Associations of 24‐h rest‐activity patterns with plasma markers of neurodegeneration and Alzheimer’s disease pathology in cognitively unimpaired individuals

Abstract

AbstractBackgroundAltered 24‐h rest‐activity rhythms have been previously associated with higher burden of Alzheimer’s disease (AD) pathological hallmarks, as measured with positron emission tomography or cerebrospinal fluid collection. Recent developments in fluid biomarkers now allow to non‐invasively measure levels of AD‐related pathology in the plasma. Here, we examined whether actigraphy‐derived 24‐h rest‐activity patterns could be linked to plasma markers of neurodegeneration and AD pathology in a sample of cognitively unimpaired participants.MethodNinety‐three asymptomatic individuals (mean age = 59.73 ± 13.74 y., range = 30 – 85 y., 48 females, Table 1) underwent 10 days of actigraphic recordings, and blood drawing. Standard non‐parametric indices of 24‐h rest‐activity rhythm fragmentation (intradaily variability, IV) and stability (interdaily stability, IS) were extracted using the GGIR package (v2.8‐2) in R. Plasma concentrations of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), 40 and 42 amino acid‐long amyloid‐β (Aβ40 and Aβ42, respectively), total tau, and phosphorylated tau at threonine 181 (pTau181) or threonine 231 (pTau231) were measured using Single molecule array technology.ResultMultiple linear regression models adjusted for age, sex, education, and body mass index, showed that worse rest‐activity rhythm fragmentation, as indicated by higher IV values, was strongly associated with elevated levels of plasma NfL (t = 4.53, p < .0001, Figure 1), but also with higher levels of plasma GFAP (t = 2.44, p = .02, Figure 2) and lower plasma Aβ42/40 ratio (t = ‐2.23, p = .03, Figure 2). Similarly, increased day‐to‐day rest‐activity rhythm stability, as indicated by higher IS values, was associated with lower levels of plasma NfL (t = ‐2.37, p = .02, Figure 1). By contrast, no significant relationships were found between IV or IS values and total tau or phosphorylated tau plasma biomarkers (all p > .27).ConclusionThese findings provide further evidence that disrupted rest‐activity patterns, in particular fragmentation of rest‐activity rhythms, may constitute a sensitive marker of incipient AD pathology and neurodegeneration in cognitively unimpaired individuals. Our study therefore highlights the clinical utility of monitoring rest‐activity patterns for improved detection of individuals at‐risk for neurodegenerative diseases, including AD.