Excessive Brain Activity Linked to Shorter Life Span

Video: New research links excess neural activity — the flickering light seen in this image — to reduced longevity. Credit: Yankner lab, Harvard Medical School.

The brain’s neural activity — long implicated in disorders ranging from dementia to epilepsy — also plays a role in how long we live.

The study, led by scientists in the Blavatnik Institute at Harvard Medical School and based on findings from human brains, mice, and worms, suggests that excessive activity in the brain is linked to shorter life spans, while suppressing overactivity can extend life.

Neural activity refers to the constant flicker of electrical currents and transmissions in the brain. Excessive activity, or excitation, could manifest in numerous ways, from a muscle twitch to a change in mood or thought, according to the researchers.

“An intriguing aspect of our findings is that something as transient as the activity state of neural circuits could have such far-ranging consequences for physiology and life span,” said study senior author Dr. Bruce Yankner, a professor of genetics and co-director of the Paul F. Glenn Center for the Biology of Aging.

Neural excitation appears to act along a chain of molecular events famously known to influence longevity — the insulin and insulin-like growth factor (IGF) signaling pathway, the researchers explain.

The key in this signaling cascade appears to be a protein called REST, previously shown by researchers in the Yankner Lab to protect aging brains from dementia and other stresses.

Study results could lead to the design of new therapies for conditions that involve neural overactivity, such as Alzheimer’s disease and bipolar disorder, the researchers said.

The findings also raise the possibility that certain medicines, such as drugs that target REST, or certain behaviors, such as meditation, could extend life span by modulating neural activity, they said.

Human variation in neural activity might have both genetic and environmental causes, which would open future avenues for therapeutic intervention, Yankner added.

The researchers began their investigation by analyzing gene expression patterns — the extent to which various genes are turned on and off — in donated brain tissue from hundreds of people who died at ages ranging from 60 to over 100.

The information was collected through three separate research studies of older adults. Those analyzed in the current study were cognitively intact, meaning they had no dementia, the researchers noted.

The researchers immediately noticed a striking difference between the older and younger study participants, Yankner said. The longest-lived people — those over 85 — had lower expression of genes related to neural excitation than those who died between the ages of 60 and 80.

Next came the question that all scientists confront: Correlation or causation? Was this disparity in neural excitation merely occurring alongside more important factors determining life span or were excitation levels directly affecting longevity? If so, how?

To answer these questions, the researchers conducted a barrage of experiments, including genetic, cell, and molecular biology tests in the model organism Caenorhabditis elegans, analyses of genetically altered mice, and additional brain tissue analyses of people who lived for more than a century.

These experiments revealed that altering neural excitation does indeed affect life span and illuminated what might be happening on a molecular level, the researchers said, noting all signs pointed to the protein REST.

REST, which is known to regulate genes, also suppresses neural excitation, the researchers found.

Blocking REST or its equivalent in the animals led to higher neural activity and earlier deaths, while boosting REST did the opposite.

The researchers also discovered that people who lived to 100 and beyond had significantly more REST in the nuclei of their brain cells than people who died in their 70s or 80s.

“It was extremely exciting to see how all these different lines of evidence converged,” said study co-author Dr. Monica Colaiácovo, a professor of genetics at Harvard Medical School, whose lab collaborated on the C. elegans work.

The researchers found that from worms to mammals, REST suppresses the expression of genes that are centrally involved in neural excitation, such as ion channels, neurotransmitter receptors, and structural components of synapses.

Lower excitation activates a family of proteins known as forkhead transcription factors. These proteins have been shown to mediate a “longevity pathway” via insulin/IGF signaling in many animals. It’s the same pathway that scientists believe can be activated by caloric restriction, according to the researchers.

In addition to its emerging role in staving off neurodegeneration, discovery of REST’s role in longevity provides additional motivation to develop drugs that target the protein, the researchers said.

Although it will take time and many tests to determine whether such treatments reduce neural excitation, promote healthy aging, or extend life span, the concept has captivated some researchers.

“The possibility that being able to activate REST would reduce excitatory neural activity and slow aging in humans is extremely exciting,” said Colaiácovo.

The study was published in Nature.

Source: Harvard Medical School

 

Chair Yoga May Improve Quality of Life in Dementia Patients

Chair yoga may help improve quality of life in older adults with moderate-to-severe dementia, according to a new study by Florida Atlantic University (FAU).

Chair yoga provides a safe environment for stretching, strengthening and flexibility while decreasing the risk of falls by using a chair. It also provides important breathing and relaxation techniques through stationary poses and guided relaxation of various muscle groups.

“We think that the physical poses we used in the chair yoga and chair-based exercise groups were an important factor in improving quality of life for the participants in our study,” said Juyoung Park, Ph.D., lead author and an associate professor in the Phyllis and Harvey Sandler School of Social Work within FAU’s College for Design and Social Inquiry.

