). It plays an important role in brain development and homeostasis, and it is expressed at lower levels in the frontal cortex and hippocampus of patients with Alzheimer’s disease. The company’s small-molecule drug candidate boosts the HGF/MET pathway, leading to downstream neuroprotection and neurotrophic effects. It also promotes formation of new synapses.
Dr. Moebius presented the results of a phase 2 trial showing that the drug, called fosgonimeton, led to significant cognitive improvement compared with placebo. The company is conducting a phase 3 clinical trial.
Type 3 diabetes?
In his talk, John Didsbury, PhD, founder and CEO of T3D Therapeutics, framed Alzheimer’s disease as a disease of metabolic dysfunction. He believes alterations to glucose and lipids in the brain cause structural changes that lead to symptoms. He pointed out that the strongest genetic Alzheimer’s disease risk factor is a mutant form of the lipid transport protein APOE4.
“What we have is dysregulated glucose energy metabolism and lipid metabolism that really cause, in our mind, the structural event changes and the stress event changes – plaques, tangles, inflammation, etc. – but these events perpetuate the dysregulated metabolism. It’s a massive positive feedback loop that many have called type 3 diabetes – a brain-specific form of diabetes,” said Dr. Didsbury.
The company’s approach is to use systems biology to identify a drug target that can bypass multiple aberrant insulin signaling pathways. Its drug candidate regulates the expression of multiple genes involved in glucose metabolism. Dr. Didsbury presented interim results from a phase 2 study showing improvement over placebo.
Focusing on neurotoxic proteins
The final presentation of the session was by Maria Maccecchini, PhD, founder, president, and CEO of Annovis Bio. The company’s drug, buntanetap, reduces expression of a range of neurotoxic proteins. The downstream effects include restoration of axonal transport, reduction of inflammation, and protection of nerve cells. The company believes that Alzheimer’s disease results from acute and chronic stress events that lead to high levels of neurotoxic proteins, which include A-beta, tau, alpha-synuclein, and TDP43. The proteins aren’t just players in Alzheimer’s disease – they are present in abnormal levels in Parkinson’s disease and a range of other brain pathologies.
“In the brain of an Alzheimer’s and of a Parkinson’s [patient], you’re going to find all four proteins. You’ll find them in different concentrations, at different time points, in different brain areas. If you just remove one, you still have the other three that cause impairment in axonal transport, and that leads to inflammation that leads to neurodegeneration,” said Dr. Maccecchini.
The company’s drug manages to reduce levels of all four proteins by binding to a segment of messenger RNA (mRNA) shared by all of them. mRNA serves as a template for protein synthesis. Under normal conditions, the neurotoxic protein concentrations are kept low because the mRNA segment remains bound to a regulatory protein that prevents synthesis from occurring. However, when stress leads to high levels of iron, this regulatory binding protein releases the mRNA segment (along with the rest of the mRNA). The freed mRNA becomes available to the cell’s protein synthesis machinery, which starts producing high levels of neurotoxic proteins. Annovis Bio’s drug improves the ability of the regulatory protein to bind to the mRNA segment, preventing protein expression even in high-iron conditions. It works on all four neurotoxic proteins because they all have the regulatory segment in their mRNA.
The drug led to improvements in phase 2 studies of Alzheimer’s disease and Parkinson’s disease, and the company is currently recruiting for a phase 3 study in Parkinson’s disease and a phase 2/3 dose-response study in Alzheimer’s disease.
Combination treatments for a complex disease
Taken together, the presentations provided a snapshot of the post–A-beta/tau Alzheimer’s development world, and the future could be messy. Alzheimer’s disease and other dementias are likely to require combination treatments, according to Dr. Snyder. “This is a complex disease, not just Alzheimer’s but other dementias. It’s not going to be a single drug, a single target. It’s going to require some type of combinatorial approach, whether that be with medication and lifestyle interventions, or risk reduction, and different medications,” she said.
The latest results are good news for that approach: “We’re seeing that maturation of the science in these trials,” said Dr. Snyder.
Cheng Fang, PhD, senior vice president of research and development at Annovis Bio, agreed with that sentiment. “I believe [Alzheimer’s disease and dementia] is a very complicated disease. I always call them diseases instead of a disease because it’s a spectrum. I don’t believe one drug can cure them all, as much as I am confident in our drug. I think it’s extremely important to encourage this kind of diverse thinking,” said Dr. Fang.
Dr. Snyder has no relevant financial disclosures. Dr. Tesi, Dr. Moebius, Dr. Didsbury, Dr. Maccecchini, and Dr. Fang are employees and in some cases stockholders of their respective companies.
SAN DIEGO – In 1906, a neuroanatomist and psychiatrist named Alois Alzheimer examined the brain of a 50-year-old woman whom he had treated for paranoia, sleep and memory problems, aggression, and confusion. His autopsy revealed plaques and tangles in her brain. The most common components of these tangles are beta-amyloid peptide (A-beta) and the microtubule binding protein tau. Over the past few decades, that finding has launched many clinical development programs and dozens of clinical trials.
To date, all but one program has failed. In 2021, amidst much controversy, FDA granted accelerated approval to Biogen’s Aduhelm, which effectively clears A-beta and tau deposits from patients’ brains. The problem is that the clinical benefit is small, and uptake has been so low that the company was forced to abandon a planned postmarketing observational trial.
Chasing the wrong target?
At a session at the 2022 Alzheimer’s Association International Conference, Raymond J. Tesi, MD, rather forcefully refuted that approach. “Amyloid and tau therapies have had 20 years to prove themselves. We have multiple cases where we’ve been able to decrease amyloid, maybe not so much tau, but certainly amyloid, and the benefits are mild at best. So I think that the Alzheimer’s drug development community, whether you look at the NIH, whether you look at academia, whether you look at biopharma, has focused on a target that has not proven itself, and it’s time to move on,” said Dr. Tesi, who is president, CEO, and chief medical officer at INmune Bio.
Later in the session,
One audience member defended the potential importance of A-beta and tau, especially in astrogliosis, which is a reaction to stress by astrocytes that attempts to limit tissue damage. The questioner suggested that it was still important to measure the effect of a novel drug on A-beta and tau. “What would be the cause of the reactive astrogliosis and microglia activation, if we are not giving a damn about amyloid and tau?” he asked.
After a bit of back and forth, Dr. Tesi replied: “We both have a religious belief here, and sooner or later we’ll get the answer.”
A diverse clinical pipeline
The session itself focused on four companies, including Dr. Tesi’s INmune Bio, which have drugs with alternative mechanisms entering the advanced stages of clinical development. That’s good news, according to Heather Snyder, PhD, who is vice president of Medical & Scientific Relations at the Alzheimer’s Association. “One of the things that I think is really important is the diversity of what’s in the clinical pipeline, and it’s not just in the very beginning anymore. We’re seeing [companies] now reporting phase 2 [studies] and planning their next stage. That’s something that as a field we should be excited about. As we understand more and more about the biology, we’re now seeing that translating into clinical trials and we’re seeing that translate through the clinical pipeline of development,” said Dr. Snyder in an interview.
Targeting neuroinflammation
Dr. Tesi kicked off the session describing INmune Bio’s focus on neuroinflammation. The company’s drug candidate targets soluble tumor necrosis factor (TNF), which the company believes is a direct cause of Alzheimer’s disease through promotion of inflammation. He noted that TNF is a primary mediator of inflammation in rheumatoid arthritis, and patients with RA have an eightfold increased risk of developing Alzheimer’s disease, compared with the general population, while patients with RA who are taking anti-TNF medication have a 60% lower risk than the general population.
The company’s TNF inhibitor XPro is also unique in that it induces remyelination in mice, while other TNF inhibitors potentially “abuse” the brain by causing demyelination. Earlier research showed that it reduces neuroinflammation, improves nerve cell survival, and improves synaptic function. The company is conducting two phase 2 clinical trials, one in patients with mild cognitive impairment (MCI) and one in mild Alzheimer’s disease. They also use the MCI Alzheimer’s Cognitive Composite (EMACC) tool for assessing outcomes rather than the more commonly used Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). “ADAS-Cog is like trying to make sushi with an axe. It is designed for moderate to severe disease, and trying to use it for mild (Alzheimer’s disease) or MCI is a mistake. EMACC is purpose built for mild [AD] and MCI patients,” said Dr. Tesi.
Maintaining homeostatis
Next, Hans Moebius, MD, PhD, chief medical officer of Athira Pharma, described his company’s focus on the hepatocyte growth factor (HGF) receptor, also known as tyrosine kinase MET (HGF/MET). It plays an important role in brain development and homeostasis, and it is expressed at lower levels in the frontal cortex and hippocampus of patients with Alzheimer’s disease. The company’s small-molecule drug candidate boosts the HGF/MET pathway, leading to downstream neuroprotection and neurotrophic effects. It also promotes formation of new synapses.
Dr. Moebius presented the results of a phase 2 trial showing that the drug, called fosgonimeton, led to significant cognitive improvement compared with placebo. The company is conducting a phase 3 clinical trial.
Type 3 diabetes?
In his talk, John Didsbury, PhD, founder and CEO of T3D Therapeutics, framed Alzheimer’s disease as a disease of metabolic dysfunction. He believes alterations to glucose and lipids in the brain cause structural changes that lead to symptoms. He pointed out that the strongest genetic Alzheimer’s disease risk factor is a mutant form of the lipid transport protein APOE4.
“What we have is dysregulated glucose energy metabolism and lipid metabolism that really cause, in our mind, the structural event changes and the stress event changes – plaques, tangles, inflammation, etc. – but these events perpetuate the dysregulated metabolism. It’s a massive positive feedback loop that many have called type 3 diabetes – a brain-specific form of diabetes,” said Dr. Didsbury.
The company’s approach is to use systems biology to identify a drug target that can bypass multiple aberrant insulin signaling pathways. Its drug candidate regulates the expression of multiple genes involved in glucose metabolism. Dr. Didsbury presented interim results from a phase 2 study showing improvement over placebo.
Focusing on neurotoxic proteins
The final presentation of the session was by Maria Maccecchini, PhD, founder, president, and CEO of Annovis Bio. The company’s drug, buntanetap, reduces expression of a range of neurotoxic proteins. The downstream effects include restoration of axonal transport, reduction of inflammation, and protection of nerve cells. The company believes that Alzheimer’s disease results from acute and chronic stress events that lead to high levels of neurotoxic proteins, which include A-beta, tau, alpha-synuclein, and TDP43. The proteins aren’t just players in Alzheimer’s disease – they are present in abnormal levels in Parkinson’s disease and a range of other brain pathologies.
“In the brain of an Alzheimer’s and of a Parkinson’s [patient], you’re going to find all four proteins. You’ll find them in different concentrations, at different time points, in different brain areas. If you just remove one, you still have the other three that cause impairment in axonal transport, and that leads to inflammation that leads to neurodegeneration,” said Dr. Maccecchini.
The company’s drug manages to reduce levels of all four proteins by binding to a segment of messenger RNA (mRNA) shared by all of them. mRNA serves as a template for protein synthesis. Under normal conditions, the neurotoxic protein concentrations are kept low because the mRNA segment remains bound to a regulatory protein that prevents synthesis from occurring. However, when stress leads to high levels of iron, this regulatory binding protein releases the mRNA segment (along with the rest of the mRNA). The freed mRNA becomes available to the cell’s protein synthesis machinery, which starts producing high levels of neurotoxic proteins. Annovis Bio’s drug improves the ability of the regulatory protein to bind to the mRNA segment, preventing protein expression even in high-iron conditions. It works on all four neurotoxic proteins because they all have the regulatory segment in their mRNA.
The drug led to improvements in phase 2 studies of Alzheimer’s disease and Parkinson’s disease, and the company is currently recruiting for a phase 3 study in Parkinson’s disease and a phase 2/3 dose-response study in Alzheimer’s disease.
Combination treatments for a complex disease
Taken together, the presentations provided a snapshot of the post–A-beta/tau Alzheimer’s development world, and the future could be messy. Alzheimer’s disease and other dementias are likely to require combination treatments, according to Dr. Snyder. “This is a complex disease, not just Alzheimer’s but other dementias. It’s not going to be a single drug, a single target. It’s going to require some type of combinatorial approach, whether that be with medication and lifestyle interventions, or risk reduction, and different medications,” she said.
The latest results are good news for that approach: “We’re seeing that maturation of the science in these trials,” said Dr. Snyder.
Cheng Fang, PhD, senior vice president of research and development at Annovis Bio, agreed with that sentiment. “I believe [Alzheimer’s disease and dementia] is a very complicated disease. I always call them diseases instead of a disease because it’s a spectrum. I don’t believe one drug can cure them all, as much as I am confident in our drug. I think it’s extremely important to encourage this kind of diverse thinking,” said Dr. Fang.
Dr. Snyder has no relevant financial disclosures. Dr. Tesi, Dr. Moebius, Dr. Didsbury, Dr. Maccecchini, and Dr. Fang are employees and in some cases stockholders of their respective companies.
AT AAIC 2022
Plasma biomarkers predict COVID’s neurological sequelae
SAN DIEGO – Even after recovery of an acute COVID-19 infection, some patients experience extended or even long-term symptoms that can range from mild to debilitating. Some of these symptoms are neurological: headaches, brain fog, cognitive impairment, loss of taste or smell, and even cerebrovascular complications such stroke. There are even hints that COVID-19 infection could lead to future neurodegeneration.
Those issues have prompted efforts to identify biomarkers that can help track and monitor neurological complications of COVID-19. “Throughout the course of the pandemic, it has become apparent that COVID-19 can cause various neurological symptoms. Because of this, ,” Jennifer Cooper said during a lecture at the Alzheimer’s Association International Conference. She presented new research suggesting that neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) may prove useful.
Ms. Cooper is a master’s degree student at the University of British Columbia and Canada.
Looking for sensitivity and specificity in plasma biomarkers
The researchers turned to plasma-based markers because they can reflect underlying pathology in the central nervous system. They focused on NfL, which reflects axonal damage, and GFAP, which is a marker of astrocyte activation.
The researchers analyzed data from 209 patients with COVID-19 who were admitted to the Vancouver (B.C.) General Hospital intensive care unit. Sixty-four percent were male, and the median age was 61 years. Sixty percent were ventilated, and 17% died.
The researchers determined if an individual patient’s biomarker level at hospital admission fell within a normal biomarker reference interval. A total of 53% had NfL levels outside the normal range, and 42% had GFAP levels outside the normal range. In addition, 31% of patients had both GFAP and NfL levels outside of the normal range.
Among all patients, 12% experienced ischemia, 4% hemorrhage, 2% seizures, and 10% degeneration.
At admission, NfL predicted a neurological complication with an area under the curve (AUC) of 0.702. GFAP had an AUC of 0.722. In combination, they had an AUC of 0.743. At 1 week, NfL had an AUC of 0.802, GFAP an AUC of 0.733, and the combination an AUC of 0.812.
Using age-specific cutoff values, the researchers found increased risks for neurological complications at admission (NfL odds ratio [OR], 2.9; GFAP OR, 1.6; combined OR, 2.1) and at 1 week (NfL OR, not significant; GFAP OR, 4.8; combined OR, 6.6). “We can see that both NFL and GFAP have utility in detecting neurological complications. And combining both of our markers improves detection at both time points. NfL is a marker that provides more sensitivity, where in this cohort GFAP is a marker that provides a little bit more specificity,” said Ms. Cooper.
