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Human brain patterns may help build a better AI system
new research suggests. “This work opens new opportunities to discover how the network organization of the brain optimizes cognitive capacity,” wrote researchers from The Neuro (Montreal Neurological Institute–Hospital) and the Quebec Artificial Intelligence Institute.
Senior investigator Bratislav Misic, PhD, said the research has potential clinical application for studying diseases of the brain, which is something his team is actively working on. “For example, using MRI techniques, we can measure different patterns of atrophy in neurodegenerative diseases such as Alzheimer’s disease,” he said.
“We can use these disease patterns from real patients to artificially lesion these connectomes and to ask how a particular disease causes a particular pattern of symptoms and cognitive deficits,” he added.
The findings were published online in Nature Machine Intelligence.
Unique approach
Using brain imaging data, the investigators reconstructed a human brain connectivity pattern and applied it to an artificial neural network. After training, the artificial neural network successfully performed a working memory task more flexibly and efficiently than other “benchmark” AI systems.
The researchers noted that their approach is unique because previous work on brain connectivity, also known as connectomics, has focused on describing brain organization without regard to how it actually functions.
Traditional artificial neural network have arbitrary structures that do not reflect how real brain networks are organized. Integrating brain connectomics into the construction of artificial neural network can reveal how the wiring of the brain supports specific cognitive skills, the investigators wrote.
“Up until now, if you look at how neural networks are constructed, the architectures that are used are very ad hoc and very problem specific,” Dr. Misic said. “But the connectomics revolution that’s happened in neuroscience over the past 20 years or so has given us the ability to really measure and trace out connection patterns in a variety of organisms, including the human brain.”
He noted that the researchers took wiring patterns of the real human brain and implemented it as an artificial neural network. They then “trained that network to perform a very simple cognitive task, and when you compare it to other benchmark architectures, it actually does better.”
This shows that there is “something fundamentally different about how the human brain is wired up and that the design principles that we can see in the human brain could be used to potentially build better artificial networks,” Dr. Misic concluded.
Funding for the research was provided by the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains, Healthy Lives initiative, and by the Natural Sciences and Engineering Research Council of Canada, Fonds de Recherche du Quebec – Santé, the Canadian Institute for Advanced Research, Canada Research Chairs, Fonds de Recherche du Quebec – Nature et Technologies, and the Centre UNIQUE (Union of Neuroscience and Artificial Intelligence). The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests. “This work opens new opportunities to discover how the network organization of the brain optimizes cognitive capacity,” wrote researchers from The Neuro (Montreal Neurological Institute–Hospital) and the Quebec Artificial Intelligence Institute.
Senior investigator Bratislav Misic, PhD, said the research has potential clinical application for studying diseases of the brain, which is something his team is actively working on. “For example, using MRI techniques, we can measure different patterns of atrophy in neurodegenerative diseases such as Alzheimer’s disease,” he said.
“We can use these disease patterns from real patients to artificially lesion these connectomes and to ask how a particular disease causes a particular pattern of symptoms and cognitive deficits,” he added.
The findings were published online in Nature Machine Intelligence.
Unique approach
Using brain imaging data, the investigators reconstructed a human brain connectivity pattern and applied it to an artificial neural network. After training, the artificial neural network successfully performed a working memory task more flexibly and efficiently than other “benchmark” AI systems.
The researchers noted that their approach is unique because previous work on brain connectivity, also known as connectomics, has focused on describing brain organization without regard to how it actually functions.
Traditional artificial neural network have arbitrary structures that do not reflect how real brain networks are organized. Integrating brain connectomics into the construction of artificial neural network can reveal how the wiring of the brain supports specific cognitive skills, the investigators wrote.
“Up until now, if you look at how neural networks are constructed, the architectures that are used are very ad hoc and very problem specific,” Dr. Misic said. “But the connectomics revolution that’s happened in neuroscience over the past 20 years or so has given us the ability to really measure and trace out connection patterns in a variety of organisms, including the human brain.”
He noted that the researchers took wiring patterns of the real human brain and implemented it as an artificial neural network. They then “trained that network to perform a very simple cognitive task, and when you compare it to other benchmark architectures, it actually does better.”
This shows that there is “something fundamentally different about how the human brain is wired up and that the design principles that we can see in the human brain could be used to potentially build better artificial networks,” Dr. Misic concluded.
Funding for the research was provided by the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains, Healthy Lives initiative, and by the Natural Sciences and Engineering Research Council of Canada, Fonds de Recherche du Quebec – Santé, the Canadian Institute for Advanced Research, Canada Research Chairs, Fonds de Recherche du Quebec – Nature et Technologies, and the Centre UNIQUE (Union of Neuroscience and Artificial Intelligence). The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests. “This work opens new opportunities to discover how the network organization of the brain optimizes cognitive capacity,” wrote researchers from The Neuro (Montreal Neurological Institute–Hospital) and the Quebec Artificial Intelligence Institute.
Senior investigator Bratislav Misic, PhD, said the research has potential clinical application for studying diseases of the brain, which is something his team is actively working on. “For example, using MRI techniques, we can measure different patterns of atrophy in neurodegenerative diseases such as Alzheimer’s disease,” he said.
“We can use these disease patterns from real patients to artificially lesion these connectomes and to ask how a particular disease causes a particular pattern of symptoms and cognitive deficits,” he added.
The findings were published online in Nature Machine Intelligence.
Unique approach
Using brain imaging data, the investigators reconstructed a human brain connectivity pattern and applied it to an artificial neural network. After training, the artificial neural network successfully performed a working memory task more flexibly and efficiently than other “benchmark” AI systems.
The researchers noted that their approach is unique because previous work on brain connectivity, also known as connectomics, has focused on describing brain organization without regard to how it actually functions.
Traditional artificial neural network have arbitrary structures that do not reflect how real brain networks are organized. Integrating brain connectomics into the construction of artificial neural network can reveal how the wiring of the brain supports specific cognitive skills, the investigators wrote.
“Up until now, if you look at how neural networks are constructed, the architectures that are used are very ad hoc and very problem specific,” Dr. Misic said. “But the connectomics revolution that’s happened in neuroscience over the past 20 years or so has given us the ability to really measure and trace out connection patterns in a variety of organisms, including the human brain.”
He noted that the researchers took wiring patterns of the real human brain and implemented it as an artificial neural network. They then “trained that network to perform a very simple cognitive task, and when you compare it to other benchmark architectures, it actually does better.”
This shows that there is “something fundamentally different about how the human brain is wired up and that the design principles that we can see in the human brain could be used to potentially build better artificial networks,” Dr. Misic concluded.
Funding for the research was provided by the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains, Healthy Lives initiative, and by the Natural Sciences and Engineering Research Council of Canada, Fonds de Recherche du Quebec – Santé, the Canadian Institute for Advanced Research, Canada Research Chairs, Fonds de Recherche du Quebec – Nature et Technologies, and the Centre UNIQUE (Union of Neuroscience and Artificial Intelligence). The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NATURE MACHINE INTELLIGENCE
Nonmotor symptoms common in Parkinson’s
The hallmark of Parkinson’s disease is the accompanying motor symptoms, but the condition can bring other challenges. Among those are nonmotor symptoms, including depression, dementia, and even psychosis.
The culprit is Lewy bodies, which are also responsible for Lewy body dementia. “What we call Lewy body dementia and Parkinson’s disease are caused by the same pathological process – the formation of Lewy bodies in the brain,” Leslie Citrome, MD, MPH, said in an interview. Dr. Citrome discussed some of the psychiatric comorbidities associated with Parkinson’s disease at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In fact, the association goes both ways. “Many people with Parkinson’s disease develop a dementia. Many people with Lewy body dementia develop motor symptoms that look just like Parkinson’s disease,” said Dr. Citrome, professor of psychiatry and behavioral sciences at New York Medical College, Valhalla, and president of the American Society for Clinical Psychopharmacology.
The motor symptoms of Parkinson’s disease are generally attributable to loss of striatal dopaminergic neurons, while nonmotor symptoms can be traced to loss of neurons in nondopaminergic regions. Nonmotor symptoms – often including sleep disorders, depression, cognitive changes, and psychosis – may occur before motor symptoms. Other problems may include autonomic dysfunction, such as constipation, sexual dysfunction, sweating, or urinary retention.
Patients might not be aware that nonmotor symptoms can occur with Parkinson’s disease and may not even consider mentioning mood changes or hallucinations to their neurologist. Family members may also be unaware.
Sleep problems are common in Parkinson’s disease, including rapid eye-movement sleep behavior disorders, vivid dreams, restless legs syndrome, insomnia, and daytime somnolence. Dopamine agonists may also cause unintended sleep.
Depression is extremely common, affecting up to 90% of Parkinson’s disease patients, and this may be related to dopaminergic losses. Antidepressant medications can worsen Parkinson’s disease symptoms: Tricyclic antidepressants increase risk of adverse events from anticholinergic drugs. Selective serotonin reuptake inhibitors (SSRIs) can exacerbate tremor and may increase risk of serotonin syndrome when combined with MAO‐B inhibitors.
Dr. Citrome was not aware of any antidepressant drugs that have been tested specifically in Parkinson’s disease patients, though “I’d be surprised if there wasn’t,” he said during the Q&A session. “There’s no one perfect antidepressant for people with depression associated with Parkinson’s disease. I would make sure to select one that they would tolerate and be willing to take and that doesn’t interfere with their treatment of their movement disorder, and (I would make sure) that there’s no drug-drug interaction,” he said.
This can include reduced working memory, learning, and planning, and generally does not manifest until at least 1 year after motor symptoms have begun. Rivastigmine is Food and Drug Administration–approved for treatment of cognitive impairment in Parkinson’s disease.
As many as 60% of Parkinson’s disease patients suffer from psychosis at some point, often visual hallucinations or delusions, which can include beliefs of spousal infidelity.
Many clinicians prescribe quetiapine off label, but there are not compelling data to support that it reduces intensity and frequency of hallucinations and delusions, according to Dr. Citrome. However, it is relatively easy to prescribe, requiring no preauthorizations, it is inexpensive, and it may improve sleep.
The FDA approved pimavanserin in 2016 for hallucinations and delusions in Parkinson’s disease, and it doesn’t worsen motor symptoms, Dr. Citrome said. That’s because pimavanserin is a highly selective antagonist of the 5-HT2A receptor, with no effect on dopaminergic, histaminergic, adrenergic, or muscarinic receptors.
The drug improves positive symptoms beginning at days 29 and 43, compared with placebo. An analysis by Dr. Citrome’s group found a number needed to treat (NNT) of 7 to gain a benefit over placebo if the metric is a ≥ 30% reduction in baseline symptom score. The drug had an NNT of 9 to achieve a ≥ 50% reduction, and an NNT of 5 to achieve a score of much improved or very much improved on the Clinical Global Impression–Improvement (CGI-I) scale. In general, an NNT less than 10 suggests that a drug is clinically useful.
In contrast, the number needed to harm (NNH) represents the number of patients who would need to receive a therapy to add one adverse event, compared with placebo. A number greater than 10 indicates that the therapy may be tolerable.
Using various measures, the NNH was well over 10 for pimavanserin. With respect to somnolence, the NNH over placebo was 138, and for a weight gain of 7% or more, the NNH was 594.
Overall, the study found that 4 patients would need to be treated to achieve a benefit over placebo with respect to a ≥ 3–point improvement in the Scale of Positive Symptoms–Parkinson’s Disease (SAPS-PD), while 21 would need to receive the drug to lead to one additional discontinuation because of an adverse event, compared to placebo.
When researchers compared pimavanserin to off-label use of quetiapine, olanzapine, and clozapine, they found a Cohen’s d value of 0.50, which was better than quetiapine and olanzapine, but lower than for clozapine. However, there is no requirement of blood monitoring, and clozapine can potentially worsen motor symptoms.
Dr. Citrome’s presentation should be a reminder to neurologists that psychiatric disorders are an important patient concern, said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who moderated the session.
“I think this serves as a model to recognize that many neurological disorders actually present with numerous psychiatric disorders,” Dr. Nasrallah said during the meeting, presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
Dr. Citrome has consulted for AbbVie, Acadia, Alkermes, Allergan, Angelini, Astellas, Avanir, Axsome, BioXcel, Boehringer-Ingelheim, Cadent Therapeutics, Eisai, Impel, Intra-Cellular, Janssen, Karuna, Lundbeck, Lyndra, MedAvante-ProPhase, Merck, Neurocrine, Noven, Otsuka, Ovid, Relmada, Sage, Sunovion, and Teva. He has been a speaker for most of those companies, and he holds stock in Bristol Myers Squibb, Eli Lilly, J&J, Merck, and Pfizer.
Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan, Boehringer-Ingelheim, Indivior, Intra-Cellular, Janssen, Neurocrine, Otsuka, Sunovion, and Teva. He has served on a speakers bureau for most of those companies, in addition to that of Noven.
The hallmark of Parkinson’s disease is the accompanying motor symptoms, but the condition can bring other challenges. Among those are nonmotor symptoms, including depression, dementia, and even psychosis.
The culprit is Lewy bodies, which are also responsible for Lewy body dementia. “What we call Lewy body dementia and Parkinson’s disease are caused by the same pathological process – the formation of Lewy bodies in the brain,” Leslie Citrome, MD, MPH, said in an interview. Dr. Citrome discussed some of the psychiatric comorbidities associated with Parkinson’s disease at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In fact, the association goes both ways. “Many people with Parkinson’s disease develop a dementia. Many people with Lewy body dementia develop motor symptoms that look just like Parkinson’s disease,” said Dr. Citrome, professor of psychiatry and behavioral sciences at New York Medical College, Valhalla, and president of the American Society for Clinical Psychopharmacology.
The motor symptoms of Parkinson’s disease are generally attributable to loss of striatal dopaminergic neurons, while nonmotor symptoms can be traced to loss of neurons in nondopaminergic regions. Nonmotor symptoms – often including sleep disorders, depression, cognitive changes, and psychosis – may occur before motor symptoms. Other problems may include autonomic dysfunction, such as constipation, sexual dysfunction, sweating, or urinary retention.
Patients might not be aware that nonmotor symptoms can occur with Parkinson’s disease and may not even consider mentioning mood changes or hallucinations to their neurologist. Family members may also be unaware.
Sleep problems are common in Parkinson’s disease, including rapid eye-movement sleep behavior disorders, vivid dreams, restless legs syndrome, insomnia, and daytime somnolence. Dopamine agonists may also cause unintended sleep.
Depression is extremely common, affecting up to 90% of Parkinson’s disease patients, and this may be related to dopaminergic losses. Antidepressant medications can worsen Parkinson’s disease symptoms: Tricyclic antidepressants increase risk of adverse events from anticholinergic drugs. Selective serotonin reuptake inhibitors (SSRIs) can exacerbate tremor and may increase risk of serotonin syndrome when combined with MAO‐B inhibitors.
Dr. Citrome was not aware of any antidepressant drugs that have been tested specifically in Parkinson’s disease patients, though “I’d be surprised if there wasn’t,” he said during the Q&A session. “There’s no one perfect antidepressant for people with depression associated with Parkinson’s disease. I would make sure to select one that they would tolerate and be willing to take and that doesn’t interfere with their treatment of their movement disorder, and (I would make sure) that there’s no drug-drug interaction,” he said.
This can include reduced working memory, learning, and planning, and generally does not manifest until at least 1 year after motor symptoms have begun. Rivastigmine is Food and Drug Administration–approved for treatment of cognitive impairment in Parkinson’s disease.