“It is fascinating that, although some participants showed mild levels of agitation or wandering in the intervention room prior to the yoga session, they became calm and attentive when the yoga interventionist started demonstrating yoga poses.”

“Although they did not understand the interventionist’s verbal instructions due to their cognitive impairment associated with advanced dementia, they followed the instructor’s poses.”

For the study, published in the American Journal of Alzheimer’s Disease & Other Dementias, researchers from FAU compared chair yoga with two other types of non-pharmacological interventions: chair-based exercise and music intervention.

The study involved older adults (mean average age was 84 years old) with moderate-to-severe dementia, including Alzheimer’s disease (the largest diagnostic group), Lewy Body dementia and Parkinson disease dementia. The patients were unable to participate in regular exercise or standing yoga due to cognitive impairment, problems with balance, or fear of falling.

Participants in each of the three groups attended 45-minute sessions twice a week for 12 weeks. Researchers collected data at baseline, after six weeks and after completing the 12-week intervention.

Results showed that participants with moderate-to-severe dementia could safely adhere to non-pharmacological interventions, and more than 97% of the participants fully engaged in each session.

The findings show that those in the chair yoga group improved significantly in quality-of-life scores compared to the music intervention group. Both the chair yoga and chair-exercise groups showed improvement over time, while the music intervention group declined.

In addition, both the chair yoga and chair-based exercise groups showed lower depression across all three time points when compared to the music intervention group.

The team did not find any differences in the three intervention groups on physical function, with the exception of handgrip strength, which was higher in the chair yoga group compared to the music intervention group. None of the three groups declined significantly in any of the investigated physical functional measures.

Researchers also did not find any significant between-group differences in anxiety at any time point. There were no significant between-group differences in change in depression and anxiety. The researchers also did not find significant differences among the three intervention groups for sleep quality at any of the three time points.

“We did see an increase in agitation in the chair yoga group even though this group reported a higher quality of life score, including physical condition, mood, functional abilities, interpersonal relationships, ability to participate in meaningful activities, and final situations,” said Park.

“It’s important to note that quality of life is a more comprehensive approach to biopsychosocial and behavioral function than a mere measure of agitation. Meditation and the mind-body connection component of the chair yoga program may have increased quality of life for participants in this study. This finding is consistent with our earlier studies that showed a targeted approach was successful in increasing quality of life in patients with dementia.”

Source: Florida Atlantic University

Menopausal Night Sweats Linked to Impaired Cognitive Performance

A new study suggests that women who experience night sweats are more vulnerable to cognitive dysfunction as their sleep duration increases.

Previous studies have shown a link between daytime hot flashes and worse memory performance.

In this new study involving women with a history of breast cancer, however, researchers focused on night sweats and how they relate to total sleep time. Surprisingly, more frequent night sweats were associated with greater sleep duration, according to the researchers.

Even more surprising, they said, was the finding that these same women experiencing night sweats became more vulnerable to prefrontal cortex deficits, including decreased attention and executive function, as their sleep duration increased.

Total sleep time, however, was unrelated to memory performance, they noted.

The researchers also discovered that daytime hot flashes had no impact on total sleep time.

“This work presents novel insights into the influence of menopause symptoms on cognitive performance among women with a history of breast cancer and raises the possibility that hot flash treatments could benefit cognition in these women through effects on sleep,” said lead author John Bark, doctoral student in behavioral neuroscience the University of Illinois at Chicago.

“Studies like this are valuable in helping health care providers develop effective treatment options for menopausal women complaining of cognitive decline as they focus on modifiable risk factors,” added Dr. Stephanie Faubion, medical director for The North American Menopause Society.

The study findings were presented during 2019 North American Menopause Society (NAMS) annual meeting.

Source: The North American Menopause Society

Walking Patterns Differ Between Alzheimer’s Disease, Lewy Body Dementia

A new U.K. study reveals distinct walking variations between people with Lewy body dementia and those with Alzheimer’s disease.

Researchers from Newcastle University in England found that people with Lewy body dementia change their walking steps more often — varying step time and length — and are asymmetric when they move, in comparison to those with Alzheimer’s disease.

The study, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, suggests gait could be used as a clinical biomarker for various subtypes of dementia and could lead to improved treatment plans for patients.

“The way we walk can reflect changes in thinking and memory that highlight problems in our brain, such as dementia,” said Dr. Ríona McArdle, post-doctoral researcher at Newcastle University’s Faculty of Medical Sciences and leader of the Alzheimer’s Society-funded study.

“Correctly identifying what type of dementia someone has is important for clinicians and researchers as it allows patients to be given the most appropriate treatment for their needs as soon as possible.”

“The results from this study are exciting as they suggest that walking could be a useful tool to add to the diagnostic toolbox for dementia.

“It is a key development as a more accurate diagnosis means that we know that people are getting the right treatment, care and management for the dementia they have.”

