MON-188 Polycystic Ovary Syndrome and Alzheimer's Disease or Dementia: A Narrative Review

Abstract Disclosure: M. Amiri: None. S. Hatoum: None. A. Sheidaei: None. R.P. Buyalos: None. D. Farkas: None. R. Azziz: None. Background: Polycystic Ovary Syndrome (PCOS) affects 6-11% of reproductive-age women globally and is associated with reproductive and metabolic complications, including insulin resistance (IR), obesity, and chronic inflammation. These complications further increase the risk of type 2 diabetes and cardiovascular disease. Evidence suggests a potential link between PCOS and neurodegenerative conditions like Alzheimer's disease (AD) and dementia, particularly through shared metabolic pathways. However, this association remains under-explored and often debated. Objective: This narrative review explores the potential association between PCOS and cognitive disorders, including AD and dementia, by synthesizing current evidence regarding shared risk factors, mechanistic links, and potential underlying pathways, aiming to identify research gaps and inform future studies. Methods: A comprehensive literature search of PubMed (up to February 1, 2024) was conducted using MeSH terms and keywords related to PCOS and cognitive decline, including AD and dementia. Human studies were prioritized, with animal studies used to elucidate mechanisms. Results: The literature review identified potential shared risk factors and mechanistic links between PCOS and cognitive disorders, including AD and dementia. Some studies have observed alterations in AD-related protein markers in women with PCOS, though their clinical significance is unclear. Several pathways implicated in AD, and potentially relevant to PCOS, include the kynurenine pathway, the hypothalamic-pituitary-gonadal axis, and IR, all linked to AD-related processes like amyloid-beta aggregation. Insulin resistance, a key PCOS feature often driven by obesity-related mechanisms (inflammation, mitochondrial dysfunction, gut dysbiosis), contributes to metabolic dysfunction, cardiovascular risk, and potentially cognitive decline. This potential cognitive decline may involve mechanisms such as altered brain reward circuitry, neurobiological changes, and differential expression of genes involved in AD/dementia-related pathways (gene expression analysis in adipose tissue). Additionally, SE translocation overexpression contributes to AD development. The complex interplay of genetic factors, altered protein markers, IR, obesity, related metabolic factors, and the described pathways in the potential PCOS-AD/dementia association requires further investigation. Conclusion: This review suggests a potential link between PCOS and cognitive disorders, highlighting shared risk factors and mechanisms such as IR, inflammation, and altered brain function. However, the precise nature and clinical significance of these associations require further investigation through both clinical and basic research. Presentation: Monday, July 14, 2025