Characteristics of Hypothalamic Structural and Functional MRI Changes in Alzheimer's Disease Patients With Sleep Dysfunction

Sleep dysfunction (SD) is common in Alzheimer's disease (AD) and associated with cognitive impairment. The hypothalamus regulates circadian rhythms and exhibits AD pathology; we investigated the abnormal alterations in the structure and function of the hypothalamus in AD patients with sleep dysfunction (ADSD). Twelve ADSD patients, 19 AD patients without sleep dysfunction (ADNSD), and 13 age- and sex-matched healthy controls (HCs) underwent neuropsychological assessments, including the Montreal Cognitive Assessment and Mini-Mental State Examination, and sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). Hypothalamic volume and its subregional volumes were derived from T1-weighted magnetic resonance imaging (MRI), whereas resting-state functional MRI was used to assess functional connectivity (FC) with the hypothalamus. We found reduced volumes in the bilateral anterior inferior and left anterior superior hypothalamic subregions in both AD groups compared to HCs. Compared to HCs, the ADNSD group exhibited enhanced hypothalamic FC with the left middle frontal gyrus (MFG) and right inferior parietal lobule (IPL) and reduced FC with right MFG, whereas the ADSD group exhibited enhanced FC with the left MFG and right superior frontal gyrus and reduced FC with right IPL. Furthermore, the ADSD group exhibited reduced FC with the right IPL and enhanced FC with right MFG relative to the ADNSD group. Crucially, within the combined AD cohort, FC with the right IPL was negatively correlated with PSQI, whereas FC with the right MFG was positively correlated. These findings indicate the hypothalamus is a critical target for interventions to improve sleep quality and cognition in AD.