Will additional biomarkers help?
The researchers are continuing to follow up patients at 6 months and 18 months post diagnosis, using neuropsychiatric tests and additional biomarker analysis, as well as PET and MRI scans. The patient sample is being expanded to those in the general hospital ward and some who were not hospitalized.
During the Q&A session, Ms. Cooper was asked if the group had collected reference data from patients who were admitted to the ICU with non-COVID disease. She responded that the group has some of that data, but as the pandemic went on they had difficulty finding patients who had never been infected with COVID to serve as reliable controls. To date, they have identified 33 controls who had a respiratory condition when admitted to the ICU. “What we see is the neurological biomarker levels in COVID are slightly lower than those with another respiratory condition in the ICU. But the data has a massive spread and the significance is very small between the two groups,” said Ms. Cooper.
Unanswered questions
The study is interesting, but leaves a lot of unanswered questions, according to Wiesje van der Flier, PhD, who moderated the session where the study was presented. “There are a lot of unknowns still: Will [the biomarkers] become normal again, once the COVID is over? Also, there was an increased risk, but it was not a one-to-one correspondence, so you can also have the increased markers but not have the neurological signs or symptoms. So I thought there were lots of questions as well,” said Dr. van der Flier, professor of neurology at Amsterdam University Medical Center.
She noted that researchers at her institution in Amsterdam have observed similar relationships, and that the associations between neurological complications and plasma biomarkers over time will be an important topic of study.
The work could provide more information on neurological manifestations of long COVID, such as long-haul fatigue. “You might also think that’s some response in their brain. It would be great if we could actually capture that [using biomarkers],” said Dr. van der Flier.
Ms. Cooper and Dr. van der Flier have no relevant financial disclosures.
SAN DIEGO – Even after recovery of an acute COVID-19 infection, some patients experience extended or even long-term symptoms that can range from mild to debilitating. Some of these symptoms are neurological: headaches, brain fog, cognitive impairment, loss of taste or smell, and even cerebrovascular complications such stroke. There are even hints that COVID-19 infection could lead to future neurodegeneration.
Those issues have prompted efforts to identify biomarkers that can help track and monitor neurological complications of COVID-19. “Throughout the course of the pandemic, it has become apparent that COVID-19 can cause various neurological symptoms. Because of this, ,” Jennifer Cooper said during a lecture at the Alzheimer’s Association International Conference. She presented new research suggesting that neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) may prove useful.
Ms. Cooper is a master’s degree student at the University of British Columbia and Canada.
Looking for sensitivity and specificity in plasma biomarkers
The researchers turned to plasma-based markers because they can reflect underlying pathology in the central nervous system. They focused on NfL, which reflects axonal damage, and GFAP, which is a marker of astrocyte activation.
The researchers analyzed data from 209 patients with COVID-19 who were admitted to the Vancouver (B.C.) General Hospital intensive care unit. Sixty-four percent were male, and the median age was 61 years. Sixty percent were ventilated, and 17% died.
The researchers determined if an individual patient’s biomarker level at hospital admission fell within a normal biomarker reference interval. A total of 53% had NfL levels outside the normal range, and 42% had GFAP levels outside the normal range. In addition, 31% of patients had both GFAP and NfL levels outside of the normal range.
Among all patients, 12% experienced ischemia, 4% hemorrhage, 2% seizures, and 10% degeneration.
At admission, NfL predicted a neurological complication with an area under the curve (AUC) of 0.702. GFAP had an AUC of 0.722. In combination, they had an AUC of 0.743. At 1 week, NfL had an AUC of 0.802, GFAP an AUC of 0.733, and the combination an AUC of 0.812.
Using age-specific cutoff values, the researchers found increased risks for neurological complications at admission (NfL odds ratio [OR], 2.9; GFAP OR, 1.6; combined OR, 2.1) and at 1 week (NfL OR, not significant; GFAP OR, 4.8; combined OR, 6.6). “We can see that both NFL and GFAP have utility in detecting neurological complications. And combining both of our markers improves detection at both time points. NfL is a marker that provides more sensitivity, where in this cohort GFAP is a marker that provides a little bit more specificity,” said Ms. Cooper.
Will additional biomarkers help?
The researchers are continuing to follow up patients at 6 months and 18 months post diagnosis, using neuropsychiatric tests and additional biomarker analysis, as well as PET and MRI scans. The patient sample is being expanded to those in the general hospital ward and some who were not hospitalized.
During the Q&A session, Ms. Cooper was asked if the group had collected reference data from patients who were admitted to the ICU with non-COVID disease. She responded that the group has some of that data, but as the pandemic went on they had difficulty finding patients who had never been infected with COVID to serve as reliable controls. To date, they have identified 33 controls who had a respiratory condition when admitted to the ICU. “What we see is the neurological biomarker levels in COVID are slightly lower than those with another respiratory condition in the ICU. But the data has a massive spread and the significance is very small between the two groups,” said Ms. Cooper.
Unanswered questions
The study is interesting, but leaves a lot of unanswered questions, according to Wiesje van der Flier, PhD, who moderated the session where the study was presented. “There are a lot of unknowns still: Will [the biomarkers] become normal again, once the COVID is over? Also, there was an increased risk, but it was not a one-to-one correspondence, so you can also have the increased markers but not have the neurological signs or symptoms. So I thought there were lots of questions as well,” said Dr. van der Flier, professor of neurology at Amsterdam University Medical Center.
She noted that researchers at her institution in Amsterdam have observed similar relationships, and that the associations between neurological complications and plasma biomarkers over time will be an important topic of study.
The work could provide more information on neurological manifestations of long COVID, such as long-haul fatigue. “You might also think that’s some response in their brain. It would be great if we could actually capture that [using biomarkers],” said Dr. van der Flier.
Ms. Cooper and Dr. van der Flier have no relevant financial disclosures.
SAN DIEGO – Even after recovery of an acute COVID-19 infection, some patients experience extended or even long-term symptoms that can range from mild to debilitating. Some of these symptoms are neurological: headaches, brain fog, cognitive impairment, loss of taste or smell, and even cerebrovascular complications such stroke. There are even hints that COVID-19 infection could lead to future neurodegeneration.
Those issues have prompted efforts to identify biomarkers that can help track and monitor neurological complications of COVID-19. “Throughout the course of the pandemic, it has become apparent that COVID-19 can cause various neurological symptoms. Because of this, ,” Jennifer Cooper said during a lecture at the Alzheimer’s Association International Conference. She presented new research suggesting that neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) may prove useful.
Ms. Cooper is a master’s degree student at the University of British Columbia and Canada.
Looking for sensitivity and specificity in plasma biomarkers
The researchers turned to plasma-based markers because they can reflect underlying pathology in the central nervous system. They focused on NfL, which reflects axonal damage, and GFAP, which is a marker of astrocyte activation.
The researchers analyzed data from 209 patients with COVID-19 who were admitted to the Vancouver (B.C.) General Hospital intensive care unit. Sixty-four percent were male, and the median age was 61 years. Sixty percent were ventilated, and 17% died.
The researchers determined if an individual patient’s biomarker level at hospital admission fell within a normal biomarker reference interval. A total of 53% had NfL levels outside the normal range, and 42% had GFAP levels outside the normal range. In addition, 31% of patients had both GFAP and NfL levels outside of the normal range.
Among all patients, 12% experienced ischemia, 4% hemorrhage, 2% seizures, and 10% degeneration.
At admission, NfL predicted a neurological complication with an area under the curve (AUC) of 0.702. GFAP had an AUC of 0.722. In combination, they had an AUC of 0.743. At 1 week, NfL had an AUC of 0.802, GFAP an AUC of 0.733, and the combination an AUC of 0.812.
Using age-specific cutoff values, the researchers found increased risks for neurological complications at admission (NfL odds ratio [OR], 2.9; GFAP OR, 1.6; combined OR, 2.1) and at 1 week (NfL OR, not significant; GFAP OR, 4.8; combined OR, 6.6). “We can see that both NFL and GFAP have utility in detecting neurological complications. And combining both of our markers improves detection at both time points. NfL is a marker that provides more sensitivity, where in this cohort GFAP is a marker that provides a little bit more specificity,” said Ms. Cooper.
Will additional biomarkers help?
The researchers are continuing to follow up patients at 6 months and 18 months post diagnosis, using neuropsychiatric tests and additional biomarker analysis, as well as PET and MRI scans. The patient sample is being expanded to those in the general hospital ward and some who were not hospitalized.
During the Q&A session, Ms. Cooper was asked if the group had collected reference data from patients who were admitted to the ICU with non-COVID disease. She responded that the group has some of that data, but as the pandemic went on they had difficulty finding patients who had never been infected with COVID to serve as reliable controls. To date, they have identified 33 controls who had a respiratory condition when admitted to the ICU. “What we see is the neurological biomarker levels in COVID are slightly lower than those with another respiratory condition in the ICU. But the data has a massive spread and the significance is very small between the two groups,” said Ms. Cooper.
Unanswered questions
The study is interesting, but leaves a lot of unanswered questions, according to Wiesje van der Flier, PhD, who moderated the session where the study was presented. “There are a lot of unknowns still: Will [the biomarkers] become normal again, once the COVID is over? Also, there was an increased risk, but it was not a one-to-one correspondence, so you can also have the increased markers but not have the neurological signs or symptoms. So I thought there were lots of questions as well,” said Dr. van der Flier, professor of neurology at Amsterdam University Medical Center.
She noted that researchers at her institution in Amsterdam have observed similar relationships, and that the associations between neurological complications and plasma biomarkers over time will be an important topic of study.
The work could provide more information on neurological manifestations of long COVID, such as long-haul fatigue. “You might also think that’s some response in their brain. It would be great if we could actually capture that [using biomarkers],” said Dr. van der Flier.
Ms. Cooper and Dr. van der Flier have no relevant financial disclosures.
AT AAIC 2022
In MCI, combo training boosts effect
SAN DIEGO – The findings were drawn from an unusual study design that split patients into five groups, one of which included both interventions.
After the study was completed, researchers collapsed the groups into a single analysis to compare the different regimens, according to Manuel Montero-Odasso, MD, PhD, who presented the work at the Alzheimer’s Association International Conference. He is a geriatrician at Parkwood Institute, London, Ont.
Two previous trials looked at whether the combination of exercise plus cognitive training could outperform either intervention alone. In both, the combination improved cognition but not as much as either intervention alone. “So it seemed that when they combine it, they didn’t do as well,” said Dr. Montero-Odasso. Those findings left doubt about whether or not there is synergism between the two approaches.
Sequential, not simultaneous
A possible explanation for the finding is that patients who are doing both cognitive training and physical exercise simultaneously might not be able to focus enough on either task to do get the maximum benefit. “When we try to combine concurrently, participants or patients cannot focus and do enough progression in both at the same time. That’s the reason we designed the trial in a way that the interventions were sequential. You got a very good quality (cognitive) training, and later you got the exercise,” said Dr. Montero-Odasso.
In the new study, patients receiving both interventions conducted the cognitive training first, then did physical exercises 30 minutes later. “The practical message is that you should follow a program. Something I see in my patients, when they do the two things at the same time, they don’t pay enough attention,” said Dr. Montero-Odasso.
The researchers added vitamin D to the regimen as there have been small studies reporting that vitamin D supplementation can lead to greater muscle mass resulting from exercise.
The study included 176 patients aged 60-85 with MCI. The researchers excluded patients already participating in an active exercise program with a personal trainer, as well as those taking vitamin D at doses higher than 1,000 IU/day.
Over 20 weeks, the randomized groups included combination exercise and cognitive training with vitamin D (10,000 IU three times per week), exercise and cognitive training with placebo, exercise with a cognitive control and vitamin D, exercise with a cognitive control and placebo, and an exercise control (balance and toning) with cognitive control and placebo.
The interventions were completed three times per week. Cognitive training employed a tablet with multifunctional tasks and memory components. It was adaptive, becoming more difficult as patients improved or simplifying the task if a patient struggled. The exercise component included 40 minutes of progressive, supervised resistance training, followed by 20 minutes of aerobic exercise.
Compared with the double-placebo group, the double-intervention group had significant improvement in cognitive performance. “Exercise alone without cognitive training shows an effect, but that effect was lower than a combination with cognitive training,” said Dr. Montero-Odasso.
The combined groups had medium effect sizes on cognition when combined with vitamin D (Cohen’s d, 0.65; P = .003) and with vitamin D placebo (Cohen’s d, 0.58; P = .013). There were nonsignificant improvements in the exercise and vitamin D group (Cohen’s d, 0.30; P = .241) and the exercise plus placebo group (Cohen’s d, 0.42; P = .139)
After collapsing the arms, the researchers found that the exercise plus cognitive training regimen had an effect size of 0.62 (P = .002), while exercise alone only trended toward improvement and with a small effect size (Cohen’s d, 0.36; P = .13). There was no apparent effect of vitamin D supplementation, though Dr. Montero-Odasso pointed out that most participants were taking vitamin D supplements before study entry and had normal to high serum levels of vitamin D.
‘Optimistic’ results
The study was limited by an inability to retain patients due to the COVID-19 pandemic, leading to a dropout rate of 17%.
“I think the idea of combining risk reduction strategies together in a population and individuals with MCI is really exciting. These are optimistic results. You certainly need to look into a larger and more diverse population as it goes forward,” said Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, who was asked to comment on the study.
She noted that the study looked at all-cause cognitive impairment. It would be interesting, Dr. Snyder said, to see how individuals with different underlying conditions handle the combination intervention.
The researchers are now in the planning stage of the Synergic 2 trial, which will incorporate exercise and cognitive training, plus diet and sleep counseling. It will be conducted virtually, involving one-to-one interactions with coaches.
Dr. Montero-Odasso and Dr. Snyder have no relevant financial disclosures.
SAN DIEGO – The findings were drawn from an unusual study design that split patients into five groups, one of which included both interventions.
After the study was completed, researchers collapsed the groups into a single analysis to compare the different regimens, according to Manuel Montero-Odasso, MD, PhD, who presented the work at the Alzheimer’s Association International Conference. He is a geriatrician at Parkwood Institute, London, Ont.
Two previous trials looked at whether the combination of exercise plus cognitive training could outperform either intervention alone. In both, the combination improved cognition but not as much as either intervention alone. “So it seemed that when they combine it, they didn’t do as well,” said Dr. Montero-Odasso. Those findings left doubt about whether or not there is synergism between the two approaches.
Sequential, not simultaneous
A possible explanation for the finding is that patients who are doing both cognitive training and physical exercise simultaneously might not be able to focus enough on either task to do get the maximum benefit. “When we try to combine concurrently, participants or patients cannot focus and do enough progression in both at the same time. That’s the reason we designed the trial in a way that the interventions were sequential. You got a very good quality (cognitive) training, and later you got the exercise,” said Dr. Montero-Odasso.
In the new study, patients receiving both interventions conducted the cognitive training first, then did physical exercises 30 minutes later. “The practical message is that you should follow a program. Something I see in my patients, when they do the two things at the same time, they don’t pay enough attention,” said Dr. Montero-Odasso.
