• People with PCOS/PMOS have worse performance on cognitive function tests compared with healthy controls.
• More research is needed to determine which mechanisms may drive the association.

Women with polycystic ovary syndrome, now known as polyendocrine metabolic ovarian syndrome, may have elevated risk for Alzheimer’s disease and related dementias, a review article stated.

However, the higher risk may be mediated by metabolic disorders, the researchers wrote.

In findings published in the Journal of the Endocrine Society, researchers identified multiple studies that reported people with PCOS/PMOS have increased risk for Alzheimer’s disease and dementia. However, there remain several unanswered questions, including whether PCOS/PMOS independently raises Alzheimer’s disease risk and if any interventions may reduce the elevated risk in the PCOS/PMOS population.

“The data indicate that it is critical to further assess the possible link between PMOS, metabolic dysfunction and Alzheimer’s disease, but we should recognize that according to the information we reviewed, this link is still hypothetical and much more research is needed,” Ricardo Azziz, MD, MPH, MBA, executive director at the Foundation for Research & Education Excellence and professor in the School of Medicine and School of Public Health at University of Alabama at Birmingham, told Healio.

Researchers conducted a review of studies in PubMed that address PCOS/PMOS and Alzheimer’s disease, dementia, cognitive function and neuroimaging. Both clinical and mechanistic studies were examined.

“Alzheimer’s disease and PMOS are two disorders that frequently affect women and often may present in the same individual,” Azziz said. “Thus, we felt it was important to determine whether PMOS predisposes to Alzheimer’s disease, or the two disorders are unrelated.”

In clinical studies, people with PCOS/PMOS had worse performance on executive function and attention tests, as well as more memory impairments than those without the condition. Some studies found people with PCOS/PMOS have increased levels of amyloid precursor protein and apolipoprotein E that are similar to adults with type 2 diabetes and Alzheimer’s disease. Those elevated plasma levels are more commonly seen in people with obesity, according to the authors. Adults with PCOS/PMOS without obesity who are also not insulin resistant only have increased levels of serum amyloid P component.

Data on incidence of dementia are mixed, with some studies finding a higher incidence of dementia in people with PCOS/PMOS and others finding no difference between those with PCOS/PMOS and the general population.

There are also limited data on intervention studies for people with PCOS/PMOS. The researchers said most published studies have small cohorts and varying findings.

In the review of mechanistic studies, the researchers said the link between PCOS/PMOS and adverse brain outcomes is mostly driven by metabolic disorders such as obesity and insulin resistance.

For obesity, the authors stated the disease “appears to be a central modifier of neurological risk in PCOS/PMOS,” but added that there is a lack of direct evidence tying adipose-derived amyloid beta to brain pathology among people with PCOS/PMOS. Studies have tied diabetes to increased risk for Alzheimer’s disease and dementia, and biomarker profiles indicative of Alzheimer’s disease are more robust among those with obesity and insulin resistance.

The authors also said conditions such as dyslipidemia, autonomic and cardiovascular dysfunction, gut microbiome dysbiosis, chronic inflammation and changes to sex hormones may explain the link between PCOS/PMOS and Alzheimer’s disease and dementias. However, they noted many of those conditions have features that overlap with obesity and insulin resistance.

The authors found a link between PCOS/PMOS and Alzheimer’s disease and dementia, but they concluded that routine dementia screening is not needed for people with PCOS/PMOS.

“Intervention data examining cognitive outcomes remain limited and inconsistent, and well-designed randomized controlled trials with standardized cognitive endpoints, adequate metabolic phenotyping and longer follow-up are required before recommending PCOS/PMOS-specific treatments for neuroprotection,” the researchers wrote. “Until such data are available, neurological benefits of PCOS/PMOS-directed therapies remain speculative.”

Azziz said more cross-sectional and longitudinal studies are needed to assess whether Alzheimer’s disease and dementia are more common among people with PCOS/PMOS compared with those without the conditions.

“If this were to be confirmed, then more studies assessing potential mechanisms, and potential preventive measures, would be needed,” Azziz said.

Ricardo Azziz, MD, MPH, MBA, can be reached at razziz@uabmc.edu or on X @ricardoazziz.