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Polycystic ovary syndrome (PCOS) was linked with lower cognitive test scores in middle age, a cohort study suggested.

After 30 years of follow-up, women who were diagnosed as having PCOS in young adulthood performed lower on a composite of five cognitive function tests (ß coefficient for mean z scores difference -0.190, 95% CI -0.327 to -0.052), Heather Huddleston, MD, from the University of California San Francisco, and colleagues reported in .

This difference was driven by lower scores in three separate cognitive tests measuring executive functioning, memory, and verbal fluency:

• Stroop test: -0.323 (95% CI -0.69 to -7.37, P=0.008)
• Rey Auditory Verbal Learning Test (RAVLT): -0.254 (95% CI -0.473 to -0.034, P=0.002)
• Category fluency: -0.267 (95% CI -0.480 to -0.040, P=0.02)

Women with PCOS had higher rates of depressive symptoms (28% vs 19%), diabetes (27.3% vs 13.8%), higher glucose levels (108.2 mg/dL vs 99.3 mg/dL), free testosterone at year 2 (0.53 vs 0.29), and total testosterone at year 2 (77.3 vs 40.6) compared with those who did not have PCOS.

"Given that up to 10% of women may be affected by PCOS, these results have important implications for public health at large," Huddleston and co-authors wrote.

"Although our cognitive findings were robust to models controlling for depressive symptoms, it remains possible that greater attention to the mental health needs of those with PCOS might represent a window of opportunity to improve cognitive health," they added.

Among a subset who had MRI, total white matter fractional anisotropy -- a measure of white matter integrity -- was lower in women with PCOS (-0.013, 95% CI -0.021 to -0.005, P=0.002). This included lower frontal, parietal, temporary, occipital, limbic, and corpus callosum white matter. Abnormal white matter didn't significantly differ between the groups (0.206, 95% CI -0.208 to 0.620, P=0.33).

While she suspected there might be differences in brain health at midlife for women with PCOS, Huddleston told 麻豆传媒 she wasn't expecting to find visible changes that may suggest early brain aging. However, the imaging part of the study involved a very small sample and needs to be confirmed with more research, she said.

Reproductive and metabolic factors have important intersections with the brain, Huddleston noted. "We tend to think of them as separate entities, but they are profoundly connected," she said. Some factors driving the cognitive differences that emerged in this study may be modifiable with lifestyle changes, she added.

The researchers used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, which included Black and white individuals from four U.S. study centers. Baseline exams were performed from 1985 to 1986 in individuals who were ages 18-30 years at the time.

An ancillary study, dubbed the CARDIA Women's Study, was used to identify 1,163 women. Of these, 907 completed cognitive testing, and 66 (7.1%) met the criteria for PCOS, which was defined as elevated androgen levels and/or hirsutism in conjunction with symptoms of oligomenorrhea. Pregnant women or women without ovaries were excluded.

The average age of women with PCOS was about 55; 61.6% were white and 39.4% were Black. Of the subset of 291 women who underwent MRI, 25 of them met PCOS criteria.

While Stroop, RAVLT, and category fluency scores showed significant differences, there were no differences on Digit Symbol Substitution Test (DSST) and letter fluency scores. The researchers didn't find any significant interaction between PCOS and age, education, or race for cognitive outcomes.

Sample sizes in this analysis were small and the findings need to be confirmed for larger studies. Unmeasured confounders may have influenced results, the researchers said. In addition, the study was unable to assess the degree to which the findings represented a clinically important deficit.

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