The researchers added vitamin D to the regimen as there have been small studies reporting that vitamin D supplementation can lead to greater muscle mass resulting from exercise.
The study included 176 patients aged 60-85 with MCI. The researchers excluded patients already participating in an active exercise program with a personal trainer, as well as those taking vitamin D at doses higher than 1,000 IU/day.
Over 20 weeks, the randomized groups included combination exercise and cognitive training with vitamin D (10,000 IU three times per week), exercise and cognitive training with placebo, exercise with a cognitive control and vitamin D, exercise with a cognitive control and placebo, and an exercise control (balance and toning) with cognitive control and placebo.
The interventions were completed three times per week. Cognitive training employed a tablet with multifunctional tasks and memory components. It was adaptive, becoming more difficult as patients improved or simplifying the task if a patient struggled. The exercise component included 40 minutes of progressive, supervised resistance training, followed by 20 minutes of aerobic exercise.
Compared with the double-placebo group, the double-intervention group had significant improvement in cognitive performance. “Exercise alone without cognitive training shows an effect, but that effect was lower than a combination with cognitive training,” said Dr. Montero-Odasso.
The combined groups had medium effect sizes on cognition when combined with vitamin D (Cohen’s d, 0.65; P = .003) and with vitamin D placebo (Cohen’s d, 0.58; P = .013). There were nonsignificant improvements in the exercise and vitamin D group (Cohen’s d, 0.30; P = .241) and the exercise plus placebo group (Cohen’s d, 0.42; P = .139)
After collapsing the arms, the researchers found that the exercise plus cognitive training regimen had an effect size of 0.62 (P = .002), while exercise alone only trended toward improvement and with a small effect size (Cohen’s d, 0.36; P = .13). There was no apparent effect of vitamin D supplementation, though Dr. Montero-Odasso pointed out that most participants were taking vitamin D supplements before study entry and had normal to high serum levels of vitamin D.
‘Optimistic’ results
The study was limited by an inability to retain patients due to the COVID-19 pandemic, leading to a dropout rate of 17%.
“I think the idea of combining risk reduction strategies together in a population and individuals with MCI is really exciting. These are optimistic results. You certainly need to look into a larger and more diverse population as it goes forward,” said Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, who was asked to comment on the study.
She noted that the study looked at all-cause cognitive impairment. It would be interesting, Dr. Snyder said, to see how individuals with different underlying conditions handle the combination intervention.
The researchers are now in the planning stage of the Synergic 2 trial, which will incorporate exercise and cognitive training, plus diet and sleep counseling. It will be conducted virtually, involving one-to-one interactions with coaches.
Dr. Montero-Odasso and Dr. Snyder have no relevant financial disclosures.
SAN DIEGO – The findings were drawn from an unusual study design that split patients into five groups, one of which included both interventions.
After the study was completed, researchers collapsed the groups into a single analysis to compare the different regimens, according to Manuel Montero-Odasso, MD, PhD, who presented the work at the Alzheimer’s Association International Conference. He is a geriatrician at Parkwood Institute, London, Ont.
Two previous trials looked at whether the combination of exercise plus cognitive training could outperform either intervention alone. In both, the combination improved cognition but not as much as either intervention alone. “So it seemed that when they combine it, they didn’t do as well,” said Dr. Montero-Odasso. Those findings left doubt about whether or not there is synergism between the two approaches.
Sequential, not simultaneous
A possible explanation for the finding is that patients who are doing both cognitive training and physical exercise simultaneously might not be able to focus enough on either task to do get the maximum benefit. “When we try to combine concurrently, participants or patients cannot focus and do enough progression in both at the same time. That’s the reason we designed the trial in a way that the interventions were sequential. You got a very good quality (cognitive) training, and later you got the exercise,” said Dr. Montero-Odasso.
In the new study, patients receiving both interventions conducted the cognitive training first, then did physical exercises 30 minutes later. “The practical message is that you should follow a program. Something I see in my patients, when they do the two things at the same time, they don’t pay enough attention,” said Dr. Montero-Odasso.
The researchers added vitamin D to the regimen as there have been small studies reporting that vitamin D supplementation can lead to greater muscle mass resulting from exercise.
The study included 176 patients aged 60-85 with MCI. The researchers excluded patients already participating in an active exercise program with a personal trainer, as well as those taking vitamin D at doses higher than 1,000 IU/day.
Over 20 weeks, the randomized groups included combination exercise and cognitive training with vitamin D (10,000 IU three times per week), exercise and cognitive training with placebo, exercise with a cognitive control and vitamin D, exercise with a cognitive control and placebo, and an exercise control (balance and toning) with cognitive control and placebo.
The interventions were completed three times per week. Cognitive training employed a tablet with multifunctional tasks and memory components. It was adaptive, becoming more difficult as patients improved or simplifying the task if a patient struggled. The exercise component included 40 minutes of progressive, supervised resistance training, followed by 20 minutes of aerobic exercise.
Compared with the double-placebo group, the double-intervention group had significant improvement in cognitive performance. “Exercise alone without cognitive training shows an effect, but that effect was lower than a combination with cognitive training,” said Dr. Montero-Odasso.
The combined groups had medium effect sizes on cognition when combined with vitamin D (Cohen’s d, 0.65; P = .003) and with vitamin D placebo (Cohen’s d, 0.58; P = .013). There were nonsignificant improvements in the exercise and vitamin D group (Cohen’s d, 0.30; P = .241) and the exercise plus placebo group (Cohen’s d, 0.42; P = .139)
After collapsing the arms, the researchers found that the exercise plus cognitive training regimen had an effect size of 0.62 (P = .002), while exercise alone only trended toward improvement and with a small effect size (Cohen’s d, 0.36; P = .13). There was no apparent effect of vitamin D supplementation, though Dr. Montero-Odasso pointed out that most participants were taking vitamin D supplements before study entry and had normal to high serum levels of vitamin D.
‘Optimistic’ results
The study was limited by an inability to retain patients due to the COVID-19 pandemic, leading to a dropout rate of 17%.
“I think the idea of combining risk reduction strategies together in a population and individuals with MCI is really exciting. These are optimistic results. You certainly need to look into a larger and more diverse population as it goes forward,” said Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, who was asked to comment on the study.
She noted that the study looked at all-cause cognitive impairment. It would be interesting, Dr. Snyder said, to see how individuals with different underlying conditions handle the combination intervention.
The researchers are now in the planning stage of the Synergic 2 trial, which will incorporate exercise and cognitive training, plus diet and sleep counseling. It will be conducted virtually, involving one-to-one interactions with coaches.
Dr. Montero-Odasso and Dr. Snyder have no relevant financial disclosures.
AT AAIC 2022
Regular exercise appears to slow cognitive decline in MCI
(MCI), new research from the largest study of its kind suggests. Topline results from the EXERT trial showed patients with MCI who participated regularly in either aerobic exercise or stretching/balance/range-of-motion exercises maintained stable global cognitive function over 12 months of follow-up – with no differences between the two types of exercise.
“We’re excited about these findings, because these types of exercises that we’re seeing can protect against cognitive decline are accessible to everyone and therefore scalable to the public,” study investigator Laura Baker, PhD, Wake Forest University School of Medicine, Winston-Salem, N.C., said at a press briefing.
The topline results were presented at the 2022 Alzheimer’s Association International Conference.
No decline
The 18-month EXERT trial was designed to be the definitive study to answer the question about whether exercise can slow cognitive decline in older adults with amnestic MCI, Dr. Baker reported. Investigators enrolled 296 sedentary men and women with MCI (mean age, about 75 years). All were randomly allocated to either an aerobic exercise group (maintaining a heart rate at about 70%-85%) or a stretching and balance group (maintaining heart rate less than 35%).
Both groups exercised four times per week for about 30-40 minutes. In the first 12 months they were supervised by a trainer at the YMCA and then they exercised independently for the final 6 months.
Participants were assessed at baseline and every 6 months. The primary endpoint was change from baseline on the ADAS-Cog-Exec, a validated measure of global cognitive function, at the end of the 12 months of supervised exercise.
During the first 12 months, participants completed over 31,000 sessions of exercise, which is “quite impressive,” Dr. Baker said.
Over the first 12 months, neither the aerobic group nor the stretch/balance group showed a decline on the ADAS-Cog-Exec.
“We saw no group differences, and importantly, no decline after 12 months,” Dr. Baker reported.
Supported exercise is ‘crucial’
To help “make sense” of these findings, Dr. Baker noted that 12-month changes in the ADAS-Cog-Exec for the EXERT intervention groups were also compared with a “usual care” cohort of adults matched for age, sex, education, baseline cognitive status, and APOE4 genotype.
In this “apples-to-apples” comparison, the usual care cohort showed the expected decline or worsening of cognitive function over 12 months on the ADAS-Cog-Exec, but the EXERT exercise groups did not.
Dr. Baker noted that both exercise groups received equal amounts of weekly socialization, which may have contributed to the apparent protective effects on the brain.
A greater volume of exercise in EXERT, compared with other trials, may also be a factor. Each individual participant in EXERT completed more than 100 hours of exercise.
“The take-home message is that an increased amount of either low-intensity or high-intensity exercise for 120-150 minutes per week for 12 months may slow cognitive decline in sedentary older adults with MCI,” Dr. Baker said.
“What’s critical is that this regular exercise must be supported in these older [patients] with MCI. It must be supervised. There has to be some social component,” she added.
In her view, 120 minutes of regular supported exercise for sedentary individuals with MCI “needs to be part of the recommendation for risk reduction.”
Important study
Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that several studies over the years have suggested that different types of exercise can have benefits on the brain.
“What’s important about this study is that it’s in a population of people that have MCI and are already experiencing memory changes,” Dr. Snyder said.
“The results suggest that engaging in both of these types of exercise may be beneficial for our brain. And given that this is the largest study of its kind in a population of people with MCI, it suggests it’s ‘never too late’ to start exercising,” she added.
Dr. Snyder noted the importance of continuing this work and to continue following these individuals “over time as well.”
The study was funded by the National Institutes of Health, National Institute on Aging. Dr. Baker and Dr. Snyder have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(MCI), new research from the largest study of its kind suggests. Topline results from the EXERT trial showed patients with MCI who participated regularly in either aerobic exercise or stretching/balance/range-of-motion exercises maintained stable global cognitive function over 12 months of follow-up – with no differences between the two types of exercise.
“We’re excited about these findings, because these types of exercises that we’re seeing can protect against cognitive decline are accessible to everyone and therefore scalable to the public,” study investigator Laura Baker, PhD, Wake Forest University School of Medicine, Winston-Salem, N.C., said at a press briefing.
The topline results were presented at the 2022 Alzheimer’s Association International Conference.
No decline
The 18-month EXERT trial was designed to be the definitive study to answer the question about whether exercise can slow cognitive decline in older adults with amnestic MCI, Dr. Baker reported. Investigators enrolled 296 sedentary men and women with MCI (mean age, about 75 years). All were randomly allocated to either an aerobic exercise group (maintaining a heart rate at about 70%-85%) or a stretching and balance group (maintaining heart rate less than 35%).
Both groups exercised four times per week for about 30-40 minutes. In the first 12 months they were supervised by a trainer at the YMCA and then they exercised independently for the final 6 months.
Participants were assessed at baseline and every 6 months. The primary endpoint was change from baseline on the ADAS-Cog-Exec, a validated measure of global cognitive function, at the end of the 12 months of supervised exercise.
During the first 12 months, participants completed over 31,000 sessions of exercise, which is “quite impressive,” Dr. Baker said.
Over the first 12 months, neither the aerobic group nor the stretch/balance group showed a decline on the ADAS-Cog-Exec.
“We saw no group differences, and importantly, no decline after 12 months,” Dr. Baker reported.
Supported exercise is ‘crucial’
To help “make sense” of these findings, Dr. Baker noted that 12-month changes in the ADAS-Cog-Exec for the EXERT intervention groups were also compared with a “usual care” cohort of adults matched for age, sex, education, baseline cognitive status, and APOE4 genotype.
In this “apples-to-apples” comparison, the usual care cohort showed the expected decline or worsening of cognitive function over 12 months on the ADAS-Cog-Exec, but the EXERT exercise groups did not.
Dr. Baker noted that both exercise groups received equal amounts of weekly socialization, which may have contributed to the apparent protective effects on the brain.
A greater volume of exercise in EXERT, compared with other trials, may also be a factor. Each individual participant in EXERT completed more than 100 hours of exercise.
“The take-home message is that an increased amount of either low-intensity or high-intensity exercise for 120-150 minutes per week for 12 months may slow cognitive decline in sedentary older adults with MCI,” Dr. Baker said.
“What’s critical is that this regular exercise must be supported in these older [patients] with MCI. It must be supervised. There has to be some social component,” she added.
In her view, 120 minutes of regular supported exercise for sedentary individuals with MCI “needs to be part of the recommendation for risk reduction.”
Important study
Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that several studies over the years have suggested that different types of exercise can have benefits on the brain.
“What’s important about this study is that it’s in a population of people that have MCI and are already experiencing memory changes,” Dr. Snyder said.
“The results suggest that engaging in both of these types of exercise may be beneficial for our brain. And given that this is the largest study of its kind in a population of people with MCI, it suggests it’s ‘never too late’ to start exercising,” she added.
Dr. Snyder noted the importance of continuing this work and to continue following these individuals “over time as well.”
The study was funded by the National Institutes of Health, National Institute on Aging. Dr. Baker and Dr. Snyder have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(MCI), new research from the largest study of its kind suggests. Topline results from the EXERT trial showed patients with MCI who participated regularly in either aerobic exercise or stretching/balance/range-of-motion exercises maintained stable global cognitive function over 12 months of follow-up – with no differences between the two types of exercise.
“We’re excited about these findings, because these types of exercises that we’re seeing can protect against cognitive decline are accessible to everyone and therefore scalable to the public,” study investigator Laura Baker, PhD, Wake Forest University School of Medicine, Winston-Salem, N.C., said at a press briefing.
The topline results were presented at the 2022 Alzheimer’s Association International Conference.
No decline
The 18-month EXERT trial was designed to be the definitive study to answer the question about whether exercise can slow cognitive decline in older adults with amnestic MCI, Dr. Baker reported. Investigators enrolled 296 sedentary men and women with MCI (mean age, about 75 years). All were randomly allocated to either an aerobic exercise group (maintaining a heart rate at about 70%-85%) or a stretching and balance group (maintaining heart rate less than 35%).
Both groups exercised four times per week for about 30-40 minutes. In the first 12 months they were supervised by a trainer at the YMCA and then they exercised independently for the final 6 months.
Participants were assessed at baseline and every 6 months. The primary endpoint was change from baseline on the ADAS-Cog-Exec, a validated measure of global cognitive function, at the end of the 12 months of supervised exercise.
During the first 12 months, participants completed over 31,000 sessions of exercise, which is “quite impressive,” Dr. Baker said.
Over the first 12 months, neither the aerobic group nor the stretch/balance group showed a decline on the ADAS-Cog-Exec.
“We saw no group differences, and importantly, no decline after 12 months,” Dr. Baker reported.
Supported exercise is ‘crucial’
To help “make sense” of these findings, Dr. Baker noted that 12-month changes in the ADAS-Cog-Exec for the EXERT intervention groups were also compared with a “usual care” cohort of adults matched for age, sex, education, baseline cognitive status, and APOE4 genotype.
