User login
Men and women react differently to acute stress
Topline
Methodology
- The study included 80 healthy participants, mean age 24 years.
- Half the subjects immersed their nondominant hand (including the wrist) in ice water for up to 3 minutes; the other half, which served as the control group, immersed their hand in warm water for 3 minutes.
- Participants were asked to deliberately downregulate emotional responses to high-intensity negative pictures.
- Participants regularly provided saliva samples to check cortisol levels and were monitored for cardiovascular activity.
- Researchers assessed pupil dilation, which along with subject ratings of their affective state served as emotion regulation (ER) outcome measures.
Takeaway
- In men, stress rapidly improved the ability to downregulate emotional arousal via distraction that was fully mediated by cortisol.
- In women, sympathetic nervous system (SNS) reactivity was linked to decreased regulatory performances.
- Direct stress effects on ER were smaller than expected.
In practice
The study contributes to a “better understanding of the neuroendocrinological mechanisms of stress effects on ER that may help to develop adequate preventive and curative interventions of stress- and emotion-related disorders,” the researchers write.
Source
The study was conducted by Katja Langer, Valerie Jentsch, and Oliver Wolf from the Department of Cognitive Psychology, Ruhr University Bochum (Germany). It was published in the May 2023 issue of Psychoneuroendocrinology.
Limitations
The results have some inconsistencies. The ER paradigm is somewhat artificial and not fully comparable with emotional trigger and regulatory requirements in everyday life. The study did not directly assess levels of catecholamines such as adrenaline and noradrenaline.
Disclosures
The study received support from the German Research Foundation (DFG). The authors have no reported conflicts of interest.
A version of this article originally appeared on Medscape.com.
Topline
Methodology
- The study included 80 healthy participants, mean age 24 years.
- Half the subjects immersed their nondominant hand (including the wrist) in ice water for up to 3 minutes; the other half, which served as the control group, immersed their hand in warm water for 3 minutes.
- Participants were asked to deliberately downregulate emotional responses to high-intensity negative pictures.
- Participants regularly provided saliva samples to check cortisol levels and were monitored for cardiovascular activity.
- Researchers assessed pupil dilation, which along with subject ratings of their affective state served as emotion regulation (ER) outcome measures.
Takeaway
- In men, stress rapidly improved the ability to downregulate emotional arousal via distraction that was fully mediated by cortisol.
- In women, sympathetic nervous system (SNS) reactivity was linked to decreased regulatory performances.
- Direct stress effects on ER were smaller than expected.
In practice
The study contributes to a “better understanding of the neuroendocrinological mechanisms of stress effects on ER that may help to develop adequate preventive and curative interventions of stress- and emotion-related disorders,” the researchers write.
Source
The study was conducted by Katja Langer, Valerie Jentsch, and Oliver Wolf from the Department of Cognitive Psychology, Ruhr University Bochum (Germany). It was published in the May 2023 issue of Psychoneuroendocrinology.
Limitations
The results have some inconsistencies. The ER paradigm is somewhat artificial and not fully comparable with emotional trigger and regulatory requirements in everyday life. The study did not directly assess levels of catecholamines such as adrenaline and noradrenaline.
Disclosures
The study received support from the German Research Foundation (DFG). The authors have no reported conflicts of interest.
A version of this article originally appeared on Medscape.com.
Topline
Methodology
- The study included 80 healthy participants, mean age 24 years.
- Half the subjects immersed their nondominant hand (including the wrist) in ice water for up to 3 minutes; the other half, which served as the control group, immersed their hand in warm water for 3 minutes.
- Participants were asked to deliberately downregulate emotional responses to high-intensity negative pictures.
- Participants regularly provided saliva samples to check cortisol levels and were monitored for cardiovascular activity.
- Researchers assessed pupil dilation, which along with subject ratings of their affective state served as emotion regulation (ER) outcome measures.
Takeaway
- In men, stress rapidly improved the ability to downregulate emotional arousal via distraction that was fully mediated by cortisol.
- In women, sympathetic nervous system (SNS) reactivity was linked to decreased regulatory performances.
- Direct stress effects on ER were smaller than expected.
In practice
The study contributes to a “better understanding of the neuroendocrinological mechanisms of stress effects on ER that may help to develop adequate preventive and curative interventions of stress- and emotion-related disorders,” the researchers write.
Source
The study was conducted by Katja Langer, Valerie Jentsch, and Oliver Wolf from the Department of Cognitive Psychology, Ruhr University Bochum (Germany). It was published in the May 2023 issue of Psychoneuroendocrinology.
Limitations
The results have some inconsistencies. The ER paradigm is somewhat artificial and not fully comparable with emotional trigger and regulatory requirements in everyday life. The study did not directly assess levels of catecholamines such as adrenaline and noradrenaline.
Disclosures
The study received support from the German Research Foundation (DFG). The authors have no reported conflicts of interest.
A version of this article originally appeared on Medscape.com.
New consensus on biomarkers for diagnosis of neurocognitive disorders
A new European consensus statement offers expert guidance on which biomarkers to use for patients presenting with cognitive complaints.
Led by Giovanni B. Frisoni, MD, laboratory of neuroimaging of aging, University of Geneva, and director of the memory clinic at Geneva University Hospital, the multidisciplinary task force set out to define a patient-centered diagnostic workflow for the rational and cost-effective use of biomarkers in memory clinics.
The new algorithm is part of a consensus statement presented at the Congress of the European Academy of Neurology 2023. An interim update was published in June in Alzheimer’s and Dementia.
Which biomarker?
Many biomarkers can aid diagnosis, said Dr. Frisoni; the challenge is choosing which biomarker to use for an individual patient.
A literature-based search, he said, yields a number of recommendations, but the vast majority of these are either disease based or biomarker based. The task force notes that “in vivo biomarkers enable early etiological diagnosis of neurocognitive disorders. While they have good analytical validity, their clinical validity and utility are uncertain.”
“When you have a patient in front of you, you don’ t know whether they have Alzheimer’s disease,” Dr. Frisoni said.
“You have a differential diagnosis to make, and you have a number of biomarkers – a number of weapons in your armamentarium – you have to choose. You can’t use all of them – we would like to, but we cannot.”
He added that trying to determine from the literature which biomarker is most appropriate given individual clinical conditions and all of the potential combinations is impossible.
“You will not find evidence of the comparative diagnostic value and the added diagnostic value” of one test vs, another, he noted.
“Is CSF [cerebrospinal fluid] better than amyloid PET in a particular clinical situation? What do I gain in terms of positive and negative predictive value in all the possible clinical conditions that I encounter in my clinical practice?”
Dr. Frisoni said the reality is that clinicians in memory clinics end up using biomarkers that are “based on clinical opportunities.”
For instance, “if you have a proficient nuclear medic, you use PET a lot.” In contrast, “if you have a proficient laboratory medic,” CSF markers will be favored – a situation that he said is “not ideal” and has resulted in large discrepancies in diagnostic approaches across Europe.
Harmonizing clinical practice
In a bid to harmonize clinical practice, 22 European experts from 11 European scientific societies and the executive director of Alzheimer Europe set out to develop a multidisciplinary consensus algorithm for the biomarker-based diagnosis of neurocognitive disorders in general, rather than specific neurocognitive disorders.
They used the Delphi method, in which a systematic literature review of the literature was followed by the drafting of a series of clinical statements by an executive board. These were then presented to the expert panel. If a majority consensus was reached on a given statement, it was considered closed. Questions for which there was no consensus were revised and presented to the panel again. The process was repeated until a consensus was reached.
A total of 56 statements underwent six rounds of discussion. A final online meeting led to the development of a diagnostic algorithm for patients who attend memory clinics for cognitive complaints.
The algorithm features three potential assessment waves. Wave 1 defines 11 clinical profiles that are based on the results of clinical and neuropsychological assessments, blood exams, brain imaging, and, in specific cases, electroencephalography. Wave 2 defines first-line biomarkers based on Wave 1 clinical profiles, and Wave 3 defines the second-line biomarker based on Wave 2 biomarker results.
When a patient’s clinical profile suggests Alzheimer’s disease and, in undefined cases, cerebrospinal fluid biomarkers are used first line. When CSF is inconclusive, 18-fluorodeoxyglucose positron emission tomography (FDG-PET) is used second line.
When the clinical profile suggests frontotemporal lobar degeneration or motor tauopathies, FDG-PET is first line and CSF biomarkers second line in atypical metabolic patter cases. When the clinical profile suggests Lewy body disease, dopamine transporter SPECT is first line and cardia I23I-metaiodobenzylguanidine scintigraphy is second line.
Dr. Frisoni noted that the panel strongly recommends performing biomarker tests for patients younger than 70. For those aged 70-85 years, biomarker testing is only recommended for patients with specific clinical features. For patients older than 85, biomarker testing is recommended only in “exceptional circumstances.”
Dr. Frisoni noted that the consensus document has a number of limitations.
“First of all, we could not capture all the theoretical possible combinations” of potential diagnosis and relevant biomarker tests. “There are so many that it’s virtually impossible.”
He also noted that the agreement among the panel for the use of some markers was “relatively low” at “barely 50%,” while for others, the agreement was approximately 70%.
The consensus document also does not explicitly address patients with “mixed pathologies,” which are common. In addition, it does not include emerging biomarkers, such as neurofilament light polypeptide levels, an indicator of axonal compromise.
“Last, but not least,” Dr. Frisoni said, the consensus document requires validation.
“This is a paper and pencil exercise. We, as self-appointed experts, can recommend ... whatever we want, but we must check whether what we write is applicable, feasible.”
In other words, it must be determined whether the “real patient journey” fits with the “ideal patient journey” set out in the consensus document.
This kind of validation, Dr. Frisoni said, is “usually not done for this type of exercise,” but “we want to do it in this case.”
