Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults

INTRODUCTION: Sleep dysfunction in those at higher risk of dementia may be associated with early structural changes to the hypothalamus. METHODS: We used multivariate regression to analyze self-reported sleep (Pittsburgh Sleep Quality Index [PSQI]) from cognitively healthy participants in the PREVENT Dementia and Alzheimer's and Families (ALFA) studies (n = 1939), stratified by apolipoprotein E (APOE) genotype as homozygotes, heterozygotes, and non-carriers. FreeSurfer was used to extract hypothalamic subunit volumes from T1-weighted magnetic resonance images. RESULTS: APOE ε4 homozygotes had a larger anterior–superior hypothalamus compared to heterozygotes and non-carriers, an effect which was driven by younger people in the cohort. APOE ε4 carriers had a higher PSQI global score after age 55, and smaller anterior–superior and tubular–superior subunits were associated with more sleep disturbances. Sleep duration and efficiency worsened with age, but only in participants with a small anterior–inferior hypothalamus. DISCUSSION: This suggests that aging and APOE ε4 are associated with hypothalamic changes, highlighting mechanisms linking sleep dysfunction to dementia. Highlights: Apolipoprotein E (APOE) ε4 homozygotes ha a larger anterior–superior hypothalamus. APOE ε4 carriers have worse sleep, but only after age 55. Worse sleep in APOE ε4 carriers was associated with smaller hypothalamic subunits. Higher age was associated with worse sleep in people with a small hypothalamus.