Association of Rest-Activity Rhythm and Risk of Developing Dementia or Mild Cognitive Impairment in the Middle-Aged and Older Population: Prospective Cohort Study

Abstract

Background: The relationship between 24-hour rest-activity rhythms (RARs) and risk for dementia or mild cognitive impairment (MCI) remains an area of growing interest. Previous studies were often limited by small sample sizes, short follow-ups, and older participants. More studies are required to fully explore the link between disrupted RARs and dementia or MCI in middle-aged and older adults.

Objective: We leveraged the UK Biobank data to examine how RAR disturbances correlate with the risk of developing dementia and MCI in middle-aged and older adults.

Methods: We analyzed the data of 91,517 UK Biobank participants aged between 43 and 79 years. Wrist actigraphy recordings were used to derive nonparametric RAR metrics, including the activity level of the most active 10-hour period (M10) and its midpoint, the activity level of the least active 5-hour period (L5) and its midpoint, relative amplitude (RA) of the 24-hour cycle [RA=(M10-L5)/(M10+L5)], interdaily stability, and intradaily variability, as well as the amplitude and acrophase of 24-hour rhythms (cosinor analysis). We used Cox proportional hazards models to examine the associations between baseline RAR and subsequent incidence of dementia or MCI, adjusting for demographic characteristics, comorbidities, lifestyle factors, shiftwork status, and genetic risk for Alzheimer's disease.

Results: During the follow-up of up to 7.5 years, 555 participants developed MCI or dementia. The dementia or MCI risk increased for those with lower M10 activity (hazard ratio [HR] 1.28, 95% CI 1.14-1.44, per 1-SD decrease), higher L5 activity (HR 1.15, 95% CI 1.10-1.21, per 1-SD increase), lower RA (HR 1.23, 95% CI 1.16-1.29, per 1-SD decrease), lower amplitude (HR 1.32, 95% CI 1.17-1.49, per 1-SD decrease), and higher intradaily variability (HR 1.14, 95% CI 1.05-1.24, per 1-SD increase) as well as advanced L5 midpoint (HR 0.92, 95% CI 0.85-0.99, per 1-SD advance). These associations were similar in people aged <70 and >70 years, and in non-shift workers, and they were independent of genetic and cardiovascular risk factors. No significant associations were observed for M10 midpoint, interdaily stability, or acrophase.

Conclusions: Based on findings from a large sample of middle-to-older adults with objective RAR assessment and almost 8-years of follow-up, we suggest that suppressed and fragmented daily activity rhythms precede the onset of dementia or MCI and may serve as risk biomarkers for preclinical dementia in middle-aged and older adults.

Keywords: RAR; actigraphy; circadian rhythm; cognitive decline; cognitive impairment; dementia; rest-activity rhythms.

Figure 1

Rest-activity rhythm and risk of developing dementia or MCI. Survival curves for dementia or MCI since baseline (actigraphy assessment) for (A) participants with lower RA (1st quartile) and higher RA (4th quartile), (B) participants with lower M10 (1st quartile) and higher M10 (4th quartile), (C) participants with lower L5 (1st quartile) and higher L5 (4th quartile), (D) participants with lower IV (1st quartile) and higher IV (4th quartile), (E) participants with lower amplitude (1st quartile) and higher amplitude (4th quartile), (F) participants with lower IS (1st quartile) and higher IS (4th quartile), (G) participants with earlier L5 midpoint (1st tertile) and later L5 midpoint (3rd tertile), (H) participants with earlier M10 midpoint (1st tertile) and later M10 midpoint (3rd tertile), and (I) participants with earlier acrophase (1st tertile) and later acrophase (3rd tertile). IS: interdaily stability; IV: intradaily variability; L5: activity level of the least active 5-hour period; M10: activity level of the most active 10-hour period; MCI: mild cognitive impairment; RA: relative amplitude.