Different hypothalamic regions in late-onset Alzheimer's disease and aging: involvement and links with cognitive and non-cognitive features

Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) have different clinical and neuroimaging characteristics, and non-cognitive deficits usually observed are suggestive of hypothalamic dysfunctions. Here, we assessed in vivo the hypothalamic volumetry in EOAD and LOAD and explored its association with cognitive and non-cognitive features. The hypothalamus and its subunits were segmented on T1-weighted MRIs from 14 younger and 23 elderly controls (EC), 14 EOAD, and 28 LOAD. Amyloid or fluid biomarker confirmation was not available for all participants, and diagnostic classification was primarily based on clinical criteria. Volumes were correlated with cognitive (global cognition, memory) and non-cognitive (mood, body mass index) features. Lower bilateral volumes of the whole and posterior hypothalamus were observed in LOAD compared with EC (p < 0.010), while lower right anterior-inferior subunit was a common feature in patients than in controls (p = 0.007). These alterations were associated with abnormal cognition (rho ranging from -0.35 to -0.30, p < 0.041), as well as with memory (rho = 0.30, p = 0.041) and depressive mood (rho ranging from -0.82 to -0.68, p < 0.031) in the LOAD-EC pooled group. Our study provided a valuable insight into the heterogeneity of EOAD and LOAD, extending current understanding of the differential involvement of brain regions and highlighting the importance of hypothalamic involvement as a potential target for further investigation in conjunction with clinical assessment.