Brain structural alterations in young women with premature ovarian insufficiency: Implications for dementia risk

Abstract

INTRODUCTION: Premature ovarian insufficiency (POI), marked by ovarian function loss before age 40, is linked to a higher risk of dementia, including Alzheimer's disease (AD). However, the associated brain structural changes remain poorly understood. METHODS: We analyzed T1-weighted and diffusion tensor imaging in 33 idiopathic POI women and 51 healthy controls, using voxel-based, surface-based morphometry, and network analyses to assess gray matter volume (GMV), cortical thickness, and brain connectivity. RESULTS: Women with POI showed significant GMV and cortical thickness reductions in the frontal, parietal, and temporal regions (p < 0.05), alongside impaired connectivity with key regions such as the hippocampus, thalamus, and amygdala (p < 0.05). Younger POI subgroups exhibited changes in more widespread brain regions. In additionally, notable atrophy was observed in specific hippocampal and thalamic subregions in POI (p < 0.05). DISCUSSION: This preliminary study suggests early neurodegenerative patterns in POI, potentially contributing to dementia risk. Further research is needed to explore the underlying mechanisms and potential interventions. Highlights: We evaluated brain structural changes in participants with idiopathic premature ovarian insufficiency (POI). The observed brain alterations in POI participants closely resemble those seen in early dementia, including regions specifically associated with Alzheimer's disease (AD). These findings highlight the critical need for early interventions to reduce the long-term risks of cognitive impairment and dementia in women with POI.