Work

Relationships between locus coeruleus microstructural integrity, sleep, and 24‐h rest‐activity rhythm in the context of plasma markers of Alzheimer’s disease: a 7T MRI study of asymptomatic older individuals

Year: 2024

Type: article

Abstract: Background The brainstem locus coeruleus (LC) is among the first sites of Alzheimer’s disease (AD) pathology, accruing hyperphosphorylated tau as early as in young adulthood. Animal studies indicate that the LC is crucially involved in sleep‐wake regulation, a recently established factor contributing to AD‐related pathophysiological processes. However, the associations between LC integrity and sleep‐wake phenotypes in the context of AD pathology remain poorly characterized in humans. Here, we examined the relationships between in vivo 7T MRI‐derived LC microstructural integrity and objective measures of sleep or circadian rest‐activity patterns at different levels of AD pathology. Method Thirty‐eight cognitively unimpaired older adults (mean age = 66.53±9.22y., 18 females, Table 1) underwent dedicated LC imaging combined with whole‐brain neurite orientation dispersion and density imaging (NODDI) at 7T to extract microstructural indices of neurite density (NDI) and orientation dispersion (ODI) within the bilateral LC. In addition, they performed 10 days of actigraphy from which objective measures of sleep (average sleep duration and proportion of wake after sleep onset (WASO%)) and 24‐h rest‐activity rhythm (intradaily variability (IV), interdaily stability (IS)) were computed. Plasma concentrations of GFAP and phosphorylated tau epitopes were derived from blood samples using Single molecule array technology (p‐tau181, p‐tau231) and the Meso Scale Discovery platform (p‐tau217). Result Multiple linear regression models adjusted for age, sex, BMI, and actigraphic recording duration showed that higher LC ODI was associated with longer sleep duration (t(32) = 3.93, p<.001) and lower WASO% (t(32) = ‐2.33, p = .03, Figure 1). Importantly, interaction models revealed a synergistic deleterious effect of displaying lower LC ODI and elevated levels of p‐tau217 on WASO% as well as cross‐over interactions between LC NDI or ODI and p‐tau181, p‐tau217, or GFAP on IV and IS (Figure 2). Conclusion These preliminary results suggest that poorer LC microstructural integrity is linked to worse proxy measures of sleep quality and circadian rest‐activity patterns, but only in individuals with elevated levels of AD pathology. Our findings therefore provide novel evidence of the involvement of the LC in sleep‐wake phenotypes in older adults in the context of AD pathophysiological processes, and have implications for the identification of individuals at higher risk for AD‐related sleep‐wake disturbances.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz.085381

Author: Maxime Van Egroo

Institutions: Maastricht University, Gordon Center for Medical Imaging, Massachusetts General Hospital

Language: English

Topic: Dementia and Cognitive Impairment Research

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,000