In this “apples-to-apples” comparison, the usual care cohort showed the expected decline or worsening of cognitive function over 12 months on the ADAS-Cog-Exec, but the EXERT exercise groups did not.
Dr. Baker noted that both exercise groups received equal amounts of weekly socialization, which may have contributed to the apparent protective effects on the brain.
A greater volume of exercise in EXERT, compared with other trials, may also be a factor. Each individual participant in EXERT completed more than 100 hours of exercise.
“The take-home message is that an increased amount of either low-intensity or high-intensity exercise for 120-150 minutes per week for 12 months may slow cognitive decline in sedentary older adults with MCI,” Dr. Baker said.
“What’s critical is that this regular exercise must be supported in these older [patients] with MCI. It must be supervised. There has to be some social component,” she added.
In her view, 120 minutes of regular supported exercise for sedentary individuals with MCI “needs to be part of the recommendation for risk reduction.”
Important study
Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that several studies over the years have suggested that different types of exercise can have benefits on the brain.
“What’s important about this study is that it’s in a population of people that have MCI and are already experiencing memory changes,” Dr. Snyder said.
“The results suggest that engaging in both of these types of exercise may be beneficial for our brain. And given that this is the largest study of its kind in a population of people with MCI, it suggests it’s ‘never too late’ to start exercising,” she added.
Dr. Snyder noted the importance of continuing this work and to continue following these individuals “over time as well.”
The study was funded by the National Institutes of Health, National Institute on Aging. Dr. Baker and Dr. Snyder have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From AAIC 2022
Chronically low wages linked to subsequent memory decline
, new research suggests. In a new analysis of more than 3,000 participants in the Health and Retirement Study, those who sustained low wages in midlife showed significantly faster memory decline than their peers who never earned low wages.
The findings could have implications for future public policy and research initiatives, the investigators noted.
“Our findings, which suggest a pattern of sustained low-wage earning is harmful for cognitive health, [are] broadly applicable to researchers across numerous health disciplines,” said co-investigator Katrina Kezios, PhD, postdoctoral researcher, department of epidemiology, Mailman School of Public Health, Columbia University, New York.
The findings were presented at the 2022 Alzheimer’s Association International Conference.
Growing number of low-wage workers
Low-wage workers make up a growing share of the U.S. labor market. Yet little research has examined the long-term relationship between earning low wages and memory decline.
The current investigators assessed 1992-2016 data from the Health and Retirement Study, a longitudinal survey of nationally representative samples of Americans aged 50 years and older. Study participants are interviewed every 2 years and provide, among other things, information on work-related factors, including hourly wages.
Memory function was measured at each visit from 2004 to 2016 using a memory composite score. The score included immediate and delayed word recall memory assessments. For those who became too impaired to complete cognitive assessment, memory tests by proxy informants were utilized.
On average, participants completed 4.8 memory assessments over the course of the study.
Researchers defined “low wage” as an hourly wage lower than two-thirds of the federal median wage for the corresponding year. They categorized low-wage exposure history as “never” or “intermittent” or “sustained” on the basis of wages earned from 1992 to 2004.
The current analysis included 3,803 participants, 1,913 of whom were men. All participants were born from 1936 to 1941. In 2004, the average age was 65 years, and the mean memory score was 1.15 standard units.
The investigators adjusted for factors that could confound the relationship between wages and cognition, including the participant’s education, parental education, household wealth, and marital status. Later, whether the participants’ occupation type was of low skill or not was also included.
Cognitive harm
The confounder-adjusted annual rate of memory decline among workers who never earned low wages was –0.12 standard units (95% confidence interval, –0.14 to –0.10).
Compared with these workers, memory decline was significantly faster among participants with sustained low wage–earning during midlife (beta for interaction between time and exposure group, –0.012; 95% CI, –0.02 to 0.01), corresponding to an annual rate of –0.13 standard units.
Put another way, the cognitive aging experienced by workers earning low wages over a 10-year period was equivalent to what workers who never earned low wages would experience over 11 years.
Although similar associations were found for men and women, it was stronger in magnitude for men – a finding Dr. Kezios said was somewhat surprising. She noted that women are commonly more at risk for dementia than men.
However, she advises caution in interpreting this finding, as there were so few men in the sustained low-wage group. “Women disproportionately make up the group of workers earning low wages,” she said.
The negative low coefficient found for those who persistently earned low wages was also observed for those who intermittently earned low wages, but this was not statistically significant.
“We can speculate or hypothesize the cumulative effect of earning low wages at each exposure interval produces more cognitive harm than maybe earning low wages at some time points over that exposure period,” said Dr. Kezios.
A sensitivity analysis that examined wage earning at the same ages but in two different birth cohorts showed similar results for the two groups. When researchers removed self-employed workers from the study sample, the same association between sustained low wages and memory decline was found.
“Our findings held up, which gave us a little more reassurance that what we were seeing is at least signaling there might be something there,” said Dr. Kezios.
She described the study as a “first pass” for documenting the harmful cognitive effects of consistently earning low wages.
It would be interesting, she said, to now determine whether there’s a “dose effect” for having a low salary. However, other studies with different designs would be needed to determine at what income level cognitive health starts to be protected and the impact of raising the minimum wage, she added.
Unique study
Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, said the study was unique. “I don’t think we have seen anything like this before,” said Dr. Snyder.
The study, which links sustained low-wage earning in midlife to later memory decline, “is looking beyond some of the other measures we’ve seen when we looked at socioeconomic status,” she noted.
The results “beg the question” of whether people who earn low wages have less access to health care, she added.
“We should think about how to ensure access and equity around health care and around potential ways that may address components of risk individuals have during their life course,” Dr. Snyder said.
She noted that the study provides a “start” at considering potential policies to address the impact of sustained low wages on overall health, particularly cognitive health, throughout life.
The study had no outside funding. Dr. Kezios has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. In a new analysis of more than 3,000 participants in the Health and Retirement Study, those who sustained low wages in midlife showed significantly faster memory decline than their peers who never earned low wages.
The findings could have implications for future public policy and research initiatives, the investigators noted.
“Our findings, which suggest a pattern of sustained low-wage earning is harmful for cognitive health, [are] broadly applicable to researchers across numerous health disciplines,” said co-investigator Katrina Kezios, PhD, postdoctoral researcher, department of epidemiology, Mailman School of Public Health, Columbia University, New York.
The findings were presented at the 2022 Alzheimer’s Association International Conference.
Growing number of low-wage workers
Low-wage workers make up a growing share of the U.S. labor market. Yet little research has examined the long-term relationship between earning low wages and memory decline.
The current investigators assessed 1992-2016 data from the Health and Retirement Study, a longitudinal survey of nationally representative samples of Americans aged 50 years and older. Study participants are interviewed every 2 years and provide, among other things, information on work-related factors, including hourly wages.
Memory function was measured at each visit from 2004 to 2016 using a memory composite score. The score included immediate and delayed word recall memory assessments. For those who became too impaired to complete cognitive assessment, memory tests by proxy informants were utilized.
On average, participants completed 4.8 memory assessments over the course of the study.
Researchers defined “low wage” as an hourly wage lower than two-thirds of the federal median wage for the corresponding year. They categorized low-wage exposure history as “never” or “intermittent” or “sustained” on the basis of wages earned from 1992 to 2004.
The current analysis included 3,803 participants, 1,913 of whom were men. All participants were born from 1936 to 1941. In 2004, the average age was 65 years, and the mean memory score was 1.15 standard units.
The investigators adjusted for factors that could confound the relationship between wages and cognition, including the participant’s education, parental education, household wealth, and marital status. Later, whether the participants’ occupation type was of low skill or not was also included.
Cognitive harm
The confounder-adjusted annual rate of memory decline among workers who never earned low wages was –0.12 standard units (95% confidence interval, –0.14 to –0.10).
Compared with these workers, memory decline was significantly faster among participants with sustained low wage–earning during midlife (beta for interaction between time and exposure group, –0.012; 95% CI, –0.02 to 0.01), corresponding to an annual rate of –0.13 standard units.
Put another way, the cognitive aging experienced by workers earning low wages over a 10-year period was equivalent to what workers who never earned low wages would experience over 11 years.
Although similar associations were found for men and women, it was stronger in magnitude for men – a finding Dr. Kezios said was somewhat surprising. She noted that women are commonly more at risk for dementia than men.
However, she advises caution in interpreting this finding, as there were so few men in the sustained low-wage group. “Women disproportionately make up the group of workers earning low wages,” she said.
The negative low coefficient found for those who persistently earned low wages was also observed for those who intermittently earned low wages, but this was not statistically significant.
“We can speculate or hypothesize the cumulative effect of earning low wages at each exposure interval produces more cognitive harm than maybe earning low wages at some time points over that exposure period,” said Dr. Kezios.
A sensitivity analysis that examined wage earning at the same ages but in two different birth cohorts showed similar results for the two groups. When researchers removed self-employed workers from the study sample, the same association between sustained low wages and memory decline was found.
“Our findings held up, which gave us a little more reassurance that what we were seeing is at least signaling there might be something there,” said Dr. Kezios.
She described the study as a “first pass” for documenting the harmful cognitive effects of consistently earning low wages.
It would be interesting, she said, to now determine whether there’s a “dose effect” for having a low salary. However, other studies with different designs would be needed to determine at what income level cognitive health starts to be protected and the impact of raising the minimum wage, she added.
Unique study
Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, said the study was unique. “I don’t think we have seen anything like this before,” said Dr. Snyder.
The study, which links sustained low-wage earning in midlife to later memory decline, “is looking beyond some of the other measures we’ve seen when we looked at socioeconomic status,” she noted.
The results “beg the question” of whether people who earn low wages have less access to health care, she added.
“We should think about how to ensure access and equity around health care and around potential ways that may address components of risk individuals have during their life course,” Dr. Snyder said.
She noted that the study provides a “start” at considering potential policies to address the impact of sustained low wages on overall health, particularly cognitive health, throughout life.
The study had no outside funding. Dr. Kezios has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. In a new analysis of more than 3,000 participants in the Health and Retirement Study, those who sustained low wages in midlife showed significantly faster memory decline than their peers who never earned low wages.
The findings could have implications for future public policy and research initiatives, the investigators noted.
“Our findings, which suggest a pattern of sustained low-wage earning is harmful for cognitive health, [are] broadly applicable to researchers across numerous health disciplines,” said co-investigator Katrina Kezios, PhD, postdoctoral researcher, department of epidemiology, Mailman School of Public Health, Columbia University, New York.
The findings were presented at the 2022 Alzheimer’s Association International Conference.
Growing number of low-wage workers
Low-wage workers make up a growing share of the U.S. labor market. Yet little research has examined the long-term relationship between earning low wages and memory decline.
The current investigators assessed 1992-2016 data from the Health and Retirement Study, a longitudinal survey of nationally representative samples of Americans aged 50 years and older. Study participants are interviewed every 2 years and provide, among other things, information on work-related factors, including hourly wages.
Memory function was measured at each visit from 2004 to 2016 using a memory composite score. The score included immediate and delayed word recall memory assessments. For those who became too impaired to complete cognitive assessment, memory tests by proxy informants were utilized.
On average, participants completed 4.8 memory assessments over the course of the study.
Researchers defined “low wage” as an hourly wage lower than two-thirds of the federal median wage for the corresponding year. They categorized low-wage exposure history as “never” or “intermittent” or “sustained” on the basis of wages earned from 1992 to 2004.
The current analysis included 3,803 participants, 1,913 of whom were men. All participants were born from 1936 to 1941. In 2004, the average age was 65 years, and the mean memory score was 1.15 standard units.
The investigators adjusted for factors that could confound the relationship between wages and cognition, including the participant’s education, parental education, household wealth, and marital status. Later, whether the participants’ occupation type was of low skill or not was also included.
Cognitive harm
The confounder-adjusted annual rate of memory decline among workers who never earned low wages was –0.12 standard units (95% confidence interval, –0.14 to –0.10).
Compared with these workers, memory decline was significantly faster among participants with sustained low wage–earning during midlife (beta for interaction between time and exposure group, –0.012; 95% CI, –0.02 to 0.01), corresponding to an annual rate of –0.13 standard units.
Put another way, the cognitive aging experienced by workers earning low wages over a 10-year period was equivalent to what workers who never earned low wages would experience over 11 years.
Although similar associations were found for men and women, it was stronger in magnitude for men – a finding Dr. Kezios said was somewhat surprising. She noted that women are commonly more at risk for dementia than men.
However, she advises caution in interpreting this finding, as there were so few men in the sustained low-wage group. “Women disproportionately make up the group of workers earning low wages,” she said.
The negative low coefficient found for those who persistently earned low wages was also observed for those who intermittently earned low wages, but this was not statistically significant.
“We can speculate or hypothesize the cumulative effect of earning low wages at each exposure interval produces more cognitive harm than maybe earning low wages at some time points over that exposure period,” said Dr. Kezios.
A sensitivity analysis that examined wage earning at the same ages but in two different birth cohorts showed similar results for the two groups. When researchers removed self-employed workers from the study sample, the same association between sustained low wages and memory decline was found.
“Our findings held up, which gave us a little more reassurance that what we were seeing is at least signaling there might be something there,” said Dr. Kezios.
She described the study as a “first pass” for documenting the harmful cognitive effects of consistently earning low wages.
It would be interesting, she said, to now determine whether there’s a “dose effect” for having a low salary. However, other studies with different designs would be needed to determine at what income level cognitive health starts to be protected and the impact of raising the minimum wage, she added.
Unique study
Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, said the study was unique. “I don’t think we have seen anything like this before,” said Dr. Snyder.
The study, which links sustained low-wage earning in midlife to later memory decline, “is looking beyond some of the other measures we’ve seen when we looked at socioeconomic status,” she noted.
The results “beg the question” of whether people who earn low wages have less access to health care, she added.
“We should think about how to ensure access and equity around health care and around potential ways that may address components of risk individuals have during their life course,” Dr. Snyder said.
She noted that the study provides a “start” at considering potential policies to address the impact of sustained low wages on overall health, particularly cognitive health, throughout life.
The study had no outside funding. Dr. Kezios has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From AAIC 2022
Individualized sensory care for older patients with dementia
Everyone gets by using environmental cues: For example, if you have to go to use the toilet in public, a bathroom sign prompts an immediate response. However, patients with dementia often struggle with environmental cues, which can complicate the already difficult task faced by their caregivers.
Individuals with dementia can lose awareness of such signs, and even colors, making it harder for them to interpret environmental cues.
The study, presented at the Alzheimer’s Association International Conference, recruited 30 pairs of patients and their caregivers. The approach is based on the Dunn model of sensory processing, which focuses on altering environments to maximize chances of success. It “explains that sensory processing is the information coming in, and then our ability to regulate and habituate to those sensations (creates) behavior,” Elizabeth Rhodus, MD, PhD, said during her talk. Dr. Rhodus is assistant professor of medicine at the University of Kentucky, Lexington.
Sensory-based interventions are not uncommon, but most are applied to pediatric populations and tend to focus on sensory processing disorders and autism spectrum disorder. The few programs that do focus on adults have varying methods and produce mixed results. Dr. Rhodus thinks that the key to success is individualization of therapy. “You’re going to like a certain sensation, and I might not like it. You can’t put us in the same room and expect the same results. We have to identify the preferences of how people interact with their environment, and what their brain does at a neuroscience level with that information,” she said.