As many as 60% of Parkinson’s disease patients suffer from psychosis at some point, often visual hallucinations or delusions, which can include beliefs of spousal infidelity.
Many clinicians prescribe quetiapine off label, but there are not compelling data to support that it reduces intensity and frequency of hallucinations and delusions, according to Dr. Citrome. However, it is relatively easy to prescribe, requiring no preauthorizations, it is inexpensive, and it may improve sleep.
The FDA approved pimavanserin in 2016 for hallucinations and delusions in Parkinson’s disease, and it doesn’t worsen motor symptoms, Dr. Citrome said. That’s because pimavanserin is a highly selective antagonist of the 5-HT2A receptor, with no effect on dopaminergic, histaminergic, adrenergic, or muscarinic receptors.
The drug improves positive symptoms beginning at days 29 and 43, compared with placebo. An analysis by Dr. Citrome’s group found a number needed to treat (NNT) of 7 to gain a benefit over placebo if the metric is a ≥ 30% reduction in baseline symptom score. The drug had an NNT of 9 to achieve a ≥ 50% reduction, and an NNT of 5 to achieve a score of much improved or very much improved on the Clinical Global Impression–Improvement (CGI-I) scale. In general, an NNT less than 10 suggests that a drug is clinically useful.
In contrast, the number needed to harm (NNH) represents the number of patients who would need to receive a therapy to add one adverse event, compared with placebo. A number greater than 10 indicates that the therapy may be tolerable.
Using various measures, the NNH was well over 10 for pimavanserin. With respect to somnolence, the NNH over placebo was 138, and for a weight gain of 7% or more, the NNH was 594.
Overall, the study found that 4 patients would need to be treated to achieve a benefit over placebo with respect to a ≥ 3–point improvement in the Scale of Positive Symptoms–Parkinson’s Disease (SAPS-PD), while 21 would need to receive the drug to lead to one additional discontinuation because of an adverse event, compared to placebo.
When researchers compared pimavanserin to off-label use of quetiapine, olanzapine, and clozapine, they found a Cohen’s d value of 0.50, which was better than quetiapine and olanzapine, but lower than for clozapine. However, there is no requirement of blood monitoring, and clozapine can potentially worsen motor symptoms.
Dr. Citrome’s presentation should be a reminder to neurologists that psychiatric disorders are an important patient concern, said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who moderated the session.
“I think this serves as a model to recognize that many neurological disorders actually present with numerous psychiatric disorders,” Dr. Nasrallah said during the meeting, presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
Dr. Citrome has consulted for AbbVie, Acadia, Alkermes, Allergan, Angelini, Astellas, Avanir, Axsome, BioXcel, Boehringer-Ingelheim, Cadent Therapeutics, Eisai, Impel, Intra-Cellular, Janssen, Karuna, Lundbeck, Lyndra, MedAvante-ProPhase, Merck, Neurocrine, Noven, Otsuka, Ovid, Relmada, Sage, Sunovion, and Teva. He has been a speaker for most of those companies, and he holds stock in Bristol Myers Squibb, Eli Lilly, J&J, Merck, and Pfizer.
Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan, Boehringer-Ingelheim, Indivior, Intra-Cellular, Janssen, Neurocrine, Otsuka, Sunovion, and Teva. He has served on a speakers bureau for most of those companies, in addition to that of Noven.
The hallmark of Parkinson’s disease is the accompanying motor symptoms, but the condition can bring other challenges. Among those are nonmotor symptoms, including depression, dementia, and even psychosis.
The culprit is Lewy bodies, which are also responsible for Lewy body dementia. “What we call Lewy body dementia and Parkinson’s disease are caused by the same pathological process – the formation of Lewy bodies in the brain,” Leslie Citrome, MD, MPH, said in an interview. Dr. Citrome discussed some of the psychiatric comorbidities associated with Parkinson’s disease at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In fact, the association goes both ways. “Many people with Parkinson’s disease develop a dementia. Many people with Lewy body dementia develop motor symptoms that look just like Parkinson’s disease,” said Dr. Citrome, professor of psychiatry and behavioral sciences at New York Medical College, Valhalla, and president of the American Society for Clinical Psychopharmacology.
The motor symptoms of Parkinson’s disease are generally attributable to loss of striatal dopaminergic neurons, while nonmotor symptoms can be traced to loss of neurons in nondopaminergic regions. Nonmotor symptoms – often including sleep disorders, depression, cognitive changes, and psychosis – may occur before motor symptoms. Other problems may include autonomic dysfunction, such as constipation, sexual dysfunction, sweating, or urinary retention.
Patients might not be aware that nonmotor symptoms can occur with Parkinson’s disease and may not even consider mentioning mood changes or hallucinations to their neurologist. Family members may also be unaware.
Sleep problems are common in Parkinson’s disease, including rapid eye-movement sleep behavior disorders, vivid dreams, restless legs syndrome, insomnia, and daytime somnolence. Dopamine agonists may also cause unintended sleep.
Depression is extremely common, affecting up to 90% of Parkinson’s disease patients, and this may be related to dopaminergic losses. Antidepressant medications can worsen Parkinson’s disease symptoms: Tricyclic antidepressants increase risk of adverse events from anticholinergic drugs. Selective serotonin reuptake inhibitors (SSRIs) can exacerbate tremor and may increase risk of serotonin syndrome when combined with MAO‐B inhibitors.
Dr. Citrome was not aware of any antidepressant drugs that have been tested specifically in Parkinson’s disease patients, though “I’d be surprised if there wasn’t,” he said during the Q&A session. “There’s no one perfect antidepressant for people with depression associated with Parkinson’s disease. I would make sure to select one that they would tolerate and be willing to take and that doesn’t interfere with their treatment of their movement disorder, and (I would make sure) that there’s no drug-drug interaction,” he said.
This can include reduced working memory, learning, and planning, and generally does not manifest until at least 1 year after motor symptoms have begun. Rivastigmine is Food and Drug Administration–approved for treatment of cognitive impairment in Parkinson’s disease.
As many as 60% of Parkinson’s disease patients suffer from psychosis at some point, often visual hallucinations or delusions, which can include beliefs of spousal infidelity.
Many clinicians prescribe quetiapine off label, but there are not compelling data to support that it reduces intensity and frequency of hallucinations and delusions, according to Dr. Citrome. However, it is relatively easy to prescribe, requiring no preauthorizations, it is inexpensive, and it may improve sleep.
The FDA approved pimavanserin in 2016 for hallucinations and delusions in Parkinson’s disease, and it doesn’t worsen motor symptoms, Dr. Citrome said. That’s because pimavanserin is a highly selective antagonist of the 5-HT2A receptor, with no effect on dopaminergic, histaminergic, adrenergic, or muscarinic receptors.
The drug improves positive symptoms beginning at days 29 and 43, compared with placebo. An analysis by Dr. Citrome’s group found a number needed to treat (NNT) of 7 to gain a benefit over placebo if the metric is a ≥ 30% reduction in baseline symptom score. The drug had an NNT of 9 to achieve a ≥ 50% reduction, and an NNT of 5 to achieve a score of much improved or very much improved on the Clinical Global Impression–Improvement (CGI-I) scale. In general, an NNT less than 10 suggests that a drug is clinically useful.
In contrast, the number needed to harm (NNH) represents the number of patients who would need to receive a therapy to add one adverse event, compared with placebo. A number greater than 10 indicates that the therapy may be tolerable.
Using various measures, the NNH was well over 10 for pimavanserin. With respect to somnolence, the NNH over placebo was 138, and for a weight gain of 7% or more, the NNH was 594.
Overall, the study found that 4 patients would need to be treated to achieve a benefit over placebo with respect to a ≥ 3–point improvement in the Scale of Positive Symptoms–Parkinson’s Disease (SAPS-PD), while 21 would need to receive the drug to lead to one additional discontinuation because of an adverse event, compared to placebo.
When researchers compared pimavanserin to off-label use of quetiapine, olanzapine, and clozapine, they found a Cohen’s d value of 0.50, which was better than quetiapine and olanzapine, but lower than for clozapine. However, there is no requirement of blood monitoring, and clozapine can potentially worsen motor symptoms.
Dr. Citrome’s presentation should be a reminder to neurologists that psychiatric disorders are an important patient concern, said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who moderated the session.
“I think this serves as a model to recognize that many neurological disorders actually present with numerous psychiatric disorders,” Dr. Nasrallah said during the meeting, presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
Dr. Citrome has consulted for AbbVie, Acadia, Alkermes, Allergan, Angelini, Astellas, Avanir, Axsome, BioXcel, Boehringer-Ingelheim, Cadent Therapeutics, Eisai, Impel, Intra-Cellular, Janssen, Karuna, Lundbeck, Lyndra, MedAvante-ProPhase, Merck, Neurocrine, Noven, Otsuka, Ovid, Relmada, Sage, Sunovion, and Teva. He has been a speaker for most of those companies, and he holds stock in Bristol Myers Squibb, Eli Lilly, J&J, Merck, and Pfizer.
Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan, Boehringer-Ingelheim, Indivior, Intra-Cellular, Janssen, Neurocrine, Otsuka, Sunovion, and Teva. He has served on a speakers bureau for most of those companies, in addition to that of Noven.
FROM FOCUS ON NEUROPSYCHIATRY 2021
Stimulating jobs may help stave off dementia onset
Individuals with cognitively stimulating jobs are at a lower risk of developing dementia than their peers with less challenging employment, new research suggests.
Results from a large, multicohort study also showed an association between cognitive stimulation and lower levels of certain plasma proteins, providing possible clues on a protective biological mechanism.
“These new findings support the hypothesis that mental stimulation in adulthood may postpone the onset of dementia,” Mika Kivimäki, PhD, professor and director of the Whitehall II Study, department of epidemiology, University College London, said in an interview.
The results were published online Aug. 19, 2021, in the BMJ.
‘Work fast and hard’
Researchers assessed the association between workplace cognitive stimulation and dementia incidence in seven cohorts that included almost 108,000 men and women (mean age, 44.6 years). All were free of dementia at baseline.
Participants included civil servants, public sector employees, forestry workers, and others from the general working population.
Investigators separated the participants into three categories of workplace cognitive stimulation: “high,” which referred to both high job demand and high job control; “low,” which referred to low demands and low control; and “medium,” which referred to all other combinations of job demand and job control.
“Highly cognitively stimulating jobs require you to work fast and hard, learn new things, be creative, and have a high level of skill,” said Dr. Kivimäki.
The researchers controlled for low education, hypertension, smoking, obesity, depression, physical inactivity, diabetes, low social contact, excessive alcohol consumption, and traumatic brain injury. These represent 10 of the 12 dementia risk factors named by the 2020 Lancet Commission on Dementia Prevention as having convincing evidence, Dr. Kivimäki noted.
Although the investigators had no data on the other two risk factors of hearing loss and air pollution, these are unlikely to be confounding factors, he said.
Follow-up for incident dementia varied from 13.7 to 30.1 years, depending on the cohort, and was 16.7 years in the total patient population. The mean age at dementia onset was 71.2 years.
Benefits across the life course
Results showed that incident dementia per 10,000 person years was 7.3 in the low–cognitive stimulation group and 4.8 in the high-stimulation group, for a difference of 2.5.
“These differences were relatively small because the incidence of dementia in this relatively young population was low,” Dr. Kivimäki said.
Compared with those with low stimulation, the adjusted hazard ratio for dementia for this with high stimulation was 0.77 (95% CI, 0.65-0.92).
The results were similar for men and women, and for those younger and older than 60 years. However, the link between workplace cognitive stimulation appeared stronger for Alzheimer’s disease than for other dementias.
There also appeared to be additive effects of higher cognitive stimulation in both childhood, as indicated by higher educational attainment, and adulthood, based on work characteristics, said Dr. Kivimäki.
“These findings support the benefits of cognitive stimulation across the life course, with education leading to higher peak cognitive performance and cognitive stimulation at work lowering age-related cognitive decline,” he added.
The findings don’t seem to be the result of workers with cognitive impairment remaining in unchallenging jobs, he noted. Separate analyses showed lower dementia incidence even when 10 years or more separated the assessment of cognitive stimulation and the dementia diagnosis.
“This suggests that the findings are unlikely to be biased due to reverse causation,” Dr. Kivimäki said.
Possible mechanism
Findings were similar when the researchers assessed effect from job changes. “This is probably because people in highly stimulating jobs are more likely to change to another highly stimulating job than to a low-stimulating job,” said Dr. Kivimäki. “Similarly, people with less stimulating jobs are seldom able to change to a substantially more stimulating job.”
As a dementia risk factor, low workplace stimulation is comparable with high alcohol intake and physical inactivity, but is weaker than education, diabetes, smoking, hypertension, and obesity, Dr. Kivimäki noted.
When asked about individuals with less cognitively stimulating jobs who are enormously stimulated outside work, he said that “previous large-scale studies have failed to find evidence that leisure time cognitive activity would significantly reduce risk of dementia.”
To explore potential underlying mechanisms, the investigators examined almost 5,000 plasma proteins in more than 2,200 individuals from one cohort in the Whitehall II study. They found six proteins were significantly lower among participants with high versus low cognitive stimulation.
In another analysis that included more than 13,500 participants from the Whitehall and another cohort, higher levels of three of these plasma proteins were associated with increased dementia risk – or conversely, lower protein levels with lower dementia risk.
The findings suggest a “novel plausible explanation” for the link between workplace cognitive stimulation and dementia risk, said Dr. Kivimäki.
He noted that higher levels of certain proteins prevent brain cells from forming new connections.
‘Some of the most compelling evidence to date’
In an accompanying editorial, Serhiy Dekhtyar, PhD, assistant professor (Docent), Aging Research Center, Karolinska Institute, Stockholm, noted that the study is “an important piece of work” and “some of the most compelling evidence to date” on the role of occupational cognitive stimulation in dementia risk.
The large-scale investigation in multiple cohorts and contexts has “advanced the field” and could help “explain previously mixed findings in the literature,” Dekhtyar said in an interview.
Importantly, the researchers provide “an indication of biological mechanisms potentially connecting work mental stimulation and dementia,” he added.
However, Dr. Dekhtyar noted that the difference of 2.5 incident cases of dementia per 10,000 person years of follow-up between the low and high mental-stimulation groups “is not especially large” – although it is comparable with other established risk factors for dementia.
He suspects the effect size would have been larger had the follow-up for dementia been longer.
Dr. Dekhtyar also raised the possibility that “innate cognition” might affect both educational and occupational attainment, and the subsequent dementia risk.
“Without taking this into account, we may inadvertently conclude that education or occupational stimulation help differentially preserve cognition into late life – when in reality, it may be initial differences in cognitive ability that are preserved throughout life,” he concluded.
Funding sources for the study included Nordic Research Programme on Health and Welfare (NordForsk), Medical Research Council, Wellcome Trust, Academy of Finland, and Helsinki Institute of Life Science. Dr. Kivimäki has received support from NordForsk, the UK Medical Research Council, the Wellcome Trust, the Academy of Finland, and the Helsinki Institute of Life Science. Dr. Dekhtyar disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Individuals with cognitively stimulating jobs are at a lower risk of developing dementia than their peers with less challenging employment, new research suggests.
Results from a large, multicohort study also showed an association between cognitive stimulation and lower levels of certain plasma proteins, providing possible clues on a protective biological mechanism.
“These new findings support the hypothesis that mental stimulation in adulthood may postpone the onset of dementia,” Mika Kivimäki, PhD, professor and director of the Whitehall II Study, department of epidemiology, University College London, said in an interview.
The results were published online Aug. 19, 2021, in the BMJ.
