Clinical Psychiatry News

Individuals with anxiety have at least a twofold higher risk of developing Parkinson’s disease than those without anxiety, new research suggested.

Investigators drew on 10-year data from primary care registry to compare almost 110,000 patients who developed anxiety after the age of 50 years with close to 900,000 matched controls without anxiety.

After adjusting for a variety of sociodemographic, lifestyle, psychiatric, and neurological factors, they found that the risk of developing Parkinson’s disease was double in those with anxiety, compared with controls.

“Anxiety is known to be a feature of the early stages of Parkinson’s disease, but prior to our study, the prospective risk of Parkinson’s in those over the age of 50 with new-onset anxiety was unknown,” colead author Juan Bazo Alvarez, a senior research fellow in the Division of Epidemiology and Health at University College London, London, England, said in a news release.

The study was published online in the British Journal of General Practice.

The presence of anxiety is increased in prodromal Parkinson’s disease, but the prospective risk for Parkinson’s disease in those aged 50 years or older with new-onset anxiety was largely unknown.

Investigators analyzed data from a large UK primary care dataset that includes all people aged between 50 and 99 years who were registered with a participating practice from Jan. 1, 2008, to Dec. 31, 2018.

They identified 109,435 people (35% men) with more than one anxiety record in the database but no previous record of anxiety for 1 year or more and 878,256 people (37% men) with no history of anxiety (control group).

Features of Parkinson’s disease such as sleep problems, depression, tremor, and impaired balance were then tracked from the point of the anxiety diagnosis until 1 year before the Parkinson’s disease diagnosis.

Among those with anxiety, 331 developed Parkinson’s disease during the follow-up period, with a median time to diagnosis of 4.9 years after the first recorded episode of anxiety.

The incidence of Parkinson’s disease was 1.2 per 1000 person-years (95% CI, 0.92-1.13) in those with anxiety versus 0.49 (95% CI, 0.47-0.52) in those without anxiety.

After adjustment for age, sex, social deprivation, lifestyle factors, severe mental illness, head trauma, and dementia, the risk for Parkinson’s disease was double in those with anxiety, compared with the non-anxiety group (hazard ratio, 2.1; 95% CI, 1.9-2.4).

Individuals without anxiety also developed Parkinson’s disease later than those with anxiety.

The researchers identified specific symptoms that were associated with later development of Parkinson’s disease in those with anxiety, including depression, sleep disturbance, fatigue, and cognitive impairment, among other symptoms.

“The results suggest that there is a strong association between anxiety and diagnosis of Parkinson’s disease in patients aged over 50 years who present with a new diagnosis of anxiety,” the authors wrote. “This provides evidence for anxiety as a prodromal presentation of Parkinson’s disease.”

Future research “should explore anxiety in relation to other prodromal symptoms and how this symptom complex is associated with the incidence of Parkinson’s disease,” the researchers wrote. Doing so “may lead to earlier diagnosis and better management of Parkinson’s disease.”

This study was funded by the European Union. Specific authors received funding from the National Institute for Health and Care Research and the Alzheimer’s Society Clinical Training Fellowship program. The authors declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Individuals with anxiety have at least a twofold higher risk of developing Parkinson’s disease than those without anxiety, new research suggested.

Investigators drew on 10-year data from primary care registry to compare almost 110,000 patients who developed anxiety after the age of 50 years with close to 900,000 matched controls without anxiety.

After adjusting for a variety of sociodemographic, lifestyle, psychiatric, and neurological factors, they found that the risk of developing Parkinson’s disease was double in those with anxiety, compared with controls.

“Anxiety is known to be a feature of the early stages of Parkinson’s disease, but prior to our study, the prospective risk of Parkinson’s in those over the age of 50 with new-onset anxiety was unknown,” colead author Juan Bazo Alvarez, a senior research fellow in the Division of Epidemiology and Health at University College London, London, England, said in a news release.

The study was published online in the British Journal of General Practice.

The presence of anxiety is increased in prodromal Parkinson’s disease, but the prospective risk for Parkinson’s disease in those aged 50 years or older with new-onset anxiety was largely unknown.

Investigators analyzed data from a large UK primary care dataset that includes all people aged between 50 and 99 years who were registered with a participating practice from Jan. 1, 2008, to Dec. 31, 2018.

They identified 109,435 people (35% men) with more than one anxiety record in the database but no previous record of anxiety for 1 year or more and 878,256 people (37% men) with no history of anxiety (control group).

Features of Parkinson’s disease such as sleep problems, depression, tremor, and impaired balance were then tracked from the point of the anxiety diagnosis until 1 year before the Parkinson’s disease diagnosis.

Among those with anxiety, 331 developed Parkinson’s disease during the follow-up period, with a median time to diagnosis of 4.9 years after the first recorded episode of anxiety.

The incidence of Parkinson’s disease was 1.2 per 1000 person-years (95% CI, 0.92-1.13) in those with anxiety versus 0.49 (95% CI, 0.47-0.52) in those without anxiety.

After adjustment for age, sex, social deprivation, lifestyle factors, severe mental illness, head trauma, and dementia, the risk for Parkinson’s disease was double in those with anxiety, compared with the non-anxiety group (hazard ratio, 2.1; 95% CI, 1.9-2.4).

Individuals without anxiety also developed Parkinson’s disease later than those with anxiety.

The researchers identified specific symptoms that were associated with later development of Parkinson’s disease in those with anxiety, including depression, sleep disturbance, fatigue, and cognitive impairment, among other symptoms.

“The results suggest that there is a strong association between anxiety and diagnosis of Parkinson’s disease in patients aged over 50 years who present with a new diagnosis of anxiety,” the authors wrote. “This provides evidence for anxiety as a prodromal presentation of Parkinson’s disease.”

Future research “should explore anxiety in relation to other prodromal symptoms and how this symptom complex is associated with the incidence of Parkinson’s disease,” the researchers wrote. Doing so “may lead to earlier diagnosis and better management of Parkinson’s disease.”

This study was funded by the European Union. Specific authors received funding from the National Institute for Health and Care Research and the Alzheimer’s Society Clinical Training Fellowship program. The authors declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Individuals with anxiety have at least a twofold higher risk of developing Parkinson’s disease than those without anxiety, new research suggested.

Investigators drew on 10-year data from primary care registry to compare almost 110,000 patients who developed anxiety after the age of 50 years with close to 900,000 matched controls without anxiety.

After adjusting for a variety of sociodemographic, lifestyle, psychiatric, and neurological factors, they found that the risk of developing Parkinson’s disease was double in those with anxiety, compared with controls.

“Anxiety is known to be a feature of the early stages of Parkinson’s disease, but prior to our study, the prospective risk of Parkinson’s in those over the age of 50 with new-onset anxiety was unknown,” colead author Juan Bazo Alvarez, a senior research fellow in the Division of Epidemiology and Health at University College London, London, England, said in a news release.

The study was published online in the British Journal of General Practice.

The presence of anxiety is increased in prodromal Parkinson’s disease, but the prospective risk for Parkinson’s disease in those aged 50 years or older with new-onset anxiety was largely unknown.

Investigators analyzed data from a large UK primary care dataset that includes all people aged between 50 and 99 years who were registered with a participating practice from Jan. 1, 2008, to Dec. 31, 2018.

They identified 109,435 people (35% men) with more than one anxiety record in the database but no previous record of anxiety for 1 year or more and 878,256 people (37% men) with no history of anxiety (control group).

Features of Parkinson’s disease such as sleep problems, depression, tremor, and impaired balance were then tracked from the point of the anxiety diagnosis until 1 year before the Parkinson’s disease diagnosis.

Among those with anxiety, 331 developed Parkinson’s disease during the follow-up period, with a median time to diagnosis of 4.9 years after the first recorded episode of anxiety.

The incidence of Parkinson’s disease was 1.2 per 1000 person-years (95% CI, 0.92-1.13) in those with anxiety versus 0.49 (95% CI, 0.47-0.52) in those without anxiety.

After adjustment for age, sex, social deprivation, lifestyle factors, severe mental illness, head trauma, and dementia, the risk for Parkinson’s disease was double in those with anxiety, compared with the non-anxiety group (hazard ratio, 2.1; 95% CI, 1.9-2.4).

Individuals without anxiety also developed Parkinson’s disease later than those with anxiety.

The researchers identified specific symptoms that were associated with later development of Parkinson’s disease in those with anxiety, including depression, sleep disturbance, fatigue, and cognitive impairment, among other symptoms.

“The results suggest that there is a strong association between anxiety and diagnosis of Parkinson’s disease in patients aged over 50 years who present with a new diagnosis of anxiety,” the authors wrote. “This provides evidence for anxiety as a prodromal presentation of Parkinson’s disease.”

Future research “should explore anxiety in relation to other prodromal symptoms and how this symptom complex is associated with the incidence of Parkinson’s disease,” the researchers wrote. Doing so “may lead to earlier diagnosis and better management of Parkinson’s disease.”

This study was funded by the European Union. Specific authors received funding from the National Institute for Health and Care Research and the Alzheimer’s Society Clinical Training Fellowship program. The authors declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

New research supports current guidelines cautioning against long-term use of benzodiazepines.

The study of more than 5000 older adults found that benzodiazepine use was associated with an accelerated reduction in the volume of the hippocampus and amygdala — brain regions involved in memory and mood regulation. However, benzodiazepine use overall was not associated with an increased risk for dementia.

The findings suggest that benzodiazepine use “may have subtle, long-term impact on brain health,” lead investigator Frank Wolters, MD, PhD, with Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues wrote.

The study was published online in BMC Medicine.
 

Conflicting Evidence 

Benzodiazepines are commonly prescribed in older adults for anxiety and sleep disorders. Though the short-term cognitive side effects are well documented, the long-term impact on neurodegeneration and dementia risk remains unclear. Some studies have linked benzodiazepine use to an increased risk for dementia, whereas others have not.

Dr. Wolters and colleagues assessed the effect of benzodiazepine use on long-term dementia risk and on imaging markers of neurodegeneration in 5443 cognitively healthy adults (mean age, 71 years; 57% women) from the population-based Rotterdam Study. 

Benzodiazepine use between 1991 and 2008 was determined using pharmacy dispensing records, and dementia incidence was determined from medical records. 

Half of the participants had used benzodiazepines at any time in the 15 years before baseline (2005-2008); 47% used anxiolytics, 20% used sedative-hypnotics, 34% used both, and 13% were still using the drugs at the baseline assessment. 

During an average follow-up of 11 years, 13% of participants developed dementia. 

Overall, use of benzodiazepines was not associated with dementia risk, compared with never-use (hazard ratio [HR], 1.06), irrespective of cumulative dose. 

The risk for dementia was somewhat higher with any use of anxiolytics than with sedative-hypnotics (HR, 1.17 vs HR, 0.92), although neither was statistically significant. The highest risk estimates were observed for high cumulative dose of anxiolytics (HR, 1.33). 

Sensitivity analyses of the two most commonly used anxiolytics found no differences in risk between use of short half-life oxazepam and long half-life diazepam (HR, 1.01 and HR, 1.06, respectively, for ever-use, compared with never-use for oxazepam and diazepam).
 

Brain Atrophy

The researchers investigated potential associations between benzodiazepine use and brain volumes using brain MRI imaging from 4836 participants.

They found that current use of a benzodiazepine at baseline was significantly associated with lower total brain volume — as well as lower hippocampus, amygdala, and thalamus volume cross-sectionally — and with accelerated volume loss of the hippocampus and, to a lesser extent, amygdala longitudinally. 

Imaging findings did not differ by type of benzodiazepine used or cumulative dose. 

“Given the availability of effective alternative pharmacological and nonpharmacological treatments for anxiety and sleep problems, it is important to carefully consider the necessity of prolonged benzodiazepine use in light of potential detrimental effects on brain health,” the authors wrote. 
 

Risks Go Beyond the Brain

Commenting on the study, Shaheen Lakhan, MD, PhD, a neurologist and researcher based in Miami, Florida, noted that “chronic benzodiazepine use may reduce neuroplasticity, potentially interfering with the brain’s ability to form new connections and adapt.

“Long-term use can lead to down-regulation of GABA receptors, altering the brain’s natural inhibitory mechanisms and potentially contributing to tolerance and withdrawal symptoms. Prolonged use can also disrupt the balance of various neurotransmitter systems beyond just GABA, potentially affecting mood, cognition, and overall brain function,” said Dr. Lakhan, who was not involved in the study. 

“While the literature is mixed on chronic benzodiazepine use and dementia risk, prolonged use has consistently been associated with accelerated volume loss in certain brain regions, particularly the hippocampus and amygdala,” which are responsible for memory, learning, and emotional regulation, he noted. 

“Beyond cognitive impairments and brain volume loss, chronic benzodiazepine use is associated with tolerance and dependence, potential for abuse, interactions with other drugs, and increased fall risk, especially in older adults,” Dr. Lakhan added.