Caregiving hacks
The program employs telehealth to work with caregivers so they can also create sensory environments within the home, using environment to trigger behavior.
For example, although individuals with dementia may have reduced response to color, the color red is unique. “Red is a cortical trigger. Red always stands out to people, so in our package that we send out as part of this intervention, we send out a roll of red duct tape,” said Dr. Rhodus.
An example of the use of red was a patient with dementia who had stopped drinking on his own, causing his caregiver daughter to be concerned that he would soon have to enter a nursing home. Examining the room, the occupational therapist realized that the water was kept out of sight, and suggested that the water glass be placed within the patient’s view, atop a square created with the red duct tape.
“These are just some of the simple concepts. They kind of seem easy. Some of my participants call them caregiving hacks, but it’s things that are grounded in neuroscience – how the brain processes the environment, and then how can we plug in supports and cues in whatever area is missing,” said Dr. Rhodus.
In the program, the caregiver fills out several online surveys, and an occupational therapist conducts an interview to identify specific challenges, such as bathing, or using the toilet, or going to church. Then an adult sensory profile reveals how the patient perceives his or her environment. “It’s taking those individual pieces, and then boiling it down to these mechanisms at the behavioral and neuroscience level,” said Dr. Rhodus. She said the entire setup process takes about an hour.
Impactful care
The individualized approach of the HARMONY (Helping Older Adults Create and Manage Occupations Successfully) method is promising, according to Monika Gross, executive director of the Poise Project, which uses the Alexander Technique to help people with chronic conditions such as Parkinson’s disease.
“Although it’s always a very simple idea that human beings need sensory processing aspects in their lives, from the time they’re infants through to the end of life, we don’t really focus on the end of life in a way that can bring meaning between the care partner and the person living with dementia. The other thing that was impressive is that this is in a rural community, where there often aren’t a lot of resources available, (such as) classes that the care partner can take their loved one to. So having something where the care partner has some confidence that they can really make an impact in that person that they are seeing decline, that they can see their behavior change [is good],” said Ms. Gross.
Empowering caregivers
The study included 30 pairs of patients and caregivers who were randomized to the individualized care (I), standardized care, or a control group. Adherence to weekly visits was high (I, 88%; S, 100%; C, 60%; P = .061). Retention was strong (I, 80%; S, 60%; C, 50%).
“It was feasible ... and at the end, we found a significant improvement in care partner satisfaction. We actually empowered these people to care for their loved ones, and in doing that, and helping them set up environmental cues, it allowed that person to perform at a more independent level,” said Dr. Rhodus.
The trial was only a proof of concept, so although the researchers saw signs of efficacy, it wasn’t powered to show that. They are currently enrolling additional patients and caregivers for larger studies to further test the approach.
Dr. Rhodus and Ms. Gross have no relevant financial disclosures.
Everyone gets by using environmental cues: For example, if you have to go to use the toilet in public, a bathroom sign prompts an immediate response. However, patients with dementia often struggle with environmental cues, which can complicate the already difficult task faced by their caregivers.
Individuals with dementia can lose awareness of such signs, and even colors, making it harder for them to interpret environmental cues.
The study, presented at the Alzheimer’s Association International Conference, recruited 30 pairs of patients and their caregivers. The approach is based on the Dunn model of sensory processing, which focuses on altering environments to maximize chances of success. It “explains that sensory processing is the information coming in, and then our ability to regulate and habituate to those sensations (creates) behavior,” Elizabeth Rhodus, MD, PhD, said during her talk. Dr. Rhodus is assistant professor of medicine at the University of Kentucky, Lexington.
Sensory-based interventions are not uncommon, but most are applied to pediatric populations and tend to focus on sensory processing disorders and autism spectrum disorder. The few programs that do focus on adults have varying methods and produce mixed results. Dr. Rhodus thinks that the key to success is individualization of therapy. “You’re going to like a certain sensation, and I might not like it. You can’t put us in the same room and expect the same results. We have to identify the preferences of how people interact with their environment, and what their brain does at a neuroscience level with that information,” she said.
Caregiving hacks
The program employs telehealth to work with caregivers so they can also create sensory environments within the home, using environment to trigger behavior.
For example, although individuals with dementia may have reduced response to color, the color red is unique. “Red is a cortical trigger. Red always stands out to people, so in our package that we send out as part of this intervention, we send out a roll of red duct tape,” said Dr. Rhodus.
An example of the use of red was a patient with dementia who had stopped drinking on his own, causing his caregiver daughter to be concerned that he would soon have to enter a nursing home. Examining the room, the occupational therapist realized that the water was kept out of sight, and suggested that the water glass be placed within the patient’s view, atop a square created with the red duct tape.
“These are just some of the simple concepts. They kind of seem easy. Some of my participants call them caregiving hacks, but it’s things that are grounded in neuroscience – how the brain processes the environment, and then how can we plug in supports and cues in whatever area is missing,” said Dr. Rhodus.
In the program, the caregiver fills out several online surveys, and an occupational therapist conducts an interview to identify specific challenges, such as bathing, or using the toilet, or going to church. Then an adult sensory profile reveals how the patient perceives his or her environment. “It’s taking those individual pieces, and then boiling it down to these mechanisms at the behavioral and neuroscience level,” said Dr. Rhodus. She said the entire setup process takes about an hour.
Impactful care
The individualized approach of the HARMONY (Helping Older Adults Create and Manage Occupations Successfully) method is promising, according to Monika Gross, executive director of the Poise Project, which uses the Alexander Technique to help people with chronic conditions such as Parkinson’s disease.
“Although it’s always a very simple idea that human beings need sensory processing aspects in their lives, from the time they’re infants through to the end of life, we don’t really focus on the end of life in a way that can bring meaning between the care partner and the person living with dementia. The other thing that was impressive is that this is in a rural community, where there often aren’t a lot of resources available, (such as) classes that the care partner can take their loved one to. So having something where the care partner has some confidence that they can really make an impact in that person that they are seeing decline, that they can see their behavior change [is good],” said Ms. Gross.
Empowering caregivers
The study included 30 pairs of patients and caregivers who were randomized to the individualized care (I), standardized care, or a control group. Adherence to weekly visits was high (I, 88%; S, 100%; C, 60%; P = .061). Retention was strong (I, 80%; S, 60%; C, 50%).
“It was feasible ... and at the end, we found a significant improvement in care partner satisfaction. We actually empowered these people to care for their loved ones, and in doing that, and helping them set up environmental cues, it allowed that person to perform at a more independent level,” said Dr. Rhodus.
The trial was only a proof of concept, so although the researchers saw signs of efficacy, it wasn’t powered to show that. They are currently enrolling additional patients and caregivers for larger studies to further test the approach.
Dr. Rhodus and Ms. Gross have no relevant financial disclosures.
Everyone gets by using environmental cues: For example, if you have to go to use the toilet in public, a bathroom sign prompts an immediate response. However, patients with dementia often struggle with environmental cues, which can complicate the already difficult task faced by their caregivers.
Individuals with dementia can lose awareness of such signs, and even colors, making it harder for them to interpret environmental cues.
The study, presented at the Alzheimer’s Association International Conference, recruited 30 pairs of patients and their caregivers. The approach is based on the Dunn model of sensory processing, which focuses on altering environments to maximize chances of success. It “explains that sensory processing is the information coming in, and then our ability to regulate and habituate to those sensations (creates) behavior,” Elizabeth Rhodus, MD, PhD, said during her talk. Dr. Rhodus is assistant professor of medicine at the University of Kentucky, Lexington.
Sensory-based interventions are not uncommon, but most are applied to pediatric populations and tend to focus on sensory processing disorders and autism spectrum disorder. The few programs that do focus on adults have varying methods and produce mixed results. Dr. Rhodus thinks that the key to success is individualization of therapy. “You’re going to like a certain sensation, and I might not like it. You can’t put us in the same room and expect the same results. We have to identify the preferences of how people interact with their environment, and what their brain does at a neuroscience level with that information,” she said.
Caregiving hacks
The program employs telehealth to work with caregivers so they can also create sensory environments within the home, using environment to trigger behavior.
For example, although individuals with dementia may have reduced response to color, the color red is unique. “Red is a cortical trigger. Red always stands out to people, so in our package that we send out as part of this intervention, we send out a roll of red duct tape,” said Dr. Rhodus.
An example of the use of red was a patient with dementia who had stopped drinking on his own, causing his caregiver daughter to be concerned that he would soon have to enter a nursing home. Examining the room, the occupational therapist realized that the water was kept out of sight, and suggested that the water glass be placed within the patient’s view, atop a square created with the red duct tape.
“These are just some of the simple concepts. They kind of seem easy. Some of my participants call them caregiving hacks, but it’s things that are grounded in neuroscience – how the brain processes the environment, and then how can we plug in supports and cues in whatever area is missing,” said Dr. Rhodus.
In the program, the caregiver fills out several online surveys, and an occupational therapist conducts an interview to identify specific challenges, such as bathing, or using the toilet, or going to church. Then an adult sensory profile reveals how the patient perceives his or her environment. “It’s taking those individual pieces, and then boiling it down to these mechanisms at the behavioral and neuroscience level,” said Dr. Rhodus. She said the entire setup process takes about an hour.
Impactful care
The individualized approach of the HARMONY (Helping Older Adults Create and Manage Occupations Successfully) method is promising, according to Monika Gross, executive director of the Poise Project, which uses the Alexander Technique to help people with chronic conditions such as Parkinson’s disease.
“Although it’s always a very simple idea that human beings need sensory processing aspects in their lives, from the time they’re infants through to the end of life, we don’t really focus on the end of life in a way that can bring meaning between the care partner and the person living with dementia. The other thing that was impressive is that this is in a rural community, where there often aren’t a lot of resources available, (such as) classes that the care partner can take their loved one to. So having something where the care partner has some confidence that they can really make an impact in that person that they are seeing decline, that they can see their behavior change [is good],” said Ms. Gross.
Empowering caregivers
The study included 30 pairs of patients and caregivers who were randomized to the individualized care (I), standardized care, or a control group. Adherence to weekly visits was high (I, 88%; S, 100%; C, 60%; P = .061). Retention was strong (I, 80%; S, 60%; C, 50%).
“It was feasible ... and at the end, we found a significant improvement in care partner satisfaction. We actually empowered these people to care for their loved ones, and in doing that, and helping them set up environmental cues, it allowed that person to perform at a more independent level,” said Dr. Rhodus.
The trial was only a proof of concept, so although the researchers saw signs of efficacy, it wasn’t powered to show that. They are currently enrolling additional patients and caregivers for larger studies to further test the approach.
Dr. Rhodus and Ms. Gross have no relevant financial disclosures.
FROM AAIC 2022
More evidence that ultraprocessed foods are detrimental for the brain
Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), which included participants aged 35 and older, showed that higher intake of UPFs was significantly associated with a faster rate of decline in both executive and global cognitive function.
“Based on these findings, doctors might counsel patients to prefer cooking at home [and] choosing fresher ingredients instead of buying ready-made meals and snacks,” said coinvestigator Natalia Gonçalves, PhD, University of São Paulo, Brazil.
Presented at the Alzheimer’s Association International Conference, the findings align with those from a recent study in Neurology. That study linked a diet high in UPFs to an increased risk for dementia.
Increasing worldwide consumption
UPFs are highly manipulated, are packed with added ingredients, including sugar, fat, and salt, and are low in protein and fiber. Examples of UPFs include soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, fries, and many more.
Over the past 30 years, there has been a steady increase in consumption of UPFs worldwide. They are thought to induce systemic inflammation and oxidative stress and have been linked to a variety of ailments, such as overweight/obesity, cardiovascular disease, and cancer.
UPFs may also be a risk factor for cognitive decline, although data are scarce as to their effects on the brain.
To investigate, Dr. Gonçalves and colleagues evaluated longitudinal data on 10,775 adults (mean age, 50.6 years; 56% women; 55% White) who participated in the ELSA-Brasil study. They were evaluated in three waves (2008-2010, 2012-2014, and 2017-2019).
Information on diet was obtained via food frequency questionnaires and included information regarding consumption of unprocessed foods, minimally processed foods, and UPFs.
Participants were grouped according to UPF consumption quartiles (lowest to highest). Cognitive performance was evaluated by use of a standardized battery of tests.
Significant decline
Using linear mixed effects models that were adjusted for sociodemographic, lifestyle, and clinical variables, the investigators assessed the association of dietary UPFs as a percentage of total daily calories with cognitive performance over time.
During a median follow-up of 8 years, UPF intake in quartiles 2 to 4 (vs. quartile 1) was associated with a significant decline in global cognition (P = .003) and executive function (P = .015).
“Participants who reported consumption of more than 20% of daily calories from ultraprocessed foods had a 28% faster rate of global cognitive decline and a 25% faster decrease of the executive function compared to those who reported eating less than 20% of daily calories from ultraprocessed foods,” Dr. Gonçalves reported.
“Considering a person who eats a total of 2,000 kcal per day, 20% of daily calories from ultraprocessed foods are about two 1.5-ounce bars of KitKat, or five slices of bread, or about a third of an 8.5-ounce package of chips,” she explained.
Dr. Gonçalves noted that the reasons UPFs may harm the brain remain a “very relevant but not yet well-studied topic.”
Hypotheses include secondary effects from cerebrovascular lesions or chronic inflammation processes. More studies are needed to investigate the possible mechanisms that might explain the harm of UPFs to the brain, she said.
‘Troubling but not surprising’
Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, said there is “growing evidence that what we eat can impact our brains as we age.”
He added that many previous studies have suggested it is best for the brain for one to eat a heart-healthy, balanced diet that is low in processed foods and high in whole, nutritional foods, such as vegetables and fruits.
“These new data from the Alzheimer’s Association International Conference suggest eating a large amount of ultraprocessed food can significantly accelerate cognitive decline,” said Dr. Griffin, who was not involved with the research.
He noted that an increase in the availability and consumption of fast foods, processed foods, and UPFs is due to a number of socioeconomic factors, including low access to healthy foods, less time to prepare foods from scratch, and an inability to afford whole foods.
“Ultraprocessed foods make up more than half of American diets. It’s troubling but not surprising to see new data suggesting these foods can significantly accelerate cognitive decline,” Dr. Griffin said.
“The good news is there are steps we can take to reduce risk of cognitive decline as we age. These include eating a balanced diet, exercising regularly, getting good sleep, staying cognitively engaged, protecting from head injury, not smoking, and managing heart health,” he added.
Past research has suggested that the greatest benefit is from engaging in combinations of these lifestyle changes and that they are beneficial at any age, he noted.
“Even if you begin with one or two healthful actions, you’re moving in the right direction. It’s never too early or too late to incorporate these habits into your life,” Dr. Griffin said.
The study had no specific funding. Dr. Gonçalves and Dr. Griffin have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), which included participants aged 35 and older, showed that higher intake of UPFs was significantly associated with a faster rate of decline in both executive and global cognitive function.
“Based on these findings, doctors might counsel patients to prefer cooking at home [and] choosing fresher ingredients instead of buying ready-made meals and snacks,” said coinvestigator Natalia Gonçalves, PhD, University of São Paulo, Brazil.