‘Work fast and hard’
Researchers assessed the association between workplace cognitive stimulation and dementia incidence in seven cohorts that included almost 108,000 men and women (mean age, 44.6 years). All were free of dementia at baseline.
Participants included civil servants, public sector employees, forestry workers, and others from the general working population.
Investigators separated the participants into three categories of workplace cognitive stimulation: “high,” which referred to both high job demand and high job control; “low,” which referred to low demands and low control; and “medium,” which referred to all other combinations of job demand and job control.
“Highly cognitively stimulating jobs require you to work fast and hard, learn new things, be creative, and have a high level of skill,” said Dr. Kivimäki.
The researchers controlled for low education, hypertension, smoking, obesity, depression, physical inactivity, diabetes, low social contact, excessive alcohol consumption, and traumatic brain injury. These represent 10 of the 12 dementia risk factors named by the 2020 Lancet Commission on Dementia Prevention as having convincing evidence, Dr. Kivimäki noted.
Although the investigators had no data on the other two risk factors of hearing loss and air pollution, these are unlikely to be confounding factors, he said.
Follow-up for incident dementia varied from 13.7 to 30.1 years, depending on the cohort, and was 16.7 years in the total patient population. The mean age at dementia onset was 71.2 years.
Benefits across the life course
Results showed that incident dementia per 10,000 person years was 7.3 in the low–cognitive stimulation group and 4.8 in the high-stimulation group, for a difference of 2.5.
“These differences were relatively small because the incidence of dementia in this relatively young population was low,” Dr. Kivimäki said.
Compared with those with low stimulation, the adjusted hazard ratio for dementia for this with high stimulation was 0.77 (95% CI, 0.65-0.92).
The results were similar for men and women, and for those younger and older than 60 years. However, the link between workplace cognitive stimulation appeared stronger for Alzheimer’s disease than for other dementias.
There also appeared to be additive effects of higher cognitive stimulation in both childhood, as indicated by higher educational attainment, and adulthood, based on work characteristics, said Dr. Kivimäki.
“These findings support the benefits of cognitive stimulation across the life course, with education leading to higher peak cognitive performance and cognitive stimulation at work lowering age-related cognitive decline,” he added.
The findings don’t seem to be the result of workers with cognitive impairment remaining in unchallenging jobs, he noted. Separate analyses showed lower dementia incidence even when 10 years or more separated the assessment of cognitive stimulation and the dementia diagnosis.
“This suggests that the findings are unlikely to be biased due to reverse causation,” Dr. Kivimäki said.
Possible mechanism
Findings were similar when the researchers assessed effect from job changes. “This is probably because people in highly stimulating jobs are more likely to change to another highly stimulating job than to a low-stimulating job,” said Dr. Kivimäki. “Similarly, people with less stimulating jobs are seldom able to change to a substantially more stimulating job.”
As a dementia risk factor, low workplace stimulation is comparable with high alcohol intake and physical inactivity, but is weaker than education, diabetes, smoking, hypertension, and obesity, Dr. Kivimäki noted.
When asked about individuals with less cognitively stimulating jobs who are enormously stimulated outside work, he said that “previous large-scale studies have failed to find evidence that leisure time cognitive activity would significantly reduce risk of dementia.”
To explore potential underlying mechanisms, the investigators examined almost 5,000 plasma proteins in more than 2,200 individuals from one cohort in the Whitehall II study. They found six proteins were significantly lower among participants with high versus low cognitive stimulation.
In another analysis that included more than 13,500 participants from the Whitehall and another cohort, higher levels of three of these plasma proteins were associated with increased dementia risk – or conversely, lower protein levels with lower dementia risk.
The findings suggest a “novel plausible explanation” for the link between workplace cognitive stimulation and dementia risk, said Dr. Kivimäki.
He noted that higher levels of certain proteins prevent brain cells from forming new connections.
‘Some of the most compelling evidence to date’
In an accompanying editorial, Serhiy Dekhtyar, PhD, assistant professor (Docent), Aging Research Center, Karolinska Institute, Stockholm, noted that the study is “an important piece of work” and “some of the most compelling evidence to date” on the role of occupational cognitive stimulation in dementia risk.
The large-scale investigation in multiple cohorts and contexts has “advanced the field” and could help “explain previously mixed findings in the literature,” Dekhtyar said in an interview.
Importantly, the researchers provide “an indication of biological mechanisms potentially connecting work mental stimulation and dementia,” he added.
However, Dr. Dekhtyar noted that the difference of 2.5 incident cases of dementia per 10,000 person years of follow-up between the low and high mental-stimulation groups “is not especially large” – although it is comparable with other established risk factors for dementia.
He suspects the effect size would have been larger had the follow-up for dementia been longer.
Dr. Dekhtyar also raised the possibility that “innate cognition” might affect both educational and occupational attainment, and the subsequent dementia risk.
“Without taking this into account, we may inadvertently conclude that education or occupational stimulation help differentially preserve cognition into late life – when in reality, it may be initial differences in cognitive ability that are preserved throughout life,” he concluded.
Funding sources for the study included Nordic Research Programme on Health and Welfare (NordForsk), Medical Research Council, Wellcome Trust, Academy of Finland, and Helsinki Institute of Life Science. Dr. Kivimäki has received support from NordForsk, the UK Medical Research Council, the Wellcome Trust, the Academy of Finland, and the Helsinki Institute of Life Science. Dr. Dekhtyar disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Individuals with cognitively stimulating jobs are at a lower risk of developing dementia than their peers with less challenging employment, new research suggests.
Results from a large, multicohort study also showed an association between cognitive stimulation and lower levels of certain plasma proteins, providing possible clues on a protective biological mechanism.
“These new findings support the hypothesis that mental stimulation in adulthood may postpone the onset of dementia,” Mika Kivimäki, PhD, professor and director of the Whitehall II Study, department of epidemiology, University College London, said in an interview.
The results were published online Aug. 19, 2021, in the BMJ.
‘Work fast and hard’
Researchers assessed the association between workplace cognitive stimulation and dementia incidence in seven cohorts that included almost 108,000 men and women (mean age, 44.6 years). All were free of dementia at baseline.
Participants included civil servants, public sector employees, forestry workers, and others from the general working population.
Investigators separated the participants into three categories of workplace cognitive stimulation: “high,” which referred to both high job demand and high job control; “low,” which referred to low demands and low control; and “medium,” which referred to all other combinations of job demand and job control.
“Highly cognitively stimulating jobs require you to work fast and hard, learn new things, be creative, and have a high level of skill,” said Dr. Kivimäki.
The researchers controlled for low education, hypertension, smoking, obesity, depression, physical inactivity, diabetes, low social contact, excessive alcohol consumption, and traumatic brain injury. These represent 10 of the 12 dementia risk factors named by the 2020 Lancet Commission on Dementia Prevention as having convincing evidence, Dr. Kivimäki noted.
Although the investigators had no data on the other two risk factors of hearing loss and air pollution, these are unlikely to be confounding factors, he said.
Follow-up for incident dementia varied from 13.7 to 30.1 years, depending on the cohort, and was 16.7 years in the total patient population. The mean age at dementia onset was 71.2 years.
Benefits across the life course
Results showed that incident dementia per 10,000 person years was 7.3 in the low–cognitive stimulation group and 4.8 in the high-stimulation group, for a difference of 2.5.
“These differences were relatively small because the incidence of dementia in this relatively young population was low,” Dr. Kivimäki said.
Compared with those with low stimulation, the adjusted hazard ratio for dementia for this with high stimulation was 0.77 (95% CI, 0.65-0.92).
The results were similar for men and women, and for those younger and older than 60 years. However, the link between workplace cognitive stimulation appeared stronger for Alzheimer’s disease than for other dementias.
There also appeared to be additive effects of higher cognitive stimulation in both childhood, as indicated by higher educational attainment, and adulthood, based on work characteristics, said Dr. Kivimäki.
“These findings support the benefits of cognitive stimulation across the life course, with education leading to higher peak cognitive performance and cognitive stimulation at work lowering age-related cognitive decline,” he added.
The findings don’t seem to be the result of workers with cognitive impairment remaining in unchallenging jobs, he noted. Separate analyses showed lower dementia incidence even when 10 years or more separated the assessment of cognitive stimulation and the dementia diagnosis.
“This suggests that the findings are unlikely to be biased due to reverse causation,” Dr. Kivimäki said.
Possible mechanism
Findings were similar when the researchers assessed effect from job changes. “This is probably because people in highly stimulating jobs are more likely to change to another highly stimulating job than to a low-stimulating job,” said Dr. Kivimäki. “Similarly, people with less stimulating jobs are seldom able to change to a substantially more stimulating job.”
As a dementia risk factor, low workplace stimulation is comparable with high alcohol intake and physical inactivity, but is weaker than education, diabetes, smoking, hypertension, and obesity, Dr. Kivimäki noted.
When asked about individuals with less cognitively stimulating jobs who are enormously stimulated outside work, he said that “previous large-scale studies have failed to find evidence that leisure time cognitive activity would significantly reduce risk of dementia.”
To explore potential underlying mechanisms, the investigators examined almost 5,000 plasma proteins in more than 2,200 individuals from one cohort in the Whitehall II study. They found six proteins were significantly lower among participants with high versus low cognitive stimulation.
In another analysis that included more than 13,500 participants from the Whitehall and another cohort, higher levels of three of these plasma proteins were associated with increased dementia risk – or conversely, lower protein levels with lower dementia risk.
The findings suggest a “novel plausible explanation” for the link between workplace cognitive stimulation and dementia risk, said Dr. Kivimäki.
He noted that higher levels of certain proteins prevent brain cells from forming new connections.
‘Some of the most compelling evidence to date’
In an accompanying editorial, Serhiy Dekhtyar, PhD, assistant professor (Docent), Aging Research Center, Karolinska Institute, Stockholm, noted that the study is “an important piece of work” and “some of the most compelling evidence to date” on the role of occupational cognitive stimulation in dementia risk.
The large-scale investigation in multiple cohorts and contexts has “advanced the field” and could help “explain previously mixed findings in the literature,” Dekhtyar said in an interview.
Importantly, the researchers provide “an indication of biological mechanisms potentially connecting work mental stimulation and dementia,” he added.
However, Dr. Dekhtyar noted that the difference of 2.5 incident cases of dementia per 10,000 person years of follow-up between the low and high mental-stimulation groups “is not especially large” – although it is comparable with other established risk factors for dementia.
He suspects the effect size would have been larger had the follow-up for dementia been longer.
Dr. Dekhtyar also raised the possibility that “innate cognition” might affect both educational and occupational attainment, and the subsequent dementia risk.
“Without taking this into account, we may inadvertently conclude that education or occupational stimulation help differentially preserve cognition into late life – when in reality, it may be initial differences in cognitive ability that are preserved throughout life,” he concluded.
Funding sources for the study included Nordic Research Programme on Health and Welfare (NordForsk), Medical Research Council, Wellcome Trust, Academy of Finland, and Helsinki Institute of Life Science. Dr. Kivimäki has received support from NordForsk, the UK Medical Research Council, the Wellcome Trust, the Academy of Finland, and the Helsinki Institute of Life Science. Dr. Dekhtyar disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Explosive aggression may be neurologic
Aggression is an underappreciated mental health issue, and biological mechanisms might help explain more extreme forms like intermittent explosive disorder (IED), which is characterized by episodes of sudden impulses and inappropriate aggression, violence, or even verbal outbursts. IED can lead to road rage, domestic abuse, in addition to throwing objects and engaging in other destructive behaviors.
Despite those consequences, aggression hasn’t gained the same level of attention as other psychiatric conditions, according to Emil F. Coccaro, MD, who spoke about the topic at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“People seem to think that aggressive behavior is bad behavior, and therefore people just need an attitude adjustment. So there’s this sort of stigma, and there are no advocacy groups for it. There are no poster children for it. But there’s a whole lot of biology and neuroscience behind it,” said Dr. Coccaro, in an interview. He is a professor and vice chair of research in psychiatry and behavioral health at Ohio State University, Columbus.
, who spoke at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
There is a general view that psychiatric conditions may lead to increased aggression, but there is little evidence of that. “As a general statement, having a psychological [illness] in and of itself does not really increase the risk of being aggressive. What does is being aggressive in general, and substance use disorder. And the thing with [people who have] substance use disorders is that they only get aggressive when they are aggressive to begin with,” said Dr. Coccaro, noting that the strongest case for the relationship surrounds alcohol abuse.
The DSM-5 criteria for IED include: verbal or physical aggression without destruction, at least twice per week, or three or more episodes of assault or physical destruction within a year. The behavior must be out of proportion to the provocation, cause distress or impairment, and not be accountable by other diagnoses. “If they’re blowing up twice a week, for a few months, and usually they’re doing it for a long time, then that’s different than just blowing up very occasionally. Healthy people, nonaggressive people, maybe they blow up once a year, or even less frequently than that,” Dr. Coccaro said.
Functional magnetic resonance imaging and other imaging studies consistently show differences associated with aggression.
“The IEDs really do distinguish themselves from the psychiatric controls. They also have other stuff going on with them; they have a hostile attribution. And they’re kind of irritable at baseline. They’re not walking around irritable all the time, but the people around them may be walking on eggshells,” Dr. Coccaro said.
The results from these sorts of studies aren’t fully conclusive and can’t be used for diagnosis, in part because of a lack of power. “It’s hard to do these MRI studies and lots and lots of subjects, because they’re kind of expensive,” Dr. Coccaro said. “We’re just not there yet.”
Other, less expensive imaging techniques like near-infrared spectroscopy may improve matters. “That might be something down the road that could lead to something (diagnostic). Right now, most imaging studies are being done to really understand mechanisms,” said Dr. Coccaro.
Those mechanistic studies suggest that the culprit for IED may be a combination of too much drive from subcortical structures like the amygdala and insufficient inhibitor function in the frontal part of the brain. The frontal cortex may suffer a loss of gray matter, according to Dr. Coccaro, and there may be insufficient connectivity, which could weaken signals coming from the frontal areas that might otherwise inhibit lower centers of the brain.
Treatment for IED could be aimed at improving that connectivity and signaling. Ketamine and other anesthetic agents like nitrous oxide may increase connectivity to nerve cells by increasing branching at synaptic dendrites.
Selective serotonin reuptake inhibitors have the potential to treat IED, but their utility is limited because they bind to the presynaptic transporter for serotonin, and more aggressive people have fewer of those transporters. “You only get so much bang for your buck,” Dr. Coccaro said.
Cognitive-behavioral therapy that focuses on anger management and relaxation shows promise. “CBT does help people deal with what’s coming at them. So it’s like, ‘oh, I’m getting angry, I better start doing those relaxation (techniques).’ It teaches them to rethink things.”
During the Q&A session following the presentation, Henry A. Nasrallah, MD, who moderated the session, pointed out that misattribution can occur, leading an affected individual to misread someone’s facial expression and react aggressively, which is a problem also seen in psychosis.
“There are studies showing [that if] you show them a series of faces with different affects, many times paranoid patients read a normal facial expression as threatening. So it may be that it’s the same thing with aggression,” said Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.
In the midst of the ongoing COVID-19 pandemic, it’s also possible that mask-wearing could improve or worsen such misunderstandings. “There is expression in the eyes that you can see, but you miss a lot,” Dr. Coccaro said.
For now, the effects of masks remain largely unknown. But that will change. “Sooner or later we will have a bunch of papers coming out about how masks have changed a lot of behaviors,” Dr. Nasrallah said.