Current guidelines discourage long-term use of benzodiazepines because of risk for psychological and physical dependence; falls; and cognitive impairment, especially in older adults. Nevertheless, research shows that 30%-40% of older benzodiazepine users stay on the medication beyond the recommended period of several weeks.

Donovan T. Maust, MD, Department of Psychiatry, University of Michigan Medical School, Ann Arbor, said in an interview these new findings are consistent with other recently published observational research that suggest benzodiazepine use is not linked to dementia risk. 

“I realize that such meta-analyses that find a positive relationship between benzodiazepines and dementia are out there, but they include older, less rigorous studies,” said Dr. Maust, who was not part of the new study. “In my opinion, the jury is not still out on this topic. However, there are plenty of other reasons to avoid them — and in particular, starting them — in older adults, most notably the increased risk of fall injury as well as increased overdose risk when taken along with opioids.”

A version of this article first appeared on Medscape.com.

New research supports current guidelines cautioning against long-term use of benzodiazepines.

The study of more than 5000 older adults found that benzodiazepine use was associated with an accelerated reduction in the volume of the hippocampus and amygdala — brain regions involved in memory and mood regulation. However, benzodiazepine use overall was not associated with an increased risk for dementia.

The findings suggest that benzodiazepine use “may have subtle, long-term impact on brain health,” lead investigator Frank Wolters, MD, PhD, with Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues wrote.

The study was published online in BMC Medicine.
 

Conflicting Evidence 

Benzodiazepines are commonly prescribed in older adults for anxiety and sleep disorders. Though the short-term cognitive side effects are well documented, the long-term impact on neurodegeneration and dementia risk remains unclear. Some studies have linked benzodiazepine use to an increased risk for dementia, whereas others have not.

Dr. Wolters and colleagues assessed the effect of benzodiazepine use on long-term dementia risk and on imaging markers of neurodegeneration in 5443 cognitively healthy adults (mean age, 71 years; 57% women) from the population-based Rotterdam Study. 

Benzodiazepine use between 1991 and 2008 was determined using pharmacy dispensing records, and dementia incidence was determined from medical records. 

Half of the participants had used benzodiazepines at any time in the 15 years before baseline (2005-2008); 47% used anxiolytics, 20% used sedative-hypnotics, 34% used both, and 13% were still using the drugs at the baseline assessment. 

During an average follow-up of 11 years, 13% of participants developed dementia. 

Overall, use of benzodiazepines was not associated with dementia risk, compared with never-use (hazard ratio [HR], 1.06), irrespective of cumulative dose. 

The risk for dementia was somewhat higher with any use of anxiolytics than with sedative-hypnotics (HR, 1.17 vs HR, 0.92), although neither was statistically significant. The highest risk estimates were observed for high cumulative dose of anxiolytics (HR, 1.33). 

Sensitivity analyses of the two most commonly used anxiolytics found no differences in risk between use of short half-life oxazepam and long half-life diazepam (HR, 1.01 and HR, 1.06, respectively, for ever-use, compared with never-use for oxazepam and diazepam).
 

Brain Atrophy

The researchers investigated potential associations between benzodiazepine use and brain volumes using brain MRI imaging from 4836 participants.

They found that current use of a benzodiazepine at baseline was significantly associated with lower total brain volume — as well as lower hippocampus, amygdala, and thalamus volume cross-sectionally — and with accelerated volume loss of the hippocampus and, to a lesser extent, amygdala longitudinally. 

Imaging findings did not differ by type of benzodiazepine used or cumulative dose. 

“Given the availability of effective alternative pharmacological and nonpharmacological treatments for anxiety and sleep problems, it is important to carefully consider the necessity of prolonged benzodiazepine use in light of potential detrimental effects on brain health,” the authors wrote. 
 

Risks Go Beyond the Brain

Commenting on the study, Shaheen Lakhan, MD, PhD, a neurologist and researcher based in Miami, Florida, noted that “chronic benzodiazepine use may reduce neuroplasticity, potentially interfering with the brain’s ability to form new connections and adapt.

“Long-term use can lead to down-regulation of GABA receptors, altering the brain’s natural inhibitory mechanisms and potentially contributing to tolerance and withdrawal symptoms. Prolonged use can also disrupt the balance of various neurotransmitter systems beyond just GABA, potentially affecting mood, cognition, and overall brain function,” said Dr. Lakhan, who was not involved in the study. 

“While the literature is mixed on chronic benzodiazepine use and dementia risk, prolonged use has consistently been associated with accelerated volume loss in certain brain regions, particularly the hippocampus and amygdala,” which are responsible for memory, learning, and emotional regulation, he noted. 

“Beyond cognitive impairments and brain volume loss, chronic benzodiazepine use is associated with tolerance and dependence, potential for abuse, interactions with other drugs, and increased fall risk, especially in older adults,” Dr. Lakhan added.

Current guidelines discourage long-term use of benzodiazepines because of risk for psychological and physical dependence; falls; and cognitive impairment, especially in older adults. Nevertheless, research shows that 30%-40% of older benzodiazepine users stay on the medication beyond the recommended period of several weeks.

Donovan T. Maust, MD, Department of Psychiatry, University of Michigan Medical School, Ann Arbor, said in an interview these new findings are consistent with other recently published observational research that suggest benzodiazepine use is not linked to dementia risk. 

“I realize that such meta-analyses that find a positive relationship between benzodiazepines and dementia are out there, but they include older, less rigorous studies,” said Dr. Maust, who was not part of the new study. “In my opinion, the jury is not still out on this topic. However, there are plenty of other reasons to avoid them — and in particular, starting them — in older adults, most notably the increased risk of fall injury as well as increased overdose risk when taken along with opioids.”

A version of this article first appeared on Medscape.com.

New research supports current guidelines cautioning against long-term use of benzodiazepines.

The study of more than 5000 older adults found that benzodiazepine use was associated with an accelerated reduction in the volume of the hippocampus and amygdala — brain regions involved in memory and mood regulation. However, benzodiazepine use overall was not associated with an increased risk for dementia.

The findings suggest that benzodiazepine use “may have subtle, long-term impact on brain health,” lead investigator Frank Wolters, MD, PhD, with Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues wrote.

The study was published online in BMC Medicine.
 

Conflicting Evidence 

Benzodiazepines are commonly prescribed in older adults for anxiety and sleep disorders. Though the short-term cognitive side effects are well documented, the long-term impact on neurodegeneration and dementia risk remains unclear. Some studies have linked benzodiazepine use to an increased risk for dementia, whereas others have not.

Dr. Wolters and colleagues assessed the effect of benzodiazepine use on long-term dementia risk and on imaging markers of neurodegeneration in 5443 cognitively healthy adults (mean age, 71 years; 57% women) from the population-based Rotterdam Study. 

Benzodiazepine use between 1991 and 2008 was determined using pharmacy dispensing records, and dementia incidence was determined from medical records. 

Half of the participants had used benzodiazepines at any time in the 15 years before baseline (2005-2008); 47% used anxiolytics, 20% used sedative-hypnotics, 34% used both, and 13% were still using the drugs at the baseline assessment. 

During an average follow-up of 11 years, 13% of participants developed dementia. 

Overall, use of benzodiazepines was not associated with dementia risk, compared with never-use (hazard ratio [HR], 1.06), irrespective of cumulative dose. 

The risk for dementia was somewhat higher with any use of anxiolytics than with sedative-hypnotics (HR, 1.17 vs HR, 0.92), although neither was statistically significant. The highest risk estimates were observed for high cumulative dose of anxiolytics (HR, 1.33). 

Sensitivity analyses of the two most commonly used anxiolytics found no differences in risk between use of short half-life oxazepam and long half-life diazepam (HR, 1.01 and HR, 1.06, respectively, for ever-use, compared with never-use for oxazepam and diazepam).
 

Brain Atrophy

The researchers investigated potential associations between benzodiazepine use and brain volumes using brain MRI imaging from 4836 participants.

They found that current use of a benzodiazepine at baseline was significantly associated with lower total brain volume — as well as lower hippocampus, amygdala, and thalamus volume cross-sectionally — and with accelerated volume loss of the hippocampus and, to a lesser extent, amygdala longitudinally. 

Imaging findings did not differ by type of benzodiazepine used or cumulative dose. 

“Given the availability of effective alternative pharmacological and nonpharmacological treatments for anxiety and sleep problems, it is important to carefully consider the necessity of prolonged benzodiazepine use in light of potential detrimental effects on brain health,” the authors wrote. 
 

Risks Go Beyond the Brain

Commenting on the study, Shaheen Lakhan, MD, PhD, a neurologist and researcher based in Miami, Florida, noted that “chronic benzodiazepine use may reduce neuroplasticity, potentially interfering with the brain’s ability to form new connections and adapt.

“Long-term use can lead to down-regulation of GABA receptors, altering the brain’s natural inhibitory mechanisms and potentially contributing to tolerance and withdrawal symptoms. Prolonged use can also disrupt the balance of various neurotransmitter systems beyond just GABA, potentially affecting mood, cognition, and overall brain function,” said Dr. Lakhan, who was not involved in the study. 

“While the literature is mixed on chronic benzodiazepine use and dementia risk, prolonged use has consistently been associated with accelerated volume loss in certain brain regions, particularly the hippocampus and amygdala,” which are responsible for memory, learning, and emotional regulation, he noted. 

“Beyond cognitive impairments and brain volume loss, chronic benzodiazepine use is associated with tolerance and dependence, potential for abuse, interactions with other drugs, and increased fall risk, especially in older adults,” Dr. Lakhan added.

Current guidelines discourage long-term use of benzodiazepines because of risk for psychological and physical dependence; falls; and cognitive impairment, especially in older adults. Nevertheless, research shows that 30%-40% of older benzodiazepine users stay on the medication beyond the recommended period of several weeks.

Donovan T. Maust, MD, Department of Psychiatry, University of Michigan Medical School, Ann Arbor, said in an interview these new findings are consistent with other recently published observational research that suggest benzodiazepine use is not linked to dementia risk. 

“I realize that such meta-analyses that find a positive relationship between benzodiazepines and dementia are out there, but they include older, less rigorous studies,” said Dr. Maust, who was not part of the new study. “In my opinion, the jury is not still out on this topic. However, there are plenty of other reasons to avoid them — and in particular, starting them — in older adults, most notably the increased risk of fall injury as well as increased overdose risk when taken along with opioids.”

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

There’s a growing scandal in mental health care. Recent studies are showing that certain medications that basically are used to, if you will, quiet patients — antipsychotic drugs — are being overused, particularly in facilities that serve poorer people and people who are minorities. This situation is utterly, ethically unacceptable and it’s something that we are starting to get really pressed to solve. 

Part of this is due to the fact that numbers of caregivers are in short supply. We need to get more people trained. We need to get more mental health providers at all levels into facilities in order to provide care, and not substitute that inability to have a provider present and minimize risk to patients by having drug-induced sleepiness, soporific behavior, or, if you will, snowing them just because we don’t have enough people to keep an eye on them. Furthermore, we can’t let them engage in some activities, even things like walking around, because we’re worried about falls. The nursing homes or mental health facilities don’t want anybody to get injured, much less killed, because that’s going to really bring government agencies down on them.

What do we do, aside from trying to get more numbers in there? California came up with a law not too long ago that basically put the burden of using these drugs on consent. They passed a law that said the patient, before going under and being administered any type of psychoactive drug, has to consent; or if they’re really unable to do that, their relative or next of kin should have to consent.

California law now puts the burden on getting consent from the patient in order to use these drugs. It’s not a good solution. It still permits the use of the drugs to substitute for the inability to provide adequate numbers of people to provide care in safe environments. It’s almost like saying, “We know you’re going into a dangerous place. We can’t really reduce the danger, so we’re going to make sure that you stay in your seat. You better consent to that because otherwise things could not go well for you in this mental institution.” 

That’s not a sound argument for the use of informed consent. Moreover, I’m very skeptical that many of these people in mental institutions do have the capacity to either say, “Fine, give me psychoactive drugs if I have to stay here,” or “No, I don’t want that. I’ll take my chances.”

They’re vulnerable people. Many of them may not be fully incompetent, but they often have compromised competency. Relatives may be thinking, Well, the right thing to do is just to make sure they don’t get hurt or injure themselves. Yes, give them the drugs. 

Consent, while I support it, is not the solution to what is fundamentally an infrastructure problem, a personnel problem, and one of the shames of American healthcare, which is lousy long-term mental health care. For too many people, their care is in the street. For too many people, their care is taking place in institutions that have dangerous designs where people either get injured, can’t provide enough spacing, or just don’t have the people to do it. 

Let’s move to fix the mental health care system and not be in a situation where we say to people, “The system stinks and you’re at risk. Is it okay with you if we drug you because we can’t think of any other way to keep you safe, given the rotten nature of the institutions that we’ve got?” 