Presented at the Alzheimer’s Association International Conference, the findings align with those from a recent study in Neurology. That study linked a diet high in UPFs to an increased risk for dementia.
Increasing worldwide consumption
UPFs are highly manipulated, are packed with added ingredients, including sugar, fat, and salt, and are low in protein and fiber. Examples of UPFs include soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, fries, and many more.
Over the past 30 years, there has been a steady increase in consumption of UPFs worldwide. They are thought to induce systemic inflammation and oxidative stress and have been linked to a variety of ailments, such as overweight/obesity, cardiovascular disease, and cancer.
UPFs may also be a risk factor for cognitive decline, although data are scarce as to their effects on the brain.
To investigate, Dr. Gonçalves and colleagues evaluated longitudinal data on 10,775 adults (mean age, 50.6 years; 56% women; 55% White) who participated in the ELSA-Brasil study. They were evaluated in three waves (2008-2010, 2012-2014, and 2017-2019).
Information on diet was obtained via food frequency questionnaires and included information regarding consumption of unprocessed foods, minimally processed foods, and UPFs.
Participants were grouped according to UPF consumption quartiles (lowest to highest). Cognitive performance was evaluated by use of a standardized battery of tests.
Significant decline
Using linear mixed effects models that were adjusted for sociodemographic, lifestyle, and clinical variables, the investigators assessed the association of dietary UPFs as a percentage of total daily calories with cognitive performance over time.
During a median follow-up of 8 years, UPF intake in quartiles 2 to 4 (vs. quartile 1) was associated with a significant decline in global cognition (P = .003) and executive function (P = .015).
“Participants who reported consumption of more than 20% of daily calories from ultraprocessed foods had a 28% faster rate of global cognitive decline and a 25% faster decrease of the executive function compared to those who reported eating less than 20% of daily calories from ultraprocessed foods,” Dr. Gonçalves reported.
“Considering a person who eats a total of 2,000 kcal per day, 20% of daily calories from ultraprocessed foods are about two 1.5-ounce bars of KitKat, or five slices of bread, or about a third of an 8.5-ounce package of chips,” she explained.
Dr. Gonçalves noted that the reasons UPFs may harm the brain remain a “very relevant but not yet well-studied topic.”
Hypotheses include secondary effects from cerebrovascular lesions or chronic inflammation processes. More studies are needed to investigate the possible mechanisms that might explain the harm of UPFs to the brain, she said.
‘Troubling but not surprising’
Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, said there is “growing evidence that what we eat can impact our brains as we age.”
He added that many previous studies have suggested it is best for the brain for one to eat a heart-healthy, balanced diet that is low in processed foods and high in whole, nutritional foods, such as vegetables and fruits.
“These new data from the Alzheimer’s Association International Conference suggest eating a large amount of ultraprocessed food can significantly accelerate cognitive decline,” said Dr. Griffin, who was not involved with the research.
He noted that an increase in the availability and consumption of fast foods, processed foods, and UPFs is due to a number of socioeconomic factors, including low access to healthy foods, less time to prepare foods from scratch, and an inability to afford whole foods.
“Ultraprocessed foods make up more than half of American diets. It’s troubling but not surprising to see new data suggesting these foods can significantly accelerate cognitive decline,” Dr. Griffin said.
“The good news is there are steps we can take to reduce risk of cognitive decline as we age. These include eating a balanced diet, exercising regularly, getting good sleep, staying cognitively engaged, protecting from head injury, not smoking, and managing heart health,” he added.
Past research has suggested that the greatest benefit is from engaging in combinations of these lifestyle changes and that they are beneficial at any age, he noted.
“Even if you begin with one or two healthful actions, you’re moving in the right direction. It’s never too early or too late to incorporate these habits into your life,” Dr. Griffin said.
The study had no specific funding. Dr. Gonçalves and Dr. Griffin have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), which included participants aged 35 and older, showed that higher intake of UPFs was significantly associated with a faster rate of decline in both executive and global cognitive function.
“Based on these findings, doctors might counsel patients to prefer cooking at home [and] choosing fresher ingredients instead of buying ready-made meals and snacks,” said coinvestigator Natalia Gonçalves, PhD, University of São Paulo, Brazil.
Presented at the Alzheimer’s Association International Conference, the findings align with those from a recent study in Neurology. That study linked a diet high in UPFs to an increased risk for dementia.
Increasing worldwide consumption
UPFs are highly manipulated, are packed with added ingredients, including sugar, fat, and salt, and are low in protein and fiber. Examples of UPFs include soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, fries, and many more.
Over the past 30 years, there has been a steady increase in consumption of UPFs worldwide. They are thought to induce systemic inflammation and oxidative stress and have been linked to a variety of ailments, such as overweight/obesity, cardiovascular disease, and cancer.
UPFs may also be a risk factor for cognitive decline, although data are scarce as to their effects on the brain.
To investigate, Dr. Gonçalves and colleagues evaluated longitudinal data on 10,775 adults (mean age, 50.6 years; 56% women; 55% White) who participated in the ELSA-Brasil study. They were evaluated in three waves (2008-2010, 2012-2014, and 2017-2019).
Information on diet was obtained via food frequency questionnaires and included information regarding consumption of unprocessed foods, minimally processed foods, and UPFs.
Participants were grouped according to UPF consumption quartiles (lowest to highest). Cognitive performance was evaluated by use of a standardized battery of tests.
Significant decline
Using linear mixed effects models that were adjusted for sociodemographic, lifestyle, and clinical variables, the investigators assessed the association of dietary UPFs as a percentage of total daily calories with cognitive performance over time.
During a median follow-up of 8 years, UPF intake in quartiles 2 to 4 (vs. quartile 1) was associated with a significant decline in global cognition (P = .003) and executive function (P = .015).
“Participants who reported consumption of more than 20% of daily calories from ultraprocessed foods had a 28% faster rate of global cognitive decline and a 25% faster decrease of the executive function compared to those who reported eating less than 20% of daily calories from ultraprocessed foods,” Dr. Gonçalves reported.
“Considering a person who eats a total of 2,000 kcal per day, 20% of daily calories from ultraprocessed foods are about two 1.5-ounce bars of KitKat, or five slices of bread, or about a third of an 8.5-ounce package of chips,” she explained.
Dr. Gonçalves noted that the reasons UPFs may harm the brain remain a “very relevant but not yet well-studied topic.”
Hypotheses include secondary effects from cerebrovascular lesions or chronic inflammation processes. More studies are needed to investigate the possible mechanisms that might explain the harm of UPFs to the brain, she said.
‘Troubling but not surprising’
Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, said there is “growing evidence that what we eat can impact our brains as we age.”
He added that many previous studies have suggested it is best for the brain for one to eat a heart-healthy, balanced diet that is low in processed foods and high in whole, nutritional foods, such as vegetables and fruits.
“These new data from the Alzheimer’s Association International Conference suggest eating a large amount of ultraprocessed food can significantly accelerate cognitive decline,” said Dr. Griffin, who was not involved with the research.
He noted that an increase in the availability and consumption of fast foods, processed foods, and UPFs is due to a number of socioeconomic factors, including low access to healthy foods, less time to prepare foods from scratch, and an inability to afford whole foods.
“Ultraprocessed foods make up more than half of American diets. It’s troubling but not surprising to see new data suggesting these foods can significantly accelerate cognitive decline,” Dr. Griffin said.
“The good news is there are steps we can take to reduce risk of cognitive decline as we age. These include eating a balanced diet, exercising regularly, getting good sleep, staying cognitively engaged, protecting from head injury, not smoking, and managing heart health,” he added.
Past research has suggested that the greatest benefit is from engaging in combinations of these lifestyle changes and that they are beneficial at any age, he noted.
“Even if you begin with one or two healthful actions, you’re moving in the right direction. It’s never too early or too late to incorporate these habits into your life,” Dr. Griffin said.
The study had no specific funding. Dr. Gonçalves and Dr. Griffin have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From AAIC 2022
Racism tied to cognition in middle-aged, elderly
It is generally understood that racism, whether structural or personal, harms the well-being of the individual who experiences it. It has harmful health effects, and it contributes to ethnic inequality.
That was the fundamental message behind two studies presented at a press conference at the Alzheimer’s Association International Conference.
“We know that there are communities like black African Americans and Hispanic Latinos who are at greater risk for developing Alzheimer’s or another dementia,” said Carl Hill, PhD, who served as a moderator during the press conference. He pointed out that the genetic and lifestyle factors linked to dementia tell only part of the story. “It’s important that the science also examines the unique experiences of those at greater risk for dementia in our society,” said Dr. Hill, who is Alzheimer’s Association Chief Diversity Equity and Inclusion Officer.
Racism, memory, and cognition in middle-aged patients
Jennifer J. Manly, PhD, professor of neuropsychology at Columbia University, New York, presented a study of experience of racism and memory scores among a highly diverse, middle-aged cohort.
“There’s little understanding of how the multiple levels of racism – including intrapersonal, institutional, and structural racism – influence cognitive aging and dementia risk,” Dr. Manly said during the press conference.
Among 1,095 participants, 19.5% were non-Latinx White (61% female, mean age 57), 26.0% were non-Latinx Black (63% female, mean age 56), 32.3% were English-speaking Latinx (66% female, mean age 50), and 21.2% were Spanish-speaking Latinx (68% female, mean age 58).
The researchers used the Everyday Discrimination (ED) scale to measure experience of individual racism, the Major Discrimination (MD) scale to measure experience of institutional racism, and residential segregation of the census block group for an individual’s parents to measure residential segregation. Outcome measures included the Digit Span to assess attention and working memory, and the Selective Reminding Test to assess episodic memory.
The study found a clear association between racism and cognition. “The association of interpersonal racism to memory corresponds to 3 years of chronological age, and was driven by non-Hispanic black participants. Next, there was a reliable relationship between institutional racism and memory scores among non-Hispanic black participants, such that each reported civil rights violation corresponded to the effect of about 4.5 years of age on memory,” said Dr. Manly.
“The bottom line is that our results suggest that exposure to racism is a substantial driver of later life memory function, even in middle age, and especially for Black people,” Dr. Manly added.
The results should alert physicians to the complexities of racism and its impact. “Health providers need to be aware that many accumulated risks are historical and structural, and not controlled by the individual. Maybe more importantly, the medical system itself may perpetuate discriminatory experiences that contribute to worse health,” said Dr. Manly.
Latinx concerns
Also at the press conference, Adriana Perez, PhD, emphasized the challenges that Spanish-speaking Latinxs have with health care. Just 5%-7% of nurses are Latinx. “The same could be said for physicians, for clinical psychologists ... as you look at the really critical positions to address brain health equity, we are not represented there,” said Dr. Perez, an assistant professor and senior fellow at the University of Pennsylvania School of Nursing in Philadelphia.
She also pointed out that Latinx representation in clinical trials is very low, even though surveys performed by the Alzheimer’s Association show that this population values medical science and is willing to participate. In fact, 85% said they would participate if invited. The trouble is that many clinical trial announcements state that participants must speak English. Even the many Latinos who are bilingual may be put off by that wording: “That is a message that you’re not invited. That’s how it’s perceived,” said Dr. Perez.
Racism and cognition in the elderly
At the press conference, Kristen George, PhD, presented results from a study of individuals over age 90. “Racial disparities in dementia have been well characterized, particularly among those people who are aged 65 and older, but we don’t know very much about the oldest old individuals who are aged 90 and older. This group is one of the fastest growing segments of the population, and it’s becoming increasingly diverse,” said Dr. George, assistant professor of epidemiology at the University of California, Davis.
The group enrolled 445 Asian, Black, Latinx, White, and multiracial individuals who were members of Kaiser Permanente Northern California, with a mean age of 92.7 years. They used the Major Experiences of Discrimination Scale to assess discrimination.
The researchers divided them into three groups based on gender, race, and responses to the 10-item scale. Class 1 included largely White men who had reported workplace discrimination, with an average of two major discrimination experiences. Class 2 was made up of White women and non-Whites who reported little or no discrimination, with an average of 0 experiences. Class 3 included all non-White participants, and they reported a mean of four discrimination experiences.
Using class 2 as a reference, executive function was better among class 1 individuals (beta = 0.28; 95% CI, 0.03-0.52) but there was no significant difference between class 3 and class 2. Class 1 had better baseline semantic memory than class 2 (beta = 0.33; 95% CI, 0.07-0.58), and those in class 3 performed significantly worse than class 2 (beta = –0.24; 95% CI, –0.48 to –0.00). There were no between-group differences in baseline verbal or episodic memory.
Dr. Perez, Dr. Manly, Dr. George, and Dr. Hill have no relevant financial disclosures.
It is generally understood that racism, whether structural or personal, harms the well-being of the individual who experiences it. It has harmful health effects, and it contributes to ethnic inequality.
That was the fundamental message behind two studies presented at a press conference at the Alzheimer’s Association International Conference.
“We know that there are communities like black African Americans and Hispanic Latinos who are at greater risk for developing Alzheimer’s or another dementia,” said Carl Hill, PhD, who served as a moderator during the press conference. He pointed out that the genetic and lifestyle factors linked to dementia tell only part of the story. “It’s important that the science also examines the unique experiences of those at greater risk for dementia in our society,” said Dr. Hill, who is Alzheimer’s Association Chief Diversity Equity and Inclusion Officer.
Racism, memory, and cognition in middle-aged patients
Jennifer J. Manly, PhD, professor of neuropsychology at Columbia University, New York, presented a study of experience of racism and memory scores among a highly diverse, middle-aged cohort.
“There’s little understanding of how the multiple levels of racism – including intrapersonal, institutional, and structural racism – influence cognitive aging and dementia risk,” Dr. Manly said during the press conference.
Among 1,095 participants, 19.5% were non-Latinx White (61% female, mean age 57), 26.0% were non-Latinx Black (63% female, mean age 56), 32.3% were English-speaking Latinx (66% female, mean age 50), and 21.2% were Spanish-speaking Latinx (68% female, mean age 58).
The researchers used the Everyday Discrimination (ED) scale to measure experience of individual racism, the Major Discrimination (MD) scale to measure experience of institutional racism, and residential segregation of the census block group for an individual’s parents to measure residential segregation. Outcome measures included the Digit Span to assess attention and working memory, and the Selective Reminding Test to assess episodic memory.
The study found a clear association between racism and cognition. “The association of interpersonal racism to memory corresponds to 3 years of chronological age, and was driven by non-Hispanic black participants. Next, there was a reliable relationship between institutional racism and memory scores among non-Hispanic black participants, such that each reported civil rights violation corresponded to the effect of about 4.5 years of age on memory,” said Dr. Manly.
“The bottom line is that our results suggest that exposure to racism is a substantial driver of later life memory function, even in middle age, and especially for Black people,” Dr. Manly added.
The results should alert physicians to the complexities of racism and its impact. “Health providers need to be aware that many accumulated risks are historical and structural, and not controlled by the individual. Maybe more importantly, the medical system itself may perpetuate discriminatory experiences that contribute to worse health,” said Dr. Manly.
Latinx concerns
Also at the press conference, Adriana Perez, PhD, emphasized the challenges that Spanish-speaking Latinxs have with health care. Just 5%-7% of nurses are Latinx. “The same could be said for physicians, for clinical psychologists ... as you look at the really critical positions to address brain health equity, we are not represented there,” said Dr. Perez, an assistant professor and senior fellow at the University of Pennsylvania School of Nursing in Philadelphia.
