Self‐reported sleep quality interacts with Alzheimer’s disease biomarkers on brain structure and metabolism in cognitively unimpaired adults

Abstract

AbstractBackgroundPoor sleep quality has been associated with a greater burden of AD pathology and altered brain structure in cognitively unimpaired (CU) individuals. However, there is a lack of studies analysing associations between sleep quality and brain structure and function, while taking into account AD pathology. We aimed to test associations of self‐reported sleep quality with grey matter volume (GMv) and brain glucose metabolism in middle‐aged CU and sought interactions with biomarkers of AD pathology.MethodThis study included 340 CU adults from the ALFA+ cohort (Table 1). Sleep quality was assessed using the Pittsburgh sleep quality index (PSQI) questionnaire. We used Statistical Parametric Mapping software to process T1‐weighted MRI and [18F]fluorodeoxyglucose (FDG) PET scans, and analyse voxel‐wise associations with sleep quality. We created separate general linear models with GMv and FDG metabolism as dependent variables, and PSQI total score, age, sex, APOE‐ε4 status, education level and sleep medication as predictors. GMv analyses were additionally corrected for total intracranial volume. In additional models, CSF Aβ42/40 and phosphorylated tau (p‐tau181) ‐ were entered as covariates. We also tested the interaction between PSQI and AD biomarker status, (A+: Aβ42/40<0.071, T+: p‐tau181>24 pg/mL). Statistical significance was set at p<0.005 uncorrected for multiple comparisons, with a cluster‐level threshold of 50 voxels.ResultHigher PSQI scores, indicating poorer sleep quality, were significantly associated with lower GMv in the left occipital fusiform gyrus and right middle orbitofrontal gyrus, and with lower brain glucose metabolism in the right temporal pole and parahippocampal gyrus (Figure 1.). Interaction analyses showed poorer sleep quality is associated with higher GMv in bilateral supramarginal gyrus in A+T‐ vs A‐T‐, and with higher glucose metabolism in bilateral thalamus in A+T+ vs A‐T‐ individuals (Figure 2).ConclusionPoorer sleep quality is associated with lower GMv and glucose metabolism in CU individuals, involving AD‐vulnerable regions. Sleep quality interacted with altered AD biomarkers to determine GMv and glucose metabolism in brain areas in which they are commonly found to be increased in preclinical AD stages. Altogether, our findings support sleep quality as a relevant factor early in the AD continuum.