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 ¹⁸F-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).

Keywords: Amyloid burden; Cognition; Dementia; Medial temporal lobe; Mesor, L5 onset time; Mild cognitive impairment; Rest-activity patterns.