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He disclosed ties with Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position) and serves as a contributing author and adviser for Medscape.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

There’s a growing scandal in mental health care. Recent studies are showing that certain medications that basically are used to, if you will, quiet patients — antipsychotic drugs — are being overused, particularly in facilities that serve poorer people and people who are minorities. This situation is utterly, ethically unacceptable and it’s something that we are starting to get really pressed to solve. 

Part of this is due to the fact that numbers of caregivers are in short supply. We need to get more people trained. We need to get more mental health providers at all levels into facilities in order to provide care, and not substitute that inability to have a provider present and minimize risk to patients by having drug-induced sleepiness, soporific behavior, or, if you will, snowing them just because we don’t have enough people to keep an eye on them. Furthermore, we can’t let them engage in some activities, even things like walking around, because we’re worried about falls. The nursing homes or mental health facilities don’t want anybody to get injured, much less killed, because that’s going to really bring government agencies down on them.

What do we do, aside from trying to get more numbers in there? California came up with a law not too long ago that basically put the burden of using these drugs on consent. They passed a law that said the patient, before going under and being administered any type of psychoactive drug, has to consent; or if they’re really unable to do that, their relative or next of kin should have to consent.

California law now puts the burden on getting consent from the patient in order to use these drugs. It’s not a good solution. It still permits the use of the drugs to substitute for the inability to provide adequate numbers of people to provide care in safe environments. It’s almost like saying, “We know you’re going into a dangerous place. We can’t really reduce the danger, so we’re going to make sure that you stay in your seat. You better consent to that because otherwise things could not go well for you in this mental institution.” 

That’s not a sound argument for the use of informed consent. Moreover, I’m very skeptical that many of these people in mental institutions do have the capacity to either say, “Fine, give me psychoactive drugs if I have to stay here,” or “No, I don’t want that. I’ll take my chances.”

They’re vulnerable people. Many of them may not be fully incompetent, but they often have compromised competency. Relatives may be thinking, Well, the right thing to do is just to make sure they don’t get hurt or injure themselves. Yes, give them the drugs. 

Consent, while I support it, is not the solution to what is fundamentally an infrastructure problem, a personnel problem, and one of the shames of American healthcare, which is lousy long-term mental health care. For too many people, their care is in the street. For too many people, their care is taking place in institutions that have dangerous designs where people either get injured, can’t provide enough spacing, or just don’t have the people to do it. 

Let’s move to fix the mental health care system and not be in a situation where we say to people, “The system stinks and you’re at risk. Is it okay with you if we drug you because we can’t think of any other way to keep you safe, given the rotten nature of the institutions that we’ve got?” 

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He disclosed ties with Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position) and serves as a contributing author and adviser for Medscape.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

There’s a growing scandal in mental health care. Recent studies are showing that certain medications that basically are used to, if you will, quiet patients — antipsychotic drugs — are being overused, particularly in facilities that serve poorer people and people who are minorities. This situation is utterly, ethically unacceptable and it’s something that we are starting to get really pressed to solve. 

Part of this is due to the fact that numbers of caregivers are in short supply. We need to get more people trained. We need to get more mental health providers at all levels into facilities in order to provide care, and not substitute that inability to have a provider present and minimize risk to patients by having drug-induced sleepiness, soporific behavior, or, if you will, snowing them just because we don’t have enough people to keep an eye on them. Furthermore, we can’t let them engage in some activities, even things like walking around, because we’re worried about falls. The nursing homes or mental health facilities don’t want anybody to get injured, much less killed, because that’s going to really bring government agencies down on them.

What do we do, aside from trying to get more numbers in there? California came up with a law not too long ago that basically put the burden of using these drugs on consent. They passed a law that said the patient, before going under and being administered any type of psychoactive drug, has to consent; or if they’re really unable to do that, their relative or next of kin should have to consent.

California law now puts the burden on getting consent from the patient in order to use these drugs. It’s not a good solution. It still permits the use of the drugs to substitute for the inability to provide adequate numbers of people to provide care in safe environments. It’s almost like saying, “We know you’re going into a dangerous place. We can’t really reduce the danger, so we’re going to make sure that you stay in your seat. You better consent to that because otherwise things could not go well for you in this mental institution.” 

That’s not a sound argument for the use of informed consent. Moreover, I’m very skeptical that many of these people in mental institutions do have the capacity to either say, “Fine, give me psychoactive drugs if I have to stay here,” or “No, I don’t want that. I’ll take my chances.”

They’re vulnerable people. Many of them may not be fully incompetent, but they often have compromised competency. Relatives may be thinking, Well, the right thing to do is just to make sure they don’t get hurt or injure themselves. Yes, give them the drugs. 

Consent, while I support it, is not the solution to what is fundamentally an infrastructure problem, a personnel problem, and one of the shames of American healthcare, which is lousy long-term mental health care. For too many people, their care is in the street. For too many people, their care is taking place in institutions that have dangerous designs where people either get injured, can’t provide enough spacing, or just don’t have the people to do it. 

Let’s move to fix the mental health care system and not be in a situation where we say to people, “The system stinks and you’re at risk. Is it okay with you if we drug you because we can’t think of any other way to keep you safe, given the rotten nature of the institutions that we’ve got?” 

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He disclosed ties with Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position) and serves as a contributing author and adviser for Medscape.

A version of this article first appeared on Medscape.com.

In a shifting landscape in dementia risk factors, cardiovascular health is now taking precedence.

That’s according to researchers from University College London (UCL) in the United Kingdom who analyzed 27 papers about dementia that had data collected over more than 70 years. They calculated what share of dementia cases were due to different risk factors. Their findings were recently published in the Lancet Public Health.

Top risk factors for dementia over the years have been hypertension, obesity, diabetes, education, and smoking, according to a news release on the findings. But the prevalence of risk factors has changed over the decades.

Researchers said smoking and education have become less important risk factors because of “population-level interventions,” such as stop-smoking campaigns and compulsory public education. On the other hand, obesity and diabetes rates have increased and become bigger risk factors.

Hypertension remains the greatest risk factor, even though doctors and public health groups are putting more emphasis on managing the condition, the study said.

“Cardiovascular risk factors may have contributed more to dementia risk over time, so these deserve more targeted action for future dementia prevention efforts,” said Naaheed Mukadam, PhD, an associate professor at UCL and the lead author of the study.

Eliminating modifiable risk factors could theoretically prevent 40% of dementia cases, the release said. 

The CDC says that an estimated 5.8 million people in the United States have Alzheimer’s disease and related dementias, including 5.6 million people ages 65 and older and about 200,000 under age 65. The UCL release said an estimated 944,000 in the U.K. have dementia. 

A version of this article first appeared on WebMD.com.

In a shifting landscape in dementia risk factors, cardiovascular health is now taking precedence.

That’s according to researchers from University College London (UCL) in the United Kingdom who analyzed 27 papers about dementia that had data collected over more than 70 years. They calculated what share of dementia cases were due to different risk factors. Their findings were recently published in the Lancet Public Health.

Top risk factors for dementia over the years have been hypertension, obesity, diabetes, education, and smoking, according to a news release on the findings. But the prevalence of risk factors has changed over the decades.

Researchers said smoking and education have become less important risk factors because of “population-level interventions,” such as stop-smoking campaigns and compulsory public education. On the other hand, obesity and diabetes rates have increased and become bigger risk factors.

Hypertension remains the greatest risk factor, even though doctors and public health groups are putting more emphasis on managing the condition, the study said.

“Cardiovascular risk factors may have contributed more to dementia risk over time, so these deserve more targeted action for future dementia prevention efforts,” said Naaheed Mukadam, PhD, an associate professor at UCL and the lead author of the study.

Eliminating modifiable risk factors could theoretically prevent 40% of dementia cases, the release said. 

The CDC says that an estimated 5.8 million people in the United States have Alzheimer’s disease and related dementias, including 5.6 million people ages 65 and older and about 200,000 under age 65. The UCL release said an estimated 944,000 in the U.K. have dementia. 

A version of this article first appeared on WebMD.com.

In a shifting landscape in dementia risk factors, cardiovascular health is now taking precedence.

That’s according to researchers from University College London (UCL) in the United Kingdom who analyzed 27 papers about dementia that had data collected over more than 70 years. They calculated what share of dementia cases were due to different risk factors. Their findings were recently published in the Lancet Public Health.

Top risk factors for dementia over the years have been hypertension, obesity, diabetes, education, and smoking, according to a news release on the findings. But the prevalence of risk factors has changed over the decades.

Researchers said smoking and education have become less important risk factors because of “population-level interventions,” such as stop-smoking campaigns and compulsory public education. On the other hand, obesity and diabetes rates have increased and become bigger risk factors.

Hypertension remains the greatest risk factor, even though doctors and public health groups are putting more emphasis on managing the condition, the study said.

“Cardiovascular risk factors may have contributed more to dementia risk over time, so these deserve more targeted action for future dementia prevention efforts,” said Naaheed Mukadam, PhD, an associate professor at UCL and the lead author of the study.

Eliminating modifiable risk factors could theoretically prevent 40% of dementia cases, the release said. 

The CDC says that an estimated 5.8 million people in the United States have Alzheimer’s disease and related dementias, including 5.6 million people ages 65 and older and about 200,000 under age 65. The UCL release said an estimated 944,000 in the U.K. have dementia. 

A version of this article first appeared on WebMD.com.

A work group convened by the Alzheimer’s Association has released revised biology-based criteria for the diagnosis and staging of Alzheimer’s disease, including a new biomarker classification system that incorporates fluid and imaging biomarkers as well as an updated disease staging system. 

“Plasma markers are here now, and it’s very important to incorporate them into the criteria for diagnosis,” said senior author Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer and medical affairs lead. 

The revised criteria are the first updates since 2018.

“Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine — including cancer, heart disease, and diabetes — and is becoming a unifying concept common to all neurodegenerative diseases,” lead author Clifford Jack Jr, MD, with Mayo Clinic, Rochester, Minnesota, said in a news release from the Alzheimer’s Association. 

“These updates to the diagnostic criteria are needed now because we know more about the underlying biology of Alzheimer’s and we are able to measure those changes,” Dr. Jack added. 

The 2024 revised criteria for diagnosis and staging of Alzheimer’s disease were published online in Alzheimer’s & Dementia. 
 

Core Biomarkers Defined

The revised criteria define Alzheimer’s disease as a biologic process that begins with the appearance of Alzheimer’s disease neuropathologic change (ADNPC) in the absence of symptoms. Progression of the neuropathologic burden leads to the later appearance and progression of clinical symptoms.

The work group organized Alzheimer’s disease biomarkers into three broad categories: (1) core biomarkers of ADNPC, (2) nonspecific biomarkers that are important in Alzheimer’s disease but are also involved in other brain diseases, and (3) biomarkers of diseases or conditions that commonly coexist with Alzheimer’s disease.

Core Alzheimer’s biomarkers are subdivided into Core 1 and Core 2. 

Core 1 biomarkers become abnormal early in the disease course and directly measure either amyloid plaques or phosphorylated tau (p-tau). They include amyloid PET; cerebrospinal fluid (CSF) amyloid beta 42/40 ratio, CSF p-tau181/amyloid beta 42 ratio, and CSF total (t)-tau/amyloid beta 42 ratio; and “accurate” plasma biomarkers, such as p-tau217. 

“An abnormal Core 1 biomarker result is sufficient to establish a diagnosis of Alzheimer’s disease and to inform clinical decision making [sic] throughout the disease continuum,” the work group wrote. 

Core 2 biomarkers become abnormal later in the disease process and are more closely linked with the onset of symptoms. Core 2 biomarkers include tau PET and certain soluble tau fragments associated with tau proteinopathy (eg, MTBR-tau243) but also pT205 and nonphosphorylated mid-region tau fragments. 

Core 2 biomarkers, when combined with Core 1, may be used to stage biologic disease severity; abnormal Core 2 biomarkers “increase confidence that Alzheimer’s disease is contributing to symptoms,” the work group noted. 

The revised criteria give clinicians “the flexibility to use plasma or PET scans or CSF,” Dr. Carrillo said. “They will have several tools that they can choose from and offer this variety of tools to their patients. We need different tools for different individuals. There will be differences in coverage and access to these diagnostics.” 

The revised criteria also include an integrated biologic and clinical staging scheme that acknowledges the fact that common co-pathologies, cognitive reserve, and resistance may modify relationships between clinical and biologic Alzheimer’s disease stages. 
 

Formal Guidelines to Come 

The work group noted that currently, the clinical use of Alzheimer’s disease biomarkers is intended for the evaluation of symptomatic patients, not cognitively unimpaired individuals.

Disease-targeted therapies have not yet been approved for cognitively unimpaired individuals. For this reason, the work group currently recommends against diagnostic testing in cognitively unimpaired individuals outside the context of observational or therapeutic research studies. 

This recommendation would change in the future if disease-targeted therapies that are currently being evaluated in trials demonstrate a benefit in preventing cognitive decline and are approved for use in preclinical Alzheimer’s disease, they wrote. 