Pros and cons
Bogdan Draganski, MD, consultant in neurology at the department of clinical neurosciences and director of the neuroimaging research laboratory, University Hospital of Lausanne (Switzerland), who cochaired the session, told this news organization that he was “swaying between two extremes” when considering the usefulness of the consensus document.
On one hand, the “reductionist approach” of breaking down a “complex issue into an algorithm” via the Delphi method risks introducing subjective bias.
He said machine learning and artificial intelligence could answer some of the questions posed by clinicians and, by extension, the statements included in the Delphi process by assessing the available data in a more objective manner.
On the other hand, Dr. Draganski said that reducing the options available to clinicians when making a differential diagnosis into the current algorithm is, pragmatically speaking, a “good approach.”
From this standpoint, the danger of using machine learning to answer clinical questions is that it “doesn’t take the responsibility” for the final decision, which means “we’re closing the loop of subjective decision-making for an individual doctor.”
He also applauded the idea of trying to provide more uniform patient assessment across Europe, although he believes “we have a long way to go” before it can deliver on the promise of personalized medicine.
Like Dr. Frisoni, Dr. Draganski noted the fact that patients with potential neurocognitive disorders often have multiple pathologies, which can include cardiovascular problems, depression, and cancer and that that could affect the choice of diagnostic biomarkers.
The second issue, he said, concerns implementation of the consensus document, which is a political decision that centers around “how politicians will define ‘uniformity’ and equal access to technological or nontechnological platforms.”
Achieving uniformity will require a pan-regional collaboration, he noted.
The task force was supported by unrestricted grants from F. Hoffmann-La Roche, Biogen International GmbH, Eisai Europe Limited, Life Molecular Imaging GmbH, and OM Pharma Suisse SA. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new European consensus statement offers expert guidance on which biomarkers to use for patients presenting with cognitive complaints.
Led by Giovanni B. Frisoni, MD, laboratory of neuroimaging of aging, University of Geneva, and director of the memory clinic at Geneva University Hospital, the multidisciplinary task force set out to define a patient-centered diagnostic workflow for the rational and cost-effective use of biomarkers in memory clinics.
The new algorithm is part of a consensus statement presented at the Congress of the European Academy of Neurology 2023. An interim update was published in June in Alzheimer’s and Dementia.
Which biomarker?
Many biomarkers can aid diagnosis, said Dr. Frisoni; the challenge is choosing which biomarker to use for an individual patient.
A literature-based search, he said, yields a number of recommendations, but the vast majority of these are either disease based or biomarker based. The task force notes that “in vivo biomarkers enable early etiological diagnosis of neurocognitive disorders. While they have good analytical validity, their clinical validity and utility are uncertain.”
“When you have a patient in front of you, you don’ t know whether they have Alzheimer’s disease,” Dr. Frisoni said.
“You have a differential diagnosis to make, and you have a number of biomarkers – a number of weapons in your armamentarium – you have to choose. You can’t use all of them – we would like to, but we cannot.”
He added that trying to determine from the literature which biomarker is most appropriate given individual clinical conditions and all of the potential combinations is impossible.
“You will not find evidence of the comparative diagnostic value and the added diagnostic value” of one test vs, another, he noted.
“Is CSF [cerebrospinal fluid] better than amyloid PET in a particular clinical situation? What do I gain in terms of positive and negative predictive value in all the possible clinical conditions that I encounter in my clinical practice?”
Dr. Frisoni said the reality is that clinicians in memory clinics end up using biomarkers that are “based on clinical opportunities.”
For instance, “if you have a proficient nuclear medic, you use PET a lot.” In contrast, “if you have a proficient laboratory medic,” CSF markers will be favored – a situation that he said is “not ideal” and has resulted in large discrepancies in diagnostic approaches across Europe.
Harmonizing clinical practice
In a bid to harmonize clinical practice, 22 European experts from 11 European scientific societies and the executive director of Alzheimer Europe set out to develop a multidisciplinary consensus algorithm for the biomarker-based diagnosis of neurocognitive disorders in general, rather than specific neurocognitive disorders.
They used the Delphi method, in which a systematic literature review of the literature was followed by the drafting of a series of clinical statements by an executive board. These were then presented to the expert panel. If a majority consensus was reached on a given statement, it was considered closed. Questions for which there was no consensus were revised and presented to the panel again. The process was repeated until a consensus was reached.
A total of 56 statements underwent six rounds of discussion. A final online meeting led to the development of a diagnostic algorithm for patients who attend memory clinics for cognitive complaints.
The algorithm features three potential assessment waves. Wave 1 defines 11 clinical profiles that are based on the results of clinical and neuropsychological assessments, blood exams, brain imaging, and, in specific cases, electroencephalography. Wave 2 defines first-line biomarkers based on Wave 1 clinical profiles, and Wave 3 defines the second-line biomarker based on Wave 2 biomarker results.
When a patient’s clinical profile suggests Alzheimer’s disease and, in undefined cases, cerebrospinal fluid biomarkers are used first line. When CSF is inconclusive, 18-fluorodeoxyglucose positron emission tomography (FDG-PET) is used second line.
When the clinical profile suggests frontotemporal lobar degeneration or motor tauopathies, FDG-PET is first line and CSF biomarkers second line in atypical metabolic patter cases. When the clinical profile suggests Lewy body disease, dopamine transporter SPECT is first line and cardia I23I-metaiodobenzylguanidine scintigraphy is second line.
Dr. Frisoni noted that the panel strongly recommends performing biomarker tests for patients younger than 70. For those aged 70-85 years, biomarker testing is only recommended for patients with specific clinical features. For patients older than 85, biomarker testing is recommended only in “exceptional circumstances.”
Dr. Frisoni noted that the consensus document has a number of limitations.
“First of all, we could not capture all the theoretical possible combinations” of potential diagnosis and relevant biomarker tests. “There are so many that it’s virtually impossible.”
He also noted that the agreement among the panel for the use of some markers was “relatively low” at “barely 50%,” while for others, the agreement was approximately 70%.
The consensus document also does not explicitly address patients with “mixed pathologies,” which are common. In addition, it does not include emerging biomarkers, such as neurofilament light polypeptide levels, an indicator of axonal compromise.
“Last, but not least,” Dr. Frisoni said, the consensus document requires validation.
“This is a paper and pencil exercise. We, as self-appointed experts, can recommend ... whatever we want, but we must check whether what we write is applicable, feasible.”
In other words, it must be determined whether the “real patient journey” fits with the “ideal patient journey” set out in the consensus document.
This kind of validation, Dr. Frisoni said, is “usually not done for this type of exercise,” but “we want to do it in this case.”
Pros and cons
Bogdan Draganski, MD, consultant in neurology at the department of clinical neurosciences and director of the neuroimaging research laboratory, University Hospital of Lausanne (Switzerland), who cochaired the session, told this news organization that he was “swaying between two extremes” when considering the usefulness of the consensus document.
On one hand, the “reductionist approach” of breaking down a “complex issue into an algorithm” via the Delphi method risks introducing subjective bias.
He said machine learning and artificial intelligence could answer some of the questions posed by clinicians and, by extension, the statements included in the Delphi process by assessing the available data in a more objective manner.
On the other hand, Dr. Draganski said that reducing the options available to clinicians when making a differential diagnosis into the current algorithm is, pragmatically speaking, a “good approach.”
From this standpoint, the danger of using machine learning to answer clinical questions is that it “doesn’t take the responsibility” for the final decision, which means “we’re closing the loop of subjective decision-making for an individual doctor.”
He also applauded the idea of trying to provide more uniform patient assessment across Europe, although he believes “we have a long way to go” before it can deliver on the promise of personalized medicine.
Like Dr. Frisoni, Dr. Draganski noted the fact that patients with potential neurocognitive disorders often have multiple pathologies, which can include cardiovascular problems, depression, and cancer and that that could affect the choice of diagnostic biomarkers.
The second issue, he said, concerns implementation of the consensus document, which is a political decision that centers around “how politicians will define ‘uniformity’ and equal access to technological or nontechnological platforms.”
Achieving uniformity will require a pan-regional collaboration, he noted.
The task force was supported by unrestricted grants from F. Hoffmann-La Roche, Biogen International GmbH, Eisai Europe Limited, Life Molecular Imaging GmbH, and OM Pharma Suisse SA. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new European consensus statement offers expert guidance on which biomarkers to use for patients presenting with cognitive complaints.
Led by Giovanni B. Frisoni, MD, laboratory of neuroimaging of aging, University of Geneva, and director of the memory clinic at Geneva University Hospital, the multidisciplinary task force set out to define a patient-centered diagnostic workflow for the rational and cost-effective use of biomarkers in memory clinics.
The new algorithm is part of a consensus statement presented at the Congress of the European Academy of Neurology 2023. An interim update was published in June in Alzheimer’s and Dementia.
Which biomarker?
Many biomarkers can aid diagnosis, said Dr. Frisoni; the challenge is choosing which biomarker to use for an individual patient.
A literature-based search, he said, yields a number of recommendations, but the vast majority of these are either disease based or biomarker based. The task force notes that “in vivo biomarkers enable early etiological diagnosis of neurocognitive disorders. While they have good analytical validity, their clinical validity and utility are uncertain.”
“When you have a patient in front of you, you don’ t know whether they have Alzheimer’s disease,” Dr. Frisoni said.
“You have a differential diagnosis to make, and you have a number of biomarkers – a number of weapons in your armamentarium – you have to choose. You can’t use all of them – we would like to, but we cannot.”
He added that trying to determine from the literature which biomarker is most appropriate given individual clinical conditions and all of the potential combinations is impossible.
“You will not find evidence of the comparative diagnostic value and the added diagnostic value” of one test vs, another, he noted.
“Is CSF [cerebrospinal fluid] better than amyloid PET in a particular clinical situation? What do I gain in terms of positive and negative predictive value in all the possible clinical conditions that I encounter in my clinical practice?”
Dr. Frisoni said the reality is that clinicians in memory clinics end up using biomarkers that are “based on clinical opportunities.”
