Hypothalamic microstructure and function are related to body mass, but not mental or cognitive abilities across the adult lifespan.

Physical, mental, and cognitive resources are essential for healthy aging. Aging impacts on the structural integrity of various brain regions, including the hippocampus. Even though recent rodent studies hint towards a critical role of the hypothalamus, there is limited evidence on functional consequences of age-related changes of this region in humans. Given its central role in metabolic regulation and affective processing and its connections to the hippocampus, it is plausible that hypothalamic integrity and connectivity are associated with functional age-related decline. We used data of n = 369 participants (18-88 years) from the Cambridge Centre for Ageing and Neuroscience repository to determine functional impacts of potential changes in hypothalamic microstructure across the lifespan. First, we identified age-related changes in microstructure as a function of physical, mental, and cognitive health and compared those findings to changes in hippocampal microstructure. Second, we investigated the relationship of hypothalamic microstructure and resting-state functional connectivity and related those changes to age as well as physical health. Our results showed that hypothalamic microstructure is not affected by depressive symptoms (mental health), cognitive performance (cognitive health), and comparatively stable across the lifespan, but affected by body mass (physical health). Furthermore, body mass changes connectivity to limbic regions including the hippocampus, amygdala, and nucleus accumbens, suggesting functional alterations in the metabolic and reward systems. Our results demonstrate that hypothalamic structure and function are affected by body mass, focused on neural density and dispersion, but not inflammation. Still, observed effect sizes were small, encouraging detailed investigations of individual hypothalamic subunits.