Adults with polyendocrine metabolic ovarian syndrome, previously known as polycystic ovary syndrome, show some brain changes on imaging, but a direct link to Alzheimer’s disease has not been proven. A review published in the Journal of the Endocrine Society found that neuroimaging studies identify structural and metabolic changes in these patients, yet the authors say evidence remains inconclusive regarding a higher risk of Alzheimer’s.
Metabolic comorbidities may explain the brain changes
The researchers hypothesize that metabolic conditions, not the syndrome itself, likely drive any connection to cognitive impairment. Obesity and insulin resistance appear to be the main factors, while the independent contribution of endocrine abnormalities linked to PMOS is less certain. Mina Amiri, PhD, who led the work at Tehran University of Medical Sciences, notes that metabolic comorbidities are the principal mediators of any potential association between PMOS and adverse brain outcomes.
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Studies that control for confounders like body mass index and insulin resistance often find no increased risk of dementia, supporting the idea that metabolic health, rather than the reproductive condition, is the key factor.
When researchers look at the biological pathways, they see a convergence of endocrine and metabolic issues. Features of PMOS include hyperandrogenism and disordered control of the hypothalamic–pituitary–ovarian axis. At the same time, many patients have obesity, insulin resistance, dyslipidemia, and sleep problems. These conditions can trigger chronic inflammation, oxidative stress, and mitochondrial impairment, all of which are known contributors to neurodegeneration. The researchers suggest that the overlap of these pathways may contribute to the poor insulin signaling and reduced glucose metabolism seen in the brains of women with PMOS, but they stop short of confirming that this leads to Alzheimer’s disease.
Dr. Ricardo Azziz, senior author and professor at the University of Alabama at Birmingham, says it is still too early to tell if PMOS actually increases the risk of Alzheimer’s. He points out that epidemiological studies examining dementia incidence in PMOS are inconsistent. Some retrospective studies report higher dementia rates, while a large prospective study of more than 6,000 women found no significant association between PCOS and all-cause dementia, even when the group was divided by androgenic phenotype.
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Dr. Ricardo Azziz said, “It is still too early to tell whether PMOS actually increases the risk of Alzheimer’s disease.” He also stated, “We need large cross-sectional studies to assess the comparative risk of PMOS and Alzheimer’s disease, and even more, we need long-term longitudinal controlled studies to assess whether women with PMOS are actually at increased risk for Alzheimer’s disease.”
Longitudinal studies controlling for metabolic confounders are needed to determine whether PMOS independently increases Alzheimer’s disease risk. Similarly, interventional studies on the effect of PMOS treatments on cognitive function are not conclusive, with most studies limited by small sample size, lack of controls, and none evaluating dementia as an actual endpoint.
