How do daytime sleepiness and disrupted rest-activity rhythms relate to incident dementia and white matter pathology?

Two different sleep signals, one dementia outcome

Daytime sleepiness and disrupted rest-activity rhythms are not the same thing. Daytime sleepiness is a feeling of being unusually sleepy during the day, often measured with a questionnaire called the Epworth Sleepiness Scale. Rest-activity rhythms are the 24-hour pattern of when a person is active and when they rest, usually captured with a wrist-worn actigraphy device. Both have been linked to dementia, but through somewhat different studies and mechanisms.

In the Shanghai Aging Study, 617 dementia-free older adults were followed for up to 10 years. About 11% had excessive daytime sleepiness at baseline, and those people had about twice the risk of developing dementia (hazard ratio 2.06) [1]. The association held even after accounting for sleep disturbance at night, suggesting daytime sleepiness is not simply a marker of poor nocturnal sleep.

Rest-activity rhythm studies point in a similar direction. In more than 53,000 UK Biobank participants, a suppressed 24-hour activity rhythm and a more fragmented rhythm each predicted higher delirium risk, and suppressed rhythm amplitude predicted progression from delirium to new-onset dementia [4]. Delirium is a state of acute confusion, and the study suggests rhythm disturbance may appear before both delirium and dementia.

White matter injury may be the common ground

White matter is the brain's wiring—bundles of nerve fibers that connect different regions. Injury to this wiring, visible as white matter lesions or measured through diffusion imaging, is common in aging and is associated with cognitive decline. Several studies suggest it may be where sleep problems and dementia risk meet.

In the Shanghai cohort, higher daytime sleepiness was associated with a higher burden of white matter injury, measured by a diffusion imaging marker called PSMD (peak width of skeletonized mean diffusivity) [1]. PSMD is thought to reflect widespread white matter damage. People who had both high PSMD and excessive daytime sleepiness had the highest dementia risk, and PSMD modified the association between sleepiness and both cognitive decline and dementia [1]. The authors interpret this as supporting a vascular vulnerability pathway, meaning that blood vessel-related white matter damage may make the brain more susceptible to the effects of sleepiness.

A separate study of 108 older adults at risk for cognitive decline looked at specific white matter tracts and rest-activity rhythms. Lower interdaily stability—meaning the daily activity pattern was less consistent from day to day—was associated with greater likelihood of high white matter lesion burden in the anterior thalamic radiation, a tract involved in memory and attention (odds ratio 1.82) [3]. Later onset of the least active period was linked to lesions in the superior longitudinal fasciculus, and more activity during the rest period was linked to higher whole-brain lesion burden [3]. Overall, people with altered rhythms had 50–80% higher odds of high lesion burden.

A broader thesis project on sleep, rest-activity rhythms, and white matter in older adults at risk for cognitive decline also found associations between rhythm measures and white matter micro-architecture, and reported that clinical risk factors moderated these relationships [2]. It proposes white matter as a common neurobiological substrate that may underpin sleep-wake alterations in this population, though that is a proposed interpretation rather than an established cause.

Amyloid and vascular contributions may not be separate stories

Alzheimer's disease pathology—amyloid plaques and tau tangles—is the most common cause of dementia, but vascular damage is increasingly recognized as a contributor. The Shanghai study measured plasma p-tau217, a blood marker of Alzheimer's-related tau pathology, and found that the link between daytime sleepiness and dementia was actually strongest in people with low p-tau217 (hazard ratio 4.94) [1]. In other words, sleepiness predicted dementia most strongly in people who did not already have high Alzheimer's biomarker burden, which is consistent with a non-Alzheimer's pathway such as vascular white matter injury being important in that group.

This does not mean amyloid is irrelevant. Higher daytime sleepiness was also related to patterns of brain atrophy that depended on Alzheimer's pathology, and to higher PSMD [1]. The picture is that sleepiness may signal risk through multiple routes, and white matter injury appears to be one that operates alongside or independently of amyloid.

The rest-activity rhythm studies did not measure amyloid, so it remains unclear whether rhythm disruption relates to dementia through similar vascular pathways or through other mechanisms. The UK Biobank study adjusted for cognitive performance and comorbidities but did not include white matter imaging [4].

What this means for interpreting risk in older adults

These findings suggest that daytime sleepiness and disrupted daily rhythms are not just nuisance symptoms of aging—they may be early signals of brain vulnerability. The Shanghai study suggests that excessive daytime sleepiness could help identify older adults with low Alzheimer's biomarker burden who are nonetheless at increased dementia risk [1]. That is a potentially useful group to flag, because they might be missed by amyloid-focused screening.

The rest-activity rhythm findings come from people already at risk for cognitive decline or from large cohort studies, so the strength of the association may differ in the general population. The UK Biobank analysis found that rhythm disturbances predicted delirium and progression to dementia, but the number of dementia cases was relatively small (61), so the progression estimate is less precise [4]. The white matter lesion study was cross-sectional in its rhythm-lesion analysis, meaning it cannot show whether rhythm disruption came before or after the lesions [3].

What remains uncertain is whether improving sleep or stabilizing daily rhythms would reduce dementia risk, or whether these signals are purely markers of underlying brain changes. The studies are consistent with a causal pathway involving white matter injury, but they do not prove it. For now, the practical takeaway is that persistent daytime sleepiness and a fragmented daily activity pattern in an older adult are worth paying attention to, especially when other vascular risk factors are present.

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