'Vicious Cycle' Between Excessive Daytime Napping and Alzheimer's

Liam Davenport

March 29, 2022

A bidirectional relationship between daytime napping patterns and cognitive decline in older adults not only predicts the onset of Alzheimer's disease (AD) but also indicates disease progression in those already diagnosed with the disease, new research shows.

A large longitudinal study of more than 1000 individuals, the majority of whom were free of mild cognitive impairment (MCI) and AD at baseline, used actigraphy to measure daytime napping duration and frequency.

This revealed what the researchers described as a "vicious cycle," in which AD was associated with substantial increases in the duration and frequency of napping, while longer and more frequent naps were linked to an increased risk of the disease and worsening cognitive performance.

The findings were published online March 17 in Alzheimer's and Dementia.

Napping Tied to Brain Changes?

Key to identifying the relationship was the use of "objective measurement" of sleep via actigraphy, Peng Li, PhD, of the Division of Sleep and Circadian Disorders at Brigham and Women's Hospital, Boston, Massachusetts, told Medscape Medical News.

However, he emphasized that the technique is "something we need to further develop," inasmuch as it is "not really a standardized measurement for sleep." The gold standard, he added, remains polysomnography.

However, he added, polysomnography is impractical, especially for older patients, and is "very expensive," Li said. Actigraphy offers a means of objectively measuring sleep "in a large cohort" and is a good "compromise."

Li noted that the bidirectional relationship they found was "partially expected from what we understand from the literature," but the longitudinal nature of the study was able to "prove" that it is bidirectional and that napping and cognition "drive each other in a circular manner."

However, said Li, the open question is whether sleep is "causally related to the development of Alzheimer's, and we are not there yet" in terms of answering it.

The current evidence, however, suggests that longer and more frequent daytime napping might be a "symptom of some of the changes that are related to Alzheimer's" development.

The researchers note that excessive daytime napping has been observed "especially" in older adults with AD, and excessive daytime sleepiness has been linked to "faster cognitive decline."

Nevertheless, they underline that the results so far have been "conflicting," which may be related to the fact that "all prior studies" carried out "only one single nap assessment for each participant.

"In addition, these studies mostly used subjective nap assessments that may not be reliable, especially in older adults given their cognitive status," they write.

To overcome these hurdles, the team reports results from the Rush Memory and Aging Project, which began in 1997 and, since 2005, has provided to participants a wristwatch-like activity monitor (Actical, Philips Respironics).

The device was worn on the nondominant hand continuously for up to 14 days. Napping was defined as sleep during common daylight or active hours, between 9:00 AM and 7:00 PM.

Participants also completed annually a battery of 21 neuropsychological tests, including 19 that assess an individual's cognitive abilities across five domains.

The study involved 1401 individuals; the average age of the participants was 81.42 years. The majority (76.6%) were women, and they had received an average of 15.04 years of education.

Circular Pattern

On average, the participants napped 1.80 times per day, for a total mean of 46.60 minutes per day.

While nap frequency and duration are positively correlated with age (P < .0001), there were no significant differences between men and women, and there was no significant link with education.

Among 1065 participants who underwent at least two actigraphy assessments, 812 had no cognitive impairment at baseline. Of those, 384 went on to develop MCI, and 146 developed Alzheimer's disease. A further 209 patients had MCI at baseline, and 44 were diagnosed with Alzheimer's disease.

The team notes that nap duration increased over time, at 11.31 minutes per year overall. This rose to 24.66 minutes per year in participants diagnosed with MCI and 68.35 minutes per year in those with Alzheimer's disease (P < .0001 for all).

A similar pattern was seen for napping frequency, at increases of 0.35 times per year, 0.67 times per year, and 1.25 times per year (P < .0001 for all).

Cox proportional hazards models revealed that longer daytime napping was associated with a significantly increased risk of developing AD, with a hazard ratio of 1.20 per 1 SD increase (P = .004).

For individuals who napped for ≥1 hour per day, this translated into a 1.4-fold increased risk in comparison with those who napped for less.

In addition, more frequent naps were associated with an increased risk of AD, with a hazard ratio per 1 SD increase of 1.23 (P = .001).

This equated to a 40% increased risk for people who napped at least once a day in comparison with those who napped less than once a day on average.

The team also found that there was a bidirectional relationship between nap duration and frequency, such that global cognition was negatively correlated with nap duration and frequency in the next year, and nap duration and frequency were negatively correlated with global cognition in the following year.

"Exciting" Research

Commenting for Medscape Medical News, Percy Griffin, PhD, director of scientific engagement at the Alzheimer's Association, said that the results are "in line with what we know from other work examining the relationship between napping and cognition.

"What is particularly strong and different about this study, though, is its direct measurement, large cohort size, and longitudinal follow-up," he said.

However, he noted that a "major limitation" is that the participants were "old, and the findings cannot be translated into younger cohorts."

Griffin noted that more work is also needed to understand "what is fully going on with the impact of sleep disturbances on brain biology."

He said that the mechanisms proposed by the researchers, including the loss of wake-promoting neurons and changes in the 24-hour circadian control, are "plausible" but that "there could be other mechanisms pertaining to the immune cells in the brain, as well as selective vulnerability of certain neurons."

Nevertheless, Griffin believes that the work is "exciting," because it "suggests that napping frequency and duration could be factored into the determination of the risk of developing cognitive decline."

He added that changes in napping frequency and duration could be indicative of accelerated disease progression in those already diagnosed with Alzheimer's dementia, and "drug and nondrug approaches can be implemented to help slow the impact of these changes."

The study was supported by the NIH and the BrightFocus Foundation Alzheimer's Research Program. No relevant financial relationships have been disclosed.

Alzheimer's Dement. Published online March 17, 2022. Full text

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