Clinical Challenges: Alzheimer’s and Sleep May Share Bidirectional Links

The threads tying sleep and Alzheimer’s disease together continue to unravel. In recent work, researchers showed that Alzheimer’s progression accelerated changes in daytime napping in older adults, and that relationship may be bidirectional. And a large-scale study suggested that sleep duration decades earlier, in midlife, was tied to an increased risk of late-onset Alzheimer’s disease and dementia.

Daytime Napping and Alzheimer’s

In Alzheimer’s & Dementia, Yue Leng, MD, PhD, of the University of California San Francisco (UCSF), and colleagues recently reported how daytime napping among elderly adults may be intertwined with Alzheimer’s disease.

“This is the first study to indicate a bidirectional relationship between objectively measured daytime napping and Alzheimer’s disease,” Leng told MedPage Today.

Napping is common among older people, but how daytime napping fits in the context of cognitive aging was unknown.

“We found the association between excessive daytime napping and dementia remained after adjusting for nighttime quantity and quality of sleep,” Leng said. “This suggested the role of daytime napping is important itself and is independent of nighttime sleep.”

The researchers studied data from 1,401 people in the Rush Memory and Aging Project in Chicago, following them for 14 years. Participants whose median age was 81 at baseline wore a watch-like device to record their motor activity. Each prolonged period of non-activity from 9 a.m. to 7 p.m. was interpreted as a nap.

Those who napped for more than an hour a day had a 40% higher risk for developing Alzheimer’s disease compared with those who napped for less than an hour. In addition, people who napped at least once a day had a 40% higher risk of Alzheimer’s compared with those who napped less frequently. These associations were unchanged after adjusting for sleep and circadian daily activity rhythms, medical comorbidities and medications, and APOE4 allele carrier status.

As they aged, participants tended to nap longer and more frequently. Alzheimer’s progression accelerated this change, more than doubling the increases in nap duration and frequency from year to year.

Daytime napping and cognition showed a bidirectional relationship: longer and more frequent naps were correlated with worse cognition a year later, and worse cognition was correlated with more excessive naps a year later.

Napping and Alzheimer’s disease may be driving each other’s changes, Leng observed. “I don’t think we have enough evidence to draw conclusions about a causal relationship, that it’s the napping itself that caused cognitive aging, but excessive daytime napping might be a signal of accelerated aging or cognitive aging process,” she said.

Wake-Promoting Neurons

Those findings dovetailed with new research in JAMA Neurology led by neuropathologist Lea Grinberg, MD, PhD, also of UCSF.

The prevailing model has been that people with Alzheimer’s have fragmented sleep at night because of a combination of amyloid-related damage and obstructive sleep apnea, Grinberg said. “As a consequence of this bad sleep at night, the patients never feel completely awake during the day, need to nap at some point, and experience sundowning,” she told MedPage Today.

“In 2019, we started to demonstrate that wake-promoting neurons degenerate very early in Alzheimer’s, not because of amyloid, but because of tau accumulation,” Grinberg said. “What our most recent study did was investigate for the first time a group of individuals who underwent objective sleep measures and donated their brain for advanced postmortem studies.”

“We were able to prove what our previous research had been pointing to, that in Alzheimer’s patients who need to nap all the time, the disease has damaged the neurons that keep them awake,” Grinberg noted.

“It’s not that these patients are tired during the day because they didn’t sleep at night,” she observed. “It’s that the system in their brain that would keep them awake is gone.”

Sleep in Middle Age

Last year, a large observational study in Nature Communications suggested relationships between sleep and later-life dementia might exist even in relatively young people.

People who persistently slept 6 hours or less each night in their 50s and 60s were 30% more likely to develop dementia later in life than those who slept 7 hours, reported Séverine Sabia, PhD, of Université de Paris in France and University College London, and colleagues.

“We showed a consistent association between short sleep duration in midlife and risk of dementia,” Sabia told MedPage Today. “This association was not explained by mental disorders and other chronic conditions known to be associated with dementia. Furthermore, findings were confirmed using an objective measure of sleep duration in a subsample.”

The researchers evaluated data in the Whitehall II cohort spanning 30 years to examine the association of sleep duration at ages 50, 60, and 70 with incident dementia. They used dementia without a history of cardiovascular disease as a proxy for Alzheimer’s disease.

“The novelty of our study is to examine this association among almost 8,000 participants with a follow-up of 25 years using repeated measures of sleep duration starting in midlife,” Sabia said. This is important because Alzheimer’s dementia has a long preclinical period and studies with shorter follow-up may be subject to reverse causation, the researchers noted.

Sabia and colleagues found no significant link between sleeping 8 or more hours and dementia risk but the number of long sleepers in the study was small, they pointed out.

“While we cannot confirm that not sleeping enough actually increases the risk of dementia, there are plenty of reasons why a good night’s sleep might be good for brain health,” Sabia said. “These findings suggest that maintenance of good [sleep] hygiene over the life course is likely to be beneficial for brain health.”