They emphasize that the revised criteria are not intended to provide step-by-step clinical practice guidelines for clinicians. Rather, they provide general principles to inform diagnosis and staging of Alzheimer’s disease that reflect current science.

“This is just the beginning,” said Dr. Carrillo. “This is a gathering of the evidence to date and putting it in one place so we can have a consensus and actually a way to test it and make it better as we add new science.”

This also serves as a “springboard” for the Alzheimer’s Association to create formal clinical guidelines. “That will come, hopefully, over the next 12 months. We’ll be working on it, and we hope to have that in 2025,” Dr. Carrillo said. 

The revised criteria also emphasize the role of the clinician. 

“The biologically based diagnosis of Alzheimer’s disease is meant to assist, rather than supplant, the clinical evaluation of individuals with cognitive impairment,” the work group wrote in a related commentary published online in Nature Medicine. 

Recent diagnostics and therapeutic developments “herald a virtuous cycle in which improvements in diagnostic methods enable more sophisticated treatment approaches, which in turn steer advances in diagnostic methods,” they continued. “An unchanging principle, however, is that effective treatment will always rely on the ability to diagnose and stage the biology driving the disease process.”

Funding for this research was provided by the National Institutes of Health, Alexander family professorship, GHR Foundation, Alzheimer’s Association, Veterans Administration, Life Molecular Imaging, Michael J. Fox Foundation for Parkinson’s Research, Avid Radiopharmaceuticals, Eli Lilly, Gates Foundation, Biogen, C2N Diagnostics, Eisai, Fujirebio, GE Healthcare, Roche, National Institute on Aging, Roche/Genentech, BrightFocus Foundation, Hoffmann-La Roche, Novo Nordisk, Toyama, National MS Society, Alzheimer Drug Discovery Foundation, and others. A complete list of donors and disclosures is included in the original article.

 A version of this article appeared on Medscape.com.

A work group convened by the Alzheimer’s Association has released revised biology-based criteria for the diagnosis and staging of Alzheimer’s disease, including a new biomarker classification system that incorporates fluid and imaging biomarkers as well as an updated disease staging system. 

“Plasma markers are here now, and it’s very important to incorporate them into the criteria for diagnosis,” said senior author Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer and medical affairs lead. 

The revised criteria are the first updates since 2018.

“Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine — including cancer, heart disease, and diabetes — and is becoming a unifying concept common to all neurodegenerative diseases,” lead author Clifford Jack Jr, MD, with Mayo Clinic, Rochester, Minnesota, said in a news release from the Alzheimer’s Association. 

“These updates to the diagnostic criteria are needed now because we know more about the underlying biology of Alzheimer’s and we are able to measure those changes,” Dr. Jack added. 

The 2024 revised criteria for diagnosis and staging of Alzheimer’s disease were published online in Alzheimer’s & Dementia. 
 

Core Biomarkers Defined

The revised criteria define Alzheimer’s disease as a biologic process that begins with the appearance of Alzheimer’s disease neuropathologic change (ADNPC) in the absence of symptoms. Progression of the neuropathologic burden leads to the later appearance and progression of clinical symptoms.

The work group organized Alzheimer’s disease biomarkers into three broad categories: (1) core biomarkers of ADNPC, (2) nonspecific biomarkers that are important in Alzheimer’s disease but are also involved in other brain diseases, and (3) biomarkers of diseases or conditions that commonly coexist with Alzheimer’s disease.

Core Alzheimer’s biomarkers are subdivided into Core 1 and Core 2. 

Core 1 biomarkers become abnormal early in the disease course and directly measure either amyloid plaques or phosphorylated tau (p-tau). They include amyloid PET; cerebrospinal fluid (CSF) amyloid beta 42/40 ratio, CSF p-tau181/amyloid beta 42 ratio, and CSF total (t)-tau/amyloid beta 42 ratio; and “accurate” plasma biomarkers, such as p-tau217. 

“An abnormal Core 1 biomarker result is sufficient to establish a diagnosis of Alzheimer’s disease and to inform clinical decision making [sic] throughout the disease continuum,” the work group wrote. 

Core 2 biomarkers become abnormal later in the disease process and are more closely linked with the onset of symptoms. Core 2 biomarkers include tau PET and certain soluble tau fragments associated with tau proteinopathy (eg, MTBR-tau243) but also pT205 and nonphosphorylated mid-region tau fragments. 

Core 2 biomarkers, when combined with Core 1, may be used to stage biologic disease severity; abnormal Core 2 biomarkers “increase confidence that Alzheimer’s disease is contributing to symptoms,” the work group noted. 

The revised criteria give clinicians “the flexibility to use plasma or PET scans or CSF,” Dr. Carrillo said. “They will have several tools that they can choose from and offer this variety of tools to their patients. We need different tools for different individuals. There will be differences in coverage and access to these diagnostics.” 

The revised criteria also include an integrated biologic and clinical staging scheme that acknowledges the fact that common co-pathologies, cognitive reserve, and resistance may modify relationships between clinical and biologic Alzheimer’s disease stages. 
 

Formal Guidelines to Come 

The work group noted that currently, the clinical use of Alzheimer’s disease biomarkers is intended for the evaluation of symptomatic patients, not cognitively unimpaired individuals.

Disease-targeted therapies have not yet been approved for cognitively unimpaired individuals. For this reason, the work group currently recommends against diagnostic testing in cognitively unimpaired individuals outside the context of observational or therapeutic research studies. 

This recommendation would change in the future if disease-targeted therapies that are currently being evaluated in trials demonstrate a benefit in preventing cognitive decline and are approved for use in preclinical Alzheimer’s disease, they wrote. 

They emphasize that the revised criteria are not intended to provide step-by-step clinical practice guidelines for clinicians. Rather, they provide general principles to inform diagnosis and staging of Alzheimer’s disease that reflect current science.

“This is just the beginning,” said Dr. Carrillo. “This is a gathering of the evidence to date and putting it in one place so we can have a consensus and actually a way to test it and make it better as we add new science.”

This also serves as a “springboard” for the Alzheimer’s Association to create formal clinical guidelines. “That will come, hopefully, over the next 12 months. We’ll be working on it, and we hope to have that in 2025,” Dr. Carrillo said. 

The revised criteria also emphasize the role of the clinician. 

“The biologically based diagnosis of Alzheimer’s disease is meant to assist, rather than supplant, the clinical evaluation of individuals with cognitive impairment,” the work group wrote in a related commentary published online in Nature Medicine. 

Recent diagnostics and therapeutic developments “herald a virtuous cycle in which improvements in diagnostic methods enable more sophisticated treatment approaches, which in turn steer advances in diagnostic methods,” they continued. “An unchanging principle, however, is that effective treatment will always rely on the ability to diagnose and stage the biology driving the disease process.”

Funding for this research was provided by the National Institutes of Health, Alexander family professorship, GHR Foundation, Alzheimer’s Association, Veterans Administration, Life Molecular Imaging, Michael J. Fox Foundation for Parkinson’s Research, Avid Radiopharmaceuticals, Eli Lilly, Gates Foundation, Biogen, C2N Diagnostics, Eisai, Fujirebio, GE Healthcare, Roche, National Institute on Aging, Roche/Genentech, BrightFocus Foundation, Hoffmann-La Roche, Novo Nordisk, Toyama, National MS Society, Alzheimer Drug Discovery Foundation, and others. A complete list of donors and disclosures is included in the original article.

 A version of this article appeared on Medscape.com.

A work group convened by the Alzheimer’s Association has released revised biology-based criteria for the diagnosis and staging of Alzheimer’s disease, including a new biomarker classification system that incorporates fluid and imaging biomarkers as well as an updated disease staging system. 

“Plasma markers are here now, and it’s very important to incorporate them into the criteria for diagnosis,” said senior author Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer and medical affairs lead. 

The revised criteria are the first updates since 2018.

“Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine — including cancer, heart disease, and diabetes — and is becoming a unifying concept common to all neurodegenerative diseases,” lead author Clifford Jack Jr, MD, with Mayo Clinic, Rochester, Minnesota, said in a news release from the Alzheimer’s Association. 

“These updates to the diagnostic criteria are needed now because we know more about the underlying biology of Alzheimer’s and we are able to measure those changes,” Dr. Jack added. 

The 2024 revised criteria for diagnosis and staging of Alzheimer’s disease were published online in Alzheimer’s & Dementia. 
 

Core Biomarkers Defined

The revised criteria define Alzheimer’s disease as a biologic process that begins with the appearance of Alzheimer’s disease neuropathologic change (ADNPC) in the absence of symptoms. Progression of the neuropathologic burden leads to the later appearance and progression of clinical symptoms.

The work group organized Alzheimer’s disease biomarkers into three broad categories: (1) core biomarkers of ADNPC, (2) nonspecific biomarkers that are important in Alzheimer’s disease but are also involved in other brain diseases, and (3) biomarkers of diseases or conditions that commonly coexist with Alzheimer’s disease.

Core Alzheimer’s biomarkers are subdivided into Core 1 and Core 2. 

Core 1 biomarkers become abnormal early in the disease course and directly measure either amyloid plaques or phosphorylated tau (p-tau). They include amyloid PET; cerebrospinal fluid (CSF) amyloid beta 42/40 ratio, CSF p-tau181/amyloid beta 42 ratio, and CSF total (t)-tau/amyloid beta 42 ratio; and “accurate” plasma biomarkers, such as p-tau217. 

“An abnormal Core 1 biomarker result is sufficient to establish a diagnosis of Alzheimer’s disease and to inform clinical decision making [sic] throughout the disease continuum,” the work group wrote. 

Core 2 biomarkers become abnormal later in the disease process and are more closely linked with the onset of symptoms. Core 2 biomarkers include tau PET and certain soluble tau fragments associated with tau proteinopathy (eg, MTBR-tau243) but also pT205 and nonphosphorylated mid-region tau fragments. 

Core 2 biomarkers, when combined with Core 1, may be used to stage biologic disease severity; abnormal Core 2 biomarkers “increase confidence that Alzheimer’s disease is contributing to symptoms,” the work group noted. 

The revised criteria give clinicians “the flexibility to use plasma or PET scans or CSF,” Dr. Carrillo said. “They will have several tools that they can choose from and offer this variety of tools to their patients. We need different tools for different individuals. There will be differences in coverage and access to these diagnostics.” 

The revised criteria also include an integrated biologic and clinical staging scheme that acknowledges the fact that common co-pathologies, cognitive reserve, and resistance may modify relationships between clinical and biologic Alzheimer’s disease stages. 
 

Formal Guidelines to Come 

The work group noted that currently, the clinical use of Alzheimer’s disease biomarkers is intended for the evaluation of symptomatic patients, not cognitively unimpaired individuals.

Disease-targeted therapies have not yet been approved for cognitively unimpaired individuals. For this reason, the work group currently recommends against diagnostic testing in cognitively unimpaired individuals outside the context of observational or therapeutic research studies. 

This recommendation would change in the future if disease-targeted therapies that are currently being evaluated in trials demonstrate a benefit in preventing cognitive decline and are approved for use in preclinical Alzheimer’s disease, they wrote. 

They emphasize that the revised criteria are not intended to provide step-by-step clinical practice guidelines for clinicians. Rather, they provide general principles to inform diagnosis and staging of Alzheimer’s disease that reflect current science.

“This is just the beginning,” said Dr. Carrillo. “This is a gathering of the evidence to date and putting it in one place so we can have a consensus and actually a way to test it and make it better as we add new science.”

This also serves as a “springboard” for the Alzheimer’s Association to create formal clinical guidelines. “That will come, hopefully, over the next 12 months. We’ll be working on it, and we hope to have that in 2025,” Dr. Carrillo said. 

The revised criteria also emphasize the role of the clinician. 

“The biologically based diagnosis of Alzheimer’s disease is meant to assist, rather than supplant, the clinical evaluation of individuals with cognitive impairment,” the work group wrote in a related commentary published online in Nature Medicine. 

Recent diagnostics and therapeutic developments “herald a virtuous cycle in which improvements in diagnostic methods enable more sophisticated treatment approaches, which in turn steer advances in diagnostic methods,” they continued. “An unchanging principle, however, is that effective treatment will always rely on the ability to diagnose and stage the biology driving the disease process.”

Funding for this research was provided by the National Institutes of Health, Alexander family professorship, GHR Foundation, Alzheimer’s Association, Veterans Administration, Life Molecular Imaging, Michael J. Fox Foundation for Parkinson’s Research, Avid Radiopharmaceuticals, Eli Lilly, Gates Foundation, Biogen, C2N Diagnostics, Eisai, Fujirebio, GE Healthcare, Roche, National Institute on Aging, Roche/Genentech, BrightFocus Foundation, Hoffmann-La Roche, Novo Nordisk, Toyama, National MS Society, Alzheimer Drug Discovery Foundation, and others. A complete list of donors and disclosures is included in the original article.

 A version of this article appeared on Medscape.com.

