Increased self‐reported sleepiness is associated with larger brain volume and less ischemic brain injury in a community sample

Abstract

AbstractBackgroundSleepiness has been associated with an increased risk of Alzheimer’s disease (AD) and vascular dementia, but few studies have investigated its association with markers of accelerated brain aging. We evaluated the association between sleepiness and MRI measures; and whether the apolipoprotein E4 (APOE4) allele status moderates this relationship.MethodWe studied 492 participants (58.8 ± 8.8 years, 49.4%M) in the Framingham Heart Study aged >40 years without significant neurological diseases, such as dementia and stroke. We used the Epworth Sleepiness Scale (ESS) to assess sleepiness. Brain MRI metrics were volumes of white matter hyperintensities (WMH), total brain, cortical gray matter (GM) and subcortical GM, all investigated as a percentage of total intracranial volume; we also identified covert brain infarcts (CBI). Linear and logistic regressions were used to assess the association between ESS scores and brain structure. Model 1 adjusted for age, age squared, sex, and time between the ESS and MRI (3.3 ± 1.0 years). Model 2 additionally adjusted for APOE4 allele carrier status, Framingham Stroke Risk Profile scores, sleep medication, body mass index, and depression. We included an interaction term between APOE4 allele status and ESS score, adjusted for model 1 covariates, to evaluate potential effect modification.ResultHigher ESS scores, indicating greater sleepiness, were associated with higher total brain volume (b = 0.33; SE = 0.13; p = 0.02), higher cortical GM volume (b = 0.26; SE = 0.12; p = 0.03), and a lower risk of CBI (OR = 0.57; 95%CI = 0.36‐0.93; p = 0.02) adjusted for both models 1 and 2 covariates. These associations were present when further adjusting for the apnea‐hypopnea index, education and habitual sleep duration. A significant interaction was observed between APOE4 and ESS scores (p = 0.008), where higher ESS was associated with higher cortical GM in non‐carriers (b = 0.43; SE = 0.14; p = 0.002). Conversely, in carriers, higher ESS was associated with lower cortical GM (b = ‐0.36; SE = 0.22; p = 0.09, trend).ConclusionIncreased self‐reported sleepiness was associated with findings of better brain health, including higher cortical GM volume and less CBI. Genetic susceptibility to AD modified this relationship, where increased sleepiness was associated with higher cortical GM volume only in APOE4 non‐carriers. Better brain health may be associated with higher self‐reported sleepiness via better cognition and self‐awareness in those who are not at increased risk of developing AD.