Dr. Coccaro has consulted for Avanir, Azevan, and Brackett. Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan Janssen, Otsuka, Indivior, IntraCellular, Neurocrine, Sunovion, Teva, and Boehringer-Ingelheim. Dr. Nasrallah has been on a speaker’s bureau for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Noven, Sunovion, and Teva.
Aggression is an underappreciated mental health issue, and biological mechanisms might help explain more extreme forms like intermittent explosive disorder (IED), which is characterized by episodes of sudden impulses and inappropriate aggression, violence, or even verbal outbursts. IED can lead to road rage, domestic abuse, in addition to throwing objects and engaging in other destructive behaviors.
Despite those consequences, aggression hasn’t gained the same level of attention as other psychiatric conditions, according to Emil F. Coccaro, MD, who spoke about the topic at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“People seem to think that aggressive behavior is bad behavior, and therefore people just need an attitude adjustment. So there’s this sort of stigma, and there are no advocacy groups for it. There are no poster children for it. But there’s a whole lot of biology and neuroscience behind it,” said Dr. Coccaro, in an interview. He is a professor and vice chair of research in psychiatry and behavioral health at Ohio State University, Columbus.
, who spoke at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
There is a general view that psychiatric conditions may lead to increased aggression, but there is little evidence of that. “As a general statement, having a psychological [illness] in and of itself does not really increase the risk of being aggressive. What does is being aggressive in general, and substance use disorder. And the thing with [people who have] substance use disorders is that they only get aggressive when they are aggressive to begin with,” said Dr. Coccaro, noting that the strongest case for the relationship surrounds alcohol abuse.
The DSM-5 criteria for IED include: verbal or physical aggression without destruction, at least twice per week, or three or more episodes of assault or physical destruction within a year. The behavior must be out of proportion to the provocation, cause distress or impairment, and not be accountable by other diagnoses. “If they’re blowing up twice a week, for a few months, and usually they’re doing it for a long time, then that’s different than just blowing up very occasionally. Healthy people, nonaggressive people, maybe they blow up once a year, or even less frequently than that,” Dr. Coccaro said.
Functional magnetic resonance imaging and other imaging studies consistently show differences associated with aggression.
“The IEDs really do distinguish themselves from the psychiatric controls. They also have other stuff going on with them; they have a hostile attribution. And they’re kind of irritable at baseline. They’re not walking around irritable all the time, but the people around them may be walking on eggshells,” Dr. Coccaro said.
The results from these sorts of studies aren’t fully conclusive and can’t be used for diagnosis, in part because of a lack of power. “It’s hard to do these MRI studies and lots and lots of subjects, because they’re kind of expensive,” Dr. Coccaro said. “We’re just not there yet.”
Other, less expensive imaging techniques like near-infrared spectroscopy may improve matters. “That might be something down the road that could lead to something (diagnostic). Right now, most imaging studies are being done to really understand mechanisms,” said Dr. Coccaro.
Those mechanistic studies suggest that the culprit for IED may be a combination of too much drive from subcortical structures like the amygdala and insufficient inhibitor function in the frontal part of the brain. The frontal cortex may suffer a loss of gray matter, according to Dr. Coccaro, and there may be insufficient connectivity, which could weaken signals coming from the frontal areas that might otherwise inhibit lower centers of the brain.
Treatment for IED could be aimed at improving that connectivity and signaling. Ketamine and other anesthetic agents like nitrous oxide may increase connectivity to nerve cells by increasing branching at synaptic dendrites.
Selective serotonin reuptake inhibitors have the potential to treat IED, but their utility is limited because they bind to the presynaptic transporter for serotonin, and more aggressive people have fewer of those transporters. “You only get so much bang for your buck,” Dr. Coccaro said.
Cognitive-behavioral therapy that focuses on anger management and relaxation shows promise. “CBT does help people deal with what’s coming at them. So it’s like, ‘oh, I’m getting angry, I better start doing those relaxation (techniques).’ It teaches them to rethink things.”
During the Q&A session following the presentation, Henry A. Nasrallah, MD, who moderated the session, pointed out that misattribution can occur, leading an affected individual to misread someone’s facial expression and react aggressively, which is a problem also seen in psychosis.
“There are studies showing [that if] you show them a series of faces with different affects, many times paranoid patients read a normal facial expression as threatening. So it may be that it’s the same thing with aggression,” said Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.
In the midst of the ongoing COVID-19 pandemic, it’s also possible that mask-wearing could improve or worsen such misunderstandings. “There is expression in the eyes that you can see, but you miss a lot,” Dr. Coccaro said.
For now, the effects of masks remain largely unknown. But that will change. “Sooner or later we will have a bunch of papers coming out about how masks have changed a lot of behaviors,” Dr. Nasrallah said.
Dr. Coccaro has consulted for Avanir, Azevan, and Brackett. Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan Janssen, Otsuka, Indivior, IntraCellular, Neurocrine, Sunovion, Teva, and Boehringer-Ingelheim. Dr. Nasrallah has been on a speaker’s bureau for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Noven, Sunovion, and Teva.
Aggression is an underappreciated mental health issue, and biological mechanisms might help explain more extreme forms like intermittent explosive disorder (IED), which is characterized by episodes of sudden impulses and inappropriate aggression, violence, or even verbal outbursts. IED can lead to road rage, domestic abuse, in addition to throwing objects and engaging in other destructive behaviors.
Despite those consequences, aggression hasn’t gained the same level of attention as other psychiatric conditions, according to Emil F. Coccaro, MD, who spoke about the topic at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“People seem to think that aggressive behavior is bad behavior, and therefore people just need an attitude adjustment. So there’s this sort of stigma, and there are no advocacy groups for it. There are no poster children for it. But there’s a whole lot of biology and neuroscience behind it,” said Dr. Coccaro, in an interview. He is a professor and vice chair of research in psychiatry and behavioral health at Ohio State University, Columbus.
, who spoke at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
There is a general view that psychiatric conditions may lead to increased aggression, but there is little evidence of that. “As a general statement, having a psychological [illness] in and of itself does not really increase the risk of being aggressive. What does is being aggressive in general, and substance use disorder. And the thing with [people who have] substance use disorders is that they only get aggressive when they are aggressive to begin with,” said Dr. Coccaro, noting that the strongest case for the relationship surrounds alcohol abuse.
The DSM-5 criteria for IED include: verbal or physical aggression without destruction, at least twice per week, or three or more episodes of assault or physical destruction within a year. The behavior must be out of proportion to the provocation, cause distress or impairment, and not be accountable by other diagnoses. “If they’re blowing up twice a week, for a few months, and usually they’re doing it for a long time, then that’s different than just blowing up very occasionally. Healthy people, nonaggressive people, maybe they blow up once a year, or even less frequently than that,” Dr. Coccaro said.
Functional magnetic resonance imaging and other imaging studies consistently show differences associated with aggression.
“The IEDs really do distinguish themselves from the psychiatric controls. They also have other stuff going on with them; they have a hostile attribution. And they’re kind of irritable at baseline. They’re not walking around irritable all the time, but the people around them may be walking on eggshells,” Dr. Coccaro said.
The results from these sorts of studies aren’t fully conclusive and can’t be used for diagnosis, in part because of a lack of power. “It’s hard to do these MRI studies and lots and lots of subjects, because they’re kind of expensive,” Dr. Coccaro said. “We’re just not there yet.”
Other, less expensive imaging techniques like near-infrared spectroscopy may improve matters. “That might be something down the road that could lead to something (diagnostic). Right now, most imaging studies are being done to really understand mechanisms,” said Dr. Coccaro.
Those mechanistic studies suggest that the culprit for IED may be a combination of too much drive from subcortical structures like the amygdala and insufficient inhibitor function in the frontal part of the brain. The frontal cortex may suffer a loss of gray matter, according to Dr. Coccaro, and there may be insufficient connectivity, which could weaken signals coming from the frontal areas that might otherwise inhibit lower centers of the brain.
Treatment for IED could be aimed at improving that connectivity and signaling. Ketamine and other anesthetic agents like nitrous oxide may increase connectivity to nerve cells by increasing branching at synaptic dendrites.
Selective serotonin reuptake inhibitors have the potential to treat IED, but their utility is limited because they bind to the presynaptic transporter for serotonin, and more aggressive people have fewer of those transporters. “You only get so much bang for your buck,” Dr. Coccaro said.
Cognitive-behavioral therapy that focuses on anger management and relaxation shows promise. “CBT does help people deal with what’s coming at them. So it’s like, ‘oh, I’m getting angry, I better start doing those relaxation (techniques).’ It teaches them to rethink things.”
During the Q&A session following the presentation, Henry A. Nasrallah, MD, who moderated the session, pointed out that misattribution can occur, leading an affected individual to misread someone’s facial expression and react aggressively, which is a problem also seen in psychosis.
“There are studies showing [that if] you show them a series of faces with different affects, many times paranoid patients read a normal facial expression as threatening. So it may be that it’s the same thing with aggression,” said Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.
In the midst of the ongoing COVID-19 pandemic, it’s also possible that mask-wearing could improve or worsen such misunderstandings. “There is expression in the eyes that you can see, but you miss a lot,” Dr. Coccaro said.
For now, the effects of masks remain largely unknown. But that will change. “Sooner or later we will have a bunch of papers coming out about how masks have changed a lot of behaviors,” Dr. Nasrallah said.
Dr. Coccaro has consulted for Avanir, Azevan, and Brackett. Dr. Nasrallah has consulted for Acadia, Alkermes, Allergan Janssen, Otsuka, Indivior, IntraCellular, Neurocrine, Sunovion, Teva, and Boehringer-Ingelheim. Dr. Nasrallah has been on a speaker’s bureau for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Noven, Sunovion, and Teva.
REPORTING FROM FOCUS ON NEUROPSYCHIATRY 2021
Wisdom may counter loneliness, burnout in older adults
Wisdom increases with age, and although this personality trait is regarded as nebulous by many, there is evidence that it has biological and neuropsychiatric underpinnings. It could even hold the key to reducing loneliness and burnout among older people.
Those were some of the key messages delivered by Tanya T. Nguyen, PhD, of the department of psychiatry at the University of California, San Diego, who spoke at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“To many people, wisdom remains a fuzzy concept that’s difficult to operationalize and measure. It’s analogous to the concepts of consciousness, emotions, and cognitions, which at one point were considered nonscientific, but today we accept them as biological and scientific entities,” Dr. Nguyen said during her talk at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
Interest in quantifying and studying wisdom has picked up in recent years, and Dr. Nguyen gave a definition with six elements that includes prosocial behaviors such as empathy and compassion, as well as emotional regulation, self-reflection, decisiveness, and social decision-making. She also included a spirituality component, though she conceded that this is controversial.
She noted that there are cultural variations in the definition of wisdom, but it has changed little over time, suggesting that it may be biological rather than cultural in nature, and therefore may have a neuropsychiatric underpinning.
Loss of some or all characteristics of wisdom occurs in some behaviors and disorders, including most markedly in the neurodegenerative disorder frontotemporal dementia (FTD), which is characterized by damage only in the prefrontal cortex and anterior temporal lobes. It usually occurs before age 60, and patients exhibit poor social awareness, impulsivity, antisocial behavior, and a lack of insight and empathy.
This and other lines of evidence have led to the suggestion that wisdom may be governed by processes in the prefrontal cortex and the limbic striatum. The prefrontal cortex controls executive functions such as planning, predicting, and anticipating events, as well as managing emotional reactions and impulses. “Thus, wisdom involves parts of the brain that balance cold, hard analytical reasoning with primitive desires and drives, which ultimately leads to self-regulation, social insight, theory of mind, and empathy,” said Dr. Nguyen.
Wisdom has long been associated with age, but age is also linked to cognitive decline. A recent discovery that the brain does not stop evolving at older age may help explain this contradiction. Brains develop in a back to front order, so that the prefrontal cortex is the last to mature. As we age, neural activity shifts from the occipital lobes to the prefrontal cortex and its executive decision-making power.
“The brain may recruit higher-order networks to the prefrontal cortex that are associated with wisdom development,” said Dr. Nguyen. She also pointed out that asymmetry between the left and right hemisphere is reduced with age, as tasks that relied on circuits from one hemisphere or another more often call upon both. “In order to make up for lost synapses and neurons with aging, active older adults use more neuronal networks from both hemispheres to perform the same mental activity,” Dr. Nguyen said.
Some interventions can improve scores in traits associated with wisdom in older adults, and could be an important contributor to improvements in health and longevity, said Dr. Nguyen. Randomized, controlled trials have demonstrated that psychosocial or behavioral interventions can improve elements of wisdom such as prosocial behaviors and emotional regulation, both in people with mental illness and in the general population, with moderate to large effect sizes. But such studies don’t prove an effect on overall wisdom.
The intervention achieved positive results in 89 participants in senior housing communities, though the effect sizes were small, possibly because of high baseline resilience. A subanalysis suggested that reduction in loneliness was mediated by an increase in compassion.
“One of the most striking findings from our research on wisdom is this consistent and very strongly negative correlation between wisdom and loneliness,” Dr. Nguyen said. She highlighted other U.S. nationwide and cross-cultural studies that showed inverse relationships between loneliness and wisdom.
Loneliness is an important topic because it can contribute to burnout and suicide rates.
“Loneliness has a profound effect on how we show up in the workplace, in school, and in our communities. And that leads to anxiety, depression, depersonalization, and emotional fatigue. All are key features of burnout. And together loneliness and burnout have contributed to increased rates of suicide by 30%, and opioid-related deaths almost sixfold since the late 1990s,” Dr. Nguyen said.
Loneliness also is associated with worse physical health, and it may be linked to wisdom. “Loneliness can be conceptualized as being caused and maintained by objective circumstances, such as physical or social distancing, and by thoughts, behaviors, and feelings surrounding those experiences, including biased perceptions of social relations, and a negative assessment of one’s social skills, which then results in a discrepancy between one’s desired and perceived social relationships, which then can contribute to social withdrawal,” Dr. Nguyen said.
Dr. Nguyen highlighted the AARP Foundation’s Experience Corps program, which recruits older adults to act as mentors and tutors for children in kindergarten through third grade. It involves 15 hours per week over an entire school year, with a focus on child literacy, development, and behavioral management skills. A study revealed a significant impact. “It showed improvements in children’s grades and happiness, as well as seniors’ mental and physical health,” Dr. Nguyen said.
Dr. Nguyen concluded that wisdom “may be a vaccine against compassion fatigue and burnout that drive today’s behavioral epidemics of loneliness, opioid abuse, and suicide. It’s a tool for our times. It’s nuanced, flexible, pragmatic, compassionate, and it presents a reasonable framework for getting along in the often messy world that we all share.”
Implications for psychiatrists
Henry A. Nasrallah, MD, who organized the conference, suggested that the benefits of wisdom may not be limited to patients. He pointed out that surgeons often retire at age 60 or 65 because of declining physical skills, while psychiatrists continue to practice.
“We develop more wisdom and better skills, and we can practice into our 60s and 70s. I know psychiatrists who practice sometimes into their 80s. It’s really a wonderful thing to know that what you do in life develops or enhances the neuroplasticity of certain brain regions. In our case, in psychiatry, it is the brain regions involved in wisdom,” commented Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.
Dr. Nguyen has no financial disclosures. Dr. Nasrallah has received grants from Abbott, AstraZeneca, Forest, Janssen, Lilly, Pfizer, and Shire, and advises Abbott, AstraZeneca, and Shire.
Wisdom increases with age, and although this personality trait is regarded as nebulous by many, there is evidence that it has biological and neuropsychiatric underpinnings. It could even hold the key to reducing loneliness and burnout among older people.
