Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women

Abstract

Objective Previous cross-sectional studies have observed alterations in activity rhythms in dementia patients but the direction of causation is unclear. We determined whether circadian activity rhythms measured in community-dwelling older women are prospectively associated with incident dementia or mild cognitive impairment (MCI). Method Activity rhythm data were collected from 1,282 healthy community-dwelling women from the Study of Osteoporotic Fractures cohort (mean age 83 years) with wrist actigraphy for a minimum of three 24-hour periods. Each participant completed a neuropsychological test battery and had clinical cognitive status (dementia, MCI, normal) adjudicated by an expert panel approximately 5 years later. All analyses were adjusted for demographics, BMI, functional status, depression, medications, alcohol, caffeine, smoking, health status, and co-morbidities. Results After 4.9 years of follow-up, 195 (15%) women had developed dementia and 302 (24%) had developed MCI. Older women with decreased activity rhythms had a higher likelihood of developing dementia or MCI when comparing those in the lowest quartiles of amplitude (Odds ratio[OR]=1.57,95% CI,1.09–2.25) or rhythm robustness (OR=1.57,95%CI,1.10–2.26) to women in the highest quartiles. An increased risk of dementia or MCI (OR=1.83,95% CI,1.29–2.61) was found for women whose timing of peak activity occurred later in the day (after 3:51PM) when compared to those with average timing (1:34PM–3:51PM). Interpretation Older, healthy women with decreased circadian activity rhythm amplitude and robustness, and delayed rhythms have increased odds of developing dementia and MCI. If confirmed, future studies should examine whether interventions (physical activity, bright light exposure) that influence activity rhythms will reduce the risk of cognitive deterioration in the elderly.

Association between circadian rhythms, sleep and cognitive impairment in healthy older adults: an actigraphic study

“…Our analysis of the circadian rhythm in gross behaviour shows that there are not significant differences between the declined and the intact groups in terms of the rhythm amplitude, MESOR or percentage of variance in the activity rhythm explained by the 24-h co-sinor regression model, but that those in the declined group showed a peak in their activity rhythm that was significantly later than that for the intact group. This finding appears to be in agreement with the recent report from Tranah et al (2011), who in a large prospective study found that delayed behavioural rhythm was a significant predictor of developing MCI or dementia. However, these authors also report that dampened circadian amplitude and robustness of the rhythm were also predictors of MCI/dementia, findings that are not recapitulated in our study.…”

“…These authors report that dampened activity rhythms was a significant predictor for the development of both dementia and MCI, as was a later peak of activity rhythm, suggesting that circadian amplitude and phase may be significant factors in the development of these conditions. Interestingly, these effects were also found to be independent of sleep effects (Tranah et al (2011)). The role of actigraphically determined daytime activity in MCI and dementia was further examined by Kuhlmei et al (2011) who report that reduced activity in both dementia and MCI was present when apathy was also present.…”

“…Aside from the significant circadian dysfunction that is observed in dementia, there is also evidence that age-related cognitive decline in healthy older adults is predicted by the fragmentation of the circadian rhythm in locomotor behaviour (Oosterman et al 2009). Further evidence that circadian rhythm disturbance may be important in mild cognitive impairment was recently provided by the study of Tranah et al (2011) who examined actigraphic activity patterns of a large cohort of community-dwelling women in a longitudinal study. These authors report that dampened activity rhythms was a significant predictor for the development of both dementia and MCI, as was a later peak of activity rhythm, suggesting that circadian amplitude and phase may be significant factors in the development of these conditions.…”

“…The role of actigraphically determined daytime activity in MCI and dementia was further examined by Kuhlmei et al (2011) who report that reduced activity in both dementia and MCI was present when apathy was also present. Factors related to the circadian system, such as overall activity levels and sleep parameters also appear to be important factors contributing to age-related cognitive decline (Blackwell et al 2011;Barnes et al 2008). To add to the burgeoning evidence base on circadian rhythm disturbance in age-related cognitive decline we have conducted a study using actigraphy and a neurocognitive battery to examine the relationship between circadian rhythms, sleep, ambulatory activity and cognition in a group of community-dwelling older adults.…”

The Circadian System in Alzheimer’s Disease: Disturbances, Mechanisms, and Opportunities

“…Further evidence for the importance of circadian rhythms in AD is provided by the finding that higher daytime activity levels and lower nocturnal activity (i.e., consolidated, nonfragmented sleep/wake cycle organization), is strongly associated with increased wellbeing and functional status (20). Results from a large prospective study indicate that changes in circadian activity patterns (decreased rhythm amplitude, phase-delays) are significant predictors of subsequent AD or mild cognitive impairment, suggesting that compromised rhythms might be a preclinical phenomenon (21). Another point of interest is that anti-psychotic medication used in the clinical management of AD might impact on circadian rhythms (22), because these medications might impact on the molecular components of the circadian system (23).…”