Sleep regularity in midlife and at older ages may be a novel dementia risk factor, data from 88,000 people in Great Britain suggested.
Day-to-day consistency in sleep-wake patterns showed a U-shaped association with incident dementia, according to Matthew Pase, PhD, of Monash University in Melbourne, Australia, and co-authors.
Dementia rates were highest among people with the most erratic sleep patterns, and dipped as sleep regularity approached the median, then trended upward again at the highest estimates of sleep regularity, Pase and colleagues reported in .
Relative to the median, hazard ratios (HRs) were 1.53 (95% CI 1.24-1.89) for participants with a sleep regularity index (SRI) score at the 5th percentile and 1.16 (95% CI 0.89-1.50) for those with an SRI at the 95th percentile.
Sleep quality and sleep duration have been linked with cognitive decline, but "sleep regularity has received little attention," Pase told MedPage Today. "Our results indicate that associations between sleep regularity and dementia are independent of sleep quality and duration, suggesting sleep regularity as an important component of sleep that we should pay attention to."
The findings are based on objective assessments of sleep and wake time points over a week, Pase noted. "Rather than simply looking at the variability in overall sleep duration or the variability in bedtimes, our metric compared whether an individual was in the same state -- asleep or awake -- at any two time points, 24 hours apart," he said.
"This metric captures more rapid and nuanced shifts in sleep regularity, which may be a more sensitive way of measuring circadian disruption," he added.
Pase and colleagues studied data from 88,094 participants, following them for about 7 years. Participants were 40 to 69 years old at baseline and recruited between 2006 and 2010.
Between February 2013 and December 2015, a random selection of individuals were invited to participate in a 7-day wrist-worn accelerometer study. Some also participated in an imaging substudy.
Sleep regularity was estimated as the probability of an individual being in the same state (asleep or awake) at any two time points 24 hours apart, averaged over 7 days of accelerometry. An individual who slept and woke exactly at the same times would have an SRI of 100, and one who slept and woke entirely at random would have an SRI of 0. Multiple SRI measurements were available for each participant.
The median SRI in the study was 60. The mean age at accelerometry was 62, and 56% were women.
Over a median follow-up of 7.2 years, 480 dementia cases were identified. The U-shape relationship between sleep regularity and dementia emerged after adjusting for demographic and clinical confounders and APOE4 status.
An imaging substudy of 15,263 people showed an inverted U-shaped association between the SRI and gray matter volume (P=0.038) and hippocampal volume (P=0.035). Volumes tended to increase until the SRI neared the median, at which point they began to decrease.
"The U-shaped SRI-dementia association is intriguing because higher dementia risk in those with more regular sleep seems counterintuitive," Pase and colleagues observed.
"Of interest, we observed a similar association with gray matter volume and hippocampal volume, whereby both extremes of the SRI were associated with lower brain volumes," they added. "Thus, these two lines of evidence converge on the notion that both extremes of the SRI are linked to adverse brain health outcomes."
The pattern echoed the well-known U-shaped relationship between in which both short and long sleep durations are tied to higher dementia risk.
"We considered that short sleep duration might confound the SRI-dementia association," the researchers noted. "However, in our sensitivity analysis, results for dementia were only modestly attenuated following adjustment for sleep duration and WASO [wake after sleep onset]."
Though the analysis was adjusted for known confounders, unmeasured variables may have influenced results, the researchers acknowledged.
"We are also unable to rule out reverse causation," they added, noting that the patterns observed, especially in later follow-up stages, suggested reverse causation was unlikely to completely explain the findings.
Disclosures
Researchers were supported by the National Health and Medical Research Council of Australia, National Institute on Aging, Alzheimer's Association, Dementia Australia Research Foundation, and Banting Fellowship Program.
The authors reported no relevant disclosures.
Primary Source
Neurology
Yiallourou SR, et al "Association of the sleep regularity index with incident dementia and brain volume" Neurology 2023; DOI: 10.1212/WNL.0000000000208029.