Those were some of the key messages delivered by Tanya T. Nguyen, PhD, of the department of psychiatry at the University of California, San Diego, who spoke at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“To many people, wisdom remains a fuzzy concept that’s difficult to operationalize and measure. It’s analogous to the concepts of consciousness, emotions, and cognitions, which at one point were considered nonscientific, but today we accept them as biological and scientific entities,” Dr. Nguyen said during her talk at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
Interest in quantifying and studying wisdom has picked up in recent years, and Dr. Nguyen gave a definition with six elements that includes prosocial behaviors such as empathy and compassion, as well as emotional regulation, self-reflection, decisiveness, and social decision-making. She also included a spirituality component, though she conceded that this is controversial.
She noted that there are cultural variations in the definition of wisdom, but it has changed little over time, suggesting that it may be biological rather than cultural in nature, and therefore may have a neuropsychiatric underpinning.
Loss of some or all characteristics of wisdom occurs in some behaviors and disorders, including most markedly in the neurodegenerative disorder frontotemporal dementia (FTD), which is characterized by damage only in the prefrontal cortex and anterior temporal lobes. It usually occurs before age 60, and patients exhibit poor social awareness, impulsivity, antisocial behavior, and a lack of insight and empathy.
This and other lines of evidence have led to the suggestion that wisdom may be governed by processes in the prefrontal cortex and the limbic striatum. The prefrontal cortex controls executive functions such as planning, predicting, and anticipating events, as well as managing emotional reactions and impulses. “Thus, wisdom involves parts of the brain that balance cold, hard analytical reasoning with primitive desires and drives, which ultimately leads to self-regulation, social insight, theory of mind, and empathy,” said Dr. Nguyen.
Wisdom has long been associated with age, but age is also linked to cognitive decline. A recent discovery that the brain does not stop evolving at older age may help explain this contradiction. Brains develop in a back to front order, so that the prefrontal cortex is the last to mature. As we age, neural activity shifts from the occipital lobes to the prefrontal cortex and its executive decision-making power.
“The brain may recruit higher-order networks to the prefrontal cortex that are associated with wisdom development,” said Dr. Nguyen. She also pointed out that asymmetry between the left and right hemisphere is reduced with age, as tasks that relied on circuits from one hemisphere or another more often call upon both. “In order to make up for lost synapses and neurons with aging, active older adults use more neuronal networks from both hemispheres to perform the same mental activity,” Dr. Nguyen said.
Some interventions can improve scores in traits associated with wisdom in older adults, and could be an important contributor to improvements in health and longevity, said Dr. Nguyen. Randomized, controlled trials have demonstrated that psychosocial or behavioral interventions can improve elements of wisdom such as prosocial behaviors and emotional regulation, both in people with mental illness and in the general population, with moderate to large effect sizes. But such studies don’t prove an effect on overall wisdom.
The intervention achieved positive results in 89 participants in senior housing communities, though the effect sizes were small, possibly because of high baseline resilience. A subanalysis suggested that reduction in loneliness was mediated by an increase in compassion.
“One of the most striking findings from our research on wisdom is this consistent and very strongly negative correlation between wisdom and loneliness,” Dr. Nguyen said. She highlighted other U.S. nationwide and cross-cultural studies that showed inverse relationships between loneliness and wisdom.
Loneliness is an important topic because it can contribute to burnout and suicide rates.
“Loneliness has a profound effect on how we show up in the workplace, in school, and in our communities. And that leads to anxiety, depression, depersonalization, and emotional fatigue. All are key features of burnout. And together loneliness and burnout have contributed to increased rates of suicide by 30%, and opioid-related deaths almost sixfold since the late 1990s,” Dr. Nguyen said.
Loneliness also is associated with worse physical health, and it may be linked to wisdom. “Loneliness can be conceptualized as being caused and maintained by objective circumstances, such as physical or social distancing, and by thoughts, behaviors, and feelings surrounding those experiences, including biased perceptions of social relations, and a negative assessment of one’s social skills, which then results in a discrepancy between one’s desired and perceived social relationships, which then can contribute to social withdrawal,” Dr. Nguyen said.
Dr. Nguyen highlighted the AARP Foundation’s Experience Corps program, which recruits older adults to act as mentors and tutors for children in kindergarten through third grade. It involves 15 hours per week over an entire school year, with a focus on child literacy, development, and behavioral management skills. A study revealed a significant impact. “It showed improvements in children’s grades and happiness, as well as seniors’ mental and physical health,” Dr. Nguyen said.
Dr. Nguyen concluded that wisdom “may be a vaccine against compassion fatigue and burnout that drive today’s behavioral epidemics of loneliness, opioid abuse, and suicide. It’s a tool for our times. It’s nuanced, flexible, pragmatic, compassionate, and it presents a reasonable framework for getting along in the often messy world that we all share.”
Implications for psychiatrists
Henry A. Nasrallah, MD, who organized the conference, suggested that the benefits of wisdom may not be limited to patients. He pointed out that surgeons often retire at age 60 or 65 because of declining physical skills, while psychiatrists continue to practice.
“We develop more wisdom and better skills, and we can practice into our 60s and 70s. I know psychiatrists who practice sometimes into their 80s. It’s really a wonderful thing to know that what you do in life develops or enhances the neuroplasticity of certain brain regions. In our case, in psychiatry, it is the brain regions involved in wisdom,” commented Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.
Dr. Nguyen has no financial disclosures. Dr. Nasrallah has received grants from Abbott, AstraZeneca, Forest, Janssen, Lilly, Pfizer, and Shire, and advises Abbott, AstraZeneca, and Shire.
Wisdom increases with age, and although this personality trait is regarded as nebulous by many, there is evidence that it has biological and neuropsychiatric underpinnings. It could even hold the key to reducing loneliness and burnout among older people.
Those were some of the key messages delivered by Tanya T. Nguyen, PhD, of the department of psychiatry at the University of California, San Diego, who spoke at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“To many people, wisdom remains a fuzzy concept that’s difficult to operationalize and measure. It’s analogous to the concepts of consciousness, emotions, and cognitions, which at one point were considered nonscientific, but today we accept them as biological and scientific entities,” Dr. Nguyen said during her talk at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
Interest in quantifying and studying wisdom has picked up in recent years, and Dr. Nguyen gave a definition with six elements that includes prosocial behaviors such as empathy and compassion, as well as emotional regulation, self-reflection, decisiveness, and social decision-making. She also included a spirituality component, though she conceded that this is controversial.
She noted that there are cultural variations in the definition of wisdom, but it has changed little over time, suggesting that it may be biological rather than cultural in nature, and therefore may have a neuropsychiatric underpinning.
Loss of some or all characteristics of wisdom occurs in some behaviors and disorders, including most markedly in the neurodegenerative disorder frontotemporal dementia (FTD), which is characterized by damage only in the prefrontal cortex and anterior temporal lobes. It usually occurs before age 60, and patients exhibit poor social awareness, impulsivity, antisocial behavior, and a lack of insight and empathy.
This and other lines of evidence have led to the suggestion that wisdom may be governed by processes in the prefrontal cortex and the limbic striatum. The prefrontal cortex controls executive functions such as planning, predicting, and anticipating events, as well as managing emotional reactions and impulses. “Thus, wisdom involves parts of the brain that balance cold, hard analytical reasoning with primitive desires and drives, which ultimately leads to self-regulation, social insight, theory of mind, and empathy,” said Dr. Nguyen.
Wisdom has long been associated with age, but age is also linked to cognitive decline. A recent discovery that the brain does not stop evolving at older age may help explain this contradiction. Brains develop in a back to front order, so that the prefrontal cortex is the last to mature. As we age, neural activity shifts from the occipital lobes to the prefrontal cortex and its executive decision-making power.
“The brain may recruit higher-order networks to the prefrontal cortex that are associated with wisdom development,” said Dr. Nguyen. She also pointed out that asymmetry between the left and right hemisphere is reduced with age, as tasks that relied on circuits from one hemisphere or another more often call upon both. “In order to make up for lost synapses and neurons with aging, active older adults use more neuronal networks from both hemispheres to perform the same mental activity,” Dr. Nguyen said.
Some interventions can improve scores in traits associated with wisdom in older adults, and could be an important contributor to improvements in health and longevity, said Dr. Nguyen. Randomized, controlled trials have demonstrated that psychosocial or behavioral interventions can improve elements of wisdom such as prosocial behaviors and emotional regulation, both in people with mental illness and in the general population, with moderate to large effect sizes. But such studies don’t prove an effect on overall wisdom.
The intervention achieved positive results in 89 participants in senior housing communities, though the effect sizes were small, possibly because of high baseline resilience. A subanalysis suggested that reduction in loneliness was mediated by an increase in compassion.
“One of the most striking findings from our research on wisdom is this consistent and very strongly negative correlation between wisdom and loneliness,” Dr. Nguyen said. She highlighted other U.S. nationwide and cross-cultural studies that showed inverse relationships between loneliness and wisdom.
Loneliness is an important topic because it can contribute to burnout and suicide rates.
“Loneliness has a profound effect on how we show up in the workplace, in school, and in our communities. And that leads to anxiety, depression, depersonalization, and emotional fatigue. All are key features of burnout. And together loneliness and burnout have contributed to increased rates of suicide by 30%, and opioid-related deaths almost sixfold since the late 1990s,” Dr. Nguyen said.
Loneliness also is associated with worse physical health, and it may be linked to wisdom. “Loneliness can be conceptualized as being caused and maintained by objective circumstances, such as physical or social distancing, and by thoughts, behaviors, and feelings surrounding those experiences, including biased perceptions of social relations, and a negative assessment of one’s social skills, which then results in a discrepancy between one’s desired and perceived social relationships, which then can contribute to social withdrawal,” Dr. Nguyen said.
Dr. Nguyen highlighted the AARP Foundation’s Experience Corps program, which recruits older adults to act as mentors and tutors for children in kindergarten through third grade. It involves 15 hours per week over an entire school year, with a focus on child literacy, development, and behavioral management skills. A study revealed a significant impact. “It showed improvements in children’s grades and happiness, as well as seniors’ mental and physical health,” Dr. Nguyen said.
Dr. Nguyen concluded that wisdom “may be a vaccine against compassion fatigue and burnout that drive today’s behavioral epidemics of loneliness, opioid abuse, and suicide. It’s a tool for our times. It’s nuanced, flexible, pragmatic, compassionate, and it presents a reasonable framework for getting along in the often messy world that we all share.”
Implications for psychiatrists
Henry A. Nasrallah, MD, who organized the conference, suggested that the benefits of wisdom may not be limited to patients. He pointed out that surgeons often retire at age 60 or 65 because of declining physical skills, while psychiatrists continue to practice.
“We develop more wisdom and better skills, and we can practice into our 60s and 70s. I know psychiatrists who practice sometimes into their 80s. It’s really a wonderful thing to know that what you do in life develops or enhances the neuroplasticity of certain brain regions. In our case, in psychiatry, it is the brain regions involved in wisdom,” commented Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.
Dr. Nguyen has no financial disclosures. Dr. Nasrallah has received grants from Abbott, AstraZeneca, Forest, Janssen, Lilly, Pfizer, and Shire, and advises Abbott, AstraZeneca, and Shire.
REPORTING FROM FOCUS ON NEUROPSYCHIATRY 2021
Brain memory signals appear to regulate metabolism
Rhythmic brain signals that help encode memories also appear to influence blood sugar levels and may regulate the timing of the release of hormones, early, pre-clinical research shows.
“Our study is the first to show how clusters of brain cell firing in the hippocampus may directly regulate metabolism,” senior author György Buzsáki, MD, PhD, professor, department of neuroscience and physiology, NYU Grossman School of Medicine and NYU Langone Health, said in a news release.
“Evidence suggests that the brain evolved, for reasons of efficiency, to use the same signals to achieve two very different functions in terms of memory and hormonal regulation,” added corresponding author David Tingley, PhD, a post-doctoral scholar in Dr. Buzsáki’s lab.
The study was published online August 11 in Nature.
It’s recently been discovered that populations of hippocampal neurons fire within milliseconds of each other in cycles. This firing pattern is called a “sharp wave ripple” for the shape it takes when captured graphically by electroencephalogram.
In their study, Dr. Buzsáki, Dr. Tingley, and colleagues observed that clusters of sharp wave ripples recorded from the hippocampus of rats were “reliably” and rapidly, followed by decreases in blood sugar concentrations in the animals.
“This correlation was not dependent on circadian, ultradian, or meal-triggered fluctuations; it could be mimicked with optogenetically induced ripples in the hippocampus, but not in the parietal cortex, and was attenuated to chance levels by pharmacogenetically suppressing activity of the lateral septum (LS), the major conduit between the hippocampus and hypothalamus,” the researchers report.
These observations suggest that hippocampal sharp wave ripples may regulate the timing of the release of hormones, possibly including insulin, by the pancreas and liver, as well as other hormones by the pituitary gland, the researchers note.
As sharp wave ripples mostly occur during non-rapid eye movement sleep, the impact of sleep disturbance on sharp wave ripples may provide a mechanistic link between poor sleep and high blood sugar levels seen in type 2 diabetes, they suggest.
“There are a couple of experimental studies showing that if you deprive a young healthy person from sleep [for 48 hours], their glucose tolerance resembles” that of a person with diabetes, Dr. Buzsáki noted in an interview.
Moving forward, the researchers will seek to extend their theory that several hormones could be affected by nightly sharp wave ripples.
The research was funded by National Institutes of Health. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rhythmic brain signals that help encode memories also appear to influence blood sugar levels and may regulate the timing of the release of hormones, early, pre-clinical research shows.
“Our study is the first to show how clusters of brain cell firing in the hippocampus may directly regulate metabolism,” senior author György Buzsáki, MD, PhD, professor, department of neuroscience and physiology, NYU Grossman School of Medicine and NYU Langone Health, said in a news release.
“Evidence suggests that the brain evolved, for reasons of efficiency, to use the same signals to achieve two very different functions in terms of memory and hormonal regulation,” added corresponding author David Tingley, PhD, a post-doctoral scholar in Dr. Buzsáki’s lab.
The study was published online August 11 in Nature.
It’s recently been discovered that populations of hippocampal neurons fire within milliseconds of each other in cycles. This firing pattern is called a “sharp wave ripple” for the shape it takes when captured graphically by electroencephalogram.
In their study, Dr. Buzsáki, Dr. Tingley, and colleagues observed that clusters of sharp wave ripples recorded from the hippocampus of rats were “reliably” and rapidly, followed by decreases in blood sugar concentrations in the animals.
“This correlation was not dependent on circadian, ultradian, or meal-triggered fluctuations; it could be mimicked with optogenetically induced ripples in the hippocampus, but not in the parietal cortex, and was attenuated to chance levels by pharmacogenetically suppressing activity of the lateral septum (LS), the major conduit between the hippocampus and hypothalamus,” the researchers report.
These observations suggest that hippocampal sharp wave ripples may regulate the timing of the release of hormones, possibly including insulin, by the pancreas and liver, as well as other hormones by the pituitary gland, the researchers note.
As sharp wave ripples mostly occur during non-rapid eye movement sleep, the impact of sleep disturbance on sharp wave ripples may provide a mechanistic link between poor sleep and high blood sugar levels seen in type 2 diabetes, they suggest.
“There are a couple of experimental studies showing that if you deprive a young healthy person from sleep [for 48 hours], their glucose tolerance resembles” that of a person with diabetes, Dr. Buzsáki noted in an interview.
Moving forward, the researchers will seek to extend their theory that several hormones could be affected by nightly sharp wave ripples.
