Watts Amber, Donofry Shannon, Ripperger Hayley, Eklund Nicole M, Wan Lu, Kang Chaeryon, Grove George, Oberlin Lauren E, Gujral Swathi, Vidoni Eric D, Burns Jeffrey M, McAuley Edward, Hillman Charles H, Kramer Arthur F, Kamboh M Ilyas, Erickson Kirk I
University of Kansas Alzheimer's Disease Research Center, University of Kansas Medical Center, Fairway, KS, United States.
Behavioral Research in Aging Neuroscience Cognition and Health (BRANCH) Lab, Psychology, University of Kansas, Lawrence, KS, United States.
Front Aging Neurosci. 2025 Apr 3;17:1524474. doi: 10.3389/fnagi.2025.1524474. eCollection 2025.
Disruptions in estrogen exposure (i.e., surgically induced menopause) have been linked to poorer cognitive aging and dementia risk. Hormone therapy use (e.g., birth control, menopausal hormone therapy) has shown mixed associations with cognitive performance, possibly due to limited cognitive test batteries. To address previous inconsistencies, we investigated baseline data from Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE). We hypothesized that (1) oophorectomy prior to natural menopause would be associated with poorer cognitive performance, (2) timing and duration of birth control and menopausal hormone therapy would influence associations with cognitive performance, and (3) carrier status would interact with oophorectomy and hormone therapy to influence cognitive performance.
In 461 post-menopausal females (M age = 69.6) we assessed oophorectomy and hormone therapy use to examine associations with the Montreal Cognitive Assessment (MoCA) and factor-analytically derived composite scores for episodic memory, processing speed, working memory, executive function/attentional control, and visuospatial processing.
Hypothesis (1) We did not observe associations between oophorectomy prior to natural menopause and poorer cognitive performance. However, hormone therapy use, started on average within 2 years of oophorectomy, was associated with better episodic memory (β = 0.106, = 0.02), working memory (β = 0.120, = 0.005), and visuospatial processing (β = 0.095, = 0.03). Hypothesis (2) Birth control use was associated with better performance on the MoCA (β = 0.093, = 0.04), working memory (β = 0.102, = 0.02), and executive function/attentional control (β = 0.103, = 0.02). However, duration and timing of birth control and menopausal hormone therapy were not associated with cognitive performance. Hypothesis (3) We did not observe significant interactions between status and oophorectomy or hormone therapy in their associations with cognitive performance.
Our results suggest exposure to estrogen during adulthood, specifically birth control and hormone therapy among women undergoing pre-menopausal oophorectomy, benefits cognitive function in older adulthood. Our comprehensive cognitive battery allowed us to examine cognitive function with a high degree of granularity. Future work should evaluate causal mechanisms of associations between lifetime estrogen exposure and later life cognitive function.
雌激素暴露中断（即手术诱导的绝经）与较差的认知衰老和痴呆风险相关。激素疗法的使用（如避孕药、绝经激素疗法）与认知表现的关联不一，这可能是由于认知测试组合有限所致。为解决先前的不一致之处，我们调查了运动干预试验中神经认知增益研究（IGNITE）的基线数据。我们假设：（1）自然绝经前的卵巢切除术与较差的认知表现相关；（2）避孕药和绝经激素疗法的使用时间和持续时间会影响与认知表现的关联；（3）基因携带者状态会与卵巢切除术和激素疗法相互作用，影响认知表现。
在461名绝经后女性（平均年龄 = 69.6岁）中，我们评估了卵巢切除术和激素疗法的使用情况，以检验其与蒙特利尔认知评估（MoCA）以及情节记忆、处理速度、工作记忆、执行功能/注意力控制和视觉空间处理的因子分析得出的综合分数之间的关联。
假设（1）我们未观察到自然绝经前的卵巢切除术与较差的认知表现之间存在关联。然而，在卵巢切除术后平均2年内开始使用的激素疗法与较好的情节记忆（β = 0.106，p = 0.02）、工作记忆（β = 0.120，p = 0.005）和视觉空间处理（β = 0.095，p = 0.03）相关。假设（2）使用避孕药与MoCA表现更好（β = 0.093，p = 0.04）、工作记忆（β = 0.102，p = 0.02）和执行功能/注意力控制（β = 0.103，p = 0.02）相关。然而，避孕药和绝经激素疗法的持续时间和使用时间与认知表现无关。假设（3）我们未观察到基因携带者状态与卵巢切除术或激素疗法在与认知表现的关联中存在显著相互作用。
我们的结果表明，成年期暴露于雌激素，特别是绝经前接受卵巢切除术的女性中的避孕药和激素疗法，对老年期的认知功能有益。我们全面的认知测试组合使我们能够高度精细地检查认知功能。未来的研究应评估终生雌激素暴露与晚年认知功能之间关联的因果机制。
