Sleep fragmentation is associated with lower cerebral structural integrity in females

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AbstractBackgroundSex is a risk factor for Alzheimer’s disease (AD), with females accounting for two‐thirds of all cases. Epidemiological evidence showcases that sleep disturbances also increase AD risk, with females reporting more disrupted sleep in ageing compared to males. However, little is understood about how objective measures of sleep are associated with brain structural integrity, especially regarding the role of sex. We explored associations between actigraphy‐measured sleep and regional cortical thickness in middle‐aged cognitively unimpaired (CU) adults at risk of AD.MethodsWe included 151 CU adults from the ALFASleep project (mean age 64.6 years, 64.2% females) (Table 1). Correlates of sleep quality were measured using actigraphy (Actiwatch2®, Philips Respironics) for two weeks. The cortical thickness (CTh) of the “Alzheimer’s disease (AD) signature” composite region of interest (ROI) was calculated using FreeSurfer v6.0. We performed separate general linear models with CTh as the dependent variable, and actigraphy‐derived sleep parameters [total sleep time (TST), sleep efficiency, sleep latency, wake after sleep onset (WASO) and sleep fragmentation] as the predictors of interest. All models were corrected for age, sex, APOE‐ε4 status, sleep medication use and the time difference between MRI and actigraphy data acquisition. To investigate whether sex modified these associations we performed interactions between each actigraphy measure and sex. Finally, we performed stratified analyses to understand which group was driving any significant effects.ResultsHigher sleep fragmentation was associated with lower CTh (p = 0.006) in the whole group (Figure 1). Results remained significant after correction for sleep medication use. Significant interactions were found between sex and sleep efficiency, WASO and sleep fragmentation (Table 2, Figure 2). Stratified analyses showed that, among females, lower sleep efficiency (p = 0.003), higher WASO and higher fragmentation were significantly associated with lower CTh (p<0.001), without any significant associations among males.ConclusionsIn CU, higher sleep fragmentation is associated with reduced cortical thickness in areas vulnerable to early AD‐related neurodegeneration. Importantly, in females, lower sleep efficiency, as well as higher WASO and sleep fragmentation are associated with lower integrity in AD‐vulnerable regions. These results suggest that females in the preclinical stages of AD are more vulnerable to the effects of sleep fragmentation.