Volume changes of the limbic system and their link to age-related memory decline in healthy adults.

BACKGROUND: Global population aging highlights the need to explore age-related limbic system alterations, which are closely linked to emotion, memory, and cognition. Heterogeneous volume changes of limbic subregions and their memory-related impacts in healthy aging remain poorly understood. METHODS: A total of 315 cognitively normal adults aged 20-89 years were divided into four age cohorts. T1-weighted MRI was applied to quantify volumes of core limbic subregions. Memory and general cognition were evaluated via the Mini-Mental State Examination (MMSE) and Hopkins Verbal Learning (HOP), covering immediate recall, delayed recall, and delayed recognition. Associations between regional brain volumes and memory performance were analyzed. RESULTS: Most regions of the limbic system exhibited a trend of volume reduction across all four age groups. The right anterior basal forebrain atrophied starting from young adulthood, while the fornix, left basal forebrain, and bilateral hypothalamus shrank significantly in late middle-aged and older adults, respectively. Uniquely, the volume of the left septal nucleus exhibits an abnormal increase. MMSE scores declined gradually, with accelerated loss after 65 years. Older adults exhibited lower immediate and delayed recall scores, positively correlated with the volumes of the nucleus accumbens, hypothalamus, fornix, and basal forebrain. No correlation existed between left septal nucleus volume and memory. CONCLUSION: Healthy aging causes heterogeneous limbic structural changes, which are essential for sustaining immediate and delayed memory. This advances understanding of the neural mechanisms underlying normal cognitive aging.