Premature and early menopause and neuroimaging biomarkers of neurodegenerative diseases: a systematic review.

BACKGROUND: Premature and early menopause involve ovarian hormone deprivation, which may contribute to later-life vulnerability to cognitive decline and neurodegenerative diseases. Multimodal neuroimaging biomarkers provide a means of detecting structural, microstructural, functional, and molecular brain changes before clinical symptoms emerge. METHODS: Following PRISMA guidelines, we conducted a systematic search of PubMed. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Neuroimaging modalities included in vivo structural magnetic resonance imaging (MRI) (n = 16), functional MRI (n = 2), diffusion tensor imaging (n = 4), and positron emission tomography (n = 3). Women with premature or early menopause showed regionally specific structural and microstructural brain abnormalities, including lower gray-matter volume or cortical thickness in medial temporal, frontal, and basal forebrain regions; white-matter microstructural abnormalities in the anterior corona radiata, corpus callosum, and fronto-occipital tracts; and reduced posterior hippocampal activation during memory encoding. In one study, earlier age at menopause was associated with higher amyloid-β (Aβ) burden in women who underwent premenopausal bilateral oophorectomy (PBO), and elevated tau deposition was reported predominantly among women with higher Aβ levels. CONCLUSION: Converging multimodal neuroimaging evidence suggests that premature and early menopause may be associated with Alzheimer's disease-relevant brain changes. However, findings remain heterogeneous, and longitudinal studies are needed to clarify the temporal relationships between ovarian hormone deprivation and neurodegeneration, and to determine the clinical implication of these findings.