The research was funded by National Institutes of Health. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rhythmic brain signals that help encode memories also appear to influence blood sugar levels and may regulate the timing of the release of hormones, early, pre-clinical research shows.
“Our study is the first to show how clusters of brain cell firing in the hippocampus may directly regulate metabolism,” senior author György Buzsáki, MD, PhD, professor, department of neuroscience and physiology, NYU Grossman School of Medicine and NYU Langone Health, said in a news release.
“Evidence suggests that the brain evolved, for reasons of efficiency, to use the same signals to achieve two very different functions in terms of memory and hormonal regulation,” added corresponding author David Tingley, PhD, a post-doctoral scholar in Dr. Buzsáki’s lab.
The study was published online August 11 in Nature.
It’s recently been discovered that populations of hippocampal neurons fire within milliseconds of each other in cycles. This firing pattern is called a “sharp wave ripple” for the shape it takes when captured graphically by electroencephalogram.
In their study, Dr. Buzsáki, Dr. Tingley, and colleagues observed that clusters of sharp wave ripples recorded from the hippocampus of rats were “reliably” and rapidly, followed by decreases in blood sugar concentrations in the animals.
“This correlation was not dependent on circadian, ultradian, or meal-triggered fluctuations; it could be mimicked with optogenetically induced ripples in the hippocampus, but not in the parietal cortex, and was attenuated to chance levels by pharmacogenetically suppressing activity of the lateral septum (LS), the major conduit between the hippocampus and hypothalamus,” the researchers report.
These observations suggest that hippocampal sharp wave ripples may regulate the timing of the release of hormones, possibly including insulin, by the pancreas and liver, as well as other hormones by the pituitary gland, the researchers note.
As sharp wave ripples mostly occur during non-rapid eye movement sleep, the impact of sleep disturbance on sharp wave ripples may provide a mechanistic link between poor sleep and high blood sugar levels seen in type 2 diabetes, they suggest.
“There are a couple of experimental studies showing that if you deprive a young healthy person from sleep [for 48 hours], their glucose tolerance resembles” that of a person with diabetes, Dr. Buzsáki noted in an interview.
Moving forward, the researchers will seek to extend their theory that several hormones could be affected by nightly sharp wave ripples.
The research was funded by National Institutes of Health. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Novel antidepressant shines in phase 2 trial, but FDA has issues with its NDA
Although a novel investigational drug that combines dextromethorphan and bupropion (AXS-05, Axsome Therapeutics) met its primary and key secondary endpoints in a phase 2 trial of patients with treatment-resistant depression (TRD), the U.S. Food and Drug Administration has voiced some concerns.
In the MERIT study, AXS-05 significantly delayed time to depression relapse compared with placebo (primary endpoint) – with no relapses observed for at least 6 months. It also significantly prevented depression relapse (secondary endpoint), the company said in a news release announcing the topline results.
The drug has been granted breakthrough therapy designations by the FDA for the treatment of major depressive disorder (MDD) and agitation associated with Alzheimer’s disease.
In addition,
However, Axsome stated that the FDA has identified “deficiencies that preclude labeling discussions at this time.”
The company is “attempting to learn the nature of these deficiencies with the goal of addressing them,” Herriot Tabuteau, MD, chief executive officer of Axsome, said in a statement.
However, Dr. Tabuteau acknowledged that this development “may lead to a delay in the potential approval of AXS-05.”
‘Well tolerated’
A total of 44 adults with TRD were enrolled into the MERIT study from the long-term, open-label phase 3 trial of AXS-05.
All patients were in stable remission after treatment with AXS-05 and were randomly assigned to continued treatment with AXS-05 (45 mg dextromethorphan/105 mg bupropion twice daily) or to switch to placebo.
Compared with placebo, AXS-05 significantly delayed time to depression relapse (P = .002) and prevented depression relapse (P = .004).
The novel drug was also well tolerated, with no treatment-emergent adverse events reported in more than one participant in the AXS-05 group, the company said.
One patient treated with AXS-05 did experience gout and bacteremia, but these incidents were deemed unrelated to the medication.
A version of this article first appeared on Medscape.com.
Although a novel investigational drug that combines dextromethorphan and bupropion (AXS-05, Axsome Therapeutics) met its primary and key secondary endpoints in a phase 2 trial of patients with treatment-resistant depression (TRD), the U.S. Food and Drug Administration has voiced some concerns.
In the MERIT study, AXS-05 significantly delayed time to depression relapse compared with placebo (primary endpoint) – with no relapses observed for at least 6 months. It also significantly prevented depression relapse (secondary endpoint), the company said in a news release announcing the topline results.
The drug has been granted breakthrough therapy designations by the FDA for the treatment of major depressive disorder (MDD) and agitation associated with Alzheimer’s disease.
In addition,
However, Axsome stated that the FDA has identified “deficiencies that preclude labeling discussions at this time.”
The company is “attempting to learn the nature of these deficiencies with the goal of addressing them,” Herriot Tabuteau, MD, chief executive officer of Axsome, said in a statement.
However, Dr. Tabuteau acknowledged that this development “may lead to a delay in the potential approval of AXS-05.”
‘Well tolerated’
A total of 44 adults with TRD were enrolled into the MERIT study from the long-term, open-label phase 3 trial of AXS-05.
All patients were in stable remission after treatment with AXS-05 and were randomly assigned to continued treatment with AXS-05 (45 mg dextromethorphan/105 mg bupropion twice daily) or to switch to placebo.
Compared with placebo, AXS-05 significantly delayed time to depression relapse (P = .002) and prevented depression relapse (P = .004).
The novel drug was also well tolerated, with no treatment-emergent adverse events reported in more than one participant in the AXS-05 group, the company said.
One patient treated with AXS-05 did experience gout and bacteremia, but these incidents were deemed unrelated to the medication.
A version of this article first appeared on Medscape.com.
Although a novel investigational drug that combines dextromethorphan and bupropion (AXS-05, Axsome Therapeutics) met its primary and key secondary endpoints in a phase 2 trial of patients with treatment-resistant depression (TRD), the U.S. Food and Drug Administration has voiced some concerns.
In the MERIT study, AXS-05 significantly delayed time to depression relapse compared with placebo (primary endpoint) – with no relapses observed for at least 6 months. It also significantly prevented depression relapse (secondary endpoint), the company said in a news release announcing the topline results.
The drug has been granted breakthrough therapy designations by the FDA for the treatment of major depressive disorder (MDD) and agitation associated with Alzheimer’s disease.
In addition,
However, Axsome stated that the FDA has identified “deficiencies that preclude labeling discussions at this time.”
The company is “attempting to learn the nature of these deficiencies with the goal of addressing them,” Herriot Tabuteau, MD, chief executive officer of Axsome, said in a statement.
However, Dr. Tabuteau acknowledged that this development “may lead to a delay in the potential approval of AXS-05.”
‘Well tolerated’
A total of 44 adults with TRD were enrolled into the MERIT study from the long-term, open-label phase 3 trial of AXS-05.
All patients were in stable remission after treatment with AXS-05 and were randomly assigned to continued treatment with AXS-05 (45 mg dextromethorphan/105 mg bupropion twice daily) or to switch to placebo.
Compared with placebo, AXS-05 significantly delayed time to depression relapse (P = .002) and prevented depression relapse (P = .004).
The novel drug was also well tolerated, with no treatment-emergent adverse events reported in more than one participant in the AXS-05 group, the company said.
One patient treated with AXS-05 did experience gout and bacteremia, but these incidents were deemed unrelated to the medication.
A version of this article first appeared on Medscape.com.
Flavonoids dietary ‘powerhouses’ for cognitive decline prevention
, new research shows.
Among the different types of flavonoids, flavones (found in some spices and yellow or orange fruits and vegetables) and anthocyanins (found in blueberries, blackberries, and cherries) seem to have most protective effect, the researchers report.
“There is mounting evidence suggesting flavonoids are powerhouses when it comes to preventing your thinking skills from declining as you get older,” study investigator Walter Willett, MD, DrPH, Harvard University, Boston, said in a statement.
“Our results are exciting because they show that making simple changes to your diet could help prevent cognitive decline,” said Dr. Willett.
The study was published online July 28 in the journal Neurology.
Antioxidant punch
Flavonoids, naturally occurring phytochemicals found in plants, are strong antioxidants. Considering the likely role of oxidative stress in age-related cognitive decline, flavonoids have been proposed as a potentially important preventive.
For the study, Dr. Willett and colleagues prospectively examined associations between long-term dietary flavonoids (flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, polymeric flavonoids, and proanthocyanidins) and subjective cognitive decline in 49,493 women from the Nurses’ Health Study (1984-2006) and 27,842 men from the Health Professionals Follow-up Study (1986-2002).
Those in the highest quintile of flavonoid consumption consumed about 600 mg daily on average while those in the lowest quintile got only about 150 mg daily.
After adjusting for age, total energy intake, major nondietary factors, and specific dietary factors, a higher intake of total flavonoids was associated with lower likelihood of self-reported subjective cognitive decline during follow up.
Individuals in the highest quintile of daily consumption had about a 20% lower risk of subjective cognitive decline relative to peers in the lowest quintile (pooled multivariable-adjusted odds ratio: 0.81; 95% confidence interval, 0.76-0.89).
The strongest protective associations were found for flavones (OR, 0.62; 95% confidence interval, 0.57-0.68), flavanones (OR, 0.64; 95% CI, 0.58-0.68), and anthocyanins (OR, 0.76; 95% CI, 0.72-0.84) (P trend < .0001 for all groups).
“The people in our study who did the best over time ate an average of at least half a serving per day of foods like orange juice, oranges, peppers, celery, grapefruits, grapefruit juice, apples, and pears,” Dr. Willett said.
“While it is possible other phytochemicals are at work here, a colorful diet rich in flavonoids – and specifically flavones and anthocyanins – seems to be a good bet for promoting long-term brain health,” he added.
A limitation of the study is that participants reported on their diets and may not recall perfectly what they ate or how much.
Healthy diet best bet for brain health
Reached for comment, Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association, said this study “adds to our understanding of which elements of a healthy diet may be important in reducing dementia risk; flavonols may be one of those elements.”
“However, at this point, people should not put too much stock in specific nutrients – including subsets of flavonols – for reducing dementia risk until more research is done. Rather, they should focus on eating an overall healthy diet,” he said.
“It would be wonderful if a particular food or supplement could delay or prevent Alzheimer’s disease, but we do not have scientific evidence to support such claims. Randomized controlled clinical trials are necessary to evaluate whether any food or supplement has a scientifically proven beneficial effect,” Dr. Weber added.
For now, the Alzheimer’s Association “encourages everyone to eat a healthy and balanced diet as a way to help reduce the risk of cognitive decline,” Dr. Weber said.
“With more than 6 million Americans living with Alzheimer’s disease and other dementia today, there is a pressing need to test the effectiveness of a healthy lifestyle regimen to reduce risk of cognitive decline in a large and diverse population,” he added.
The Alzheimer’s Association has launched a 2-year clinical trial, called the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), to do just that.
“While we research that definitive lifestyle ‘recipe,’ there are things we can do today that may decrease our risk of cognitive decline as we age. Eating a heart-healthy diet, exercising regularly, and staying cognitively engaged are just a few,” Dr. Weber added.
Also weighing in, Taylor Wallace, PhD, adjunct professor, department of nutrition and food studies, George Mason University, Fairfax, Va., said the study results are not surprising.
“Scientific data on the ability of flavonoids to prevent age-related chronic diseases, including cognitive decline, has accumulated immensely over the last decade. This epidemiological study reinforces findings from smaller shorter-duration clinical trials and mechanistic studies,” said Dr. Wallace, who was not involved in the study.
“Flavonoids show great potential in reducing inflammation and oxidative stress in the body. They are also vasodilators that help improve blood flow, which is important for the cardiovascular and cerebrovascular systems,” he noted.
“Typically, foods rich in flavonoids are also nutrient-dense in vitamins, minerals, and dietary fiber (eg, fruits and vegetables). Anthocyanins in blueberries have long been known to prevent cognitive decline with age,” Dr. Wallace said.
Dr. Wallace was part of a 14-member panel of nutrition scientists who recently reviewed available evidence around fruit and vegetable intake and health.
“Our findings are consistent with this study in regard to cognitive decline and other disease states. Cruciferous vegetables, dark-green leafy vegetables, citrus fruits, and dark-colored berries seem to have superior effects on health promotion and disease prevention in general,” said Dr. Wallace.
This work was supported by grants from the National Institutes of Health. The authors have disclosed no relevant financial relationships. Dr. Weber has no relevant disclosures. Dr. Wallace is principal and chief executive officer of the Think Healthy Group; editor of the Journal of Dietary Supplements; and deputy editor-in-chief of the Journal of the American College of Nutrition.
A version of this article first appeared on Medscape.com.
, new research shows.
Among the different types of flavonoids, flavones (found in some spices and yellow or orange fruits and vegetables) and anthocyanins (found in blueberries, blackberries, and cherries) seem to have most protective effect, the researchers report.
“There is mounting evidence suggesting flavonoids are powerhouses when it comes to preventing your thinking skills from declining as you get older,” study investigator Walter Willett, MD, DrPH, Harvard University, Boston, said in a statement.
“Our results are exciting because they show that making simple changes to your diet could help prevent cognitive decline,” said Dr. Willett.
The study was published online July 28 in the journal Neurology.
Antioxidant punch
Flavonoids, naturally occurring phytochemicals found in plants, are strong antioxidants. Considering the likely role of oxidative stress in age-related cognitive decline, flavonoids have been proposed as a potentially important preventive.
For the study, Dr. Willett and colleagues prospectively examined associations between long-term dietary flavonoids (flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, polymeric flavonoids, and proanthocyanidins) and subjective cognitive decline in 49,493 women from the Nurses’ Health Study (1984-2006) and 27,842 men from the Health Professionals Follow-up Study (1986-2002).
Those in the highest quintile of flavonoid consumption consumed about 600 mg daily on average while those in the lowest quintile got only about 150 mg daily.
After adjusting for age, total energy intake, major nondietary factors, and specific dietary factors, a higher intake of total flavonoids was associated with lower likelihood of self-reported subjective cognitive decline during follow up.
Individuals in the highest quintile of daily consumption had about a 20% lower risk of subjective cognitive decline relative to peers in the lowest quintile (pooled multivariable-adjusted odds ratio: 0.81; 95% confidence interval, 0.76-0.89).
The strongest protective associations were found for flavones (OR, 0.62; 95% confidence interval, 0.57-0.68), flavanones (OR, 0.64; 95% CI, 0.58-0.68), and anthocyanins (OR, 0.76; 95% CI, 0.72-0.84) (P trend < .0001 for all groups).
“The people in our study who did the best over time ate an average of at least half a serving per day of foods like orange juice, oranges, peppers, celery, grapefruits, grapefruit juice, apples, and pears,” Dr. Willett said.
“While it is possible other phytochemicals are at work here, a colorful diet rich in flavonoids – and specifically flavones and anthocyanins – seems to be a good bet for promoting long-term brain health,” he added.
A limitation of the study is that participants reported on their diets and may not recall perfectly what they ate or how much.
Healthy diet best bet for brain health
Reached for comment, Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association, said this study “adds to our understanding of which elements of a healthy diet may be important in reducing dementia risk; flavonols may be one of those elements.”
“However, at this point, people should not put too much stock in specific nutrients – including subsets of flavonols – for reducing dementia risk until more research is done. Rather, they should focus on eating an overall healthy diet,” he said.
