Women with polyendocrine metabolic ovarian syndrome (PMOS) may experience subtle cognitive impairments and changes in brain structure and function, but evidence that the condition independently increases Alzheimer's disease (AD) and dementia risk could be inconsistent.
Investigators conducted a comprehensive PubMed search from database inception through October 2025 to examine potential links between PMOS and neurologic health. The review included observational cohorts, case-control studies, neuroimaging investigations, biomarker analyses, and preliminary intervention studies involving patients with PCOS/PMOS. No language or study design restrictions were applied. The investigators selected the most complete or recent publication when multiple reports originated from the same cohort.
They examined cognitive performance, brain structure and function, neurodegenerative biomarkers, and dementia incidence. Outcomes included executive function, attention, memory, hippocampal and white matter abnormalities, cerebral glucose metabolism, and potential biological pathways connecting PMOS with AD. The investigators also evaluated whether neurologic differences were associated with metabolic comorbidities or endocrine abnormalities specific to PMOS.
Evidence linking PMOS to dementia was inconsistent. A retrospective cohort involving 16,531 patients with PMOS and 49,335 age-matched controls reported a higher dementia prevalence among affected patients (0.48% vs. 0.22%). The mean age at dementia onset was also lower in the PMOS group (43 vs. 62 years).
In contrast, a prospective UK Biobank analysis involving 1,008 women with PMOS and 5,017 age- and body mass index–matched controls found no statistically significant association with incident dementia. Subgroup analyses involving hyperandrogenic and normoandrogenic phenotypes were also nonsignificant.
Studies examining cognitive performance identified mild but recurring differences in executive function, attention, and memory. A cross-sectional study involving 101 patients with PMOS and 72 controls reported slower reaction times on attention tasks (557 vs. 463 milliseconds) and more errors among affected patients. Other studies identified reduced working memory, slower processing speed, and poorer word recognition. However, some cognitive differences were more closely associated with glycemic control and insulin resistance than with PMOS status or circulating androgen concentrations.
Neuroimaging studies identified alterations in brain structure and function, including reduced hippocampal volume, changes in white matter integrity, altered functional connectivity, and diminished cerebral glucose metabolism. In a small study involving 7 patients with PMOS and 11 controls, cerebral glucose metabolism was 9% to 14% lower among affected patients and inversely correlated with insulin resistance. Other studies reported white matter abnormalities and differences in brain activation during cognitive tasks.
Biomarker studies identified alterations in proteins associated with AD, including amyloid precursor protein and apolipoprotein E. However, these abnormalities were less pronounced among metabolically healthy patients with PMOS. In a study involving 24 patients with PMOS without obesity and 24 matched controls, only serum amyloid P component was elevated. Broader AD-related biomarker abnormalities may be influenced by accompanying metabolic dysfunction rather than PMOS alone.
The investigators identified several overlapping biological pathways potentially connecting PMOS with neurodegenerative processes. Insulin resistance may contribute to impaired cerebral glucose metabolism, reduced amyloid-beta clearance, and tau hyperphosphorylation; while obesity, chronic inflammation, oxidative stress, and cardiovascular dysfunction may further influence neurologic vulnerability. Hormonal abnormalities, including hyperandrogenism and altered gonadotropin signaling, may also contribute independently, although supporting clinical evidence remains limited.
Preliminary intervention studies suggested that some treatments for PMOS may improve selected cognitive measures or normalize altered brain activation patterns, but findings were inconsistent.
The review was limited by substantial variation in study designs, small sample sizes in many cognitive and neuroimaging investigations, inconsistent adjustment for metabolic confounders, and limited longitudinal evidence. Most biomarker investigations relied on peripheral measurements rather than direct evidence of AD-related brain pathology. The conflicting dementia findings prevented firm conclusions about long-term risk, while preliminary intervention studies could not establish whether treatment modifies cognitive decline or dementia incidence.
“Current evidence indicates that any association between PMOS and AD is likely mediated by metabolic comorbidities rather than reflecting an independent PMOS effect,” wrote lead study author Mina Amiri, of Tehran University of Medical Sciences, and colleagues.
Full disclosures of the study authors can be found in the study.
Source: Journal of the Endocrine Society
