Saturday, March 23, 2019

Sleep Problems, Alzheimer's Disease Are Linked, But Which Comes First?

Researchers are exploring the pathophysiological relationship between poor sleep and dementia. According to researchers, "Cognitive impairment in older adults is associated with sleep and circadian rhythm disturbances."

A new article explores the pathophysiological factors that link sleep disturbances and Alzheimer's disease. Better understanding of this connection may lead to potential diagnostics and therapeutics for Alzheimer's disease and other neurodegenerative diseases and dementia. The article is published ahead of print in the Journal of Neurophysiology (JNP).

Alzheimer's research has largely focused on the presence of two proteins--amyloid beta and tau--in the brain. Amyloid beta is thought to be involved with learning and the ability of the brain to change and adapt, and tau helps regulate normal signaling between neuronal cells. People with Alzheimer's disease have been found to have both hallmarks: a buildup of amyloid beta and tau tangles in the brain.

Previous studies in healthy animals and humans have reported higher levels of amyloid beta after a single night of sleep deprivation. This is consistent with normal fluctuation patterns of the protein that occur before sleeping and upon waking. These findings suggest that sleep helps the body eliminate excess amyloid beta before too much accumulates in the brain. Research has also shown that disruption of slow-wave sleep--a deep sleep phase--causes amyloid beta levels to rise as much as 30 percent. "This evidence demonstrates the significance of sleep in clearing metabolic waste and sleep disruption as a significant mediator in the development of [Alzheimer's disease]," Shen Ning and Mehdi Jorfi, PhD, the authors of the article, wrote.

The presence of tau--the protein that is found tangled in the brain of people with Alzheimer's disease--in the fluid that surrounds the brain and spinal cord (cerebrospinal fluid) is a marker of injury to the nerve cells, the authors explained. Sleep deprivation for as little as one night has been found to increase tau levels by as much as 50 percent in cerebrospinal fluid.

The research suggests that increased production of amyloid beta and tau and reduced elimination of these proteins is the primary contributing factor to Alzheimer's disease. While quality sleep seems to be able to help the body clear excess proteins, "the question remains whether sleep disruption aggravates [Alzheimer's disease] symptoms and augments disease progression, or if sleep disruption actually initiates the cascade of [Alzheimer's disease] development," the researchers wrote.

Continuing study of the relationship between sleep and Alzheimer's disease "holds great promise in bridging the molecular and cellular biology of sleep in context of the development of [Alzheimer's disease]. It may even provide helpful therapeutic benefits in preventing not only [Alzheimer's disease], but also in improving diagnosis and treatments for psychiatric and metabolic diseases," the researchers wrote.



Contacts and sources:
American Physiological Society (APS)

Citation: Beyond the sleep-amyloid interactions in Alzheimer's disease pathogenesis
Shen Ning and Mehdi Jorfi Journal of Neurophysiology (JNP).



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More Vitamin D May Improve Memory but Too Much May Slow Reaction Time



How much vitamin D can boost memory, learning and decision-making in older adults, and how much is too much?

A unique Rutgers-led study found that overweight and obese older women who took more than three times the recommended daily dose of vitamin D showed improvements in memory and learning – but also had slower reaction times. The researchers hypothesize that slower reaction times may increase the risk of falling among older people.

The researchers, whose work is in The Journals of Gerontology: Series A, used computers to assess the impact of vitamin D on cognitive function. The researchers evaluated three groups of women between 50 and 70 years old in a randomized controlled trial.

Vitamin D capsules.
Photo: Sue Shapses/Rutgers University-New Brunswick


One group took the recommended daily dose of 600 international units (IU), equivalent to 15 micrograms, of vitamin D each day for a year. Another group took 2,000 IU per day and the third took 4,000. All women participated in lifestyle counseling and were encouraged to lose a modest amount of weight.

The researchers found that memory and learning improved in the group that took 2,000 IU per day, but not in the group that took the higher dosage. Meanwhile, the women’s reaction time showed a trend to be slower at 2,000 IU daily and was significantly slower at the higher dosage.

“The slower reaction time may have other negative outcomes such as potentially increasing the risk of falling and fractures,” said senior author Sue Shapses, a professor in the Department of Nutritional Sciences at the School of Environmental and Biological Sciences at Rutgers University-New Brunswick and director of the New Jersey Obesity Group. “This is possible since other researchers have found that vitamin D supplementation at about 2,000 IU daily or more increased risk of falls, but they did not understand the cause. Our team’s findings indicating a slower reaction time may be one answer. Many people think that more vitamin D supplementation is better, but this study shows that is not always the case.”

Shapses said 4,000 IU a day might not be a problem for younger people but for the elderly it could compromise walking or catching one’s balance to avoid a fall because their reaction time is slower. This is a presumption until future research can cover vitamin D levels, cognition and falls in one study, she added.

Vitamin D – known for its importance for bone health – is obtained through sun exposure and some foods. Researchers have also found that vitamin D has a major impact on how the body, including the brain, functions.

Cognitive impairment and dementia are significant public health problems, especially with aging, the study notes. Evidence shows that vitamin D plays a role in cognition and the normal functioning of the central nervous system.

More than one in four adults 65 and older fall each year, according to the U.S. Centers for Disease Control and Prevention. The annual U.S. toll includes 29 million falls, 3 million emergency department visits, 800,000 hospitalizations and 28,000 deaths. Falling also leads to more than $31 billion in annual Medicare costs, and the costs will surge unless the problem is recognized and prevention is stressed.

More research is needed to determine whether reaction time is related to rates of falls and injuries in at-risk populations. Examining different doses of vitamin D supplementation and from dietary sources in both men and women of different ages, and people of different races over a longer period, also needs to be studied, Shapses said. Larger studies are needed as well.

Co-authors are Monica Castle, a student researcher in the Department of Nutritional Sciences at the School of Environmental and Biological Sciences at Rutgers–New Brunswick who is now at Rutgers Robert Wood Johnson Medical School; Nancy Fiedler, Rutgers School of Public Health and Environmental and Occupational Health Sciences Institute; L. Claudia Pop, Department of Nutritional Sciences, Rutgers–New Brunswick; Stephen J. Schneider, Rutgers Robert Wood Johnson Medical School; Yvette Schlussel, Department of Nutritional Sciences, Rutgers–New Brunswick; Deeptha Sukumar at Drexel University; and Lihong Hao, Department of Nutritional Sciences, Rutgers–New Brunswick.


Contacts and sources:
Todd Bates
Rutgers University