For instance, “if you have a proficient nuclear medic, you use PET a lot.” In contrast, “if you have a proficient laboratory medic,” CSF markers will be favored – a situation that he said is “not ideal” and has resulted in large discrepancies in diagnostic approaches across Europe.
Harmonizing clinical practice
In a bid to harmonize clinical practice, 22 European experts from 11 European scientific societies and the executive director of Alzheimer Europe set out to develop a multidisciplinary consensus algorithm for the biomarker-based diagnosis of neurocognitive disorders in general, rather than specific neurocognitive disorders.
They used the Delphi method, in which a systematic literature review of the literature was followed by the drafting of a series of clinical statements by an executive board. These were then presented to the expert panel. If a majority consensus was reached on a given statement, it was considered closed. Questions for which there was no consensus were revised and presented to the panel again. The process was repeated until a consensus was reached.
A total of 56 statements underwent six rounds of discussion. A final online meeting led to the development of a diagnostic algorithm for patients who attend memory clinics for cognitive complaints.
The algorithm features three potential assessment waves. Wave 1 defines 11 clinical profiles that are based on the results of clinical and neuropsychological assessments, blood exams, brain imaging, and, in specific cases, electroencephalography. Wave 2 defines first-line biomarkers based on Wave 1 clinical profiles, and Wave 3 defines the second-line biomarker based on Wave 2 biomarker results.
When a patient’s clinical profile suggests Alzheimer’s disease and, in undefined cases, cerebrospinal fluid biomarkers are used first line. When CSF is inconclusive, 18-fluorodeoxyglucose positron emission tomography (FDG-PET) is used second line.
When the clinical profile suggests frontotemporal lobar degeneration or motor tauopathies, FDG-PET is first line and CSF biomarkers second line in atypical metabolic patter cases. When the clinical profile suggests Lewy body disease, dopamine transporter SPECT is first line and cardia I23I-metaiodobenzylguanidine scintigraphy is second line.
Dr. Frisoni noted that the panel strongly recommends performing biomarker tests for patients younger than 70. For those aged 70-85 years, biomarker testing is only recommended for patients with specific clinical features. For patients older than 85, biomarker testing is recommended only in “exceptional circumstances.”
Dr. Frisoni noted that the consensus document has a number of limitations.
“First of all, we could not capture all the theoretical possible combinations” of potential diagnosis and relevant biomarker tests. “There are so many that it’s virtually impossible.”
He also noted that the agreement among the panel for the use of some markers was “relatively low” at “barely 50%,” while for others, the agreement was approximately 70%.
The consensus document also does not explicitly address patients with “mixed pathologies,” which are common. In addition, it does not include emerging biomarkers, such as neurofilament light polypeptide levels, an indicator of axonal compromise.
“Last, but not least,” Dr. Frisoni said, the consensus document requires validation.
“This is a paper and pencil exercise. We, as self-appointed experts, can recommend ... whatever we want, but we must check whether what we write is applicable, feasible.”
In other words, it must be determined whether the “real patient journey” fits with the “ideal patient journey” set out in the consensus document.
This kind of validation, Dr. Frisoni said, is “usually not done for this type of exercise,” but “we want to do it in this case.”
Pros and cons
Bogdan Draganski, MD, consultant in neurology at the department of clinical neurosciences and director of the neuroimaging research laboratory, University Hospital of Lausanne (Switzerland), who cochaired the session, told this news organization that he was “swaying between two extremes” when considering the usefulness of the consensus document.
On one hand, the “reductionist approach” of breaking down a “complex issue into an algorithm” via the Delphi method risks introducing subjective bias.
He said machine learning and artificial intelligence could answer some of the questions posed by clinicians and, by extension, the statements included in the Delphi process by assessing the available data in a more objective manner.
On the other hand, Dr. Draganski said that reducing the options available to clinicians when making a differential diagnosis into the current algorithm is, pragmatically speaking, a “good approach.”
From this standpoint, the danger of using machine learning to answer clinical questions is that it “doesn’t take the responsibility” for the final decision, which means “we’re closing the loop of subjective decision-making for an individual doctor.”
He also applauded the idea of trying to provide more uniform patient assessment across Europe, although he believes “we have a long way to go” before it can deliver on the promise of personalized medicine.
Like Dr. Frisoni, Dr. Draganski noted the fact that patients with potential neurocognitive disorders often have multiple pathologies, which can include cardiovascular problems, depression, and cancer and that that could affect the choice of diagnostic biomarkers.
The second issue, he said, concerns implementation of the consensus document, which is a political decision that centers around “how politicians will define ‘uniformity’ and equal access to technological or nontechnological platforms.”
Achieving uniformity will require a pan-regional collaboration, he noted.
The task force was supported by unrestricted grants from F. Hoffmann-La Roche, Biogen International GmbH, Eisai Europe Limited, Life Molecular Imaging GmbH, and OM Pharma Suisse SA. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Long COVID ‘brain fog’ confounds doctors, but new research offers hope
Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.
She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.
Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.
Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.
“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”
Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.
Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.
In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.
She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.
Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.
“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.
Additionally, ABI is an actual diagnosis, whereas brain fog is not.
“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.
Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.
Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.
Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.
Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.
“The COVID virus is very invasive to the brain,” Dr. Bell said.
Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.
Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.
Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.
Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.
“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.
Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.
But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.
“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”
A version of this article first appeared on Medscape.com.
Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.
She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.
Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.
Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.
“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”
Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.
Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.
In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.
She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.
Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.
“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.
Additionally, ABI is an actual diagnosis, whereas brain fog is not.
“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.
Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.
Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.
Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.
Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.
“The COVID virus is very invasive to the brain,” Dr. Bell said.
Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.
Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.
Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.
Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.
“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.
Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.
But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.
“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”
A version of this article first appeared on Medscape.com.
Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.
She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.
Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.
Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.
“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”
Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.
Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.
In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.
She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.
Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.
“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.
Additionally, ABI is an actual diagnosis, whereas brain fog is not.
“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.
Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.
Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.
Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.
Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.
“The COVID virus is very invasive to the brain,” Dr. Bell said.
Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.
Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.
Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.
Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.
“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.
Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.
But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.
“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”
A version of this article first appeared on Medscape.com.
Lean muscle mass protective against Alzheimer’s?
Investigators analyzed data on more than 450,000 participants in the UK Biobank as well as two independent samples of more than 320,000 individuals with and without AD, and more than 260,000 individuals participating in a separate genes and intelligence study.
They estimated lean muscle and fat tissue in the arms and legs and found, in adjusted analyses, over 500 genetic variants associated with lean mass.
On average, higher genetically lean mass was associated with a “modest but statistically robust” reduction in AD risk and with superior performance on cognitive tasks.
“Using human genetic data, we found evidence for a protective effect of lean mass on risk of Alzheimer’s disease,” study investigators Iyas Daghlas, MD, a resident in the department of neurology, University of California, San Francisco, said in an interview.
Although “clinical intervention studies are needed to confirm this effect, this study supports current recommendations to maintain a healthy lifestyle to prevent dementia,” he said.
The study was published online in BMJ Medicine.
Naturally randomized research
Several measures of body composition have been investigated for their potential association with AD. Lean mass – a “proxy for muscle mass, defined as the difference between total mass and fat mass” – has been shown to be reduced in patients with AD compared with controls, the researchers noted.
“Previous research studies have tested the relationship of body mass index with Alzheimer’s disease and did not find evidence for a causal effect,” Dr. Daghlas said. “We wondered whether BMI was an insufficiently granular measure and hypothesized that disaggregating body mass into lean mass and fat mass could reveal novel associations with disease.”
Most studies have used case-control designs, which might be biased by “residual confounding or reverse causality.” Naturally randomized data “may be used as an alternative to conventional observational studies to investigate causal relations between risk factors and diseases,” the researchers wrote.
In particular, the Mendelian randomization (MR) paradigm randomly allocates germline genetic variants and uses them as proxies for a specific risk factor.
MR “is a technique that permits researchers to investigate cause-and-effect relationships using human genetic data,” Dr. Daghlas explained. “In effect, we’re studying the results of a naturally randomized experiment whereby some individuals are genetically allocated to carry more lean mass.”
The current study used MR to investigate the effect of genetically proxied lean mass on the risk of AD and the “related phenotype” of cognitive performance.
Genetic proxy
As genetic proxies for lean mass, the researchers chose single nucleotide polymorphisms (genetic variants) that were associated, in a genome-wide association study (GWAS), with appendicular lean mass.
Appendicular lean mass “more accurately reflects the effects of lean mass than whole body lean mass, which includes smooth and cardiac muscle,” the authors explained.
This GWAS used phenotypic and genetic data from 450,243 participants in the UK Biobank cohort (mean age 57 years). All participants were of European ancestry.
The researchers adjusted for age, sex, and genetic ancestry. They measured appendicular lean mass using bioimpedance – an electric current that flows at different rates through the body, depending on its composition.
In addition to the UK Biobank participants, the researchers drew on an independent sample of 21,982 people with AD; a control group of 41,944 people without AD; a replication sample of 7,329 people with and 252,879 people without AD to validate the findings; and 269,867 people taking part in a genome-wide study of cognitive performance.
The researchers identified 584 variants that met criteria for use as genetic proxies for lean mass. None were located within the APOE gene region. In the aggregate, these variants explained 10.3% of the variance in appendicular lean mass.
Each standard deviation increase in genetically proxied lean mass was associated with a 12% reduction in AD risk (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.82-0.95; P < .001). This finding was replicated in the independent consortium (OR, 0.91; 95% CI, 0.83-0.99; P = .02).
The findings remained “consistent” in sensitivity analyses.
A modifiable risk factor?
Higher appendicular lean mass was associated with higher levels of cognitive performance, with each SD increase in lean mass associated with an SD increase in cognitive performance (OR, 0.09; 95% CI, 0.06-0.11; P = .001).
“Adjusting for potential mediation through performance did not reduce the association between appendicular lean mass and risk of AD,” the authors wrote.