A tool routinely used to evaluate concussion in college athletes fails to accurately diagnose the condition in many cases, a new study showed.

Investigators found that almost half of athletes diagnosed with a concussion tested normally on the Sports Concussion Assessment Tool 5 (SCAT5), the recommended tool for measuring cognitive skills in concussion evaluations. The most accurate measure of concussion was symptoms reported by the athletes.

“If you don’t do well on the cognitive exam, it suggests you have a concussion. But many people who are concussed do fine on the exam,” lead author Kimberly Harmon, MD, professor of family medicine and section head of sports medicine at the University of Washington School of Medicine, Seattle, said in a news release.

The study was published online in JAMA Network Open.

Introduced in 2004, the SCAT was created to standardize the collection of information clinicians use to diagnose concussion, including evaluation of symptoms, orientation, and balance. It also uses a 10-word list to assess immediate memory and delayed recall.

Dr. Harmon’s own experiences as a team physician led her to wonder about the accuracy of the cognitive screening portion of the SCAT. She saw that “some people were concussed, and they did well on the recall test. Some people weren’t concussed, and they didn’t do well. So I thought we should study it,” she said.

Investigators compared 92 National Collegiate Athletic Association (NCAA) Division 1 athletes who had sustained a concussion between 2020 and 2022 and had a concussion evaluation within 48 hours to 92 matched nonconcussed teammates (overall cohort, 52% men). Most concussions occurred in those who played football, followed by volleyball.

All athletes had previously completed NCAA-required baseline concussion screenings. Participants completed the SCAT5 screening test within 2 weeks of the incident concussion.

No significant differences were found between the baseline scores of athletes with and without concussion. Moreover, responses on the word recall section of the SCAT5 held little predictive value for concussion.

Nearly half (45%) of athletes with concussion performed at or even above their baseline cognitive report, which the authors said highlights the limitations of the cognitive components of SCAT5.

The most accurate predictor of concussion was participants’ responses to questions about their symptoms.

“If you get hit in the head and go to the sideline and say, ‘I have a headache, I’m dizzy, I don’t feel right,’ I can say with pretty good assurance that you have a concussion,” Dr. Harmon continued. “I don’t need to do any testing.”

Unfortunately, the problem is “that some athletes don’t want to come out. They don’t report their symptoms or may not recognize their symptoms. So then you need an objective, accurate test to tell you whether you can safely put the athlete back on the field. We don’t have that right now.”

The study did not control for concussion history, and the all–Division 1 cohort means the findings may not be generalizable to other athletes.

Nevertheless, investigators said the study “affirms that reported symptoms are the most sensitive indicator of concussion, and there are limitations to the objective cognitive testing included in the SCAT.” They concluded that concussion “remains a clinical diagnosis that should be based on a thorough review of signs, symptoms, and clinical findings.”

This study was funded in part by donations from University of Washington alumni Jack and Luellen Cherneski and the Chisholm Foundation. Dr. Harmon reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A tool routinely used to evaluate concussion in college athletes fails to accurately diagnose the condition in many cases, a new study showed.

Investigators found that almost half of athletes diagnosed with a concussion tested normally on the Sports Concussion Assessment Tool 5 (SCAT5), the recommended tool for measuring cognitive skills in concussion evaluations. The most accurate measure of concussion was symptoms reported by the athletes.

“If you don’t do well on the cognitive exam, it suggests you have a concussion. But many people who are concussed do fine on the exam,” lead author Kimberly Harmon, MD, professor of family medicine and section head of sports medicine at the University of Washington School of Medicine, Seattle, said in a news release.

The study was published online in JAMA Network Open.

Introduced in 2004, the SCAT was created to standardize the collection of information clinicians use to diagnose concussion, including evaluation of symptoms, orientation, and balance. It also uses a 10-word list to assess immediate memory and delayed recall.

Dr. Harmon’s own experiences as a team physician led her to wonder about the accuracy of the cognitive screening portion of the SCAT. She saw that “some people were concussed, and they did well on the recall test. Some people weren’t concussed, and they didn’t do well. So I thought we should study it,” she said.

Investigators compared 92 National Collegiate Athletic Association (NCAA) Division 1 athletes who had sustained a concussion between 2020 and 2022 and had a concussion evaluation within 48 hours to 92 matched nonconcussed teammates (overall cohort, 52% men). Most concussions occurred in those who played football, followed by volleyball.

All athletes had previously completed NCAA-required baseline concussion screenings. Participants completed the SCAT5 screening test within 2 weeks of the incident concussion.

No significant differences were found between the baseline scores of athletes with and without concussion. Moreover, responses on the word recall section of the SCAT5 held little predictive value for concussion.

Nearly half (45%) of athletes with concussion performed at or even above their baseline cognitive report, which the authors said highlights the limitations of the cognitive components of SCAT5.

The most accurate predictor of concussion was participants’ responses to questions about their symptoms.

“If you get hit in the head and go to the sideline and say, ‘I have a headache, I’m dizzy, I don’t feel right,’ I can say with pretty good assurance that you have a concussion,” Dr. Harmon continued. “I don’t need to do any testing.”

Unfortunately, the problem is “that some athletes don’t want to come out. They don’t report their symptoms or may not recognize their symptoms. So then you need an objective, accurate test to tell you whether you can safely put the athlete back on the field. We don’t have that right now.”

The study did not control for concussion history, and the all–Division 1 cohort means the findings may not be generalizable to other athletes.

Nevertheless, investigators said the study “affirms that reported symptoms are the most sensitive indicator of concussion, and there are limitations to the objective cognitive testing included in the SCAT.” They concluded that concussion “remains a clinical diagnosis that should be based on a thorough review of signs, symptoms, and clinical findings.”

This study was funded in part by donations from University of Washington alumni Jack and Luellen Cherneski and the Chisholm Foundation. Dr. Harmon reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A tool routinely used to evaluate concussion in college athletes fails to accurately diagnose the condition in many cases, a new study showed.

Investigators found that almost half of athletes diagnosed with a concussion tested normally on the Sports Concussion Assessment Tool 5 (SCAT5), the recommended tool for measuring cognitive skills in concussion evaluations. The most accurate measure of concussion was symptoms reported by the athletes.

“If you don’t do well on the cognitive exam, it suggests you have a concussion. But many people who are concussed do fine on the exam,” lead author Kimberly Harmon, MD, professor of family medicine and section head of sports medicine at the University of Washington School of Medicine, Seattle, said in a news release.

The study was published online in JAMA Network Open.

Introduced in 2004, the SCAT was created to standardize the collection of information clinicians use to diagnose concussion, including evaluation of symptoms, orientation, and balance. It also uses a 10-word list to assess immediate memory and delayed recall.

Dr. Harmon’s own experiences as a team physician led her to wonder about the accuracy of the cognitive screening portion of the SCAT. She saw that “some people were concussed, and they did well on the recall test. Some people weren’t concussed, and they didn’t do well. So I thought we should study it,” she said.

Investigators compared 92 National Collegiate Athletic Association (NCAA) Division 1 athletes who had sustained a concussion between 2020 and 2022 and had a concussion evaluation within 48 hours to 92 matched nonconcussed teammates (overall cohort, 52% men). Most concussions occurred in those who played football, followed by volleyball.

All athletes had previously completed NCAA-required baseline concussion screenings. Participants completed the SCAT5 screening test within 2 weeks of the incident concussion.

No significant differences were found between the baseline scores of athletes with and without concussion. Moreover, responses on the word recall section of the SCAT5 held little predictive value for concussion.

Nearly half (45%) of athletes with concussion performed at or even above their baseline cognitive report, which the authors said highlights the limitations of the cognitive components of SCAT5.

The most accurate predictor of concussion was participants’ responses to questions about their symptoms.

“If you get hit in the head and go to the sideline and say, ‘I have a headache, I’m dizzy, I don’t feel right,’ I can say with pretty good assurance that you have a concussion,” Dr. Harmon continued. “I don’t need to do any testing.”

Unfortunately, the problem is “that some athletes don’t want to come out. They don’t report their symptoms or may not recognize their symptoms. So then you need an objective, accurate test to tell you whether you can safely put the athlete back on the field. We don’t have that right now.”

The study did not control for concussion history, and the all–Division 1 cohort means the findings may not be generalizable to other athletes.

Nevertheless, investigators said the study “affirms that reported symptoms are the most sensitive indicator of concussion, and there are limitations to the objective cognitive testing included in the SCAT.” They concluded that concussion “remains a clinical diagnosis that should be based on a thorough review of signs, symptoms, and clinical findings.”

This study was funded in part by donations from University of Washington alumni Jack and Luellen Cherneski and the Chisholm Foundation. Dr. Harmon reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Researchers have identified a form of B12 deficiency caused by autoantibodies that specifically affects the central nervous system.

Discovered while studying a puzzling case of one patient with inexplicable neurological systems, the same autoantibody was detected in a small percentage of healthy individuals and was nearly four times as prevalent in patients with neuropsychiatric systemic lupus erythematosus (SLE).

“I didn’t think this single investigation was going to yield a broader phenomenon with other patients,” lead author John V. Pluvinage, MD, PhD, a neurology resident at the University of California San Francisco, said in an interview. “It started as an N-of-one study just based on scientific curiosity.”

“It’s a beautifully done study,” added Betty Diamond, MD, director of the Institute of Molecular Medicine at the Feinstein Institutes for Medical Research in Manhasset, New York, commenting on the research. It uncovers “yet another example of a disease where antibodies getting into the brain are the problem.”

The research was published in Science Translational Medicine.
 

The Patient

The investigation began in 2014 with a 67-year-old woman presenting with difficulty speaking, ataxia, and tremor. Her blood tests showed no signs of B12 deficiency, and testing for known autoantibodies came back negative.

Solving this mystery required a more exhaustive approach. The patient enrolled in a research study focused on identifying novel autoantibodies in suspected neuroinflammatory disease, using a screening technology called phage immunoprecipitation sequencing.

“We adapted this technology to screen for autoantibodies in an unbiased manner by displaying every peptide across the human proteome and then mixing those peptides with patient antibodies in order to figure out what the antibodies are binding to,” explained Dr. Pluvinage.

Using this method, he and colleagues discovered that this woman had autoantibodies that target CD320 — a receptor important in the cellular uptake of B12. While her blood tests were normal, B12 in the patient’s cerebral spinal fluid (CSF) was “nearly undetectable,” Dr. Pluvinage said. Using an in vitro model of the blood-brain barrier (BBB), the researchers determined that anti-CD320 impaired the transport of B12 across the BBB by targeting receptors on the cell surface.

Treating the patient with a combination of immunosuppressant medication and high-dose B12 supplementation increased B12 levels in the patient’s CSF and improved clinical symptoms.
 

Identifying More Cases

Dr. Pluvinage and colleagues tested the 254 other individuals enrolled in the neuroinflammatory disease study and identified seven participants with CSF anti-CD320 autoantibodies — four of whom had low B12 in the CSF.

In a group of healthy controls, anti-CD320 seropositivity was 6%, similar to the positivity rate in 132 paired serum and CSF samples from a cohort of patients with multiple sclerosis (5.7%). In this group of patients with multiple sclerosis, anti-CD320 presence in the blood was highly predictive of high levels of CSF methylmalonic acid, a metabolic marker of B12 deficiency.

Researchers also screened for anti-CD320 seropositivity in 408 patients with non-neurologic SLE and 28 patients with neuropsychiatric SLE and found that the autoantibody was nearly four times as prevalent in patients with neurologic symptoms (21.4%) compared with in those with non-neurologic SLE (5.6%).

“The clinical relevance of anti-CD320 in healthy controls remains uncertain,” the authors wrote. However, it is not uncommon to have healthy patients with known autoantibodies.

“There are always people who have autoantibodies who don’t get disease, and why that is we don’t know,” said Dr. Diamond. Some individuals may develop clinical symptoms later, or there may be other reasons why they are protected against disease.

Pluvinage is eager to follow some seropositive healthy individuals to track their neurologic health overtime, to see if the presence of anti-CD320 “alters their neurologic trajectories.”
 

Alternative Pathways

Lastly, Dr. Pluvinage and colleagues set out to explain why patients with anti-CD320 in their blood did not show any signs of B12 deficiency. They hypothesized that another receptor may be compensating and still allowing blood cells to take up B12. Using CRISPR screening, the team identified the low-density lipoprotein receptor as an alternative pathway to B12 uptake.

“These findings suggest a model in which anti-CD320 impairs transport of B12 across the BBB, leading to autoimmune B12 central deficiency (ABCD) with varied neurologic manifestations but sparing peripheral manifestations of B12 deficiency,” the authors wrote.

The work was supported by the National Institute of Mental Health, National Center for Chronic Disease Prevention and Health Promotion, Department of Defense, UCSF Helen Diller Family Comprehensive Cancer Center Laboratory for Cell Analysis Shared Resource Facility, National Multiple Sclerosis Society, Valhalla Foundation, and the Westridge Foundation. Dr. Pluvinage is a co-inventor on a patent application related to this work. Dr. Diamond had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Researchers have identified a form of B12 deficiency caused by autoantibodies that specifically affects the central nervous system.