She also pointed out that Latinx representation in clinical trials is very low, even though surveys performed by the Alzheimer’s Association show that this population values medical science and is willing to participate. In fact, 85% said they would participate if invited. The trouble is that many clinical trial announcements state that participants must speak English. Even the many Latinos who are bilingual may be put off by that wording: “That is a message that you’re not invited. That’s how it’s perceived,” said Dr. Perez.
Racism and cognition in the elderly
At the press conference, Kristen George, PhD, presented results from a study of individuals over age 90. “Racial disparities in dementia have been well characterized, particularly among those people who are aged 65 and older, but we don’t know very much about the oldest old individuals who are aged 90 and older. This group is one of the fastest growing segments of the population, and it’s becoming increasingly diverse,” said Dr. George, assistant professor of epidemiology at the University of California, Davis.
The group enrolled 445 Asian, Black, Latinx, White, and multiracial individuals who were members of Kaiser Permanente Northern California, with a mean age of 92.7 years. They used the Major Experiences of Discrimination Scale to assess discrimination.
The researchers divided them into three groups based on gender, race, and responses to the 10-item scale. Class 1 included largely White men who had reported workplace discrimination, with an average of two major discrimination experiences. Class 2 was made up of White women and non-Whites who reported little or no discrimination, with an average of 0 experiences. Class 3 included all non-White participants, and they reported a mean of four discrimination experiences.
Using class 2 as a reference, executive function was better among class 1 individuals (beta = 0.28; 95% CI, 0.03-0.52) but there was no significant difference between class 3 and class 2. Class 1 had better baseline semantic memory than class 2 (beta = 0.33; 95% CI, 0.07-0.58), and those in class 3 performed significantly worse than class 2 (beta = –0.24; 95% CI, –0.48 to –0.00). There were no between-group differences in baseline verbal or episodic memory.
Dr. Perez, Dr. Manly, Dr. George, and Dr. Hill have no relevant financial disclosures.
It is generally understood that racism, whether structural or personal, harms the well-being of the individual who experiences it. It has harmful health effects, and it contributes to ethnic inequality.
That was the fundamental message behind two studies presented at a press conference at the Alzheimer’s Association International Conference.
“We know that there are communities like black African Americans and Hispanic Latinos who are at greater risk for developing Alzheimer’s or another dementia,” said Carl Hill, PhD, who served as a moderator during the press conference. He pointed out that the genetic and lifestyle factors linked to dementia tell only part of the story. “It’s important that the science also examines the unique experiences of those at greater risk for dementia in our society,” said Dr. Hill, who is Alzheimer’s Association Chief Diversity Equity and Inclusion Officer.
Racism, memory, and cognition in middle-aged patients
Jennifer J. Manly, PhD, professor of neuropsychology at Columbia University, New York, presented a study of experience of racism and memory scores among a highly diverse, middle-aged cohort.
“There’s little understanding of how the multiple levels of racism – including intrapersonal, institutional, and structural racism – influence cognitive aging and dementia risk,” Dr. Manly said during the press conference.
Among 1,095 participants, 19.5% were non-Latinx White (61% female, mean age 57), 26.0% were non-Latinx Black (63% female, mean age 56), 32.3% were English-speaking Latinx (66% female, mean age 50), and 21.2% were Spanish-speaking Latinx (68% female, mean age 58).
The researchers used the Everyday Discrimination (ED) scale to measure experience of individual racism, the Major Discrimination (MD) scale to measure experience of institutional racism, and residential segregation of the census block group for an individual’s parents to measure residential segregation. Outcome measures included the Digit Span to assess attention and working memory, and the Selective Reminding Test to assess episodic memory.
The study found a clear association between racism and cognition. “The association of interpersonal racism to memory corresponds to 3 years of chronological age, and was driven by non-Hispanic black participants. Next, there was a reliable relationship between institutional racism and memory scores among non-Hispanic black participants, such that each reported civil rights violation corresponded to the effect of about 4.5 years of age on memory,” said Dr. Manly.
“The bottom line is that our results suggest that exposure to racism is a substantial driver of later life memory function, even in middle age, and especially for Black people,” Dr. Manly added.
The results should alert physicians to the complexities of racism and its impact. “Health providers need to be aware that many accumulated risks are historical and structural, and not controlled by the individual. Maybe more importantly, the medical system itself may perpetuate discriminatory experiences that contribute to worse health,” said Dr. Manly.
Latinx concerns
Also at the press conference, Adriana Perez, PhD, emphasized the challenges that Spanish-speaking Latinxs have with health care. Just 5%-7% of nurses are Latinx. “The same could be said for physicians, for clinical psychologists ... as you look at the really critical positions to address brain health equity, we are not represented there,” said Dr. Perez, an assistant professor and senior fellow at the University of Pennsylvania School of Nursing in Philadelphia.
She also pointed out that Latinx representation in clinical trials is very low, even though surveys performed by the Alzheimer’s Association show that this population values medical science and is willing to participate. In fact, 85% said they would participate if invited. The trouble is that many clinical trial announcements state that participants must speak English. Even the many Latinos who are bilingual may be put off by that wording: “That is a message that you’re not invited. That’s how it’s perceived,” said Dr. Perez.
Racism and cognition in the elderly
At the press conference, Kristen George, PhD, presented results from a study of individuals over age 90. “Racial disparities in dementia have been well characterized, particularly among those people who are aged 65 and older, but we don’t know very much about the oldest old individuals who are aged 90 and older. This group is one of the fastest growing segments of the population, and it’s becoming increasingly diverse,” said Dr. George, assistant professor of epidemiology at the University of California, Davis.
The group enrolled 445 Asian, Black, Latinx, White, and multiracial individuals who were members of Kaiser Permanente Northern California, with a mean age of 92.7 years. They used the Major Experiences of Discrimination Scale to assess discrimination.
The researchers divided them into three groups based on gender, race, and responses to the 10-item scale. Class 1 included largely White men who had reported workplace discrimination, with an average of two major discrimination experiences. Class 2 was made up of White women and non-Whites who reported little or no discrimination, with an average of 0 experiences. Class 3 included all non-White participants, and they reported a mean of four discrimination experiences.
Using class 2 as a reference, executive function was better among class 1 individuals (beta = 0.28; 95% CI, 0.03-0.52) but there was no significant difference between class 3 and class 2. Class 1 had better baseline semantic memory than class 2 (beta = 0.33; 95% CI, 0.07-0.58), and those in class 3 performed significantly worse than class 2 (beta = –0.24; 95% CI, –0.48 to –0.00). There were no between-group differences in baseline verbal or episodic memory.
Dr. Perez, Dr. Manly, Dr. George, and Dr. Hill have no relevant financial disclosures.
FROM AAIC 2022
COVID smell loss tops disease severity as a predictor of long-term cognitive impairment
preliminary results of new research suggest.
The findings provide important insight into the long-term cognitive impact of COVID-19, said study investigator Gabriela Gonzalez-Alemán, PhD, professor at Pontifical Catholic University of Argentina, Buenos Aires.
The more information that can be gathered on factors increasing risks for this cognitive impact, “the better we can track it and begin to develop methods to prevent it,” she said.
The findings were presented at the Alzheimer’s Association International Conference.
Memory, attention problems
COVID-19 has infected more than 570 million people worldwide. Related infections may result in long-term sequelae, including neuropsychiatric symptoms, said Dr. Gonzalez-Alemán.
In older adults, COVID-19 sequelae may resemble early Alzheimer’s disease, and the two conditions may share risk factors and blood biomarkers.
The new study highlighted 1-year results from a large, prospective cohort study from Argentina. Researchers used measures to evaluate long-term consequences of COVID-19 in older adults recommended by the Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2).
Harmonizing definitions and methodologies for studying COVID-19’s impact on the brain allows consortium members to compare study results, said Dr. Gonzalez-Alemán.
The investigators used the health registry in the province of Jujuy, situated in the extreme northwestern part of Argentina. The registry includes all SARS-CoV-2 testing data for the entire region.
The investigators randomly invited adults aged 60 years and older from the registry to participate in the study. The current analysis included 766 adults aged 55-95 years (mean age 66.9 years; 57% female) with an average of 10.4 years of education. The education system in Argentina includes 12 years of school before university.
Investigators stratified subjects by polymerase chain reaction testing status. Of the total, 88.4% were infected with COVID and 11.6% were controls (subjects without COVID).
The neurocognitive assessment of participants included four cognitive domains: memory, attention, language, and executive function, and an olfactory test that determined degree of olfactory dysfunction. Cognitive impairment was defined as z scores below –2.
Researchers divided participants into groups according to cognitive performance. These included normal cognition, memory-only impairment (single domain; 11.7%), impairment in attention and executive function without memory impairment (two domains; 8.3%), and multiple domain impairment (11.6%).
“Our participants showed a predominance of memory impairment as would be seen in Alzheimer’s disease,” noted Dr. Gonzalez-Alemán. “And a large group showed a combination of memory and attention problems.”
About 40% of the study sample – but no controls – had olfactory dysfunction.
“All the subjects that had a severe cognitive impairment also had anosmia [loss of smell],” said Dr. Gonzalez-Alemán. “We established an association between olfactory dysfunction and cognitive performance and impairment.”
The analysis showed that severity of anosmia, but not clinical status, significantly predicted cognitive impairment. “So, anosmia could be a good predictor of cognitive impairment after COVID-19 infection,” said Dr. Gonzalez-Alemán.
For individuals older than 60 years, cognitive impairment can be persistent, as can be olfactory dysfunction, she added.
Results of a 1-year phone survey showed about 71.8% of subjects had received three vaccine doses and 24.9% two doses. About 12.5% of those with three doses were reinfected and 23.3% of those with two doses were reinfected.
Longest follow-up to date
Commenting on the research, Heather Snyder, PhD, vice president, medical and scientific relations at the Alzheimer’s Association, noted the study is “the longest follow-up we’ve seen” looking at the connection between persistent loss of smell and cognitive changes after a COVID-19 infection.
The study included a “fairly large” sample size and was “unique” in that it was set up in a part of the country with centralized testing, said Dr. Snyder.
The Argentinian group is among the most advanced of those connected to the CNS SC2, said Dr. Snyder.
Members of this Alzheimer’s Association consortium, said Dr. Snyder, regularly share updates of ongoing studies, which are at different stages and looking at various neuropsychiatric impacts of COVID-19. It is important to bring these groups together to determine what those impacts are “because no one group will be able to do this on their own,” she said. “We saw pretty early on that some individuals had changes in the brain, or changes in cognition, and loss of sense of smell or taste, which indicates there’s a connection to the brain.”
However, she added, “there’s still a lot we don’t know” about this connection.
The study was funded by Alzheimer’s Association and FULTRA.
A version of this article first appeared on Medscape.com.
preliminary results of new research suggest.
The findings provide important insight into the long-term cognitive impact of COVID-19, said study investigator Gabriela Gonzalez-Alemán, PhD, professor at Pontifical Catholic University of Argentina, Buenos Aires.
The more information that can be gathered on factors increasing risks for this cognitive impact, “the better we can track it and begin to develop methods to prevent it,” she said.
The findings were presented at the Alzheimer’s Association International Conference.
Memory, attention problems
COVID-19 has infected more than 570 million people worldwide. Related infections may result in long-term sequelae, including neuropsychiatric symptoms, said Dr. Gonzalez-Alemán.
In older adults, COVID-19 sequelae may resemble early Alzheimer’s disease, and the two conditions may share risk factors and blood biomarkers.
The new study highlighted 1-year results from a large, prospective cohort study from Argentina. Researchers used measures to evaluate long-term consequences of COVID-19 in older adults recommended by the Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2).
Harmonizing definitions and methodologies for studying COVID-19’s impact on the brain allows consortium members to compare study results, said Dr. Gonzalez-Alemán.
The investigators used the health registry in the province of Jujuy, situated in the extreme northwestern part of Argentina. The registry includes all SARS-CoV-2 testing data for the entire region.
The investigators randomly invited adults aged 60 years and older from the registry to participate in the study. The current analysis included 766 adults aged 55-95 years (mean age 66.9 years; 57% female) with an average of 10.4 years of education. The education system in Argentina includes 12 years of school before university.
Investigators stratified subjects by polymerase chain reaction testing status. Of the total, 88.4% were infected with COVID and 11.6% were controls (subjects without COVID).
The neurocognitive assessment of participants included four cognitive domains: memory, attention, language, and executive function, and an olfactory test that determined degree of olfactory dysfunction. Cognitive impairment was defined as z scores below –2.
Researchers divided participants into groups according to cognitive performance. These included normal cognition, memory-only impairment (single domain; 11.7%), impairment in attention and executive function without memory impairment (two domains; 8.3%), and multiple domain impairment (11.6%).
“Our participants showed a predominance of memory impairment as would be seen in Alzheimer’s disease,” noted Dr. Gonzalez-Alemán. “And a large group showed a combination of memory and attention problems.”
About 40% of the study sample – but no controls – had olfactory dysfunction.
“All the subjects that had a severe cognitive impairment also had anosmia [loss of smell],” said Dr. Gonzalez-Alemán. “We established an association between olfactory dysfunction and cognitive performance and impairment.”
The analysis showed that severity of anosmia, but not clinical status, significantly predicted cognitive impairment. “So, anosmia could be a good predictor of cognitive impairment after COVID-19 infection,” said Dr. Gonzalez-Alemán.
For individuals older than 60 years, cognitive impairment can be persistent, as can be olfactory dysfunction, she added.
Results of a 1-year phone survey showed about 71.8% of subjects had received three vaccine doses and 24.9% two doses. About 12.5% of those with three doses were reinfected and 23.3% of those with two doses were reinfected.
Longest follow-up to date
Commenting on the research, Heather Snyder, PhD, vice president, medical and scientific relations at the Alzheimer’s Association, noted the study is “the longest follow-up we’ve seen” looking at the connection between persistent loss of smell and cognitive changes after a COVID-19 infection.
The study included a “fairly large” sample size and was “unique” in that it was set up in a part of the country with centralized testing, said Dr. Snyder.
The Argentinian group is among the most advanced of those connected to the CNS SC2, said Dr. Snyder.
Members of this Alzheimer’s Association consortium, said Dr. Snyder, regularly share updates of ongoing studies, which are at different stages and looking at various neuropsychiatric impacts of COVID-19. It is important to bring these groups together to determine what those impacts are “because no one group will be able to do this on their own,” she said. “We saw pretty early on that some individuals had changes in the brain, or changes in cognition, and loss of sense of smell or taste, which indicates there’s a connection to the brain.”
However, she added, “there’s still a lot we don’t know” about this connection.
The study was funded by Alzheimer’s Association and FULTRA.
A version of this article first appeared on Medscape.com.
preliminary results of new research suggest.
The findings provide important insight into the long-term cognitive impact of COVID-19, said study investigator Gabriela Gonzalez-Alemán, PhD, professor at Pontifical Catholic University of Argentina, Buenos Aires.
The more information that can be gathered on factors increasing risks for this cognitive impact, “the better we can track it and begin to develop methods to prevent it,” she said.
The findings were presented at the Alzheimer’s Association International Conference.