They obtained similar results using genetically proxied trunk and whole-body lean mass, after adjusting for fat mass.
The authors noted several limitations. The bioimpedance measures “only predict, but do not directly measure, lean mass.” Moreover, the approach didn’t examine whether a “critical window of risk factor timing” exists, during which lean mass might play a role in influencing AD risk and after which “interventions would no longer be effective.” Nor could the study determine whether increasing lean mass could reverse AD pathology in patients with preclinical disease or mild cognitive impairment.
Nevertheless, the findings suggest “that lean mass might be a possible modifiable protective factor for Alzheimer’s disease,” the authors wrote. “The mechanisms underlying this finding, as well as the clinical and public health implications, warrant further investigation.”
Novel strategies
In a comment, Iva Miljkovic, MD, PhD, associate professor, department of epidemiology, University of Pittsburgh, said the investigators used “very rigorous methodology.”
The finding suggesting that lean mass is associated with better cognitive function is “important, as cognitive impairment can become stable rather than progress to a pathological state; and, in some cases, can even be reversed.”
In those cases, “identifying the underlying cause – e.g., low lean mass – can significantly improve cognitive function,” said Dr. Miljkovic, senior author of a study showing muscle fat as a risk factor for cognitive decline.
More research will enable us to “expand our understanding” of the mechanisms involved and determine whether interventions aimed at preventing muscle loss and/or increasing muscle fat may have a beneficial effect on cognitive function,” she said. “This might lead to novel strategies to prevent AD.”
Dr. Daghlas is supported by the British Heart Foundation Centre of Research Excellence at Imperial College, London, and is employed part-time by Novo Nordisk. Dr. Miljkovic reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators analyzed data on more than 450,000 participants in the UK Biobank as well as two independent samples of more than 320,000 individuals with and without AD, and more than 260,000 individuals participating in a separate genes and intelligence study.
They estimated lean muscle and fat tissue in the arms and legs and found, in adjusted analyses, over 500 genetic variants associated with lean mass.
On average, higher genetically lean mass was associated with a “modest but statistically robust” reduction in AD risk and with superior performance on cognitive tasks.
“Using human genetic data, we found evidence for a protective effect of lean mass on risk of Alzheimer’s disease,” study investigators Iyas Daghlas, MD, a resident in the department of neurology, University of California, San Francisco, said in an interview.
Although “clinical intervention studies are needed to confirm this effect, this study supports current recommendations to maintain a healthy lifestyle to prevent dementia,” he said.
The study was published online in BMJ Medicine.
Naturally randomized research
Several measures of body composition have been investigated for their potential association with AD. Lean mass – a “proxy for muscle mass, defined as the difference between total mass and fat mass” – has been shown to be reduced in patients with AD compared with controls, the researchers noted.
“Previous research studies have tested the relationship of body mass index with Alzheimer’s disease and did not find evidence for a causal effect,” Dr. Daghlas said. “We wondered whether BMI was an insufficiently granular measure and hypothesized that disaggregating body mass into lean mass and fat mass could reveal novel associations with disease.”
Most studies have used case-control designs, which might be biased by “residual confounding or reverse causality.” Naturally randomized data “may be used as an alternative to conventional observational studies to investigate causal relations between risk factors and diseases,” the researchers wrote.
In particular, the Mendelian randomization (MR) paradigm randomly allocates germline genetic variants and uses them as proxies for a specific risk factor.
MR “is a technique that permits researchers to investigate cause-and-effect relationships using human genetic data,” Dr. Daghlas explained. “In effect, we’re studying the results of a naturally randomized experiment whereby some individuals are genetically allocated to carry more lean mass.”
The current study used MR to investigate the effect of genetically proxied lean mass on the risk of AD and the “related phenotype” of cognitive performance.
Genetic proxy
As genetic proxies for lean mass, the researchers chose single nucleotide polymorphisms (genetic variants) that were associated, in a genome-wide association study (GWAS), with appendicular lean mass.
Appendicular lean mass “more accurately reflects the effects of lean mass than whole body lean mass, which includes smooth and cardiac muscle,” the authors explained.
This GWAS used phenotypic and genetic data from 450,243 participants in the UK Biobank cohort (mean age 57 years). All participants were of European ancestry.
The researchers adjusted for age, sex, and genetic ancestry. They measured appendicular lean mass using bioimpedance – an electric current that flows at different rates through the body, depending on its composition.
In addition to the UK Biobank participants, the researchers drew on an independent sample of 21,982 people with AD; a control group of 41,944 people without AD; a replication sample of 7,329 people with and 252,879 people without AD to validate the findings; and 269,867 people taking part in a genome-wide study of cognitive performance.
The researchers identified 584 variants that met criteria for use as genetic proxies for lean mass. None were located within the APOE gene region. In the aggregate, these variants explained 10.3% of the variance in appendicular lean mass.
Each standard deviation increase in genetically proxied lean mass was associated with a 12% reduction in AD risk (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.82-0.95; P < .001). This finding was replicated in the independent consortium (OR, 0.91; 95% CI, 0.83-0.99; P = .02).
The findings remained “consistent” in sensitivity analyses.
A modifiable risk factor?
Higher appendicular lean mass was associated with higher levels of cognitive performance, with each SD increase in lean mass associated with an SD increase in cognitive performance (OR, 0.09; 95% CI, 0.06-0.11; P = .001).
“Adjusting for potential mediation through performance did not reduce the association between appendicular lean mass and risk of AD,” the authors wrote.
They obtained similar results using genetically proxied trunk and whole-body lean mass, after adjusting for fat mass.
The authors noted several limitations. The bioimpedance measures “only predict, but do not directly measure, lean mass.” Moreover, the approach didn’t examine whether a “critical window of risk factor timing” exists, during which lean mass might play a role in influencing AD risk and after which “interventions would no longer be effective.” Nor could the study determine whether increasing lean mass could reverse AD pathology in patients with preclinical disease or mild cognitive impairment.
Nevertheless, the findings suggest “that lean mass might be a possible modifiable protective factor for Alzheimer’s disease,” the authors wrote. “The mechanisms underlying this finding, as well as the clinical and public health implications, warrant further investigation.”
Novel strategies
In a comment, Iva Miljkovic, MD, PhD, associate professor, department of epidemiology, University of Pittsburgh, said the investigators used “very rigorous methodology.”
The finding suggesting that lean mass is associated with better cognitive function is “important, as cognitive impairment can become stable rather than progress to a pathological state; and, in some cases, can even be reversed.”
In those cases, “identifying the underlying cause – e.g., low lean mass – can significantly improve cognitive function,” said Dr. Miljkovic, senior author of a study showing muscle fat as a risk factor for cognitive decline.
More research will enable us to “expand our understanding” of the mechanisms involved and determine whether interventions aimed at preventing muscle loss and/or increasing muscle fat may have a beneficial effect on cognitive function,” she said. “This might lead to novel strategies to prevent AD.”
Dr. Daghlas is supported by the British Heart Foundation Centre of Research Excellence at Imperial College, London, and is employed part-time by Novo Nordisk. Dr. Miljkovic reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators analyzed data on more than 450,000 participants in the UK Biobank as well as two independent samples of more than 320,000 individuals with and without AD, and more than 260,000 individuals participating in a separate genes and intelligence study.
They estimated lean muscle and fat tissue in the arms and legs and found, in adjusted analyses, over 500 genetic variants associated with lean mass.
On average, higher genetically lean mass was associated with a “modest but statistically robust” reduction in AD risk and with superior performance on cognitive tasks.
“Using human genetic data, we found evidence for a protective effect of lean mass on risk of Alzheimer’s disease,” study investigators Iyas Daghlas, MD, a resident in the department of neurology, University of California, San Francisco, said in an interview.
Although “clinical intervention studies are needed to confirm this effect, this study supports current recommendations to maintain a healthy lifestyle to prevent dementia,” he said.
The study was published online in BMJ Medicine.
Naturally randomized research
Several measures of body composition have been investigated for their potential association with AD. Lean mass – a “proxy for muscle mass, defined as the difference between total mass and fat mass” – has been shown to be reduced in patients with AD compared with controls, the researchers noted.
“Previous research studies have tested the relationship of body mass index with Alzheimer’s disease and did not find evidence for a causal effect,” Dr. Daghlas said. “We wondered whether BMI was an insufficiently granular measure and hypothesized that disaggregating body mass into lean mass and fat mass could reveal novel associations with disease.”
Most studies have used case-control designs, which might be biased by “residual confounding or reverse causality.” Naturally randomized data “may be used as an alternative to conventional observational studies to investigate causal relations between risk factors and diseases,” the researchers wrote.
In particular, the Mendelian randomization (MR) paradigm randomly allocates germline genetic variants and uses them as proxies for a specific risk factor.
MR “is a technique that permits researchers to investigate cause-and-effect relationships using human genetic data,” Dr. Daghlas explained. “In effect, we’re studying the results of a naturally randomized experiment whereby some individuals are genetically allocated to carry more lean mass.”
The current study used MR to investigate the effect of genetically proxied lean mass on the risk of AD and the “related phenotype” of cognitive performance.
Genetic proxy
As genetic proxies for lean mass, the researchers chose single nucleotide polymorphisms (genetic variants) that were associated, in a genome-wide association study (GWAS), with appendicular lean mass.
Appendicular lean mass “more accurately reflects the effects of lean mass than whole body lean mass, which includes smooth and cardiac muscle,” the authors explained.
This GWAS used phenotypic and genetic data from 450,243 participants in the UK Biobank cohort (mean age 57 years). All participants were of European ancestry.
The researchers adjusted for age, sex, and genetic ancestry. They measured appendicular lean mass using bioimpedance – an electric current that flows at different rates through the body, depending on its composition.
