Memory and Attention Woes? PCOS May Be Linked to Lower Brain Health in Midlife

A study published in the journal Neurology has linked polycystic ovary syndrome (PCOS) to poorer brain health in midlife. Researchers followed women for 30 years and found those with PCOS scored lower on tests measuring attention, memory, and language skills. Brain scans also revealed lower integrity of white matter, which helps brain regions communicate. While more research is needed, these findings suggest PCOS may contribute to cognitive decline later in life. Understanding the mechanisms behind this link could lead to interventions to improve brain health in women with PCOS.

Key points

Background: Polycystic ovary syndrome (PCOS) is linked to the early development of cardiovascular risk factors known to affect brain health. This study investigated the potential link between PCOS, midlife cognitive function, and brain structure.

Methods: Data was analyzed from the CARDIA study, following individuals since young adulthood (1985-1986) for 30 years. PCOS diagnosis was based on elevated androgen levels or hirsutism with oligomenorrhea symptoms. Cognitive testing and brain MRIs were conducted at the 30-year follow-up.

Results:

• Among 1163 women, 907 completed cognitive tests, with 66 (7.1%) diagnosed with PCOS.

• Age, BMI, smoking or drinking, and income were similar between groups.

• Women with PCOS scored lower on tests assessing:

  • Attention and cognitive control (Stroop test)

  • Verbal learning and memory (RAVLT)

  • Semantics and attention (category fluency)

• In a subset of 291 MRI participants, 25 (8.5%) had PCOS. This group showed:

  • Lower white matter integrity (a measure of brain health)

  • However, the white matter wasn't considered abnormal.

Conclusion:

• This study suggests a link between PCOS and lower cognitive performance and white matter integrity in midlife.

• More research is needed to confirm these findings and explore potential underlying mechanisms and modifiable factors.

Key points:

• This is the first study to investigate the link between PCOS and midlife brain health.

• The study identifies potential cognitive deficits in women with PCOS.

• White matter integrity, crucial for brain communication, may be affected by PCOS.

Polycystic ovary syndrome (PCOS), a prevalent disorder affecting 8%–15% of women, has long been synonymous with reproductive challenges. Characterized by hyperandrogenism, oligomenorrhea, and polycystic ovaries, PCOS unveils a complex interplay of hormonal and metabolic disruptions. While insulin resistance (IR) is a frequent companion, independent of obesity, the focus of PCOS research has traditionally revolved around fertility and cardiovascular risk management.

A Paradigm Shift: PCOS Beyond Reproductive Health

In a groundbreaking revelation, a recent longitudinal study examining a diverse cohort of black and white individuals has brought to light a previously understudied facet of PCOS—its impact on midlife cognitive health. Contrary to the prevailing narrative, individuals with PCOS exhibit lower cognitive performance compared to their non-PCOS counterparts. This novel finding prompts a critical reassessment of PCOS research priorities.

Traversing Uncharted Terrain: Cognitive Outcomes in PCOS

Despite PCOS's pervasive prevalence, remarkably few studies have delved into its cognitive implications, with an even scarcer focus on midlife women. Existing research has predominantly explored links between hyperandrogenism and cognitive test performance in younger populations. The dearth of midlife cognition investigations underscores the need for a paradigm shift in PCOS research priorities.

Unraveling Previous Studies

A comprehensive review of existing literature highlights seminal studies in 2007 and recent research by Sukhapure, shedding light on verbal fluency, memory, manual dexterity, and visuospatial learning challenges in participants with PCOS.This recent study, involving 48 participants with PCOS (mean age 31 years), unveils lower performance in verbal fluency, working memory, and cognitive control, especially in those with hyperandrogenism.

The First Glimpse: Midlife Cognitive Performance in PCOS

In a landmark achievement, this study emerges as the first to scrutinize midlife cognitive performance in PCOS. Rigorous models, meticulously controlled for age, race, education, and study center, unravel disparities in memory, cognitive control, and verbal fluency. Even the inclusion of common PCOS comorbidities like diabetes and depression merely slightly diminishes the magnitude and significance of the observed PCOS-cognitive relationship.

A Robust Connection: PCOS and Cognitive Outcomes

Persisting through a third model encompassing broader confounders, such as smoking and drinking behavior, systolic blood pressure, and BMI, the link between PCOS and cognitive performance remains unscathed. These findings collectively depict an independent and robust association between PCOS and midlife cognitive outcomes.