“It would be wonderful if a particular food or supplement could delay or prevent Alzheimer’s disease, but we do not have scientific evidence to support such claims. Randomized controlled clinical trials are necessary to evaluate whether any food or supplement has a scientifically proven beneficial effect,” Dr. Weber added.
For now, the Alzheimer’s Association “encourages everyone to eat a healthy and balanced diet as a way to help reduce the risk of cognitive decline,” Dr. Weber said.
“With more than 6 million Americans living with Alzheimer’s disease and other dementia today, there is a pressing need to test the effectiveness of a healthy lifestyle regimen to reduce risk of cognitive decline in a large and diverse population,” he added.
The Alzheimer’s Association has launched a 2-year clinical trial, called the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), to do just that.
“While we research that definitive lifestyle ‘recipe,’ there are things we can do today that may decrease our risk of cognitive decline as we age. Eating a heart-healthy diet, exercising regularly, and staying cognitively engaged are just a few,” Dr. Weber added.
Also weighing in, Taylor Wallace, PhD, adjunct professor, department of nutrition and food studies, George Mason University, Fairfax, Va., said the study results are not surprising.
“Scientific data on the ability of flavonoids to prevent age-related chronic diseases, including cognitive decline, has accumulated immensely over the last decade. This epidemiological study reinforces findings from smaller shorter-duration clinical trials and mechanistic studies,” said Dr. Wallace, who was not involved in the study.
“Flavonoids show great potential in reducing inflammation and oxidative stress in the body. They are also vasodilators that help improve blood flow, which is important for the cardiovascular and cerebrovascular systems,” he noted.
“Typically, foods rich in flavonoids are also nutrient-dense in vitamins, minerals, and dietary fiber (eg, fruits and vegetables). Anthocyanins in blueberries have long been known to prevent cognitive decline with age,” Dr. Wallace said.
Dr. Wallace was part of a 14-member panel of nutrition scientists who recently reviewed available evidence around fruit and vegetable intake and health.
“Our findings are consistent with this study in regard to cognitive decline and other disease states. Cruciferous vegetables, dark-green leafy vegetables, citrus fruits, and dark-colored berries seem to have superior effects on health promotion and disease prevention in general,” said Dr. Wallace.
This work was supported by grants from the National Institutes of Health. The authors have disclosed no relevant financial relationships. Dr. Weber has no relevant disclosures. Dr. Wallace is principal and chief executive officer of the Think Healthy Group; editor of the Journal of Dietary Supplements; and deputy editor-in-chief of the Journal of the American College of Nutrition.
A version of this article first appeared on Medscape.com.
, new research shows.
Among the different types of flavonoids, flavones (found in some spices and yellow or orange fruits and vegetables) and anthocyanins (found in blueberries, blackberries, and cherries) seem to have most protective effect, the researchers report.
“There is mounting evidence suggesting flavonoids are powerhouses when it comes to preventing your thinking skills from declining as you get older,” study investigator Walter Willett, MD, DrPH, Harvard University, Boston, said in a statement.
“Our results are exciting because they show that making simple changes to your diet could help prevent cognitive decline,” said Dr. Willett.
The study was published online July 28 in the journal Neurology.
Antioxidant punch
Flavonoids, naturally occurring phytochemicals found in plants, are strong antioxidants. Considering the likely role of oxidative stress in age-related cognitive decline, flavonoids have been proposed as a potentially important preventive.
For the study, Dr. Willett and colleagues prospectively examined associations between long-term dietary flavonoids (flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, polymeric flavonoids, and proanthocyanidins) and subjective cognitive decline in 49,493 women from the Nurses’ Health Study (1984-2006) and 27,842 men from the Health Professionals Follow-up Study (1986-2002).
Those in the highest quintile of flavonoid consumption consumed about 600 mg daily on average while those in the lowest quintile got only about 150 mg daily.
After adjusting for age, total energy intake, major nondietary factors, and specific dietary factors, a higher intake of total flavonoids was associated with lower likelihood of self-reported subjective cognitive decline during follow up.
Individuals in the highest quintile of daily consumption had about a 20% lower risk of subjective cognitive decline relative to peers in the lowest quintile (pooled multivariable-adjusted odds ratio: 0.81; 95% confidence interval, 0.76-0.89).
The strongest protective associations were found for flavones (OR, 0.62; 95% confidence interval, 0.57-0.68), flavanones (OR, 0.64; 95% CI, 0.58-0.68), and anthocyanins (OR, 0.76; 95% CI, 0.72-0.84) (P trend < .0001 for all groups).
“The people in our study who did the best over time ate an average of at least half a serving per day of foods like orange juice, oranges, peppers, celery, grapefruits, grapefruit juice, apples, and pears,” Dr. Willett said.
“While it is possible other phytochemicals are at work here, a colorful diet rich in flavonoids – and specifically flavones and anthocyanins – seems to be a good bet for promoting long-term brain health,” he added.
A limitation of the study is that participants reported on their diets and may not recall perfectly what they ate or how much.
Healthy diet best bet for brain health
Reached for comment, Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association, said this study “adds to our understanding of which elements of a healthy diet may be important in reducing dementia risk; flavonols may be one of those elements.”
“However, at this point, people should not put too much stock in specific nutrients – including subsets of flavonols – for reducing dementia risk until more research is done. Rather, they should focus on eating an overall healthy diet,” he said.
“It would be wonderful if a particular food or supplement could delay or prevent Alzheimer’s disease, but we do not have scientific evidence to support such claims. Randomized controlled clinical trials are necessary to evaluate whether any food or supplement has a scientifically proven beneficial effect,” Dr. Weber added.
For now, the Alzheimer’s Association “encourages everyone to eat a healthy and balanced diet as a way to help reduce the risk of cognitive decline,” Dr. Weber said.
“With more than 6 million Americans living with Alzheimer’s disease and other dementia today, there is a pressing need to test the effectiveness of a healthy lifestyle regimen to reduce risk of cognitive decline in a large and diverse population,” he added.
The Alzheimer’s Association has launched a 2-year clinical trial, called the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), to do just that.
“While we research that definitive lifestyle ‘recipe,’ there are things we can do today that may decrease our risk of cognitive decline as we age. Eating a heart-healthy diet, exercising regularly, and staying cognitively engaged are just a few,” Dr. Weber added.
Also weighing in, Taylor Wallace, PhD, adjunct professor, department of nutrition and food studies, George Mason University, Fairfax, Va., said the study results are not surprising.
“Scientific data on the ability of flavonoids to prevent age-related chronic diseases, including cognitive decline, has accumulated immensely over the last decade. This epidemiological study reinforces findings from smaller shorter-duration clinical trials and mechanistic studies,” said Dr. Wallace, who was not involved in the study.
“Flavonoids show great potential in reducing inflammation and oxidative stress in the body. They are also vasodilators that help improve blood flow, which is important for the cardiovascular and cerebrovascular systems,” he noted.
“Typically, foods rich in flavonoids are also nutrient-dense in vitamins, minerals, and dietary fiber (eg, fruits and vegetables). Anthocyanins in blueberries have long been known to prevent cognitive decline with age,” Dr. Wallace said.
Dr. Wallace was part of a 14-member panel of nutrition scientists who recently reviewed available evidence around fruit and vegetable intake and health.
“Our findings are consistent with this study in regard to cognitive decline and other disease states. Cruciferous vegetables, dark-green leafy vegetables, citrus fruits, and dark-colored berries seem to have superior effects on health promotion and disease prevention in general,” said Dr. Wallace.
This work was supported by grants from the National Institutes of Health. The authors have disclosed no relevant financial relationships. Dr. Weber has no relevant disclosures. Dr. Wallace is principal and chief executive officer of the Think Healthy Group; editor of the Journal of Dietary Supplements; and deputy editor-in-chief of the Journal of the American College of Nutrition.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
COVID-19 tied to acceleration of Alzheimer’s disease pathology
, a new study shows.
These results suggest that COVID-19 may accelerate Alzheimer’s disease symptoms and pathology, said study investigator Thomas Wisniewski, MD, professor of neurology, pathology, and psychiatry at New York University.
The findings were presented here at the Alzheimer’s Association International Conference (AAIC) 2021.
Strong correlation
There’s a clear association between SARS-CoV-2 infection and Alzheimer’s disease-related dementia. Patients with Alzheimer’s disease are at threefold higher risk for the infection and have a twofold higher risk for death, Dr. Wisniewski told meeting delegates.
He and his colleagues conducted a prospective study of patients who had tested positive for SARS-CoV-2 and who experienced neurologic sequelae and SARS-CoV-2 patients who were without neurologic sequelae. All patients were hospitalized from March 10 to May 20, 2020. This was during a period when New York City was overwhelmed by COVID: About 35% of hospitalized patients had COVID.
Of those who experienced neurologic events, the most common “by far and away” (51%) was toxic metabolic encephalopathy (TME), said Dr. Wisniewski. Other associations included seizures, hypoxic/anoxic injury, and ischemic stroke.
The most common TMEs were septic and hypoxic ischemia. In most patients (78%), TME had more than one cause.
Researchers followed 196 patients with COVID and neurologic complications (case patients) and 186 matched control patients who had no neurologic complications over a period of 6 months.
“Unfortunately, both groups had poor outcomes,” said Dr. Wisniewski. About 50% had impaired cognition, and 56% experienced limitations in activities of daily living.
However, those patients with COVID-19 who had neurologic sequelae “fared even worse,” said Dr. Wisniewski. Compared with control patients, they had twofold worse Modified Rankin Scale scores and worse scores on activity of daily living, and they were much less likely to return to work.
Mechanisms by which COVID-19 affects longer-term cognitive dysfunction are unclear, but inflammation likely plays a role.
The research team compared a number of Alzheimer’s disease plasma biomarkers in 158 patients with COVID-19 who had neurologic symptoms and 152 COVID patients with COVID but no neurologic symptoms. They found marked elevations of neurofilament light, a marker of neuronal injury, in those with symptoms (P = .0003) as well as increased glial fibrillary acid protein, a marker of neuroinflammation (P = .0098).
Ubiquitin carboxyl-terminal hydrolase L1, another marker of neuronal injury, was also elevated in those with neurologic symptoms. Regarding Alzheimer’s disease pathology, total tau (t-tau) and phosphorylated tau “also tracked with neurological sequelae,” said Dr. Wisniewski.
There was no difference in levels of amyloid beta 40 (A beta 40) between groups. However, A beta 42 plasma levels were significantly lower in those with neurologic effects, suggesting higher levels in the brain. In addition, the ratio of t-tau to A beta 42 “clearly differentiated the two groups,” he said.
“Serum biomarkers of neuroinflammation and neuronal injury and Alzheimer’s disease correlate strongly, perhaps suggesting that folks with COVID infection and neurological sequelae may have an acceleration of Alzheimer’s disease symptoms and pathology,” he said. “That’s something that needs longer follow-up.”
Important differentiation
Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said the study provides important information. The inclusion of plasma biomarkers in this research is “really critical to tease out what’s the impact of COVID itself on the brain,” said Dr. Edelmayer.
“We’re in an era of biomarkers when it comes to Alzheimer’s disease and other dementias, and being able to define those changes that are happening in the brain over time is going to be really critical and aid in early detection and accurate diagnoses,” she said.
What is still to be learned is what these biomarkers reveal long term, said Dr. Edelmayer. “Do those biological markers change? Do they go back to normal? A lot of that is still unknown,” she said.
She noted that many diseases that are linked to inflammation produce similar biomarkers in the brain – for example, neurofilament light.
With other viral infections, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), similar associations between the infection and cognition have been reported, said Dr. Edelmayer.
“But there are still a lot of questions around cause and effect. Is it really a direct effect of the virus on the brain itself? Is it an effect of having an enormous amount of inflammation going on in the body? A lot of that still needs to be teased out,” she commented.
The study was supported by the National Institutes of Health, the Alzheimer’s Association, and the State of New York. Dr. Wisniewski has consulted for Grifols, Amylon Pharmaceuticals, and Alzamed Neuro; 30 NYU patents are related to AD therapeutics.
A version of this article first appeared on Medscape.com.
, a new study shows.
These results suggest that COVID-19 may accelerate Alzheimer’s disease symptoms and pathology, said study investigator Thomas Wisniewski, MD, professor of neurology, pathology, and psychiatry at New York University.
The findings were presented here at the Alzheimer’s Association International Conference (AAIC) 2021.
Strong correlation
There’s a clear association between SARS-CoV-2 infection and Alzheimer’s disease-related dementia. Patients with Alzheimer’s disease are at threefold higher risk for the infection and have a twofold higher risk for death, Dr. Wisniewski told meeting delegates.
He and his colleagues conducted a prospective study of patients who had tested positive for SARS-CoV-2 and who experienced neurologic sequelae and SARS-CoV-2 patients who were without neurologic sequelae. All patients were hospitalized from March 10 to May 20, 2020. This was during a period when New York City was overwhelmed by COVID: About 35% of hospitalized patients had COVID.
Of those who experienced neurologic events, the most common “by far and away” (51%) was toxic metabolic encephalopathy (TME), said Dr. Wisniewski. Other associations included seizures, hypoxic/anoxic injury, and ischemic stroke.
The most common TMEs were septic and hypoxic ischemia. In most patients (78%), TME had more than one cause.
Researchers followed 196 patients with COVID and neurologic complications (case patients) and 186 matched control patients who had no neurologic complications over a period of 6 months.
“Unfortunately, both groups had poor outcomes,” said Dr. Wisniewski. About 50% had impaired cognition, and 56% experienced limitations in activities of daily living.
However, those patients with COVID-19 who had neurologic sequelae “fared even worse,” said Dr. Wisniewski. Compared with control patients, they had twofold worse Modified Rankin Scale scores and worse scores on activity of daily living, and they were much less likely to return to work.
Mechanisms by which COVID-19 affects longer-term cognitive dysfunction are unclear, but inflammation likely plays a role.
The research team compared a number of Alzheimer’s disease plasma biomarkers in 158 patients with COVID-19 who had neurologic symptoms and 152 COVID patients with COVID but no neurologic symptoms. They found marked elevations of neurofilament light, a marker of neuronal injury, in those with symptoms (P = .0003) as well as increased glial fibrillary acid protein, a marker of neuroinflammation (P = .0098).
Ubiquitin carboxyl-terminal hydrolase L1, another marker of neuronal injury, was also elevated in those with neurologic symptoms. Regarding Alzheimer’s disease pathology, total tau (t-tau) and phosphorylated tau “also tracked with neurological sequelae,” said Dr. Wisniewski.
There was no difference in levels of amyloid beta 40 (A beta 40) between groups. However, A beta 42 plasma levels were significantly lower in those with neurologic effects, suggesting higher levels in the brain. In addition, the ratio of t-tau to A beta 42 “clearly differentiated the two groups,” he said.
“Serum biomarkers of neuroinflammation and neuronal injury and Alzheimer’s disease correlate strongly, perhaps suggesting that folks with COVID infection and neurological sequelae may have an acceleration of Alzheimer’s disease symptoms and pathology,” he said. “That’s something that needs longer follow-up.”
Important differentiation
Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said the study provides important information. The inclusion of plasma biomarkers in this research is “really critical to tease out what’s the impact of COVID itself on the brain,” said Dr. Edelmayer.
“We’re in an era of biomarkers when it comes to Alzheimer’s disease and other dementias, and being able to define those changes that are happening in the brain over time is going to be really critical and aid in early detection and accurate diagnoses,” she said.
What is still to be learned is what these biomarkers reveal long term, said Dr. Edelmayer. “Do those biological markers change? Do they go back to normal? A lot of that is still unknown,” she said.
She noted that many diseases that are linked to inflammation produce similar biomarkers in the brain – for example, neurofilament light.
