Resting-State Functional Connectivity Changes in Older Adults with Sleep Disturbance and the Role of Amyloid Burden

Abstract

Sleep and related disorders could lead to changes in various brain networks, but little is known about the role of amyloid β (Aβ) burden—a key Alzheimer’s disease (AD) biomarker—in the relationship between sleep disturbance and altered resting state functional connectivity (rsFC) in older adults. This cross-sectional study examined the association between sleep disturbance, Aβ burden, and rsFC using a large-scale dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Sample included 489 individuals (53.6% cognitively normal, 32.5% mild cognitive impairment, and 13.9% AD) who had completed sleep measures (Neuropsychiatric Inventory), PET Aβ data, and resting-state fMRI scans at baseline. Within and between rsFC of the Salience (SN), the Default Mode (DMN) and the Frontal Parietal network (FPN) were compared between participants with sleep disturbance versus without sleep disturbance. The interaction between Aβ positivity and sleep disturbance was evaluated using linear regressions, controlling for age, diagnosis status, gender, sedatives and hypnotics use, and hypertension. Although no significant main effect of sleep disturbance was found on rsFC, a significant interaction term emerged between sleep disturbance and Aβ burden on rsFC of SN (β=0.11, P=0.006). Specifically, sleep disturbance was associated with SN hyperconnectivity, only with the presence of Aβ burden. Sleep disturbance may lead to altered connectivity in the SN when Aβ is accumulated in the brain. Individuals with AD pathology may be at increased risk for sleep-related aberrant rsFC; therefore, identifying and treating sleep problems in these individuals may help prevent further disease progression.

Sleep and physical activity measures are associated with resting-state network segregation in non-demented older adults

“…Additionally, the observation that shorter sleep duration was associated with greater salience network connectivity may be consistent with findings indicating that insomnia symptoms (which are reflective of reduced sleep duration or quality) are associated with higher insula connectivity, a critical part of the salience network ( Chen et al, 2014 , Cheng et al, 2022 ). It is also in line with a recent investigation among individuals across the AD spectrum that found that subjective sleep disturbances were associated with hyperconnectivity within the salience network in individuals who were amyloid positive vs. negative ( Kim et al, 2023 ).…”

“…Finally, Model 3 (fully adjusted) tested whether the independent association of TVPA, TST, and SE with rsFC were moderated by PET amyloid status (which can influence relationships among sleep, physical activity, and resting-state connectivity ( Kim et al, 2023 , Lin et al, 2020 , Pruzin et al, 2022 )), by additionally including an interaction term PET amyloid status x [PA or sleep measure]) in the fully adjusted model. Non-significant interaction terms between diagnosis and PET amyloid status with PA and sleep metrics are not reported.…”