In addition to the UK Biobank participants, the researchers drew on an independent sample of 21,982 people with AD; a control group of 41,944 people without AD; a replication sample of 7,329 people with and 252,879 people without AD to validate the findings; and 269,867 people taking part in a genome-wide study of cognitive performance.
The researchers identified 584 variants that met criteria for use as genetic proxies for lean mass. None were located within the APOE gene region. In the aggregate, these variants explained 10.3% of the variance in appendicular lean mass.
Each standard deviation increase in genetically proxied lean mass was associated with a 12% reduction in AD risk (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.82-0.95; P < .001). This finding was replicated in the independent consortium (OR, 0.91; 95% CI, 0.83-0.99; P = .02).
The findings remained “consistent” in sensitivity analyses.
A modifiable risk factor?
Higher appendicular lean mass was associated with higher levels of cognitive performance, with each SD increase in lean mass associated with an SD increase in cognitive performance (OR, 0.09; 95% CI, 0.06-0.11; P = .001).
“Adjusting for potential mediation through performance did not reduce the association between appendicular lean mass and risk of AD,” the authors wrote.
They obtained similar results using genetically proxied trunk and whole-body lean mass, after adjusting for fat mass.
The authors noted several limitations. The bioimpedance measures “only predict, but do not directly measure, lean mass.” Moreover, the approach didn’t examine whether a “critical window of risk factor timing” exists, during which lean mass might play a role in influencing AD risk and after which “interventions would no longer be effective.” Nor could the study determine whether increasing lean mass could reverse AD pathology in patients with preclinical disease or mild cognitive impairment.
Nevertheless, the findings suggest “that lean mass might be a possible modifiable protective factor for Alzheimer’s disease,” the authors wrote. “The mechanisms underlying this finding, as well as the clinical and public health implications, warrant further investigation.”
Novel strategies
In a comment, Iva Miljkovic, MD, PhD, associate professor, department of epidemiology, University of Pittsburgh, said the investigators used “very rigorous methodology.”
The finding suggesting that lean mass is associated with better cognitive function is “important, as cognitive impairment can become stable rather than progress to a pathological state; and, in some cases, can even be reversed.”
In those cases, “identifying the underlying cause – e.g., low lean mass – can significantly improve cognitive function,” said Dr. Miljkovic, senior author of a study showing muscle fat as a risk factor for cognitive decline.
More research will enable us to “expand our understanding” of the mechanisms involved and determine whether interventions aimed at preventing muscle loss and/or increasing muscle fat may have a beneficial effect on cognitive function,” she said. “This might lead to novel strategies to prevent AD.”
Dr. Daghlas is supported by the British Heart Foundation Centre of Research Excellence at Imperial College, London, and is employed part-time by Novo Nordisk. Dr. Miljkovic reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM BMJ MEDICINE
FDA clears new biomarker assays for early Alzheimer’s detection
The Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys total-tau CSF assays (tTau) (used as a tTau/Abeta42 ratio) are for use in adults ages 55 and older being evaluated for AD.
They join the Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys phospho-tau (181P) CSF (pTau181) assays (used as a pTau181/Abeta42 ratio) that received FDA 510(k) clearance in 2022.
“An early and accurate diagnosis can help patients, caregivers and physicians determine a path forward, and the Elecsys CSF assays support diagnosis at early disease stages, when treatment is most effective,” Brad Moore, president and CEO of Roche Diagnostics North America, said in a statement.
Appropriate use recommendations for new and emerging AD drugs call for confirmation of amyloid pathology. Currently, the only FDA-cleared methods to confirm amyloid pathology are CSF tests and PET scans.
“The Elecsys AD CSF assays are concordant with amyloid PET scan imaging and have the potential to provide a more affordable and accessible routine option to confirm the presence of amyloid pathology in the brain,” Roche said.
“They also offer detection of both amyloid and tau biomarkers from one draw, with no radiation and potential to detect Alzheimer’s pathology in early stages of disease,” the company added.
The previously approved Elecsys pTau181/Abeta42 ratio is currently available and the newly approved Elecsys tTau/Abeta42 ratio will be available in the fourth quarter of 2023.
A version of this article first appeared on Medscape.com.
The Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys total-tau CSF assays (tTau) (used as a tTau/Abeta42 ratio) are for use in adults ages 55 and older being evaluated for AD.
They join the Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys phospho-tau (181P) CSF (pTau181) assays (used as a pTau181/Abeta42 ratio) that received FDA 510(k) clearance in 2022.
“An early and accurate diagnosis can help patients, caregivers and physicians determine a path forward, and the Elecsys CSF assays support diagnosis at early disease stages, when treatment is most effective,” Brad Moore, president and CEO of Roche Diagnostics North America, said in a statement.
Appropriate use recommendations for new and emerging AD drugs call for confirmation of amyloid pathology. Currently, the only FDA-cleared methods to confirm amyloid pathology are CSF tests and PET scans.
“The Elecsys AD CSF assays are concordant with amyloid PET scan imaging and have the potential to provide a more affordable and accessible routine option to confirm the presence of amyloid pathology in the brain,” Roche said.
“They also offer detection of both amyloid and tau biomarkers from one draw, with no radiation and potential to detect Alzheimer’s pathology in early stages of disease,” the company added.
The previously approved Elecsys pTau181/Abeta42 ratio is currently available and the newly approved Elecsys tTau/Abeta42 ratio will be available in the fourth quarter of 2023.
A version of this article first appeared on Medscape.com.
The Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys total-tau CSF assays (tTau) (used as a tTau/Abeta42 ratio) are for use in adults ages 55 and older being evaluated for AD.
They join the Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys phospho-tau (181P) CSF (pTau181) assays (used as a pTau181/Abeta42 ratio) that received FDA 510(k) clearance in 2022.
“An early and accurate diagnosis can help patients, caregivers and physicians determine a path forward, and the Elecsys CSF assays support diagnosis at early disease stages, when treatment is most effective,” Brad Moore, president and CEO of Roche Diagnostics North America, said in a statement.
Appropriate use recommendations for new and emerging AD drugs call for confirmation of amyloid pathology. Currently, the only FDA-cleared methods to confirm amyloid pathology are CSF tests and PET scans.
“The Elecsys AD CSF assays are concordant with amyloid PET scan imaging and have the potential to provide a more affordable and accessible routine option to confirm the presence of amyloid pathology in the brain,” Roche said.
“They also offer detection of both amyloid and tau biomarkers from one draw, with no radiation and potential to detect Alzheimer’s pathology in early stages of disease,” the company added.
The previously approved Elecsys pTau181/Abeta42 ratio is currently available and the newly approved Elecsys tTau/Abeta42 ratio will be available in the fourth quarter of 2023.
A version of this article first appeared on Medscape.com.
No link between heartburn meds and dementia
A new study provides reassurance about the safety of long-term proton pump inhibitor (PPIs) and histamine-2 receptor antagonist (H2RA) use in older adults, finding no increased risk for dementia or cognitive changes.
It was published online in Gastroenterology.
The post hoc observational study was led by Raaj Mehta, MD, PhD, with Massachusetts General Hospital and Harvard Medical School in Boston.
The researchers analyzed results from the Aspirin in Reducing Events in the Elderly clinical trial. The randomized trial of aspirin included 18,934 adults aged 65 and older from the United States and Australia. Patients’ use of PPI and H2RA was tracked, along with dementia incidence and cognitive changes.
The results showed that there was no link to new dementia diagnoses in patients who used PPIs (25%) and H2RA (2%) at baseline, versus those who did not use either heartburn medication.
Limitations of prior studies are referenced, including the potential for residual confounding and underestimation of PPI and H2RA use, the lack of data on medication dose and duration, and the absence of apo E4 allele status.
The study was funded by grants from the National Institute on Aging, the National Cancer Institute, and other institutions. Dr. Mehta has disclosed no relevant conflicts of interest.
A version of this article originally appeared on Medscape.com.
A new study provides reassurance about the safety of long-term proton pump inhibitor (PPIs) and histamine-2 receptor antagonist (H2RA) use in older adults, finding no increased risk for dementia or cognitive changes.
It was published online in Gastroenterology.
The post hoc observational study was led by Raaj Mehta, MD, PhD, with Massachusetts General Hospital and Harvard Medical School in Boston.
The researchers analyzed results from the Aspirin in Reducing Events in the Elderly clinical trial. The randomized trial of aspirin included 18,934 adults aged 65 and older from the United States and Australia. Patients’ use of PPI and H2RA was tracked, along with dementia incidence and cognitive changes.
The results showed that there was no link to new dementia diagnoses in patients who used PPIs (25%) and H2RA (2%) at baseline, versus those who did not use either heartburn medication.
Limitations of prior studies are referenced, including the potential for residual confounding and underestimation of PPI and H2RA use, the lack of data on medication dose and duration, and the absence of apo E4 allele status.
The study was funded by grants from the National Institute on Aging, the National Cancer Institute, and other institutions. Dr. Mehta has disclosed no relevant conflicts of interest.
A version of this article originally appeared on Medscape.com.
A new study provides reassurance about the safety of long-term proton pump inhibitor (PPIs) and histamine-2 receptor antagonist (H2RA) use in older adults, finding no increased risk for dementia or cognitive changes.
It was published online in Gastroenterology.
The post hoc observational study was led by Raaj Mehta, MD, PhD, with Massachusetts General Hospital and Harvard Medical School in Boston.
The researchers analyzed results from the Aspirin in Reducing Events in the Elderly clinical trial. The randomized trial of aspirin included 18,934 adults aged 65 and older from the United States and Australia. Patients’ use of PPI and H2RA was tracked, along with dementia incidence and cognitive changes.
The results showed that there was no link to new dementia diagnoses in patients who used PPIs (25%) and H2RA (2%) at baseline, versus those who did not use either heartburn medication.
Limitations of prior studies are referenced, including the potential for residual confounding and underestimation of PPI and H2RA use, the lack of data on medication dose and duration, and the absence of apo E4 allele status.
