Progression of Dementia Assessed by Temporal Correlations of Physical Activity: Results From a 3.5-Year, Longitudinal Randomized Controlled Trial

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.

Effect of long-term nutraceutical and dietary supplement use on cognition in the elderly: a 10-year systematic review of randomised controlled trials

“…et al (53) and Snitz et al (54) Ginkgo biloba USA Global composite score (P = 0•03), verbal memory (P = 0•007) and TICS (P = 0•04) scores improved compared with placebo but only in participants that had previously participated in PHS1 (aspirin study) Hu et al (57) Melatonin The Netherlands Double-blind, placebocontrolled RCT Therefore it is difficult to draw broad conclusions from this study. The initial cognitive testing was conducted face to face; however, the end point tests were performed over the phone, potentially limiting the utility of these findings.…”

“…Variation between different stages of cognitive impairment across the included trials makes it difficult to make conclusions regarding the overall usefulness of the nutraceuticals. Only seven studies in this review included individuals with dementia (44,47,52,(57)(58)(59) , and three included studies (11,36,46) used individuals with MCI. Certainly, there is difficulty in conducting trials in individuals with cognitive impairment and several studies in this review required caregiver assistance or approval to participate from a proxy.…”

“…The MMSE (or equivalent variant) was the most commonly used, which was applied in eighteen studies (11,30,36,37,43,44,(46)(47)(48)(49)(52)(53)(54)(55)(57)(58)(59)(60) ; whereas the TICS or TICS-modified (TICS-m) was used in nine studies (36,37,40,41,46,50,53,54,56) and the ADAS-cog was used in six studies (37,44,(52)(53)(54)58) , respectively.…”

Fractal regulation and incident Alzheimer's disease in elderly individuals

“…We note that gaps identified in data recordings (see 2.2 Data collection and pre-processing) were skipped when performing the detrended fluctuation analysis to avoid any potential effects of interpolating missing data and/or manipulating the signal (e.g., stitching the rest data after removing the missing data) on F( n ) [ 10 ]. Previous studies showed that cognitive impairment in patients with dementia is associated with smaller α at time scales < ~ 90 minutes [ 11 ]. Thus, we quantified α at time scales between 1.25 and 90 minutes in this study ( Fig.…”

“…Our previous cross sectional study revealed that FR in motor activity is degraded with aging and in Alzheimer’s disease (AD) [ 10 ], and in a short longitudinal study, we found that the degradation of FR in motor activity over time is associated with cognitive decline in very old adults with dementia [ 11 ]. The goal of the present study is to determine whether FR perturbation at baseline in older individuals without dementia is associated with increased risk of the development of Alzheimer’s dementia and mild cognitive impairment (MCI) and rate of cognitive decline.…”