Discovered while studying a puzzling case of one patient with inexplicable neurological systems, the same autoantibody was detected in a small percentage of healthy individuals and was nearly four times as prevalent in patients with neuropsychiatric systemic lupus erythematosus (SLE).

“I didn’t think this single investigation was going to yield a broader phenomenon with other patients,” lead author John V. Pluvinage, MD, PhD, a neurology resident at the University of California San Francisco, said in an interview. “It started as an N-of-one study just based on scientific curiosity.”

“It’s a beautifully done study,” added Betty Diamond, MD, director of the Institute of Molecular Medicine at the Feinstein Institutes for Medical Research in Manhasset, New York, commenting on the research. It uncovers “yet another example of a disease where antibodies getting into the brain are the problem.”

The research was published in Science Translational Medicine.
 

The Patient

The investigation began in 2014 with a 67-year-old woman presenting with difficulty speaking, ataxia, and tremor. Her blood tests showed no signs of B12 deficiency, and testing for known autoantibodies came back negative.

Solving this mystery required a more exhaustive approach. The patient enrolled in a research study focused on identifying novel autoantibodies in suspected neuroinflammatory disease, using a screening technology called phage immunoprecipitation sequencing.

“We adapted this technology to screen for autoantibodies in an unbiased manner by displaying every peptide across the human proteome and then mixing those peptides with patient antibodies in order to figure out what the antibodies are binding to,” explained Dr. Pluvinage.

Using this method, he and colleagues discovered that this woman had autoantibodies that target CD320 — a receptor important in the cellular uptake of B12. While her blood tests were normal, B12 in the patient’s cerebral spinal fluid (CSF) was “nearly undetectable,” Dr. Pluvinage said. Using an in vitro model of the blood-brain barrier (BBB), the researchers determined that anti-CD320 impaired the transport of B12 across the BBB by targeting receptors on the cell surface.

Treating the patient with a combination of immunosuppressant medication and high-dose B12 supplementation increased B12 levels in the patient’s CSF and improved clinical symptoms.
 

Identifying More Cases

Dr. Pluvinage and colleagues tested the 254 other individuals enrolled in the neuroinflammatory disease study and identified seven participants with CSF anti-CD320 autoantibodies — four of whom had low B12 in the CSF.

In a group of healthy controls, anti-CD320 seropositivity was 6%, similar to the positivity rate in 132 paired serum and CSF samples from a cohort of patients with multiple sclerosis (5.7%). In this group of patients with multiple sclerosis, anti-CD320 presence in the blood was highly predictive of high levels of CSF methylmalonic acid, a metabolic marker of B12 deficiency.

Researchers also screened for anti-CD320 seropositivity in 408 patients with non-neurologic SLE and 28 patients with neuropsychiatric SLE and found that the autoantibody was nearly four times as prevalent in patients with neurologic symptoms (21.4%) compared with in those with non-neurologic SLE (5.6%).

“The clinical relevance of anti-CD320 in healthy controls remains uncertain,” the authors wrote. However, it is not uncommon to have healthy patients with known autoantibodies.

“There are always people who have autoantibodies who don’t get disease, and why that is we don’t know,” said Dr. Diamond. Some individuals may develop clinical symptoms later, or there may be other reasons why they are protected against disease.

Pluvinage is eager to follow some seropositive healthy individuals to track their neurologic health overtime, to see if the presence of anti-CD320 “alters their neurologic trajectories.”
 

Alternative Pathways

Lastly, Dr. Pluvinage and colleagues set out to explain why patients with anti-CD320 in their blood did not show any signs of B12 deficiency. They hypothesized that another receptor may be compensating and still allowing blood cells to take up B12. Using CRISPR screening, the team identified the low-density lipoprotein receptor as an alternative pathway to B12 uptake.

“These findings suggest a model in which anti-CD320 impairs transport of B12 across the BBB, leading to autoimmune B12 central deficiency (ABCD) with varied neurologic manifestations but sparing peripheral manifestations of B12 deficiency,” the authors wrote.

The work was supported by the National Institute of Mental Health, National Center for Chronic Disease Prevention and Health Promotion, Department of Defense, UCSF Helen Diller Family Comprehensive Cancer Center Laboratory for Cell Analysis Shared Resource Facility, National Multiple Sclerosis Society, Valhalla Foundation, and the Westridge Foundation. Dr. Pluvinage is a co-inventor on a patent application related to this work. Dr. Diamond had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Researchers have identified a form of B12 deficiency caused by autoantibodies that specifically affects the central nervous system.

Discovered while studying a puzzling case of one patient with inexplicable neurological systems, the same autoantibody was detected in a small percentage of healthy individuals and was nearly four times as prevalent in patients with neuropsychiatric systemic lupus erythematosus (SLE).

“I didn’t think this single investigation was going to yield a broader phenomenon with other patients,” lead author John V. Pluvinage, MD, PhD, a neurology resident at the University of California San Francisco, said in an interview. “It started as an N-of-one study just based on scientific curiosity.”

“It’s a beautifully done study,” added Betty Diamond, MD, director of the Institute of Molecular Medicine at the Feinstein Institutes for Medical Research in Manhasset, New York, commenting on the research. It uncovers “yet another example of a disease where antibodies getting into the brain are the problem.”

The research was published in Science Translational Medicine.
 

The Patient

The investigation began in 2014 with a 67-year-old woman presenting with difficulty speaking, ataxia, and tremor. Her blood tests showed no signs of B12 deficiency, and testing for known autoantibodies came back negative.

Solving this mystery required a more exhaustive approach. The patient enrolled in a research study focused on identifying novel autoantibodies in suspected neuroinflammatory disease, using a screening technology called phage immunoprecipitation sequencing.

“We adapted this technology to screen for autoantibodies in an unbiased manner by displaying every peptide across the human proteome and then mixing those peptides with patient antibodies in order to figure out what the antibodies are binding to,” explained Dr. Pluvinage.

Using this method, he and colleagues discovered that this woman had autoantibodies that target CD320 — a receptor important in the cellular uptake of B12. While her blood tests were normal, B12 in the patient’s cerebral spinal fluid (CSF) was “nearly undetectable,” Dr. Pluvinage said. Using an in vitro model of the blood-brain barrier (BBB), the researchers determined that anti-CD320 impaired the transport of B12 across the BBB by targeting receptors on the cell surface.

Treating the patient with a combination of immunosuppressant medication and high-dose B12 supplementation increased B12 levels in the patient’s CSF and improved clinical symptoms.
 

Identifying More Cases

Dr. Pluvinage and colleagues tested the 254 other individuals enrolled in the neuroinflammatory disease study and identified seven participants with CSF anti-CD320 autoantibodies — four of whom had low B12 in the CSF.

In a group of healthy controls, anti-CD320 seropositivity was 6%, similar to the positivity rate in 132 paired serum and CSF samples from a cohort of patients with multiple sclerosis (5.7%). In this group of patients with multiple sclerosis, anti-CD320 presence in the blood was highly predictive of high levels of CSF methylmalonic acid, a metabolic marker of B12 deficiency.

Researchers also screened for anti-CD320 seropositivity in 408 patients with non-neurologic SLE and 28 patients with neuropsychiatric SLE and found that the autoantibody was nearly four times as prevalent in patients with neurologic symptoms (21.4%) compared with in those with non-neurologic SLE (5.6%).

“The clinical relevance of anti-CD320 in healthy controls remains uncertain,” the authors wrote. However, it is not uncommon to have healthy patients with known autoantibodies.

“There are always people who have autoantibodies who don’t get disease, and why that is we don’t know,” said Dr. Diamond. Some individuals may develop clinical symptoms later, or there may be other reasons why they are protected against disease.

Pluvinage is eager to follow some seropositive healthy individuals to track their neurologic health overtime, to see if the presence of anti-CD320 “alters their neurologic trajectories.”
 

Alternative Pathways

Lastly, Dr. Pluvinage and colleagues set out to explain why patients with anti-CD320 in their blood did not show any signs of B12 deficiency. They hypothesized that another receptor may be compensating and still allowing blood cells to take up B12. Using CRISPR screening, the team identified the low-density lipoprotein receptor as an alternative pathway to B12 uptake.

“These findings suggest a model in which anti-CD320 impairs transport of B12 across the BBB, leading to autoimmune B12 central deficiency (ABCD) with varied neurologic manifestations but sparing peripheral manifestations of B12 deficiency,” the authors wrote.

The work was supported by the National Institute of Mental Health, National Center for Chronic Disease Prevention and Health Promotion, Department of Defense, UCSF Helen Diller Family Comprehensive Cancer Center Laboratory for Cell Analysis Shared Resource Facility, National Multiple Sclerosis Society, Valhalla Foundation, and the Westridge Foundation. Dr. Pluvinage is a co-inventor on a patent application related to this work. Dr. Diamond had no relevant disclosures.

A version of this article first appeared on Medscape.com.

TOPLINE:

A study found that patients who die by suicide within a year after discharge from inpatient mental health care are less likely to have primary care consultation in the first 2 weeks, highlighting a gap during the high-risk transition period.

METHODOLOGY:

• Researchers used a nested case-control study design, analyzing the records of 613 people who died by suicide within a year of being discharged from an inpatient psychiatric facility in England between 2001 and 2019.
• Of these, 93 (15.4%) died within 2 weeks of discharge.
• Each patient was matched with up to 20 control individuals who were discharged at a similar time but were living.
• Researchers evaluated primary care consultations after discharge.

TAKEAWAY:

• People who died by suicide within a year were less likely to have had a primary care consultation within 2 weeks of discharge (adjusted odds ratio [aOR], 0.61; P = .01).
• Those who died by suicide had higher odds for a consultation in the week preceding their death (aOR, 1.71; P < .001) and the prescription of three or more psychotropic medications (aOR, 1.73; P < .001).
• Evidence of discharge communication between the facility and primary care clinician was infrequent, highlighting a gap in continuity of care.
• Approximately 40% of people who died within 2 weeks of discharge had a documented visit with a primary care clinician during that period.

IN PRACTICE:

“Primary care clinicians have opportunities to intervene and should prioritize patients experiencing transition from inpatient care,” the authors wrote.

SOURCE:

The study was led by Rebecca Musgrove, PhD, of the Centre for Mental Health and Safety at The University of Manchester in England, and published online on June 12 in BJGP Open.

LIMITATIONS:

The study’s reliance on individuals registered with the Clinical Practice Research Datalink may have caused some suicide cases to be excluded, limiting generalizability. Lack of linked up-to-date mental health records may have led to the omission of significant post-discharge care data. Incomplete discharge documentation may undercount informational continuity, affecting multivariable analysis.

DISCLOSURES:

The study was supported by the National Institute of Health and Care Research. Some authors declared serving as members of advisory groups and receiving grants and personal fees from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A study found that patients who die by suicide within a year after discharge from inpatient mental health care are less likely to have primary care consultation in the first 2 weeks, highlighting a gap during the high-risk transition period.

METHODOLOGY:

• Researchers used a nested case-control study design, analyzing the records of 613 people who died by suicide within a year of being discharged from an inpatient psychiatric facility in England between 2001 and 2019.
• Of these, 93 (15.4%) died within 2 weeks of discharge.
• Each patient was matched with up to 20 control individuals who were discharged at a similar time but were living.
• Researchers evaluated primary care consultations after discharge.

TAKEAWAY:

• People who died by suicide within a year were less likely to have had a primary care consultation within 2 weeks of discharge (adjusted odds ratio [aOR], 0.61; P = .01).
• Those who died by suicide had higher odds for a consultation in the week preceding their death (aOR, 1.71; P < .001) and the prescription of three or more psychotropic medications (aOR, 1.73; P < .001).
• Evidence of discharge communication between the facility and primary care clinician was infrequent, highlighting a gap in continuity of care.
• Approximately 40% of people who died within 2 weeks of discharge had a documented visit with a primary care clinician during that period.

IN PRACTICE:

“Primary care clinicians have opportunities to intervene and should prioritize patients experiencing transition from inpatient care,” the authors wrote.

SOURCE:

The study was led by Rebecca Musgrove, PhD, of the Centre for Mental Health and Safety at The University of Manchester in England, and published online on June 12 in BJGP Open.

LIMITATIONS:

The study’s reliance on individuals registered with the Clinical Practice Research Datalink may have caused some suicide cases to be excluded, limiting generalizability. Lack of linked up-to-date mental health records may have led to the omission of significant post-discharge care data. Incomplete discharge documentation may undercount informational continuity, affecting multivariable analysis.

DISCLOSURES:

The study was supported by the National Institute of Health and Care Research. Some authors declared serving as members of advisory groups and receiving grants and personal fees from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A study found that patients who die by suicide within a year after discharge from inpatient mental health care are less likely to have primary care consultation in the first 2 weeks, highlighting a gap during the high-risk transition period.