The study was funded by grants from the National Institute on Aging, the National Cancer Institute, and other institutions. Dr. Mehta has disclosed no relevant conflicts of interest.
A version of this article originally appeared on Medscape.com.
FROM GASTROENTEROLOGY
Regular napping linked to greater brain volume
Investigators at University College London, and the University of the Republic of Uruguay, Montevideo, found individuals genetically predisposed to regular napping had larger total brain volume, a surrogate of better cognitive health.
“Our results suggest that napping may improve brain health,” first author Valentina Paz, MSc, a PhD candidate at the University of the Republic of Uruguay said in an interview. “Specifically, our work revealed a 15.8 cubic cm increase in total brain volume with more frequent daytime napping,” she said.
The findings were published online in Sleep Health.
Higher brain volume
Previous studies examining the potential link between napping and cognition in older adults have yielded conflicting results.
To clarify this association, Ms. Paz and colleagues used Mendelian randomization to study DNA samples, cognitive outcomes, and functional magnetic resonance imaging data in participants from the ongoing UK Biobank Study.
Starting with data from 378,932 study participants (mean age 57), investigators compared measures of brain health and cognition of those who are more genetically programmed to nap with people who did not have these genetic variations.
More specifically, the investigators examined 97 sections of genetic code previously linked to the likelihood of regular napping and correlated these results with fMRI and cognitive outcomes between those genetically predisposed to take regular naps and those who weren’t.
Study outcomes included total brain volume, hippocampal volume, reaction time, and visual memory.
The final study sample included 35,080 with neuroimaging, cognitive assessment, and genotype data.
The researchers estimated that the average difference in brain volume between individuals genetically programmed to be habitual nappers and those who were not was equivalent to 15.8 cubic cm, or 2.6-6.5 years of aging.
However, there was no difference in the other three outcomes – hippocampal volume, reaction time, and visual processing – between the two study groups.
Since investigators did not have information on the length of time participants napped, Ms. Paz suggested that “taking a short nap in the early afternoon may help cognition in those needing it.”
However, she added, the study’s findings need to be replicated before any firm conclusions can be made.
“More work is needed to examine the associations between napping and cognition, and the replication of these findings using other datasets and methods,” she said.
The investigators note that the study’s findings augment the knowledge of the “impact of habitual daytime napping on brain health, which is essential to understanding cognitive impairment in the aging population. The lack of evidence for an association between napping and hippocampal volume and cognitive outcomes (for example, alertness) may be affected by habitual daytime napping and should be studied in the future.”
Strengths, limitations
Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, said, “the study shows a small but significant increase in brain volume in people who have a genetic signature associated with taking daytime naps.”
Dr. Spires-Jones, who was not involved in the research, noted that while the study is well-conducted, it has limitations. Because Mendelian randomization uses a genetic signature, she noted, outcomes depend on the accuracy of the signature.
“The napping habits of UK Biobank participants were self-reported, which might not be entirely accurate, and the ‘napping’ signature overlapped substantially with the signature for cognitive outcomes in the study, which makes the causal link weaker,” she said.
“Even with those limitations, this study is interesting because it adds to the data indicating that sleep is important for brain health,” said Dr. Spires-Jones.
The study was supported by Diabetes UK, the British Heart Foundation, and the Diabetes Research and Wellness Foundation. In Uruguay, it was supported by Programa de Desarrollo de las Ciencias Básicas, Agencia Nacional de Investigación e Innovación, Comisión Sectorial de Investigación Científica, and Comisión Académica de Posgrado. In the United States it was supported by the National Heart, Lung, and Blood Institute. There were no disclosures reported.
A version of this article first appeared on Medscape.com.
Investigators at University College London, and the University of the Republic of Uruguay, Montevideo, found individuals genetically predisposed to regular napping had larger total brain volume, a surrogate of better cognitive health.
“Our results suggest that napping may improve brain health,” first author Valentina Paz, MSc, a PhD candidate at the University of the Republic of Uruguay said in an interview. “Specifically, our work revealed a 15.8 cubic cm increase in total brain volume with more frequent daytime napping,” she said.
The findings were published online in Sleep Health.
Higher brain volume
Previous studies examining the potential link between napping and cognition in older adults have yielded conflicting results.
To clarify this association, Ms. Paz and colleagues used Mendelian randomization to study DNA samples, cognitive outcomes, and functional magnetic resonance imaging data in participants from the ongoing UK Biobank Study.
Starting with data from 378,932 study participants (mean age 57), investigators compared measures of brain health and cognition of those who are more genetically programmed to nap with people who did not have these genetic variations.
More specifically, the investigators examined 97 sections of genetic code previously linked to the likelihood of regular napping and correlated these results with fMRI and cognitive outcomes between those genetically predisposed to take regular naps and those who weren’t.
Study outcomes included total brain volume, hippocampal volume, reaction time, and visual memory.
The final study sample included 35,080 with neuroimaging, cognitive assessment, and genotype data.
The researchers estimated that the average difference in brain volume between individuals genetically programmed to be habitual nappers and those who were not was equivalent to 15.8 cubic cm, or 2.6-6.5 years of aging.
However, there was no difference in the other three outcomes – hippocampal volume, reaction time, and visual processing – between the two study groups.
Since investigators did not have information on the length of time participants napped, Ms. Paz suggested that “taking a short nap in the early afternoon may help cognition in those needing it.”
However, she added, the study’s findings need to be replicated before any firm conclusions can be made.
“More work is needed to examine the associations between napping and cognition, and the replication of these findings using other datasets and methods,” she said.
The investigators note that the study’s findings augment the knowledge of the “impact of habitual daytime napping on brain health, which is essential to understanding cognitive impairment in the aging population. The lack of evidence for an association between napping and hippocampal volume and cognitive outcomes (for example, alertness) may be affected by habitual daytime napping and should be studied in the future.”
Strengths, limitations
Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, said, “the study shows a small but significant increase in brain volume in people who have a genetic signature associated with taking daytime naps.”
Dr. Spires-Jones, who was not involved in the research, noted that while the study is well-conducted, it has limitations. Because Mendelian randomization uses a genetic signature, she noted, outcomes depend on the accuracy of the signature.
“The napping habits of UK Biobank participants were self-reported, which might not be entirely accurate, and the ‘napping’ signature overlapped substantially with the signature for cognitive outcomes in the study, which makes the causal link weaker,” she said.
“Even with those limitations, this study is interesting because it adds to the data indicating that sleep is important for brain health,” said Dr. Spires-Jones.
The study was supported by Diabetes UK, the British Heart Foundation, and the Diabetes Research and Wellness Foundation. In Uruguay, it was supported by Programa de Desarrollo de las Ciencias Básicas, Agencia Nacional de Investigación e Innovación, Comisión Sectorial de Investigación Científica, and Comisión Académica de Posgrado. In the United States it was supported by the National Heart, Lung, and Blood Institute. There were no disclosures reported.
A version of this article first appeared on Medscape.com.
Investigators at University College London, and the University of the Republic of Uruguay, Montevideo, found individuals genetically predisposed to regular napping had larger total brain volume, a surrogate of better cognitive health.
“Our results suggest that napping may improve brain health,” first author Valentina Paz, MSc, a PhD candidate at the University of the Republic of Uruguay said in an interview. “Specifically, our work revealed a 15.8 cubic cm increase in total brain volume with more frequent daytime napping,” she said.
The findings were published online in Sleep Health.
Higher brain volume
Previous studies examining the potential link between napping and cognition in older adults have yielded conflicting results.
To clarify this association, Ms. Paz and colleagues used Mendelian randomization to study DNA samples, cognitive outcomes, and functional magnetic resonance imaging data in participants from the ongoing UK Biobank Study.
Starting with data from 378,932 study participants (mean age 57), investigators compared measures of brain health and cognition of those who are more genetically programmed to nap with people who did not have these genetic variations.
More specifically, the investigators examined 97 sections of genetic code previously linked to the likelihood of regular napping and correlated these results with fMRI and cognitive outcomes between those genetically predisposed to take regular naps and those who weren’t.
Study outcomes included total brain volume, hippocampal volume, reaction time, and visual memory.
The final study sample included 35,080 with neuroimaging, cognitive assessment, and genotype data.
The researchers estimated that the average difference in brain volume between individuals genetically programmed to be habitual nappers and those who were not was equivalent to 15.8 cubic cm, or 2.6-6.5 years of aging.
However, there was no difference in the other three outcomes – hippocampal volume, reaction time, and visual processing – between the two study groups.
Since investigators did not have information on the length of time participants napped, Ms. Paz suggested that “taking a short nap in the early afternoon may help cognition in those needing it.”
However, she added, the study’s findings need to be replicated before any firm conclusions can be made.
“More work is needed to examine the associations between napping and cognition, and the replication of these findings using other datasets and methods,” she said.
The investigators note that the study’s findings augment the knowledge of the “impact of habitual daytime napping on brain health, which is essential to understanding cognitive impairment in the aging population. The lack of evidence for an association between napping and hippocampal volume and cognitive outcomes (for example, alertness) may be affected by habitual daytime napping and should be studied in the future.”
Strengths, limitations
Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, said, “the study shows a small but significant increase in brain volume in people who have a genetic signature associated with taking daytime naps.”
Dr. Spires-Jones, who was not involved in the research, noted that while the study is well-conducted, it has limitations. Because Mendelian randomization uses a genetic signature, she noted, outcomes depend on the accuracy of the signature.
“The napping habits of UK Biobank participants were self-reported, which might not be entirely accurate, and the ‘napping’ signature overlapped substantially with the signature for cognitive outcomes in the study, which makes the causal link weaker,” she said.
“Even with those limitations, this study is interesting because it adds to the data indicating that sleep is important for brain health,” said Dr. Spires-Jones.
