A team of American scientists has suggested that polycystic ovary syndrome (PCOS) – could be linked to potential cognitive dysfunction later in life.
PCOS refers to symptoms related to a hormonal imbalance in women that can include menstrual cycle changes, skin changes like increased facial and body hair and acne, abnormal growths in the ovaries, and infertility.
Although the chronic condition affects around 8% to 13% of women and girls of reproductive age worldwide, as many as 70% could be experiencing PCOS while undiagnosed, reports CNN.
The research – published in Neurology – involved 907 women aged 18 to 30 at the beginning of the study, who were followed for 30 years. They completed tests on memory, verbal abilities, attention and processing speed.
On the attention test, the 66 people with PCOS scored about 11% lower on average compared with participants without the condition. Those with the condition also scored lower on measurements of memory and verbal abilities.
“While (PCOS) has been linked to metabolic diseases like obesity and diabetes that can lead to heart problems, less is known about how this condition affects brain health,” said first author Dr Heather Huddleston, director of the University of California San Francisco’s PCOS clinic and research programme.
“Our results suggest that people with this condition have lower memory and thinking skills, and subtle brain changes at midlife. This could affect them on many levels, including quality of life, career success and financial security.”
The authors also found, via brain scans, that compared with those without PCOS, 25 women with the condition had white matter in poorer condition, which can be an indicator of brain ageing. White matter is made of bundled nerve fibres and helps co-ordinate communication between different regions of the brain.
The findings highlight “potential cognitive vulnerabilities in women with PCOS, though it’s important to know that these are cognitive weaknesses, not impairments”, said Dr Pauline Maki, a professor and director of the Women’s Mental Health Research Programme at the University of Illinois Chicago, who wasn’t involved in the study.
“In other words, they are performing worse than other women on these tests, but they are not performing in the impaired range.”
Early yet concerning research
Several limitations of the study mean its findings should be interpreted carefully, experts said.
For one, the study showed an association between PCOS and cognitive decline, but didn’t prove that the condition causes cognitive decline.
Second, what constituted a PCOS diagnosis wasn’t a doctor’s opinion, but androgen levels and participants’ recollections of their symptoms.
High androgen levels are one of the characteristic features of PCOS doctors look for during the diagnostic process.
“Essentially, what we could be seeing here is what happens when PCOS is left untreated,” said Mateja Perović, a doctoral student in the department of psychology at the University of Toronto.
“This is important to keep in mind. If women are managing their PCOS symptoms, they are already doing a lot to protect their brain health down the line.”
Endocrinologist Dr Wiebke Arlt, who wasn’t involved in the study, had concerns about the authors’ diagnostic criteria.
Polycystic ovary syndrome “was diagnosed to unusual criteria, e.g. androgens above the 75th centile of the reference range”, said Arlt, head of Imperial College London’s Institute of Clinical Sciences.
“Usually this would be above the 95th centile of the reference range.”
Given these limitations, additional research is needed to confirm the findings and determine how these changes occur, Huddleston said, “including looking at changes that people can make to reduce their chances of thinking and memory problems”.
But for now, some experts have at least preliminary ideas about the potential processes behind the link between PCOS and cognitive decline.
“The mechanism behind accelerated cognitive ageing is that metabolic abnormalities – insulin resistance, inflammation, impaired glucose tolerance – affect not only the blood vessels and heart, but every organ including the brain,” said Dr Katherine Sherif, a professor of medicine at Thomas Jefferson University in Philadelphia, who wasn’t involved in the study,
Genetics may also play a role in the links between PCOS and cognitive decline.
Study details
Associations of Polycystic Ovary Syndrome With Indicators of Brain Health at Midlife in the CARDIA Cohort
Heather Huddleston, Eleni Jaswa, Kristine Yaffe, et al.
Published in Neurology on 31 January 2024
Abstract
Background and Objectives
Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with an adverse cardiometabolic profile early in life. Increasing evidence links cardiovascular risk factors, such as diabetes and hypertension, to accelerated cognitive ageing. However, less is known about PCOS and its relationship to brain health, particularly at midlife. Our goal was to investigate possible associations between PCOS and midlife cognitive function and brain MRI findings in an ongoing prospective study.
Methods
We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a geographically diverse prospective cohort study of individuals who were 18–30 years at baseline (1985–1986) and followed for 30 years. We identified women with PCOS from an ancillary study (CARDIA Women's study (CWS); n = 1,163) as those with elevated androgen levels and/or hirsutism in conjunction with symptoms of oligomenorrhoea. At year 30, participants completed cognitive testing, including the Montreal Cognitive Assessment, Rey Auditory Verbal Learning Test (RAVLT) (verbal learning and memory), Digit Symbol Substitution Test (processing speed and executive function), Stroop test (attention and cognitive control), and category and letter fluency tests (semantics and attention). A subset completed brain MRI to assess brain structure and white matter integrity. Multivariable linear regression models estimated the association between PCOS and outcomes, adjusting for age, race, education, and study centre.
Results
Of the 1163 women in CWS, 907 completed cognitive testing, and of these, 66 (7.1%) met criteria for PCOS (age 54.7 years). Women with and without PCOS were similar for age, BMI, smoking/drinking status, and income. At year 30, participants with PCOS performed lower (mean z score; 95% CI) on Stroop (−0.323 (−0.69 to −7.37); p = 0.008), RAVLT (−0.254 (−0.473 to −0.034); p = 0.002), and category fluency (−0.267 (−0.480 to −0.040); p = 0.02) tests. Of the 291 participants with MRI, 25 (8.5%) met PCOS criteria and demonstrated lower total white matter fractional anisotropy, a measure of white matter integrity (coefficient (95% CI) −0.013 (−0.021 to −0.005); p = 0.002), though not abnormal white matter.
Discussion
Our results suggest that women with PCOS have lower cognitive performance and lower white matter integrity at midlife. Additional research is needed to confirm these findings and to determine potential mechanistic pathways including potential modifiable factors.
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