Exploring Mechanisms: Unraveling the Underpinnings

The mechanistic foundations of this cognitive divergence beckon further exploration. While an association between free testosterone in earlier adulthood and midlife cognition suggests a potential role for androgens, the prevalence of cardiovascular risk factors in PCOS introduces an alternative hypothesis. Surprisingly, the link between PCOS and cognition persists even when controlling for diabetes and other cardiovascular risk factors, underscoring the need for nuanced investigations.

Mental Health Matters: The Role of Depressive Symptoms

Consistent elevations in depressive symptoms among individuals with PCOS raise questions about their potential impact on cognitive function. Despite robust cognitive findings resilient to models controlling for depressive symptoms, the study emphasizes the importance of addressing mental health needs in PCOS as a potential avenue for cognitive health improvement.

Unveiling Brain Health: MRI Insights

Venturing into the realm of neuroimaging, the study employs structural MRI and diffusion tensor imaging (DTI) to uncover preclinical changes that may foreshadow cognitive decline. White matter fractional anisotropy emerges as a key indicator, with lower levels associated with executive function and processing speed deficits. Although a prior small-scale study hinted at lower fractional anisotropy in the corpus callosum of PCOS participants, our findings, within the larger CARDIA cohort, call for a renewed focus on midlife brain health interventions targeting cardiometabolic health.

Strengths and Limitations: A Balanced Perspective

Acknowledging the study's strengths is crucial. Utilizing a population-based cohort and meticulous diagnostic criteria application minimizes referral bias, ensuring the robustness of observed PCOS-control differences. Rigorous quality control protocols within the CARDIA study further enhance the validity of brain health outcomes and covariate considerations.

Navigating Limitations

Despite these strengths, the study grapples with inherent limitations. As a cross-sectional examination, it cannot be definitively discerned whether observed cognitive differences signify an accelerated midlife decline or a persistent pre-midlife disparity. Unmeasured confounders' potential impact remains uncharted territory, and the reliance on self-reported PCOS diagnosis and hirsutism introduces potential misclassification, albeit towards a conservative bias.

Implications and Future Trajectories

In unveiling midlife cognition in PCOS, this study raises profound concerns about additional comorbidity for individuals with this prevalent disorder. The individual-level repercussions, spanning quality of life, professional attainment, and financial security, underscore the urgency for further research. With approximately 10% of women affected by PCOS, these findings bear significant implications for public health.

A Call for Longitudinal Exploration

Larger studies, embracing longitudinal designs, stand as imperatives to validate these midlife cognitive disparities in PCOS. Beyond validation, these studies have the potential to unravel nuanced trajectories in cognitive outcomes, paving the way for targeted interventions. The study's optimistic note suggests that managing modifiable factors like cardiovascular and mental health, in line with current PCOS recommendations, could foster improvements in brain aging for this population.

TO summarize

1. PCOS Complexity Unveiled: Polycystic ovary syndrome (PCOS) is a prevalent disorder affecting 8%–15% of women, historically known for reproductive issues, but recent research reveals its intricate links to midlife cognitive health.

2. Cognitive Decline in PCOS: A groundbreaking study exposes that individuals with PCOS exhibit lower cognitive performance in midlife, challenging conventional research priorities focused on fertility and cardiovascular risk.

3. Cognitive Disparities Across Ages: While previous studies on PCOS and cognition primarily focused on younger populations, this study pioneers an exploration into midlife cognitive outcomes, revealing significant differences.

4. Robust Association: Rigorous models demonstrate a robust and independent link between PCOS and midlife cognitive outcomes, persisting even when controlling for common comorbidities like diabetes, depression, and broader confounders.

5. Mechanistic Insights: The study suggests potential roles for androgens and cardiovascular risk factors in PCOS-related cognitive differences, urging further exploration into the complex underpinnings of this association.

6. Neuroimaging Revelations: Utilizing structural MRI and diffusion tensor imaging, the research uncovers preclinical changes in brain health, emphasizing lower white matter integrity as a key indicator in individuals with PCOS.

7. Call for Action and Future Research: With implications for approximately 10% of women affected by PCOS, the study calls for larger longitudinal investigations to validate midlife cognitive disparities, emphasizing the potential impact of modifiable factors like cardiovascular and mental health.

Reference Article

Huddleston, H. G., Jaswa, E. G., Casaletto, K. B., Neuhaus, J., Kim, C., Wellons, M., Launer, L. J., & Yaffe, K. (2024, February 27). Associations of Polycystic Ovary Syndrome with Indicators of Brain Health at Midlife in the CARDIA Cohort, Neurology, 102(4). https://doi.org/10.1212/wnl.0000000000208104

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