The study was supported by Diabetes UK, the British Heart Foundation, and the Diabetes Research and Wellness Foundation. In Uruguay, it was supported by Programa de Desarrollo de las Ciencias Básicas, Agencia Nacional de Investigación e Innovación, Comisión Sectorial de Investigación Científica, and Comisión Académica de Posgrado. In the United States it was supported by the National Heart, Lung, and Blood Institute. There were no disclosures reported.
A version of this article first appeared on Medscape.com.
FROM SLEEP HEALTH
No link between PPIs and dementia in new study
TOPLINE:
A new study provides reassurance about the long-term safety of proton pump inhibitors (PPIs) and histamine-2 receptor antagonist (H2RA) use in older adults, finding no increased risk for dementia or cognitive changes.
METHODOLOGY:
- Post hoc observational study within the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial.
- 18,934 adults aged 65+ from the United States and Australia without dementia at baseline.
- 4,667 (25%) PPI users and 368 (2%) H2RA users at baseline.
- PPI and H2RA use, dementia incidence, and cognitive changes were tracked.
TAKEAWAY:
- In multivariable analysis, baseline PPI use was not associated with incident dementia (hazard ratio, 0.88) or cognitive impairment (HR, 1.00).
- PPI use was not linked to changes in overall cognitive test scores over time (beta –0.002).
- No associations were found between H2RA use and cognitive endpoints.
IN PRACTICE:
“Long-term use of PPIs in older adults is unlikely to have negative effects on cognition,” the study team concludes.
STUDY DETAILS:
The study was led by Raaj Mehta, MD, PhD, with Massachusetts General Hospital and Harvard Medical School in Boston. The study was published online in Gastroenterology. Funding was provided by grants from the National Institute on Aging, the National Cancer Institute, and other institutions.
LIMITATIONS:
Potential for residual confounding and underestimation of PPI and H2RA use, lack of data on medication dose and duration, and the absence of ApoE4 allele status.
DISCLOSURES:
Dr. Mehta has disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
A new study provides reassurance about the long-term safety of proton pump inhibitors (PPIs) and histamine-2 receptor antagonist (H2RA) use in older adults, finding no increased risk for dementia or cognitive changes.
METHODOLOGY:
- Post hoc observational study within the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial.
- 18,934 adults aged 65+ from the United States and Australia without dementia at baseline.
- 4,667 (25%) PPI users and 368 (2%) H2RA users at baseline.
- PPI and H2RA use, dementia incidence, and cognitive changes were tracked.
TAKEAWAY:
- In multivariable analysis, baseline PPI use was not associated with incident dementia (hazard ratio, 0.88) or cognitive impairment (HR, 1.00).
- PPI use was not linked to changes in overall cognitive test scores over time (beta –0.002).
- No associations were found between H2RA use and cognitive endpoints.
IN PRACTICE:
“Long-term use of PPIs in older adults is unlikely to have negative effects on cognition,” the study team concludes.
STUDY DETAILS:
The study was led by Raaj Mehta, MD, PhD, with Massachusetts General Hospital and Harvard Medical School in Boston. The study was published online in Gastroenterology. Funding was provided by grants from the National Institute on Aging, the National Cancer Institute, and other institutions.
LIMITATIONS:
Potential for residual confounding and underestimation of PPI and H2RA use, lack of data on medication dose and duration, and the absence of ApoE4 allele status.
DISCLOSURES:
Dr. Mehta has disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
A new study provides reassurance about the long-term safety of proton pump inhibitors (PPIs) and histamine-2 receptor antagonist (H2RA) use in older adults, finding no increased risk for dementia or cognitive changes.
METHODOLOGY:
- Post hoc observational study within the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial.
- 18,934 adults aged 65+ from the United States and Australia without dementia at baseline.
- 4,667 (25%) PPI users and 368 (2%) H2RA users at baseline.
- PPI and H2RA use, dementia incidence, and cognitive changes were tracked.
TAKEAWAY:
- In multivariable analysis, baseline PPI use was not associated with incident dementia (hazard ratio, 0.88) or cognitive impairment (HR, 1.00).
- PPI use was not linked to changes in overall cognitive test scores over time (beta –0.002).
- No associations were found between H2RA use and cognitive endpoints.
IN PRACTICE:
“Long-term use of PPIs in older adults is unlikely to have negative effects on cognition,” the study team concludes.
STUDY DETAILS:
The study was led by Raaj Mehta, MD, PhD, with Massachusetts General Hospital and Harvard Medical School in Boston. The study was published online in Gastroenterology. Funding was provided by grants from the National Institute on Aging, the National Cancer Institute, and other institutions.
LIMITATIONS:
Potential for residual confounding and underestimation of PPI and H2RA use, lack of data on medication dose and duration, and the absence of ApoE4 allele status.
DISCLOSURES:
Dr. Mehta has disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
SSRI improves cognition, major depression in early dementia
TOPLINE:
METHODOLOGY:
- The multicenter MEMORY study included 82 subjects with MDD and early-stage dementia, mean age 70.3 years, mostly female (66%) and White (95%).
- Vortioxetine, a modulator of 5-hydroxytryptamine receptor activity and an inhibitor of the 5-HT transporter, initiated at 5 mg/day (recommended starting dose in older adults) with the dose up-titrated to 10 mg/day after a week and flexible dosing thereafter.
- Depression was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), and cognition with the Digit Symbol Substitution Test (DSST) and Rey Auditory Verbal Learning Test.
TAKEAWAY:
- There was significant and clinically meaningful improvement in the severity of depressive symptoms, as measured by MADRS total score (the primary outcome), at all assessment time points (P < .0001).
- Improvements in depressive symptoms were irrespective of dementia type.
- There were also significant improvements in DSST total score (P < .0001) and in daily functioning and health-related quality of life (HRQoL).
- Vortioxetine was well tolerated; side effects, including nausea and abdominal pain, were mostly mild to moderate.
IN PRACTICE:
“Vortioxetine demonstrated effectiveness in clinically significantly improving depressive symptoms, cognitive performance, daily and global functioning, and HRQoL in patients with MDD and comorbid early-stage dementia treated for 12 weeks” the researchers noted.
STUDY DETAILS:
The study was conducted by Michael Cronquist Christensen from pharmaceutical company H. Lundbeck, Valby, Denmark, and colleagues. It was published online in the Journal of Affective Disorders.
LIMITATIONS:
The study is open label and lacked a control group. Learning effects were possible, which could contribute to improved cognitive performance, although significant improvement on the RAVLT was not observed until week 4, suggesting earning effects were minimal.
DISCLOSURES:
The study was funded by H. Lundbeck. Mr. Christensen is an employee of H. Lundbeck.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- The multicenter MEMORY study included 82 subjects with MDD and early-stage dementia, mean age 70.3 years, mostly female (66%) and White (95%).
- Vortioxetine, a modulator of 5-hydroxytryptamine receptor activity and an inhibitor of the 5-HT transporter, initiated at 5 mg/day (recommended starting dose in older adults) with the dose up-titrated to 10 mg/day after a week and flexible dosing thereafter.
- Depression was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), and cognition with the Digit Symbol Substitution Test (DSST) and Rey Auditory Verbal Learning Test.
TAKEAWAY:
- There was significant and clinically meaningful improvement in the severity of depressive symptoms, as measured by MADRS total score (the primary outcome), at all assessment time points (P < .0001).
- Improvements in depressive symptoms were irrespective of dementia type.
- There were also significant improvements in DSST total score (P < .0001) and in daily functioning and health-related quality of life (HRQoL).
- Vortioxetine was well tolerated; side effects, including nausea and abdominal pain, were mostly mild to moderate.
IN PRACTICE:
“Vortioxetine demonstrated effectiveness in clinically significantly improving depressive symptoms, cognitive performance, daily and global functioning, and HRQoL in patients with MDD and comorbid early-stage dementia treated for 12 weeks” the researchers noted.
STUDY DETAILS:
The study was conducted by Michael Cronquist Christensen from pharmaceutical company H. Lundbeck, Valby, Denmark, and colleagues. It was published online in the Journal of Affective Disorders.
LIMITATIONS:
The study is open label and lacked a control group. Learning effects were possible, which could contribute to improved cognitive performance, although significant improvement on the RAVLT was not observed until week 4, suggesting earning effects were minimal.
DISCLOSURES:
The study was funded by H. Lundbeck. Mr. Christensen is an employee of H. Lundbeck.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- The multicenter MEMORY study included 82 subjects with MDD and early-stage dementia, mean age 70.3 years, mostly female (66%) and White (95%).
- Vortioxetine, a modulator of 5-hydroxytryptamine receptor activity and an inhibitor of the 5-HT transporter, initiated at 5 mg/day (recommended starting dose in older adults) with the dose up-titrated to 10 mg/day after a week and flexible dosing thereafter.
- Depression was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), and cognition with the Digit Symbol Substitution Test (DSST) and Rey Auditory Verbal Learning Test.
TAKEAWAY:
- There was significant and clinically meaningful improvement in the severity of depressive symptoms, as measured by MADRS total score (the primary outcome), at all assessment time points (P < .0001).
- Improvements in depressive symptoms were irrespective of dementia type.
- There were also significant improvements in DSST total score (P < .0001) and in daily functioning and health-related quality of life (HRQoL).
- Vortioxetine was well tolerated; side effects, including nausea and abdominal pain, were mostly mild to moderate.
IN PRACTICE:
“Vortioxetine demonstrated effectiveness in clinically significantly improving depressive symptoms, cognitive performance, daily and global functioning, and HRQoL in patients with MDD and comorbid early-stage dementia treated for 12 weeks” the researchers noted.
STUDY DETAILS:
The study was conducted by Michael Cronquist Christensen from pharmaceutical company H. Lundbeck, Valby, Denmark, and colleagues. It was published online in the Journal of Affective Disorders.
LIMITATIONS:
The study is open label and lacked a control group. Learning effects were possible, which could contribute to improved cognitive performance, although significant improvement on the RAVLT was not observed until week 4, suggesting earning effects were minimal.
