Wrist Sensors Trace Circadian Timing to Measured Tau, Not Just Diagnosis

A month of round-the-clock wrist accelerometry in 68 older adults with early cognitive impairment found that earlier, not later, timing of peak daily activity tracked with higher amyloid-beta and tau on PET scans, and that fragmented daily rhythms tracked with tau in later-stage brain regions. The study is cross-sectional and cannot say which came first.

A cross-sectional study published in Brain Communications reports that circadian rhythm measures taken from a month of wrist accelerometry associate directly with measured amyloid-beta and tau in older adults with early, subclinical cognitive impairment, a step beyond the diagnosis-only or risk-only associations that have dominated prior actigraphy research. Researchers at the University of Southern California analyzed baseline accelerometer data from 68 participants (mean age 66.8, range 55 to 80, 63.2 percent female, 26.5 percent APOE4 carriers) enrolled in the Lifestyle Enriching Activities for Research in Neuroscience trial, all of whom scored at least one standard deviation below age-matched norms on cognitive testing without yet meeting criteria for mild cognitive impairment.

Participants wore GENEActiv devices for an average of 31.8 days, from which the team derived acrotime, the average clock time of a person's daily activity peak, and intradaily variability, a measure of how fragmented that daily pattern is. After adjusting for age, sex, APOE4 status and education, earlier acrotime was associated with higher composite amyloid-beta and with higher tau across Braak staging regions on PET imaging; the amyloid association was stronger in APOE4 carriers than non-carriers. Higher intradaily variability was associated with higher tau specifically in Braak regions III and IV, a relationship that strengthened with age and appeared more pronounced in men. On cognitive testing, earlier acrotime tracked with worse verbal memory (measured by delayed recall on the California Verbal Learning Test), while later acrotime tracked with worse attention and processing speed on a digit symbol test, a split the authors say may reflect different underlying pathways.

A separate, exploratory mediation analysis found that tau burden across Braak regions I through IV statistically mediated the relationship between acrotime and verbal memory, meaning the tau measurement helps explain, in a statistical sense, why timing and memory moved together in this sample. The authors describe this analysis as post hoc and hypothesis-generating, not confirmatory. Earlier actigraphy research, including a 2024 community cohort study following participants for more than eight years, has linked disrupted 24-hour activity patterns to elevated future risk of Alzheimer's and Parkinson's disease diagnoses and to cognitive decline, but that work did not measure amyloid or tau directly. The new study's contribution is pairing wearable-derived circadian signals with PET-measured pathology in the same, small group of people.

The finding runs counter to a common assumption that later, more delayed activity timing signals more trouble; here it was earlier acrotime, not later, that tracked with higher pathology and worse memory, while later acrotime tracked with a different cognitive domain. The authors caution that circadian rhythm measures varied with age, sex and APOE4 status in ways that complicate any simple reading of the data, and they call for longitudinal replication before the measures could be considered informative outside a research setting.

The researchers say the next step is following participants over time to see whether circadian changes precede pathology changes or the reverse, something a single month of data collected at one point cannot establish.