Abstract
Cross-sectional studies show that activity fluctuations in healthy young adults possess robust temporal correlations that become altered with aging, and in dementia and depression. This study was designed to test whether or not within-subject changes of activity correlations (i) track the clinical progression of dementia, (ii) reflect the alterations of depression symptoms in patients with dementia, and (iii) can be manipulated by clinical interventions aimed at stabilizing circadian rhythmicity and improving sleep in dementia, namely timed bright light therapy and melatonin supplementation. We examined 144 patients with dementia (70–96 years old) who were assigned to daily treatment with bright light, bedtime melatonin, both or placebos only in a 3.5-year double-blinded randomized clinical trial. We found that activity correlations at temporal scales <~2 hours significantly decreased over time and that light treatment attenuated the decrease by ~73%. Moreover, the decrease of temporal activity correlations positively correlated with the degrees of cognitive decline and worsening of mood though the associations were relatively weak. These results suggest a mechanistic link between multiscale activity regulation and circadian/sleep function in dementia patients. Whether temporal activity patterns allow unobtrusive, long-term monitoring of dementia progression and mood changes is worth further investigation.
Highlights
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To better understand the clinical relevance of multiscale activity regulation and the underlying mechanisms, we examined data collected longitudinally to test four hypotheses: (1) temporal activity correlations decrease gradually over time in dementia patients; (2) long-term bright light with melatonin therapy attenuates the degradation in temporal activity correlations over time; (3) the degree of the decline in activity correlations positively correlates with the worsening of depression symptoms in patients/individuals with dementia; and (4) the degree of the decline in activity correlations positively correlates with cognitive declines
The current study provides the first analysis of within-subject changes of the temporal organization over time, the relevance of such changes to functional declines, and the effect of clinical interventions in people with dementia
Summary
The Harvard community has made this article openly available. Please share how this access benefits you. The decrease of temporal activity correlations positively correlated with the degrees of cognitive decline and worsening of mood though the associations were relatively weak These results suggest a mechanistic link between multiscale activity regulation and circadian/sleep function in dementia patients. We examined whether a nonlinear measure of activity patterns based on temporal correlations in spontaneous motor activity fluctuations can be used to objectively assess cognitive and behavioral changes in patients with dementia. In healthy young individuals these fluctuations are not random but possess robust temporal correlations that are similar at different time scales and independent of mean activity levels[6,7]. Activity fluctuations in older individuals with dementia are more random with reduced correlations at time scales >~2 hours; and the perturbation is more pronounced in AD patients with www.nature.com/scientificreports/
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