Memory, attention problems
COVID-19 has infected more than 570 million people worldwide. Related infections may result in long-term sequelae, including neuropsychiatric symptoms, said Dr. Gonzalez-Alemán.
In older adults, COVID-19 sequelae may resemble early Alzheimer’s disease, and the two conditions may share risk factors and blood biomarkers.
The new study highlighted 1-year results from a large, prospective cohort study from Argentina. Researchers used measures to evaluate long-term consequences of COVID-19 in older adults recommended by the Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2).
Harmonizing definitions and methodologies for studying COVID-19’s impact on the brain allows consortium members to compare study results, said Dr. Gonzalez-Alemán.
The investigators used the health registry in the province of Jujuy, situated in the extreme northwestern part of Argentina. The registry includes all SARS-CoV-2 testing data for the entire region.
The investigators randomly invited adults aged 60 years and older from the registry to participate in the study. The current analysis included 766 adults aged 55-95 years (mean age 66.9 years; 57% female) with an average of 10.4 years of education. The education system in Argentina includes 12 years of school before university.
Investigators stratified subjects by polymerase chain reaction testing status. Of the total, 88.4% were infected with COVID and 11.6% were controls (subjects without COVID).
The neurocognitive assessment of participants included four cognitive domains: memory, attention, language, and executive function, and an olfactory test that determined degree of olfactory dysfunction. Cognitive impairment was defined as z scores below –2.
Researchers divided participants into groups according to cognitive performance. These included normal cognition, memory-only impairment (single domain; 11.7%), impairment in attention and executive function without memory impairment (two domains; 8.3%), and multiple domain impairment (11.6%).
“Our participants showed a predominance of memory impairment as would be seen in Alzheimer’s disease,” noted Dr. Gonzalez-Alemán. “And a large group showed a combination of memory and attention problems.”
About 40% of the study sample – but no controls – had olfactory dysfunction.
“All the subjects that had a severe cognitive impairment also had anosmia [loss of smell],” said Dr. Gonzalez-Alemán. “We established an association between olfactory dysfunction and cognitive performance and impairment.”
The analysis showed that severity of anosmia, but not clinical status, significantly predicted cognitive impairment. “So, anosmia could be a good predictor of cognitive impairment after COVID-19 infection,” said Dr. Gonzalez-Alemán.
For individuals older than 60 years, cognitive impairment can be persistent, as can be olfactory dysfunction, she added.
Results of a 1-year phone survey showed about 71.8% of subjects had received three vaccine doses and 24.9% two doses. About 12.5% of those with three doses were reinfected and 23.3% of those with two doses were reinfected.
Longest follow-up to date
Commenting on the research, Heather Snyder, PhD, vice president, medical and scientific relations at the Alzheimer’s Association, noted the study is “the longest follow-up we’ve seen” looking at the connection between persistent loss of smell and cognitive changes after a COVID-19 infection.
The study included a “fairly large” sample size and was “unique” in that it was set up in a part of the country with centralized testing, said Dr. Snyder.
The Argentinian group is among the most advanced of those connected to the CNS SC2, said Dr. Snyder.
Members of this Alzheimer’s Association consortium, said Dr. Snyder, regularly share updates of ongoing studies, which are at different stages and looking at various neuropsychiatric impacts of COVID-19. It is important to bring these groups together to determine what those impacts are “because no one group will be able to do this on their own,” she said. “We saw pretty early on that some individuals had changes in the brain, or changes in cognition, and loss of sense of smell or taste, which indicates there’s a connection to the brain.”
However, she added, “there’s still a lot we don’t know” about this connection.
The study was funded by Alzheimer’s Association and FULTRA.
A version of this article first appeared on Medscape.com.
FROM AAIC 2022
Novel guidance informs plasma biomarker use for Alzheimer’s disease
SAN DIEGO – The organization has previously published recommendations for use of amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease.
The recommendations were the subject of a presentation at the 2022 Alzheimer’s Association International Conference and were published online in Alzheimer’s & Dementia.
During his presentation, Oskar Hansson, MD, PhD, stressed that the document describes recommendations, not criteria, for use of blood-based biomarkers. He suggested that the recommendations will need to be updated within 9-12 months, and that criteria for blood-based biomarkers use could come within 2 years.
The new recommendations reflect the recent acceleration of progress in the field, according to Wiesje M. van der Flier, PhD, who moderated the session. “It’s just growing so quickly. I think within 5 years the whole field will have transformed. By starting to use them in specialized memory clinics first, but then also local memory clinics, and then finally, I think that they may also transform primary care,” said Dr. van der Flier, who is a professor of neurology at Amsterdam University Medical Center.
Guidance for clinical trials and memory clinics
The guidelines were created in part because blood-based biomarkers for Alzheimer’s disease have become increasingly available, and there has been a call from the community for guidance, according to Dr. Hansson. There is also a hazard that widespread adoption could interfere with the field itself, especially if physicians don’t understand how to interpret the results. That’s a particularly acute problem since Alzheimer’s disease pathology can precede symptoms. “It’s important to have some guidance about regulating their use so we don’t get the problem that they are misused and get a bad reputation,” said Dr. Hansson in an interview.
The current recommendations are for use in clinical trials to identify patients likely to have Alzheimer’s disease, as well as in memory clinics, though “we’re still a bit cautious. We still need to confirm it with other biomarkers. The reason for that is we still don’t know how these will perform in the clinical reality. So it’s a bit trying it out. You can start using these blood biomarkers to some degree,” said Dr. Hansson.
However, he offered the caveat that plasma-based biomarkers should only be used while confirming that the blood-based biomarkers agree with CSF tests, ideally more than 90% of the time. “If suddenly only 60% of the plasma biomarkers agree with CSF, you have a problem and you need to stop,” said Dr. Hansson.
The authors recommend that blood-based biomarkers be used in clinical trials to help select patients and identify healthy controls. Dr. Hansson said that there is not enough evidence that blood-based biomarkers have sufficient positive predictive value to be used as the sole criteria for clinical trial admission. However, they could also be used to inform decision-making in adaptive clinical trials.
Specifically, plasma Abeta42/Abeta40 and P-tau assays using established thresholds can be used in clinical studies first-screening step for clinical trials, though they should be confirmed by PET or CSF in those with abnormal blood biomarker levels. The biomarkers could also be used in non–Alzheimer’s disease clinical trials to exclude patients with probable Alzheimer’s disease copathology.
In memory clinics, the authors recommend that BBMs be used only in patients who are symptomatic and, when possible, should be confirmed by PET or CSF.
More work to be done
Dr. Hansson noted that 50%-70% of patients with Alzheimer’s disease are misdiagnosed in primary care, showing a clear need for biomarkers that could improve diagnosis. However, he stressed that blood-based biomarkers are not yet ready for use in that setting.
Still, they could eventually become a boon. “The majority of patients now do not get any biomarker support to diagnosis. They do not have access to amyloid PET or [CSF] biomarkers, but when the blood-based biomarkers are good enough, that means that biomarker support for an Alzheimer’s diagnosis [will be] available to many patients … across the globe,” said Dr. van der Flier.
There are numerous research efforts underway to validate blood-based biomarkers in more diverse groups of patients. That’s because the retrospective studies typically used to identify and validate biomarkers tend to recruit carefully selected patients, with clearly defined cases and good CSF characterization, according to Charlotte Teunissen, PhD, who is also a coauthor of the guidelines and professor of neuropsychiatry at Amsterdam University Medical Center. “Now we want to go one step further to go real-life practice, and there are several initiatives,” she said.
Dr. Hansson, Dr. Tenuissen, and Dr. van der Flier have no relevant financial disclosures.
SAN DIEGO – The organization has previously published recommendations for use of amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease.
The recommendations were the subject of a presentation at the 2022 Alzheimer’s Association International Conference and were published online in Alzheimer’s & Dementia.
During his presentation, Oskar Hansson, MD, PhD, stressed that the document describes recommendations, not criteria, for use of blood-based biomarkers. He suggested that the recommendations will need to be updated within 9-12 months, and that criteria for blood-based biomarkers use could come within 2 years.
The new recommendations reflect the recent acceleration of progress in the field, according to Wiesje M. van der Flier, PhD, who moderated the session. “It’s just growing so quickly. I think within 5 years the whole field will have transformed. By starting to use them in specialized memory clinics first, but then also local memory clinics, and then finally, I think that they may also transform primary care,” said Dr. van der Flier, who is a professor of neurology at Amsterdam University Medical Center.
Guidance for clinical trials and memory clinics
The guidelines were created in part because blood-based biomarkers for Alzheimer’s disease have become increasingly available, and there has been a call from the community for guidance, according to Dr. Hansson. There is also a hazard that widespread adoption could interfere with the field itself, especially if physicians don’t understand how to interpret the results. That’s a particularly acute problem since Alzheimer’s disease pathology can precede symptoms. “It’s important to have some guidance about regulating their use so we don’t get the problem that they are misused and get a bad reputation,” said Dr. Hansson in an interview.
The current recommendations are for use in clinical trials to identify patients likely to have Alzheimer’s disease, as well as in memory clinics, though “we’re still a bit cautious. We still need to confirm it with other biomarkers. The reason for that is we still don’t know how these will perform in the clinical reality. So it’s a bit trying it out. You can start using these blood biomarkers to some degree,” said Dr. Hansson.
However, he offered the caveat that plasma-based biomarkers should only be used while confirming that the blood-based biomarkers agree with CSF tests, ideally more than 90% of the time. “If suddenly only 60% of the plasma biomarkers agree with CSF, you have a problem and you need to stop,” said Dr. Hansson.
The authors recommend that blood-based biomarkers be used in clinical trials to help select patients and identify healthy controls. Dr. Hansson said that there is not enough evidence that blood-based biomarkers have sufficient positive predictive value to be used as the sole criteria for clinical trial admission. However, they could also be used to inform decision-making in adaptive clinical trials.
Specifically, plasma Abeta42/Abeta40 and P-tau assays using established thresholds can be used in clinical studies first-screening step for clinical trials, though they should be confirmed by PET or CSF in those with abnormal blood biomarker levels. The biomarkers could also be used in non–Alzheimer’s disease clinical trials to exclude patients with probable Alzheimer’s disease copathology.
In memory clinics, the authors recommend that BBMs be used only in patients who are symptomatic and, when possible, should be confirmed by PET or CSF.
More work to be done
Dr. Hansson noted that 50%-70% of patients with Alzheimer’s disease are misdiagnosed in primary care, showing a clear need for biomarkers that could improve diagnosis. However, he stressed that blood-based biomarkers are not yet ready for use in that setting.
Still, they could eventually become a boon. “The majority of patients now do not get any biomarker support to diagnosis. They do not have access to amyloid PET or [CSF] biomarkers, but when the blood-based biomarkers are good enough, that means that biomarker support for an Alzheimer’s diagnosis [will be] available to many patients … across the globe,” said Dr. van der Flier.
There are numerous research efforts underway to validate blood-based biomarkers in more diverse groups of patients. That’s because the retrospective studies typically used to identify and validate biomarkers tend to recruit carefully selected patients, with clearly defined cases and good CSF characterization, according to Charlotte Teunissen, PhD, who is also a coauthor of the guidelines and professor of neuropsychiatry at Amsterdam University Medical Center. “Now we want to go one step further to go real-life practice, and there are several initiatives,” she said.
Dr. Hansson, Dr. Tenuissen, and Dr. van der Flier have no relevant financial disclosures.
SAN DIEGO – The organization has previously published recommendations for use of amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease.
The recommendations were the subject of a presentation at the 2022 Alzheimer’s Association International Conference and were published online in Alzheimer’s & Dementia.
During his presentation, Oskar Hansson, MD, PhD, stressed that the document describes recommendations, not criteria, for use of blood-based biomarkers. He suggested that the recommendations will need to be updated within 9-12 months, and that criteria for blood-based biomarkers use could come within 2 years.
The new recommendations reflect the recent acceleration of progress in the field, according to Wiesje M. van der Flier, PhD, who moderated the session. “It’s just growing so quickly. I think within 5 years the whole field will have transformed. By starting to use them in specialized memory clinics first, but then also local memory clinics, and then finally, I think that they may also transform primary care,” said Dr. van der Flier, who is a professor of neurology at Amsterdam University Medical Center.
Guidance for clinical trials and memory clinics
The guidelines were created in part because blood-based biomarkers for Alzheimer’s disease have become increasingly available, and there has been a call from the community for guidance, according to Dr. Hansson. There is also a hazard that widespread adoption could interfere with the field itself, especially if physicians don’t understand how to interpret the results. That’s a particularly acute problem since Alzheimer’s disease pathology can precede symptoms. “It’s important to have some guidance about regulating their use so we don’t get the problem that they are misused and get a bad reputation,” said Dr. Hansson in an interview.
The current recommendations are for use in clinical trials to identify patients likely to have Alzheimer’s disease, as well as in memory clinics, though “we’re still a bit cautious. We still need to confirm it with other biomarkers. The reason for that is we still don’t know how these will perform in the clinical reality. So it’s a bit trying it out. You can start using these blood biomarkers to some degree,” said Dr. Hansson.
However, he offered the caveat that plasma-based biomarkers should only be used while confirming that the blood-based biomarkers agree with CSF tests, ideally more than 90% of the time. “If suddenly only 60% of the plasma biomarkers agree with CSF, you have a problem and you need to stop,” said Dr. Hansson.
The authors recommend that blood-based biomarkers be used in clinical trials to help select patients and identify healthy controls. Dr. Hansson said that there is not enough evidence that blood-based biomarkers have sufficient positive predictive value to be used as the sole criteria for clinical trial admission. However, they could also be used to inform decision-making in adaptive clinical trials.
Specifically, plasma Abeta42/Abeta40 and P-tau assays using established thresholds can be used in clinical studies first-screening step for clinical trials, though they should be confirmed by PET or CSF in those with abnormal blood biomarker levels. The biomarkers could also be used in non–Alzheimer’s disease clinical trials to exclude patients with probable Alzheimer’s disease copathology.
In memory clinics, the authors recommend that BBMs be used only in patients who are symptomatic and, when possible, should be confirmed by PET or CSF.
More work to be done
Dr. Hansson noted that 50%-70% of patients with Alzheimer’s disease are misdiagnosed in primary care, showing a clear need for biomarkers that could improve diagnosis. However, he stressed that blood-based biomarkers are not yet ready for use in that setting.
Still, they could eventually become a boon. “The majority of patients now do not get any biomarker support to diagnosis. They do not have access to amyloid PET or [CSF] biomarkers, but when the blood-based biomarkers are good enough, that means that biomarker support for an Alzheimer’s diagnosis [will be] available to many patients … across the globe,” said Dr. van der Flier.
There are numerous research efforts underway to validate blood-based biomarkers in more diverse groups of patients. That’s because the retrospective studies typically used to identify and validate biomarkers tend to recruit carefully selected patients, with clearly defined cases and good CSF characterization, according to Charlotte Teunissen, PhD, who is also a coauthor of the guidelines and professor of neuropsychiatry at Amsterdam University Medical Center. “Now we want to go one step further to go real-life practice, and there are several initiatives,” she said.
Dr. Hansson, Dr. Tenuissen, and Dr. van der Flier have no relevant financial disclosures.
FROM AAIC 2022