METHODOLOGY:

• Researchers used a nested case-control study design, analyzing the records of 613 people who died by suicide within a year of being discharged from an inpatient psychiatric facility in England between 2001 and 2019.
• Of these, 93 (15.4%) died within 2 weeks of discharge.
• Each patient was matched with up to 20 control individuals who were discharged at a similar time but were living.
• Researchers evaluated primary care consultations after discharge.

TAKEAWAY:

• People who died by suicide within a year were less likely to have had a primary care consultation within 2 weeks of discharge (adjusted odds ratio [aOR], 0.61; P = .01).
• Those who died by suicide had higher odds for a consultation in the week preceding their death (aOR, 1.71; P < .001) and the prescription of three or more psychotropic medications (aOR, 1.73; P < .001).
• Evidence of discharge communication between the facility and primary care clinician was infrequent, highlighting a gap in continuity of care.
• Approximately 40% of people who died within 2 weeks of discharge had a documented visit with a primary care clinician during that period.

IN PRACTICE:

“Primary care clinicians have opportunities to intervene and should prioritize patients experiencing transition from inpatient care,” the authors wrote.

SOURCE:

The study was led by Rebecca Musgrove, PhD, of the Centre for Mental Health and Safety at The University of Manchester in England, and published online on June 12 in BJGP Open.

LIMITATIONS:

The study’s reliance on individuals registered with the Clinical Practice Research Datalink may have caused some suicide cases to be excluded, limiting generalizability. Lack of linked up-to-date mental health records may have led to the omission of significant post-discharge care data. Incomplete discharge documentation may undercount informational continuity, affecting multivariable analysis.

DISCLOSURES:

The study was supported by the National Institute of Health and Care Research. Some authors declared serving as members of advisory groups and receiving grants and personal fees from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Extended-release injectable naltrexone combined with extended-release oral bupropion (NTX + BUPN) for moderate or severe methamphetamine use disorder was associated with a significant decrease in use of the drug, a new study showed.

Investigators leading the randomized clinical trial found a 27% increase in negative methamphetamine urine tests in the treatment group — indicating reduced use — compared with an 11% increase in negative urine tests in control participants.

“These findings have important implications for pharmacological treatment for methamphetamine use disorder. There is no FDA-approved medication for it, yet methamphetamine-involved overdoses have greatly increased over the past decade,” lead author Michael Li, MD, assistant professor-in-residence of family medicine at the David Geffen School of Medicine at UCLA, Los Angeles, said in a news release.

The study was published online in Addiction.

Methamphetamine use has increased worldwide, from 33 million users in 2010 to 34 million in 2020, with overdose deaths rising fivefold in the United States over the past decade, the authors wrote.

A previous open-label study of NTX + BUPN showed efficacy for treating severe methamphetamine use disorder, and NTX and BUPN have each shown efficacy separately for this indication. 

This new study is the second phase of the multicenter ADAPT-2 trial, conducted between 2017 and 2019 in 403 participants with methamphetamine use disorder. In the first stage, 109 people received NTX + BUPN and 294 received placebo.

The treatment group received extended-release NTX (380 mg) or placebo as an intramuscular injection on weeks 1, 4, 7, and 10. Extended-release BUPN or placebo tablets were administered weekly, with BUPN doses starting at 150 mg on day 1 and increasing to 450 mg by day 3. At week 13, participants received a tapering dose for 4 days before discontinuing.

As previously reported by this news organization, the two-drug combo was effective at reducing methamphetamine use at 6 weeks. The current analysis measured change in methamphetamine use during weeks 7-12 of the trial and in posttreatment weeks 13-16.

Participants in the intervention group during stage 1 showed an additional 9.2% increase (P = .038) during stage 2 in their probability of testing negative for methamphetamine. This represented a total increase of 27.1% in negative urine tests across the complete 12 weeks of treatment, compared with a total 11.4% increase in negative tests in the placebo group.

The 12-week increase in methamphetamine-negative urine tests in the intervention group was 15.8% greater (P = .006) than the increase in the placebo group.

There was no significant change in either group at posttreatment follow-up in weeks 13-16.

“Our findings suggest that ongoing NTX + BUPN treatment yields statistically significant reductions in methamphetamine use that continue from weeks 7 to 12,” the authors wrote. The lack of change in methamphetamine use from weeks 13-16 corresponds to the conclusion of treatment in week 12, they added.

It remains to be determined “whether continued use of NTX + BUPN treatment past 12 weeks would yield further reductions in use,” the authors wrote, noting that prior stimulant use disorder trials suggest that change in use is gradual and that sustained abstinence is unlikely in merely 12 weeks of a trial. Rather, it is dependent on treatment duration.

“This warrants future clinical trials to quantify changes in methamphetamine use beyond 12 weeks and to identify the optimal duration of treatment with this medication,” they concluded.

The study was funded by awards from the National Institute on Drug Abuse (NIDA), the US Department of Health and Human Services, the National Institute of Mental Health, and the O’Donnell Clinical Neuroscience Scholar Award from the University of Texas Southwestern Medical Center. Alkermes provided Vivitrol (naltrexone for extended-release injectable suspension) and matched placebo free of charge for use in this trial under a written agreement with NIDA. Dr. Li reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper.

A version of this article first appeared on Medscape.com.

Extended-release injectable naltrexone combined with extended-release oral bupropion (NTX + BUPN) for moderate or severe methamphetamine use disorder was associated with a significant decrease in use of the drug, a new study showed.

Investigators leading the randomized clinical trial found a 27% increase in negative methamphetamine urine tests in the treatment group — indicating reduced use — compared with an 11% increase in negative urine tests in control participants.

“These findings have important implications for pharmacological treatment for methamphetamine use disorder. There is no FDA-approved medication for it, yet methamphetamine-involved overdoses have greatly increased over the past decade,” lead author Michael Li, MD, assistant professor-in-residence of family medicine at the David Geffen School of Medicine at UCLA, Los Angeles, said in a news release.

The study was published online in Addiction.

Methamphetamine use has increased worldwide, from 33 million users in 2010 to 34 million in 2020, with overdose deaths rising fivefold in the United States over the past decade, the authors wrote.

A previous open-label study of NTX + BUPN showed efficacy for treating severe methamphetamine use disorder, and NTX and BUPN have each shown efficacy separately for this indication. 

This new study is the second phase of the multicenter ADAPT-2 trial, conducted between 2017 and 2019 in 403 participants with methamphetamine use disorder. In the first stage, 109 people received NTX + BUPN and 294 received placebo.

The treatment group received extended-release NTX (380 mg) or placebo as an intramuscular injection on weeks 1, 4, 7, and 10. Extended-release BUPN or placebo tablets were administered weekly, with BUPN doses starting at 150 mg on day 1 and increasing to 450 mg by day 3. At week 13, participants received a tapering dose for 4 days before discontinuing.

As previously reported by this news organization, the two-drug combo was effective at reducing methamphetamine use at 6 weeks. The current analysis measured change in methamphetamine use during weeks 7-12 of the trial and in posttreatment weeks 13-16.

Participants in the intervention group during stage 1 showed an additional 9.2% increase (P = .038) during stage 2 in their probability of testing negative for methamphetamine. This represented a total increase of 27.1% in negative urine tests across the complete 12 weeks of treatment, compared with a total 11.4% increase in negative tests in the placebo group.

The 12-week increase in methamphetamine-negative urine tests in the intervention group was 15.8% greater (P = .006) than the increase in the placebo group.

There was no significant change in either group at posttreatment follow-up in weeks 13-16.

“Our findings suggest that ongoing NTX + BUPN treatment yields statistically significant reductions in methamphetamine use that continue from weeks 7 to 12,” the authors wrote. The lack of change in methamphetamine use from weeks 13-16 corresponds to the conclusion of treatment in week 12, they added.

It remains to be determined “whether continued use of NTX + BUPN treatment past 12 weeks would yield further reductions in use,” the authors wrote, noting that prior stimulant use disorder trials suggest that change in use is gradual and that sustained abstinence is unlikely in merely 12 weeks of a trial. Rather, it is dependent on treatment duration.

“This warrants future clinical trials to quantify changes in methamphetamine use beyond 12 weeks and to identify the optimal duration of treatment with this medication,” they concluded.

The study was funded by awards from the National Institute on Drug Abuse (NIDA), the US Department of Health and Human Services, the National Institute of Mental Health, and the O’Donnell Clinical Neuroscience Scholar Award from the University of Texas Southwestern Medical Center. Alkermes provided Vivitrol (naltrexone for extended-release injectable suspension) and matched placebo free of charge for use in this trial under a written agreement with NIDA. Dr. Li reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper.

A version of this article first appeared on Medscape.com.

Extended-release injectable naltrexone combined with extended-release oral bupropion (NTX + BUPN) for moderate or severe methamphetamine use disorder was associated with a significant decrease in use of the drug, a new study showed.

Investigators leading the randomized clinical trial found a 27% increase in negative methamphetamine urine tests in the treatment group — indicating reduced use — compared with an 11% increase in negative urine tests in control participants.

“These findings have important implications for pharmacological treatment for methamphetamine use disorder. There is no FDA-approved medication for it, yet methamphetamine-involved overdoses have greatly increased over the past decade,” lead author Michael Li, MD, assistant professor-in-residence of family medicine at the David Geffen School of Medicine at UCLA, Los Angeles, said in a news release.

The study was published online in Addiction.

Methamphetamine use has increased worldwide, from 33 million users in 2010 to 34 million in 2020, with overdose deaths rising fivefold in the United States over the past decade, the authors wrote.

A previous open-label study of NTX + BUPN showed efficacy for treating severe methamphetamine use disorder, and NTX and BUPN have each shown efficacy separately for this indication. 

This new study is the second phase of the multicenter ADAPT-2 trial, conducted between 2017 and 2019 in 403 participants with methamphetamine use disorder. In the first stage, 109 people received NTX + BUPN and 294 received placebo.

The treatment group received extended-release NTX (380 mg) or placebo as an intramuscular injection on weeks 1, 4, 7, and 10. Extended-release BUPN or placebo tablets were administered weekly, with BUPN doses starting at 150 mg on day 1 and increasing to 450 mg by day 3. At week 13, participants received a tapering dose for 4 days before discontinuing.

As previously reported by this news organization, the two-drug combo was effective at reducing methamphetamine use at 6 weeks. The current analysis measured change in methamphetamine use during weeks 7-12 of the trial and in posttreatment weeks 13-16.

Participants in the intervention group during stage 1 showed an additional 9.2% increase (P = .038) during stage 2 in their probability of testing negative for methamphetamine. This represented a total increase of 27.1% in negative urine tests across the complete 12 weeks of treatment, compared with a total 11.4% increase in negative tests in the placebo group.

The 12-week increase in methamphetamine-negative urine tests in the intervention group was 15.8% greater (P = .006) than the increase in the placebo group.

There was no significant change in either group at posttreatment follow-up in weeks 13-16.

“Our findings suggest that ongoing NTX + BUPN treatment yields statistically significant reductions in methamphetamine use that continue from weeks 7 to 12,” the authors wrote. The lack of change in methamphetamine use from weeks 13-16 corresponds to the conclusion of treatment in week 12, they added.

It remains to be determined “whether continued use of NTX + BUPN treatment past 12 weeks would yield further reductions in use,” the authors wrote, noting that prior stimulant use disorder trials suggest that change in use is gradual and that sustained abstinence is unlikely in merely 12 weeks of a trial. Rather, it is dependent on treatment duration.

“This warrants future clinical trials to quantify changes in methamphetamine use beyond 12 weeks and to identify the optimal duration of treatment with this medication,” they concluded.

The study was funded by awards from the National Institute on Drug Abuse (NIDA), the US Department of Health and Human Services, the National Institute of Mental Health, and the O’Donnell Clinical Neuroscience Scholar Award from the University of Texas Southwestern Medical Center. Alkermes provided Vivitrol (naltrexone for extended-release injectable suspension) and matched placebo free of charge for use in this trial under a written agreement with NIDA. Dr. Li reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper.

A version of this article first appeared on Medscape.com.

Posttraumatic stress disorder (PTSD) may enhance the risk for obstructive sleep apnea (OSA) in older male veterans, the results of a cross-sectional twin study suggested. However, additional high-quality research is needed and may yield important mechanistic insights into both conditions and improve treatment, experts said.

In the trial, increasing PTSD symptom severity was associated with increasing severity of OSA, even after controlling for multiple factors.

“The strength of the association was a bit surprising,” said study investigator Amit J. Shah, MD, MSCR, Emory University, Atlanta, Georgia. “Many physicians and scientists may otherwise assume that the relationship between PTSD and sleep apnea would be primarily mediated by obesity, but we did not find that obesity explained our findings.”

The study was published online in JAMA Network Open.
 