Currently, diagnosis of either type of dementia is made by identifying specific symptoms and, when required, referring to a brain scan.

For the study, researchers analyzed the walking patterns of 110 people, including 29 older adults whose cognition was intact, 36 with Alzheimer’s disease and 45 with Lewy body dementia.

The participants took part in a simple walking test at the Gait Lab of the Clinical Ageing Research Unit. Participants moved along a walkway — a mat with thousands of sensors — which captured their footsteps and gait patterns as they walked across it at their normal speed.

Participants with Lewy body dementia had a unique walking pattern in that they changed how long it took to take a step or the length of their steps more frequently than someone with Alzheimer’s disease, whose walking patterns rarely changed.

When a person has Lewy body dementia, their steps are more irregular, and this is associated with increased fall risk. Their walking is more asymmetric in step time and stride length, meaning their left and right footsteps are different.

Scientists found that analyzing both step length variability and step time asymmetry could accurately identify 60% of all dementia subtypes — which has never been shown before.

Further research will aim to identify how these characteristics enhance current diagnostic procedures and assess their effectiveness as a screening method. It is hoped that this tool will be available within five years.

“We know that research will beat dementia and provide invaluable support for the 850,000 people living with the condition in the UK today. It’s now vital that we continue to support promising research of this kind,” said Dr. James Pickett, head of research at the Alzheimer’s Society. “We look forward to seeing larger, longer studies to validate this approach and shed light on the relationship between a person’s gait and dementia diagnosis.”

Source: Newcastle University

Strong Linguistic Ability Tied to Reduced Risk of Dementia

People who speak four or more languages have a significantly reduced risk of developing dementia, according to a new study from the University of Waterloo in Canada.

The research examined the health outcomes of 325 Roman Catholic nuns who were members of the Sisters of Notre Dame in the United States. The data was drawn from a larger, internationally recognized study examining the Sisters, known as the Nun Study.

The findings show that six percent of the nuns who spoke four or more languages developed dementia, compared to 31 percent of those who only spoke one. However, knowing two or three languages did not significantly reduce the risk in this study, which differs from some previous research.

“The Nun Study is unique: It is a natural experiment, with very different lives in childhood and adolescence before entering the convent, contrasted with very similar adult lives in the convent,” said study leader Dr. Suzanne Tyas, a public health professor at Waterloo.

“This gives us the ability to look at early-life factors on health later in life without worrying about all the other factors, such as socioeconomic status and genetics, which usually vary from person to person during adulthood and can weaken other studies.”

“Language is a complex ability of the human brain, and switching between different languages takes cognitive flexibility. So it makes sense that the extra mental exercise multilinguals would get from speaking four or more languages might help their brains be in better shape than monolinguals.”

The researchers also examined 106 samples of the nuns’ written work and compared it to the broader findings. They discovered that written linguistic ability affected whether the individuals were at greater risk of developing dementia.

For example, idea density — the number of ideas expressed succinctly in written work — helped reduce the risk even more than multilingualism.

“This study shows that while multilingualism may be important, we should also be looking further into other examples of linguistic ability,” said Tyas.

“In addition, we need to know more about multilingualism and what aspects are important, such as the age when a language is first learned, how often each language is spoken, and how similar or different these languages are. This knowledge can guide strategies to promote multilingualism and other linguistic training to reduce the risk of developing dementia.”

Source: University of Waterloo

 

 

Married People May Be Less Likely to Get Dementia

A new study has found that married people are less likely to experience dementia as they age.

The study, by researchers at Michigan State University, also found that divorcees are about twice as likely as married people to develop dementia, with divorced men showing a greater disadvantage than divorced women.

For the study, a research team led by Dr. Hui Liu, a professor of sociology, analyzed four groups of unmarried individuals: divorced or separated; widowed; never married; and cohabiters.

The researchers analyzed nationally representative data from the Health and Retirement Study, from 2000 to 2014. The sample included more than 15,000 people ages 52 and older in 2000, measuring their cognitive function every two years, in person or via telephone.

The analysis revealed that the divorced had the highest risk of dementia.

“This research is important because the number of unmarried older adults in the United States continues to grow, as people live longer and their marital histories become more complex,” Liu said. “Marital status is an important, but overlooked, social risk/protective factor for dementia.”

The researchers also found differing economic resources only partly accounted for higher dementia risk among divorced, widowed, and never-married people, but couldn’t account for higher risk in cohabiters.

In addition, health-related factors, such as behaviors and chronic conditions, slightly influenced risk among the divorced and married, but didn’t seem to affect other marital statuses, the researchers said.

“These findings will be helpful for health policy makers and practitioners who seek to better identify vulnerable populations and to design effective intervention strategies to reduce dementia risk,” Liu said.

The study was published in The Journals of Gerontology: Series B.

Source: Michigan State University