Hypothalamic MRI-derived Microstructure is Associated with Neurocognitive Aging in Humans

The hypothalamus regulates homeostasis across the lifespan and is emerging as a regulator of aging. In murine models, aging-related changes in the hypothalamus, including microinflammation and gliosis, promote accelerated neurocognitive decline. We investigated relationships between hypothalamic microstructure and features of neurocognitive aging, including cortical thickness and cognition, in a cohort of community-dwelling older adults (age range 65-97 years, n=124). Hypothalamic microstructure was evaluated with two magnetic resonance imaging diffusion metrics: mean diffusivity (MD) and fractional anisotropy (FA), using a novel image processing pipeline. Hypothalamic MD was cross-sectionally positively associated with age and it was negatively associated with cortical thickness. Hypothalamic FA, independent of cortical thickness, was cross-sectionally positively associated with neurocognitive scores. An exploratory analysis of longitudinal neurocognitive performance suggested that lower hypothalamic FA may predict cognitive decline. No associations between hypothalamic MD, age, and cortical thickness were identified in a younger control cohort (age range 18-63 years, n=99). To our knowledge, this is the first study to demonstrate that hypothalamic microstructure is associated with features of neurocognitive aging in humans.