A More Rigorous Evaluation

“Prior studies have shown an association between PTSD and sleep apnea, but the size of the association was not as strong,” Dr. Shah said, possibly because many were based on symptomatic patients referred for clinical evaluation of OSA and some relied on self-report of a sleep apnea diagnosis.

The current study involved 181 male twins, aged 61-71 years, including 66 pairs discordant for PTSD symptoms and 15 pairs discordant for PTSD diagnosis, who were recruited from the Vietnam Era Twin Registry and underwent a formal psychiatric and polysomnography evaluation as follow-up of the Emory Twin Study.

PTSD symptom severity was assessed using the self-administered Posttraumatic Stress Disorder Checklist (PCL). OSA was mild in 74% of participants, moderate to severe in 40%, and severe in 18%.

The mean apnea-hypopnea index (AHI) was 17.7 events per hour, and the mean proportion of the night with SaO₂ less than 90% was 8.9%.

In fully adjusted models, each 15-point within-pair difference in PCL score was associated with a 4.6 events-per-hour higher AHI, a 6.4 events-per-hour higher oxygen desaturation index, and a 4.8% greater sleep duration with SaO₂ less than 90%.

A current PTSD diagnosis is associated with an approximate 10-unit higher adjusted AHI in separate models involving potential cardiovascular mediators (10.5-unit; 95% CI, 5.7-15.3) and sociodemographic and psychiatric confounders (10.7-unit; 95% CI, 4.0-17.4).

The investigators called for more research into the underlying mechanisms but speculated that pharyngeal collapsibility and exaggerated loop gain, among others, may play a role.

“Our findings broaden the concept of OSA as one that may involve stress pathways in addition to the traditional mechanisms involving airway collapse and obesity,” Dr. Shah said. “We should be more suspicious of OSA as an important comorbidity in PTSD, given the high OSA prevalence that we found in PTSD veterans.”
 

Questions Remain

In an accompanying editorial, Steven H. Woodward, PhD, and Ruth M. Benca, MD, PhD, VA Palo Alto Health Care Systems, Palo Alto, California, noted the study affirmatively answers the decades-old question of whether rates of OSA are elevated in PTSD and “eliminates many potential confounders that might cast doubt on the PTSD-OSA association.”

However, they noted, it’s difficult to ascertain the directionality of this association and point out that, in terms of potential mechanisms, the oft-cited 1994 study linking sleep fragmentation with upper airway collapsibility has never been replicated and that a recent study found no difference in airway collapsibility or evidence of differential loop gain in combat veterans with and without PTSD.

Dr. Woodward and Dr. Benca also highlighted the large body of evidence that psychiatric disorders such as bipolar disorder, schizophrenia, and, in particular, major depressive disorder, are strongly associated with higher rates of OSA.

“In sum, we do not believe that a fair reading of the current literature supports a conclusion that PTSD bears an association with OSA that does not overlap with those manifested by other psychiatric disorders,” they wrote.

“This commentary is not intended to discourage any specific line of inquiry. Rather, we seek to keep the door open as wide as possible to hypotheses and research designs aimed at elucidating the relationships between OSA and psychiatric disorders,” Dr. Woodward and Dr. Benca concluded.

In response, Dr. Shah said the editorialists’ “point about psychiatric conditions other than PTSD also being important in OSA is well taken. In our own cohort, we did not see such an association, but that does not mean that this does not exist.

“Autonomic physiology, which we plan to study next, may underlie not only the PTSD-OSA relationship but also the relationship between other psychiatric factors and OSA,” he added.

The study was funded by grants from the National Institutes of Health (NIH). One study author reported receiving personal fees from Idorsia, and another reported receiving personal fees from Clinilabs, Eisai, Ferring Pharmaceuticals, Huxley, Idorsia, and Merck Sharp & Dohme. Dr. Benca reported receiving grants from the NIH and Eisai and personal fees from Eisai, Idorsia, Haleon, and Sage Therapeutics. Dr. Woodward reported having no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Posttraumatic stress disorder (PTSD) may enhance the risk for obstructive sleep apnea (OSA) in older male veterans, the results of a cross-sectional twin study suggested. However, additional high-quality research is needed and may yield important mechanistic insights into both conditions and improve treatment, experts said.

In the trial, increasing PTSD symptom severity was associated with increasing severity of OSA, even after controlling for multiple factors.

“The strength of the association was a bit surprising,” said study investigator Amit J. Shah, MD, MSCR, Emory University, Atlanta, Georgia. “Many physicians and scientists may otherwise assume that the relationship between PTSD and sleep apnea would be primarily mediated by obesity, but we did not find that obesity explained our findings.”

The study was published online in JAMA Network Open.
 

A More Rigorous Evaluation

“Prior studies have shown an association between PTSD and sleep apnea, but the size of the association was not as strong,” Dr. Shah said, possibly because many were based on symptomatic patients referred for clinical evaluation of OSA and some relied on self-report of a sleep apnea diagnosis.

The current study involved 181 male twins, aged 61-71 years, including 66 pairs discordant for PTSD symptoms and 15 pairs discordant for PTSD diagnosis, who were recruited from the Vietnam Era Twin Registry and underwent a formal psychiatric and polysomnography evaluation as follow-up of the Emory Twin Study.

PTSD symptom severity was assessed using the self-administered Posttraumatic Stress Disorder Checklist (PCL). OSA was mild in 74% of participants, moderate to severe in 40%, and severe in 18%.

The mean apnea-hypopnea index (AHI) was 17.7 events per hour, and the mean proportion of the night with SaO₂ less than 90% was 8.9%.

In fully adjusted models, each 15-point within-pair difference in PCL score was associated with a 4.6 events-per-hour higher AHI, a 6.4 events-per-hour higher oxygen desaturation index, and a 4.8% greater sleep duration with SaO₂ less than 90%.

A current PTSD diagnosis is associated with an approximate 10-unit higher adjusted AHI in separate models involving potential cardiovascular mediators (10.5-unit; 95% CI, 5.7-15.3) and sociodemographic and psychiatric confounders (10.7-unit; 95% CI, 4.0-17.4).

The investigators called for more research into the underlying mechanisms but speculated that pharyngeal collapsibility and exaggerated loop gain, among others, may play a role.

“Our findings broaden the concept of OSA as one that may involve stress pathways in addition to the traditional mechanisms involving airway collapse and obesity,” Dr. Shah said. “We should be more suspicious of OSA as an important comorbidity in PTSD, given the high OSA prevalence that we found in PTSD veterans.”
 

Questions Remain

In an accompanying editorial, Steven H. Woodward, PhD, and Ruth M. Benca, MD, PhD, VA Palo Alto Health Care Systems, Palo Alto, California, noted the study affirmatively answers the decades-old question of whether rates of OSA are elevated in PTSD and “eliminates many potential confounders that might cast doubt on the PTSD-OSA association.”

However, they noted, it’s difficult to ascertain the directionality of this association and point out that, in terms of potential mechanisms, the oft-cited 1994 study linking sleep fragmentation with upper airway collapsibility has never been replicated and that a recent study found no difference in airway collapsibility or evidence of differential loop gain in combat veterans with and without PTSD.

Dr. Woodward and Dr. Benca also highlighted the large body of evidence that psychiatric disorders such as bipolar disorder, schizophrenia, and, in particular, major depressive disorder, are strongly associated with higher rates of OSA.

“In sum, we do not believe that a fair reading of the current literature supports a conclusion that PTSD bears an association with OSA that does not overlap with those manifested by other psychiatric disorders,” they wrote.

“This commentary is not intended to discourage any specific line of inquiry. Rather, we seek to keep the door open as wide as possible to hypotheses and research designs aimed at elucidating the relationships between OSA and psychiatric disorders,” Dr. Woodward and Dr. Benca concluded.

In response, Dr. Shah said the editorialists’ “point about psychiatric conditions other than PTSD also being important in OSA is well taken. In our own cohort, we did not see such an association, but that does not mean that this does not exist.

“Autonomic physiology, which we plan to study next, may underlie not only the PTSD-OSA relationship but also the relationship between other psychiatric factors and OSA,” he added.

The study was funded by grants from the National Institutes of Health (NIH). One study author reported receiving personal fees from Idorsia, and another reported receiving personal fees from Clinilabs, Eisai, Ferring Pharmaceuticals, Huxley, Idorsia, and Merck Sharp & Dohme. Dr. Benca reported receiving grants from the NIH and Eisai and personal fees from Eisai, Idorsia, Haleon, and Sage Therapeutics. Dr. Woodward reported having no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Posttraumatic stress disorder (PTSD) may enhance the risk for obstructive sleep apnea (OSA) in older male veterans, the results of a cross-sectional twin study suggested. However, additional high-quality research is needed and may yield important mechanistic insights into both conditions and improve treatment, experts said.

In the trial, increasing PTSD symptom severity was associated with increasing severity of OSA, even after controlling for multiple factors.

“The strength of the association was a bit surprising,” said study investigator Amit J. Shah, MD, MSCR, Emory University, Atlanta, Georgia. “Many physicians and scientists may otherwise assume that the relationship between PTSD and sleep apnea would be primarily mediated by obesity, but we did not find that obesity explained our findings.”

The study was published online in JAMA Network Open.
 

A More Rigorous Evaluation

“Prior studies have shown an association between PTSD and sleep apnea, but the size of the association was not as strong,” Dr. Shah said, possibly because many were based on symptomatic patients referred for clinical evaluation of OSA and some relied on self-report of a sleep apnea diagnosis.

The current study involved 181 male twins, aged 61-71 years, including 66 pairs discordant for PTSD symptoms and 15 pairs discordant for PTSD diagnosis, who were recruited from the Vietnam Era Twin Registry and underwent a formal psychiatric and polysomnography evaluation as follow-up of the Emory Twin Study.

PTSD symptom severity was assessed using the self-administered Posttraumatic Stress Disorder Checklist (PCL). OSA was mild in 74% of participants, moderate to severe in 40%, and severe in 18%.

The mean apnea-hypopnea index (AHI) was 17.7 events per hour, and the mean proportion of the night with SaO₂ less than 90% was 8.9%.

In fully adjusted models, each 15-point within-pair difference in PCL score was associated with a 4.6 events-per-hour higher AHI, a 6.4 events-per-hour higher oxygen desaturation index, and a 4.8% greater sleep duration with SaO₂ less than 90%.

A current PTSD diagnosis is associated with an approximate 10-unit higher adjusted AHI in separate models involving potential cardiovascular mediators (10.5-unit; 95% CI, 5.7-15.3) and sociodemographic and psychiatric confounders (10.7-unit; 95% CI, 4.0-17.4).

The investigators called for more research into the underlying mechanisms but speculated that pharyngeal collapsibility and exaggerated loop gain, among others, may play a role.

“Our findings broaden the concept of OSA as one that may involve stress pathways in addition to the traditional mechanisms involving airway collapse and obesity,” Dr. Shah said. “We should be more suspicious of OSA as an important comorbidity in PTSD, given the high OSA prevalence that we found in PTSD veterans.”
 

Questions Remain

In an accompanying editorial, Steven H. Woodward, PhD, and Ruth M. Benca, MD, PhD, VA Palo Alto Health Care Systems, Palo Alto, California, noted the study affirmatively answers the decades-old question of whether rates of OSA are elevated in PTSD and “eliminates many potential confounders that might cast doubt on the PTSD-OSA association.”

However, they noted, it’s difficult to ascertain the directionality of this association and point out that, in terms of potential mechanisms, the oft-cited 1994 study linking sleep fragmentation with upper airway collapsibility has never been replicated and that a recent study found no difference in airway collapsibility or evidence of differential loop gain in combat veterans with and without PTSD.

Dr. Woodward and Dr. Benca also highlighted the large body of evidence that psychiatric disorders such as bipolar disorder, schizophrenia, and, in particular, major depressive disorder, are strongly associated with higher rates of OSA.

“In sum, we do not believe that a fair reading of the current literature supports a conclusion that PTSD bears an association with OSA that does not overlap with those manifested by other psychiatric disorders,” they wrote.

“This commentary is not intended to discourage any specific line of inquiry. Rather, we seek to keep the door open as wide as possible to hypotheses and research designs aimed at elucidating the relationships between OSA and psychiatric disorders,” Dr. Woodward and Dr. Benca concluded.

In response, Dr. Shah said the editorialists’ “point about psychiatric conditions other than PTSD also being important in OSA is well taken. In our own cohort, we did not see such an association, but that does not mean that this does not exist.

“Autonomic physiology, which we plan to study next, may underlie not only the PTSD-OSA relationship but also the relationship between other psychiatric factors and OSA,” he added.

The study was funded by grants from the National Institutes of Health (NIH). One study author reported receiving personal fees from Idorsia, and another reported receiving personal fees from Clinilabs, Eisai, Ferring Pharmaceuticals, Huxley, Idorsia, and Merck Sharp & Dohme. Dr. Benca reported receiving grants from the NIH and Eisai and personal fees from Eisai, Idorsia, Haleon, and Sage Therapeutics. Dr. Woodward reported having no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.