DISCLOSURES:
The study was funded by H. Lundbeck. Mr. Christensen is an employee of H. Lundbeck.
A version of this article first appeared on Medscape.com.
Altered gut bacteria a biomarker of preclinical Alzheimer’s?
The findings open up the possibility of analyzing the gut microbiome to identify individuals at a higher risk for dementia and perhaps designing microbiome-altering preventive treatments to help stave off cognitive decline, researchers noted.
Study investigator Gautam Dantas, PhD, cautioned that it’s not known whether the gut is influencing the brain, or the brain is influencing the gut, “but this association is valuable to know in either case.
“It could be that the changes in the gut microbiome are just a readout of pathological changes in the brain. The other alternative is that the gut microbiome is contributing to AD, in which case, altering the gut microbiome with probiotics or fecal transfers might help change the course of the disease,” Dr. Dantas, Washington University, St. Louis, said in a news release.
The study was published online in Science Translational Medicine.
Stool test?
Multiple lines of evidence suggest a role for gut microbes in the evolution of AD pathogenesis. However, less is known about gut microbiome changes in the preclinical (presymptomatic) phase of AD.
To investigate, Dr. Dantas and colleagues studied 164 cognitively normal adults, 49 of whom had biomarker evidence of preclinical AD.
After the researchers accounted for clinical covariates and diet, those with preclinical AD had distinct gut microbial taxonomic profiles compared with their healthy controls.
The observed microbiome features correlated with amyloid and tau but not neurodegeneration biomarkers, “suggesting that the gut microbial community changes early in the disease process,” the researchers suggested.
They identified specific taxa that were associated with preclinical AD and including these microbiome features improved the accuracy, sensitivity, and specificity of machine learning classifiers for predicting preclinical AD status.
The findings suggest “markers in the stool might complement early screening measures for preclinical AD,” the researchers noted.
“The nice thing about using the gut microbiome as a screening tool is its simplicity and ease,” Beau Ances, MD, PhD, professor of neurology, at Washington University, St. Louis, said in the release.
“One day, individuals may be able to provide a stool sample and find out if they are at increased risk for developing AD. It would be much easier and less invasive and more accessible for a large proportion of the population, especially underrepresented groups, compared to brain scans or spinal taps,” Dr. Ances added.
The researchers have launched a 5-year follow-up study designed to help determine whether the differences in the gut microbiome are a cause or a result of the brain changes seen in early AD.
Caveats, cautionary notes
In a comment, Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach, cautioned that the study design means that it’s “not possible to prove one thing causes another. What it can show is that two or more aspects are in some way related, thus setting the stage for further research.”
Dr. Sexton noted that though the authors accounted for a number of variables in their models, including age, sex, race, education, body mass index, hypertension, and diabetes, and observed no differences in intake of any major nutrient group, “it’s still not possible to rule out that additional factors beyond the variations in gut microbiome contributed to the changes in brain markers of Alzheimer’s.”
Dr. Sexton also noted that the study population is not representative of all people living with AD, with the vast majority of those with preclinical AD in the study being White.
“If these findings are replicated and confirmed in study groups that are representative of our communities, it is possible that gut microbiome signatures could be a further addition to the suite of diagnostic tools employed in certain settings,” Dr. Sexton said.
This research was supported by the Infection Disease Society of America Foundation, the National Institute on Aging, the Brennan Fund and the Paula and Rodger Riney Foundation. Dr. Dantas, Dr. Ances and Dr. Sexton have no relevant disclosures.
A version of this article first appeared on Medscape.com.
The findings open up the possibility of analyzing the gut microbiome to identify individuals at a higher risk for dementia and perhaps designing microbiome-altering preventive treatments to help stave off cognitive decline, researchers noted.
Study investigator Gautam Dantas, PhD, cautioned that it’s not known whether the gut is influencing the brain, or the brain is influencing the gut, “but this association is valuable to know in either case.
“It could be that the changes in the gut microbiome are just a readout of pathological changes in the brain. The other alternative is that the gut microbiome is contributing to AD, in which case, altering the gut microbiome with probiotics or fecal transfers might help change the course of the disease,” Dr. Dantas, Washington University, St. Louis, said in a news release.
The study was published online in Science Translational Medicine.
Stool test?
Multiple lines of evidence suggest a role for gut microbes in the evolution of AD pathogenesis. However, less is known about gut microbiome changes in the preclinical (presymptomatic) phase of AD.
To investigate, Dr. Dantas and colleagues studied 164 cognitively normal adults, 49 of whom had biomarker evidence of preclinical AD.
After the researchers accounted for clinical covariates and diet, those with preclinical AD had distinct gut microbial taxonomic profiles compared with their healthy controls.
The observed microbiome features correlated with amyloid and tau but not neurodegeneration biomarkers, “suggesting that the gut microbial community changes early in the disease process,” the researchers suggested.
They identified specific taxa that were associated with preclinical AD and including these microbiome features improved the accuracy, sensitivity, and specificity of machine learning classifiers for predicting preclinical AD status.
The findings suggest “markers in the stool might complement early screening measures for preclinical AD,” the researchers noted.
“The nice thing about using the gut microbiome as a screening tool is its simplicity and ease,” Beau Ances, MD, PhD, professor of neurology, at Washington University, St. Louis, said in the release.
“One day, individuals may be able to provide a stool sample and find out if they are at increased risk for developing AD. It would be much easier and less invasive and more accessible for a large proportion of the population, especially underrepresented groups, compared to brain scans or spinal taps,” Dr. Ances added.
The researchers have launched a 5-year follow-up study designed to help determine whether the differences in the gut microbiome are a cause or a result of the brain changes seen in early AD.
Caveats, cautionary notes
In a comment, Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach, cautioned that the study design means that it’s “not possible to prove one thing causes another. What it can show is that two or more aspects are in some way related, thus setting the stage for further research.”
Dr. Sexton noted that though the authors accounted for a number of variables in their models, including age, sex, race, education, body mass index, hypertension, and diabetes, and observed no differences in intake of any major nutrient group, “it’s still not possible to rule out that additional factors beyond the variations in gut microbiome contributed to the changes in brain markers of Alzheimer’s.”
Dr. Sexton also noted that the study population is not representative of all people living with AD, with the vast majority of those with preclinical AD in the study being White.
“If these findings are replicated and confirmed in study groups that are representative of our communities, it is possible that gut microbiome signatures could be a further addition to the suite of diagnostic tools employed in certain settings,” Dr. Sexton said.
This research was supported by the Infection Disease Society of America Foundation, the National Institute on Aging, the Brennan Fund and the Paula and Rodger Riney Foundation. Dr. Dantas, Dr. Ances and Dr. Sexton have no relevant disclosures.
A version of this article first appeared on Medscape.com.
The findings open up the possibility of analyzing the gut microbiome to identify individuals at a higher risk for dementia and perhaps designing microbiome-altering preventive treatments to help stave off cognitive decline, researchers noted.
Study investigator Gautam Dantas, PhD, cautioned that it’s not known whether the gut is influencing the brain, or the brain is influencing the gut, “but this association is valuable to know in either case.
“It could be that the changes in the gut microbiome are just a readout of pathological changes in the brain. The other alternative is that the gut microbiome is contributing to AD, in which case, altering the gut microbiome with probiotics or fecal transfers might help change the course of the disease,” Dr. Dantas, Washington University, St. Louis, said in a news release.
The study was published online in Science Translational Medicine.
Stool test?
Multiple lines of evidence suggest a role for gut microbes in the evolution of AD pathogenesis. However, less is known about gut microbiome changes in the preclinical (presymptomatic) phase of AD.
To investigate, Dr. Dantas and colleagues studied 164 cognitively normal adults, 49 of whom had biomarker evidence of preclinical AD.
After the researchers accounted for clinical covariates and diet, those with preclinical AD had distinct gut microbial taxonomic profiles compared with their healthy controls.
The observed microbiome features correlated with amyloid and tau but not neurodegeneration biomarkers, “suggesting that the gut microbial community changes early in the disease process,” the researchers suggested.
They identified specific taxa that were associated with preclinical AD and including these microbiome features improved the accuracy, sensitivity, and specificity of machine learning classifiers for predicting preclinical AD status.
The findings suggest “markers in the stool might complement early screening measures for preclinical AD,” the researchers noted.
“The nice thing about using the gut microbiome as a screening tool is its simplicity and ease,” Beau Ances, MD, PhD, professor of neurology, at Washington University, St. Louis, said in the release.
“One day, individuals may be able to provide a stool sample and find out if they are at increased risk for developing AD. It would be much easier and less invasive and more accessible for a large proportion of the population, especially underrepresented groups, compared to brain scans or spinal taps,” Dr. Ances added.
The researchers have launched a 5-year follow-up study designed to help determine whether the differences in the gut microbiome are a cause or a result of the brain changes seen in early AD.
Caveats, cautionary notes
In a comment, Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach, cautioned that the study design means that it’s “not possible to prove one thing causes another. What it can show is that two or more aspects are in some way related, thus setting the stage for further research.”
Dr. Sexton noted that though the authors accounted for a number of variables in their models, including age, sex, race, education, body mass index, hypertension, and diabetes, and observed no differences in intake of any major nutrient group, “it’s still not possible to rule out that additional factors beyond the variations in gut microbiome contributed to the changes in brain markers of Alzheimer’s.”
Dr. Sexton also noted that the study population is not representative of all people living with AD, with the vast majority of those with preclinical AD in the study being White.
“If these findings are replicated and confirmed in study groups that are representative of our communities, it is possible that gut microbiome signatures could be a further addition to the suite of diagnostic tools employed in certain settings,” Dr. Sexton said.
This research was supported by the Infection Disease Society of America Foundation, the National Institute on Aging, the Brennan Fund and the Paula and Rodger Riney Foundation. Dr. Dantas, Dr. Ances and Dr. Sexton have no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM SCIENCE TRANSLATIONAL MEDICINE