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
Emerging research suggests a longer period of estrogen replacement therapy provides a prolonged cognitive benefit. However, investigators acknowledge that the risk-to-benefit balance of hormone therapy use is complicated and must be individualized.
Research has determined that estrogen has a significant role in overall brain health and cognitive function. This knowledge has fostered various studies on the prevention of cognitive decline as related to reduced estrogen levels during the menopause transition.
The new study suggests a cognitive benefit from a longer reproductive window complemented with hormone therapy. The study, “Lifetime estrogen exposure and cognition in late life: The Cache County Study,” appears online in Menopause, the journal of The North American Menopause Society (NAMS).
Because women comprise two-thirds of the 5.5 million cases of Alzheimer disease in the United States, researchers have long suspected that sex-specific factors such as estrogen may contribute to women’s increased risk for the disease. Moreover, multiple studies have suggested a role for estrogen in promoting memory and learning.
In this newest study involving more than 2,000 postmenopausal women, researchers followed participants over a 12-year period to examine the association between estrogen and cognitive decline.
More specifically, they focused on the duration of a woman’s exposure to estrogen, taking into account such factors as time of menarche to menopause, number of pregnancies, duration of breastfeeding, and use of hormone therapy.
Investigators concluded that a longer duration of estrogen exposure is associated with better cognitive status in older adult women. Furthermore, they documented that these beneficial effects are extended with the use of hormone therapy, especially in the oldest women in the sample.
Women who initiated hormone therapy earlier showed higher cognitive test scores than those who started taking hormones later, providing some support for the critical window hypothesis of hormone therapy.
“Although the assessment of the risk-to-benefit balance of hormone therapy use is complicated and must be individualized, this study provides additional evidence for beneficial cognitive effects of hormone therapy, particularly when initiated early after menopause.
This study also underscores the potential adverse effects of early estrogen deprivation on cognitive health in the setting of premature or early menopause without adequate estrogen replacement,” says Dr. Stephanie Faubion, NAMS medical director.
Source: The North American Menopause Society (NAMS)
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
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
Mindfulness meditation may benefit older adults with mild cognitive impairment (MCI), according to a small pilot study published in the Journal of Alzheimer’s Disease.
There’s currently no known way to prevent older adults with MCI from developing Alzheimer’s disease, but mindfulness meditation may be a safe and feasible non-pharmacological treatment that can help.
Mindfulness means maintaining a moment-by-moment, non-judgmental awareness of thoughts, feelings, bodily sensations, and surrounding environment.
“Our study showed promising evidence that adults with MCI can learn to practice mindfulness meditation, and by doing so may boost their cognitive reserve,” said Rebecca Erwin Wells, MD, MPH, associate professor of neurology at Wake Forest School of Medicine, a practicing neurologist at Wake Forest Baptist Medical Center and associate director of clinical research for its Center for Integrative Medicine.
Cognitive reserve is a person’s capacity to maintain normal cognitive function in the presence of deteriorating brain function.
“While the concept of mindfulness meditation is simple, the practice itself requires complex cognitive processes, discipline and commitment,” Wells explained. “This study suggests that the cognitive impairment in MCI is not prohibitive of what is required to learn this new skill.”
Previous research has shown that high levels of chronic stress negatively impact the hippocampus, a part of the brain involved in memory and learning, and are associated with increased incidence of MCI and Alzheimer’s. Other studies have indicated that non-drug interventions such as aerobic exercise can have positive effects on cognition, stress levels and the brain.
To determine whether a mindfulness-based stress-reduction (MBSR) program could benefit adults with MCI, the study team recruited 14 men and women between the ages of 55 and 90 with clinically diagnosed MCI and randomized them to either an eight-week course involving mindfulness meditation and yoga or a “waiting list” control group.
The researchers previously reported that the nine participants who completed the MBSR program showed trends toward improvements on measures of cognition and well-being and indications of positive impacts on the hippocampus as well as other areas of the brain associated with cognitive decline.
The new study adds context to those findings with an analysis of the MBSR participants’ responses in interviews conducted at the end of the eight-week course.
“While the MBSR course was not developed or structured to directly address MCI, the qualitative interviews revealed new and important findings specific to MCI,” Wells said. “The participants’ comments and ratings showed that most of them were able to learn the key tenets of mindfulness, demonstrating that the memory impairment of MCI does not preclude learning such skills.”
Participants who practiced at least 20 minutes a day were most likely to have understood the underlying concepts of mindfulness, Wells noted.
“Until treatment options that can prevent the progression to Alzheimer’s are found, mindfulness meditation may help patients living with MCI,” said Well.
The limitations of the study include the small sample size and that the results may not generalize to all patients with MCI, as two-thirds of the participants in this study had a college education or more. Additional research is needed to further test the preliminary hypotheses contained in this study.
Source: Wake Forest Baptist Medical Center
Informal caregivers of dementia patients often lose between 2.5 to 3.5 hours of sleep each week, a negative for themselves and potentially for those who receive their care, according to a new study at Baylor University.
The findings are published in the journal JAMA Network Open.
“Losing 3.5 hours of sleep per week does not seem much, but caregivers often experience accumulation of sleep loss over years,” said lead author Chenlu Gao, a doctoral candidate of psychology and neuroscience in Baylor’s College of Arts & Sciences.
The good news is that notably better sleep was observed in caregivers after such simple behaviors as getting more morning sunlight, establishing a regular and relaxing bedtime routine and taking part in moderate physical exercise.
“Losing 3.5 hours of sleep weekly on top of all the stress, grief and sadness can have a really strong impact on caregivers’ cognition and mental and physical health. But improving caregivers’ sleep quality through low-cost behavioral interventions can significantly improve their functions and quality of life,” said Gao.
Chronic stress is associated with short sleep and poor-quality sleep. Nighttime awakenings by a patient with dementia also can contribute to disturbed sleep in caregivers, researchers said. In fact, iformal caregiving for a person with dementia is akin to adding a part-time but unpaid job to one’s life, with family members averaging 21.9 hours of caregiving, according to The Alzheimer’s Association.
“With that extra bit of sleep loss every night, maybe a caregiver now forgets some medication doses or reacts more emotionally than he or she otherwise would,” said co-author Michael Scullin, Ph.D., director of Baylor’s Sleep Neuroscience and Cognition Laboratory and assistant professor of psychology and neuroscience at Baylor.
“Caregivers are some of the most inspiring and hardest-working people in the world, but sleep loss eventually accumulates to a level that diminishes one’s vigilance and multi-tasking.”
The researchers analyzed 35 studies in peer-reviewed journals and books addressing caregivers, sleep, dementia and Alzheimer’s disease, published through June 2018. Those studies measured sleep quality and quantity by monitoring brain electrical activity, body movements and self-reporting by caregivers. Overall, they looked at data from 3,268 caregivers.
The researchers also analyzed intervention-related changes in sleep quality, such as daytime exercise, not drinking coffee or tea past late afternoon, not drinking alcohol at night and getting more sunlight in the morning.
The team discovered that the difference in time and quality of sleep was significant when compared to non-caregivers in the same age range and with the recommended minimum of sleep: seven hours nightly for adults.
“Given the long-term, potentially cumulative health consequences of poor-quality sleep, as well as the rising need for dementia caregivers worldwide, clinicians should consider sleep interventions not only for the patient but also for the spouse, child or friend who will be providing care,” Gao said.
Source: Baylor University