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Current preventive strategies fail to address the heterogeneity of postmenopausal cognitive trajectories, where some women exhibit rapid cognitive decline while others maintain sustained resilience over decades. This divergence suggests distinct neuroendocrine mechanisms that remain poorly understood and untargeted by current interventions. Given estrogen's fundamental role in brain function, compensatory enhancement of brain\u2010local estrogen synthesis supports synaptic integrity and promotes resilience against neurodegeneration. Parvalbumin\u2010positive (PV) interneurons enhance synaptic activity\u2010dependent brain\u2010derived estradiol (BDE2) synthesis in a sex\u2010specific manner. Non\u2010invasive gamma\u2010rhythmic neuromodulation targeting PV interneurons via closed\u2010loop protocols delivered during sleep can maximize therapeutic efficacy while minimizing off\u2010target effects. A dual\u2010cohort, parallel\u2010group trial using neuronal pentraxin\u20102 (NPTX2) as a surrogate endpoint holds promise for assessing the efficacy of ADRD prevention and risk reduction in this high\u2010risk population.<\/jats:p>","DOI":"10.1002\/alz.71766","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:53:38Z","timestamp":1787205218000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Menopausal insomnia as a modifiable node of dementia risk: Mechanistic insights and intervention strategies"],"prefix":"10.1002","volume":"22","author":[{"given":"Wenjing","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology, Beijing Ditan Hospital Capital Medical University  Beijing China"},{"name":"National Center for Infectious Disease, Beijing Ditan Hospital Capital Medical University  Beijing 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