With other viral infections, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), similar associations between the infection and cognition have been reported, said Dr. Edelmayer.
“But there are still a lot of questions around cause and effect. Is it really a direct effect of the virus on the brain itself? Is it an effect of having an enormous amount of inflammation going on in the body? A lot of that still needs to be teased out,” she commented.
The study was supported by the National Institutes of Health, the Alzheimer’s Association, and the State of New York. Dr. Wisniewski has consulted for Grifols, Amylon Pharmaceuticals, and Alzamed Neuro; 30 NYU patents are related to AD therapeutics.
A version of this article first appeared on Medscape.com.
, a new study shows.
These results suggest that COVID-19 may accelerate Alzheimer’s disease symptoms and pathology, said study investigator Thomas Wisniewski, MD, professor of neurology, pathology, and psychiatry at New York University.
The findings were presented here at the Alzheimer’s Association International Conference (AAIC) 2021.
Strong correlation
There’s a clear association between SARS-CoV-2 infection and Alzheimer’s disease-related dementia. Patients with Alzheimer’s disease are at threefold higher risk for the infection and have a twofold higher risk for death, Dr. Wisniewski told meeting delegates.
He and his colleagues conducted a prospective study of patients who had tested positive for SARS-CoV-2 and who experienced neurologic sequelae and SARS-CoV-2 patients who were without neurologic sequelae. All patients were hospitalized from March 10 to May 20, 2020. This was during a period when New York City was overwhelmed by COVID: About 35% of hospitalized patients had COVID.
Of those who experienced neurologic events, the most common “by far and away” (51%) was toxic metabolic encephalopathy (TME), said Dr. Wisniewski. Other associations included seizures, hypoxic/anoxic injury, and ischemic stroke.
The most common TMEs were septic and hypoxic ischemia. In most patients (78%), TME had more than one cause.
Researchers followed 196 patients with COVID and neurologic complications (case patients) and 186 matched control patients who had no neurologic complications over a period of 6 months.
“Unfortunately, both groups had poor outcomes,” said Dr. Wisniewski. About 50% had impaired cognition, and 56% experienced limitations in activities of daily living.
However, those patients with COVID-19 who had neurologic sequelae “fared even worse,” said Dr. Wisniewski. Compared with control patients, they had twofold worse Modified Rankin Scale scores and worse scores on activity of daily living, and they were much less likely to return to work.
Mechanisms by which COVID-19 affects longer-term cognitive dysfunction are unclear, but inflammation likely plays a role.
The research team compared a number of Alzheimer’s disease plasma biomarkers in 158 patients with COVID-19 who had neurologic symptoms and 152 COVID patients with COVID but no neurologic symptoms. They found marked elevations of neurofilament light, a marker of neuronal injury, in those with symptoms (P = .0003) as well as increased glial fibrillary acid protein, a marker of neuroinflammation (P = .0098).
Ubiquitin carboxyl-terminal hydrolase L1, another marker of neuronal injury, was also elevated in those with neurologic symptoms. Regarding Alzheimer’s disease pathology, total tau (t-tau) and phosphorylated tau “also tracked with neurological sequelae,” said Dr. Wisniewski.
There was no difference in levels of amyloid beta 40 (A beta 40) between groups. However, A beta 42 plasma levels were significantly lower in those with neurologic effects, suggesting higher levels in the brain. In addition, the ratio of t-tau to A beta 42 “clearly differentiated the two groups,” he said.
“Serum biomarkers of neuroinflammation and neuronal injury and Alzheimer’s disease correlate strongly, perhaps suggesting that folks with COVID infection and neurological sequelae may have an acceleration of Alzheimer’s disease symptoms and pathology,” he said. “That’s something that needs longer follow-up.”
Important differentiation
Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said the study provides important information. The inclusion of plasma biomarkers in this research is “really critical to tease out what’s the impact of COVID itself on the brain,” said Dr. Edelmayer.
“We’re in an era of biomarkers when it comes to Alzheimer’s disease and other dementias, and being able to define those changes that are happening in the brain over time is going to be really critical and aid in early detection and accurate diagnoses,” she said.
What is still to be learned is what these biomarkers reveal long term, said Dr. Edelmayer. “Do those biological markers change? Do they go back to normal? A lot of that is still unknown,” she said.
She noted that many diseases that are linked to inflammation produce similar biomarkers in the brain – for example, neurofilament light.
With other viral infections, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), similar associations between the infection and cognition have been reported, said Dr. Edelmayer.
“But there are still a lot of questions around cause and effect. Is it really a direct effect of the virus on the brain itself? Is it an effect of having an enormous amount of inflammation going on in the body? A lot of that still needs to be teased out,” she commented.
The study was supported by the National Institutes of Health, the Alzheimer’s Association, and the State of New York. Dr. Wisniewski has consulted for Grifols, Amylon Pharmaceuticals, and Alzamed Neuro; 30 NYU patents are related to AD therapeutics.
A version of this article first appeared on Medscape.com.
From AAIC 2021
‘Alarming’ data on early cognitive decline in transgender adults
, new research shows.
Investigators found transgender adults – individuals who identify with a gender different than the one assigned to them at birth – were nearly twice as likely to report subjective cognitive decline and more than twice as likely to report SCD-related functional limitations – such as reduced ability to work, volunteer, or be social – than cisgender adults.
“Trans populations are disproportionately impacted by health disparities and also risk factors for dementia. Putting these pieces together, I wasn’t surprised by their greater risk of cognitive decline,” said study investigator Ethan Cicero, PhD, RN, an assistant professor at Emory University, Atlanta.
The findings were presented at the 2021 Alzheimer’s Association International Conference.
‘Alarming’ finding
SCD is a self-reported experience of worsening memory or thinking and is one of the first clinical manifestations of Alzheimer’s disease and related dementia (ADRD). Yet there is limited research into cognitive impairment among transgender adults.
The researchers examined SCD and associated functional limitations among transgender and cisgender adults older than age 45 years who provided health and health behavior data as part of the Behavioral Risk Factor Surveillance System (BRFSS) surveys (2015-2019).
The sample included 386,529 adults of whom 1,302 identified as transgender and 385,227 as cisgender.
Roughly 17% of transgender adults reported SCD, which is significantly higher than the 10.6% rate for cisgender adults (P < .001).
Compared with cisgender adults reporting SCD, transgender adults reporting SCD were younger (mean age 61.9 vs. 65.2 years, P = .0005), more likely to be in a racial/ethnic minority group (37.3% vs. 19.5%, P < .0001), have a high school degree or less (59.6% vs. 43.4%, P = .0003), be uninsured (17% vs. 5.5%, P = .0007) and have a depressive disorder (58.8% vs. 45.7%, P = .0028).
The fact that transgender people who reported SCD were about 3 years younger than cisgender people who reported SCD is “somewhat alarming and a red flag to ask middle-aged trans adults about their brain health and not just older or elderly trans adults,” said Dr. Cicero.
The study also showed that transgender adults reporting SCD were 2.3 times more likely to report related social and self-care limitations when compared with cisgender adults reporting SCD.
The findings align with a study reported at AAIC 2019, which showed that sexual or gender minorities (SGM) are almost 30% more likely to report subjective cognitive decline compared with the non-SGM population.
Cause unclear
“We are not certain what may be causing the elevated subjective cognitive decline rates among transgender adults. We postulate that it may be in part due to anti-transgender stigma and prejudice that expose transgender people to high rates of mistreatment and discrimination where they live, work, learn, seek health care, and age,” Dr. Cicero said.
“More research is needed to identify and target preventive intervention strategies, develop culturally relevant screenings, and shape policies to improve the health and well-being of the transgender population,” he added.
Weighing in on the study, Rebecca Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said “researchers have only just started to explore the experiences of dementia within the lesbian, gay, and bisexual community, but this is the first time we are seeing some specific research that’s looking at cognition in transgender individuals and gender nonbinary individuals.”
“We don’t know exactly why transgender and gender nonbinary individuals experience greater rates of subjective cognitive decline, but we do know that they have greater rates of health disparities that are considered risk factors for dementia, including higher rates of cardiovascular disease, depression, diabetes, tobacco and alcohol use, and obesity,” Dr. Edelmayer said.
“Alzheimer’s and dementia do not discriminate. Neither can we,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a statement.
“The Alzheimer’s Association advocates for more research to better understand the cognitive and emotional needs of transgender and nonbinary individuals so that our nation’s health care providers can offer them culturally sensitive care,” said Dr. Carrillo.
The study had no specific funding. Dr. Cicero, Dr. Carrillo, and Dr. Edelmayer have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
Investigators found transgender adults – individuals who identify with a gender different than the one assigned to them at birth – were nearly twice as likely to report subjective cognitive decline and more than twice as likely to report SCD-related functional limitations – such as reduced ability to work, volunteer, or be social – than cisgender adults.
“Trans populations are disproportionately impacted by health disparities and also risk factors for dementia. Putting these pieces together, I wasn’t surprised by their greater risk of cognitive decline,” said study investigator Ethan Cicero, PhD, RN, an assistant professor at Emory University, Atlanta.
The findings were presented at the 2021 Alzheimer’s Association International Conference.
‘Alarming’ finding
SCD is a self-reported experience of worsening memory or thinking and is one of the first clinical manifestations of Alzheimer’s disease and related dementia (ADRD). Yet there is limited research into cognitive impairment among transgender adults.
The researchers examined SCD and associated functional limitations among transgender and cisgender adults older than age 45 years who provided health and health behavior data as part of the Behavioral Risk Factor Surveillance System (BRFSS) surveys (2015-2019).
The sample included 386,529 adults of whom 1,302 identified as transgender and 385,227 as cisgender.
Roughly 17% of transgender adults reported SCD, which is significantly higher than the 10.6% rate for cisgender adults (P < .001).
Compared with cisgender adults reporting SCD, transgender adults reporting SCD were younger (mean age 61.9 vs. 65.2 years, P = .0005), more likely to be in a racial/ethnic minority group (37.3% vs. 19.5%, P < .0001), have a high school degree or less (59.6% vs. 43.4%, P = .0003), be uninsured (17% vs. 5.5%, P = .0007) and have a depressive disorder (58.8% vs. 45.7%, P = .0028).
The fact that transgender people who reported SCD were about 3 years younger than cisgender people who reported SCD is “somewhat alarming and a red flag to ask middle-aged trans adults about their brain health and not just older or elderly trans adults,” said Dr. Cicero.
The study also showed that transgender adults reporting SCD were 2.3 times more likely to report related social and self-care limitations when compared with cisgender adults reporting SCD.
The findings align with a study reported at AAIC 2019, which showed that sexual or gender minorities (SGM) are almost 30% more likely to report subjective cognitive decline compared with the non-SGM population.
Cause unclear
“We are not certain what may be causing the elevated subjective cognitive decline rates among transgender adults. We postulate that it may be in part due to anti-transgender stigma and prejudice that expose transgender people to high rates of mistreatment and discrimination where they live, work, learn, seek health care, and age,” Dr. Cicero said.
“More research is needed to identify and target preventive intervention strategies, develop culturally relevant screenings, and shape policies to improve the health and well-being of the transgender population,” he added.
Weighing in on the study, Rebecca Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said “researchers have only just started to explore the experiences of dementia within the lesbian, gay, and bisexual community, but this is the first time we are seeing some specific research that’s looking at cognition in transgender individuals and gender nonbinary individuals.”
“We don’t know exactly why transgender and gender nonbinary individuals experience greater rates of subjective cognitive decline, but we do know that they have greater rates of health disparities that are considered risk factors for dementia, including higher rates of cardiovascular disease, depression, diabetes, tobacco and alcohol use, and obesity,” Dr. Edelmayer said.
“Alzheimer’s and dementia do not discriminate. Neither can we,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a statement.
“The Alzheimer’s Association advocates for more research to better understand the cognitive and emotional needs of transgender and nonbinary individuals so that our nation’s health care providers can offer them culturally sensitive care,” said Dr. Carrillo.
The study had no specific funding. Dr. Cicero, Dr. Carrillo, and Dr. Edelmayer have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
Investigators found transgender adults – individuals who identify with a gender different than the one assigned to them at birth – were nearly twice as likely to report subjective cognitive decline and more than twice as likely to report SCD-related functional limitations – such as reduced ability to work, volunteer, or be social – than cisgender adults.
“Trans populations are disproportionately impacted by health disparities and also risk factors for dementia. Putting these pieces together, I wasn’t surprised by their greater risk of cognitive decline,” said study investigator Ethan Cicero, PhD, RN, an assistant professor at Emory University, Atlanta.
The findings were presented at the 2021 Alzheimer’s Association International Conference.
‘Alarming’ finding
SCD is a self-reported experience of worsening memory or thinking and is one of the first clinical manifestations of Alzheimer’s disease and related dementia (ADRD). Yet there is limited research into cognitive impairment among transgender adults.
The researchers examined SCD and associated functional limitations among transgender and cisgender adults older than age 45 years who provided health and health behavior data as part of the Behavioral Risk Factor Surveillance System (BRFSS) surveys (2015-2019).
The sample included 386,529 adults of whom 1,302 identified as transgender and 385,227 as cisgender.
Roughly 17% of transgender adults reported SCD, which is significantly higher than the 10.6% rate for cisgender adults (P < .001).
Compared with cisgender adults reporting SCD, transgender adults reporting SCD were younger (mean age 61.9 vs. 65.2 years, P = .0005), more likely to be in a racial/ethnic minority group (37.3% vs. 19.5%, P < .0001), have a high school degree or less (59.6% vs. 43.4%, P = .0003), be uninsured (17% vs. 5.5%, P = .0007) and have a depressive disorder (58.8% vs. 45.7%, P = .0028).
The fact that transgender people who reported SCD were about 3 years younger than cisgender people who reported SCD is “somewhat alarming and a red flag to ask middle-aged trans adults about their brain health and not just older or elderly trans adults,” said Dr. Cicero.
The study also showed that transgender adults reporting SCD were 2.3 times more likely to report related social and self-care limitations when compared with cisgender adults reporting SCD.
The findings align with a study reported at AAIC 2019, which showed that sexual or gender minorities (SGM) are almost 30% more likely to report subjective cognitive decline compared with the non-SGM population.
Cause unclear
“We are not certain what may be causing the elevated subjective cognitive decline rates among transgender adults. We postulate that it may be in part due to anti-transgender stigma and prejudice that expose transgender people to high rates of mistreatment and discrimination where they live, work, learn, seek health care, and age,” Dr. Cicero said.
“More research is needed to identify and target preventive intervention strategies, develop culturally relevant screenings, and shape policies to improve the health and well-being of the transgender population,” he added.
Weighing in on the study, Rebecca Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said “researchers have only just started to explore the experiences of dementia within the lesbian, gay, and bisexual community, but this is the first time we are seeing some specific research that’s looking at cognition in transgender individuals and gender nonbinary individuals.”
“We don’t know exactly why transgender and gender nonbinary individuals experience greater rates of subjective cognitive decline, but we do know that they have greater rates of health disparities that are considered risk factors for dementia, including higher rates of cardiovascular disease, depression, diabetes, tobacco and alcohol use, and obesity,” Dr. Edelmayer said.
“Alzheimer’s and dementia do not discriminate. Neither can we,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a statement.
“The Alzheimer’s Association advocates for more research to better understand the cognitive and emotional needs of transgender and nonbinary individuals so that our nation’s health care providers can offer them culturally sensitive care,” said Dr. Carrillo.
The study had no specific funding. Dr. Cicero, Dr. Carrillo, and Dr. Edelmayer have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From AAIC 2021