Montanari Christian, Dong Emma L, Srinivasan Shruti, De Oliveira Leite Ana Paula, Delarge Alyssa F, Maroteaux Matthieu J, Desmoulins Lucie D, Menon Riva, Walker Alice B, Lindsey Sarah H, Zsombok Andrea, Daniel Jill M
Psychology Department, Tulane University, New Orleans, LA 70118, USA.
Tulane Brain Institute, Tulane University, New Orleans, LA 70118, USA.
Endocrinology. 2025 May 19;166(7). doi: 10.1210/endocr/bqaf097.
Research in preclinical models of menopause indicates that exogenously administered estrogens positively affect cognitive aging. However, clinical evidence indicates that the effects of estrogen therapy on cognition are inconsistent and may be modulated by preexisting cardiometabolic conditions. The extent to which cardiometabolic health affects the cognitive outcomes of estrogen therapy remains unclear. This study aimed to determine whether variations in cardiometabolic health, both prior to and resulting from different estradiol treatment regimens, are related to the ability of estradiol to improve the cognitive aging trajectory in ovariectomized Long-Evans rats. Cognitive function and health status were assessed at age 10 months after which rats were ovariectomized and administered vehicle or various estradiol treatments. Rats were assessed again at 18 (middle age) and 22 (old age) months. Cognition was evaluated using a spatial memory radial-maze task. Health status was determined through body composition analysis (dual-energy x-ray absorptiometry), glucose tolerance testing, and blood pressure and heart rate measurements (tail-cuff plethysmography). Results demonstrated that both continuous ongoing estradiol treatment and a previous 40-day estradiol exposure (terminated long before testing) significantly improved the cognitive aging trajectory from middle to old age. However, only continuous estradiol treatment had positive effects on health measures; previous estradiol treatment provided no benefits to aging cardiometabolic systems. In contrast, a delayed estradiol treatment (initiated months after ovariectomy) provided no benefits for cognition but provided health benefits. Results indicated that estradiol effects on cognition in healthy aging rats are separate from and not secondary to its effects on cardiometabolic health.
更年期临床前模型的研究表明，外源性给予雌激素对认知衰老有积极影响。然而，临床证据表明，雌激素疗法对认知的影响并不一致，且可能受到预先存在的心脏代谢状况的调节。心脏代谢健康对雌激素疗法认知结果的影响程度尚不清楚。本研究旨在确定不同雌二醇治疗方案之前及之后心脏代谢健康的变化是否与雌二醇改善去卵巢长 Evans 大鼠认知衰老轨迹的能力相关。在 10 个月龄时评估认知功能和健康状况，之后对大鼠进行卵巢切除，并给予赋形剂或各种雌二醇治疗。在 18 个月（中年）和 22 个月（老年）时再次对大鼠进行评估。使用空间记忆放射状迷宫任务评估认知。通过身体成分分析（双能 X 线吸收法）、葡萄糖耐量测试以及血压和心率测量（尾袖体积描记法）确定健康状况。结果表明，持续进行的雌二醇治疗以及先前 40 天的雌二醇暴露（在测试前很久就已终止）均显著改善了从中年到老年的认知衰老轨迹。然而，只有持续的雌二醇治疗对健康指标有积极影响；先前的雌二醇治疗对衰老的心脏代谢系统没有益处。相比之下，延迟的雌二醇治疗（在卵巢切除术后数月开始）对认知没有益处，但对健康有益。结果表明，雌二醇对健康衰老大鼠认知的影响与其对心脏代谢健康的影响是分开的，并非继发于其对心脏代谢健康的影响。
