From the Department of Obstetrics, Gynecology and Reproductive Sciences (H.G.H., E.G.J.), Memory and Aging Center (K.B.C.), and Departments of Epidemiology and Biostatistics (J.N.) and Psychiatry (K.Y.), University of California, San Francisco; Department of Medicine (C.K.), University of Michigan, Ann Arbor; Department of Medicine (M.W.), Vanderbilt University, Nashville, TN; and Laboratory of Epidemiology and Population Sciences (L.J.L.), Intramural Research Program, National Institute on Aging, Gaithersburg, MD.
Neurology. 2024 Feb 27;102(4):e208104. doi: 10.1212/WNL.0000000000208104. Epub 2024 Jan 31.
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 aging. 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.
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 oligomenorrhea. 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 center.
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); = 0.008), RAVLT (-0.254 (-0.473 to -0.034); = 0.002), and category fluency (-0.267 (-0.480 to -0.040); = 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); = 0.002), though not abnormal white matter.
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.
多囊卵巢综合征（PCOS）是一种常见的生殖系统疾病，与生命早期不良的心血管代谢特征有关。越来越多的证据表明，心血管危险因素，如糖尿病和高血压，与认知老化加速有关。然而，关于 PCOS 及其与大脑健康的关系，特别是在中年期的关系，人们知之甚少。我们的目标是在一项正在进行的前瞻性研究中，研究 PCOS 与中年认知功能和大脑 MRI 结果之间的可能关联。
我们使用了来自冠状动脉风险发展在年轻人（CARDIA）研究的数据，这是一项地理上多样化的前瞻性队列研究，参与者在基线时（1985-1986 年）年龄在 18-30 岁之间，并随访 30 年。我们从一个辅助研究（CARDIA 女性研究（CWS）中确定了患有 PCOS 的女性，这些女性的雄激素水平升高，/或多毛症，同时伴有月经稀少的症状。在第 30 年，参与者完成了认知测试，包括蒙特利尔认知评估、 Rey 听觉言语学习测试（RAVLT）（言语学习和记忆）、数字符号替代测试（处理速度和执行功能）、Stroop 测试（注意力和认知控制）以及类别和字母流畅性测试（语义和注意力）。一部分参与者完成了大脑 MRI 以评估大脑结构和白质完整性。多变量线性回归模型估计了 PCOS 与结果之间的关联，调整了年龄、种族、教育程度和研究中心。
在 CWS 中的 1163 名女性中，有 907 名完成了认知测试，其中 66 名（7.1%）符合 PCOS 标准（年龄 54.7 岁）。患有和不患有 PCOS 的女性在年龄、BMI、吸烟/饮酒状况和收入方面相似。在第 30 年，患有 PCOS 的参与者在 Stroop 测试（-0.323（-0.69 至-7.37）； = 0.008）、RAVLT（-0.254（-0.473 至-0.034）； = 0.002）和类别流畅性测试（-0.267（-0.480 至-0.040）； = 0.02）上的表现较低。在 291 名有 MRI 的参与者中，有 25 名（8.5%）符合 PCOS 标准，表现出较低的全脑白质各向异性分数，这是白质完整性的一个衡量指标（系数（95% CI）-0.013（-0.021 至-0.005）； = 0.002），尽管白质没有异常。
我们的研究结果表明，患有 PCOS 的女性在中年期认知表现和白质完整性较低。需要进一步研究来证实这些发现，并确定潜在的机制途径，包括潜在的可改变的因素。
