Associations of rest-activity patterns with amyloid burden, medial temporal lobe atrophy, and cognitive impairment

Abstract

Background We sought to investigate the possible associations of rest-activity patterns with cortical amyloid burden, medial temporal lobe (MTL) neurodegeneration, and cognitive function in patients in the early stage of cognitive impairment. Methods Rest-activity patterns were assessed in 100 participants (70 with mild cognitive impairment and 30 with mild dementia) using wrist actigraphy. All participants underwent 18 F-flutemetamol positron emission tomography (PET) imaging to quantify cortical amyloid burden, structural brain magnetic resonance imaging (MRI) to quantify MTL grey matter volume, neuropsychological testing, and clinical diagnosis. We used multiple linear regression models adjusted for covariates, including demographics, diabetes, hypertension, depressive symptom, psychotropic medication, sleep medication, weekend effect, and apolipoprotein-ε allele status. Findings After adjusting for possible confounders, we found that the midline estimation of statistic of rhythm (MESOR) associated positively with frontal/executive function (estimate = 1.17, standard error [SE] = 0.37, p = 0.002). The least active 5-h (L5) onset time associated positively with MTL grey matter volume and memory function (estimate = 1.24, SE = 0.33, p = 0.001, and estimate = 3.77, SE = 1.22, p = 0.003, respectively), particularly in amyloid-negative participants. Additional path analysis revealed that MTL grey matter volume partially mediated the association between L5 onset time and memory function in amyloid-negative participants. Interpretation Decreased MESOR and advanced L5 onset time may be useful as early signs of cognitive decline or MTL neurodegeneration. Furthermore, amyloid pathology may act as a moderator of the relationships between rest-activity patterns, neurodegeneration, and cognitive function. Funding Korea Centres for Disease Control and Prevention (#4845–303); National Research Foundation of Korea (2019M3C7A1031905, 2019R1A5A2026045).

Functional MRI-Specific Alterations in Executive Control Network in Mild Cognitive Impairment: An ALE Meta-Analysis

“…Areas of the ECN that showed an upward trend are mainly in the occipital, temporal, and subcortical regions with a small portion also rising in the frontal and parietal regions, which may be the compensatory mechanism of the disruption of frontal and parietal lobes in MCI patients (Valera-Bermejo et al, 2020). It is also well-established that the frontal and parietal regions are crucial aspects of the ECN, which send rich sensory information not only for movement controls, but also for other cognitive abilities, especially in executive function (Roh et al, 2020). Although the results reveal an increase in the frontal and parietal regions, these discrepant findings may be related to the different stages of MCI (Cosentino et al, 2020).…”

Associations of Actigraphy-derived Rest-activity Patterns and Circadian Phase Parameters With Clinical Symptoms and Polysomnography Results in Patients With Chronic Insomnia

“…The mean and median values of these parameters did not deviate substantially from our previous ndings in elderly individuals with cognitive impairments and other studies assessing similar parameters. 7,8,21 PSG results indicated that total sleep time and wake after sleep onset were approximately 361.9 min and 14.4%, respectively. 2).…”

“…[3][4][5] Alterations in restactivity patterns and circadian phase have also been reported in patients with bipolar disorder, Parkinson's disease, and Alzheimer's disease. [6][7][8][9][10] Indeed, circadian rhythm disruptions and sleep di culties are frequently observed in patients with these conditions, suggesting pathophysiological roles for sleep and circadian alterations in disease initiation and progression. 11 Nevertheless, rest-activity patterns, circadian phase alterations, and their clinical implications in patients with insomnia remain poorly characterized.…”

Rest-Activity Pattern and Circadian Phase Alterations Across the Alzheimer’s Disease Clinical Spectrum

“…However, multinomial logistic regression suggested that participants showing delayed acro-phase upon cosinor analysis were more likely to present with worse cognitive function. Another study conducted in the Republic of Korea that enrolled 70 participants with MCI and 30 with mild dementia suggested that amyloid-positive participants had a later L5 onset time on nonparametric analysis as compared with their amyloid-negative counterparts [31]. However, these researchers did not evaluate rest-activity pattern or circadian phase in cognitively normal older adults or in healthy controls.…”

“…Our team presents similar results with respect to insights into the large individual variability among rest-activity patterns and circadian phase parameters in this regard. For example, in a prior paper, we extracted data on rest-activity patterns and circadian phase parameters from 100 patients with MCI or mild dementia enrolled in the Biobank Innovation for Chronic Cerebrovascular Disease with Alzheimer's Disease Study and found that rest-activity patterns and circadian phase parameters were normally distributed with a large variance [31]. Additionally, recently published articles have evaluated not only sleep, rest-activity patterns, and circadian phase parameters, but have also investigated postmortem neocortical microglial marker gene expression with respect to measured cognitive function [37].…”