Early Surgical Menopause Is Associated with a Spectrum of Cognitive Decline (IN8-2.004)

OBJECTIVE: To determine the impact of reproductive variables on the spectrum of cognitive decline. BACKGROUND: The decrease in estrogen associated with menopause has been implicated in cognitive decline. However, studies have been conflicting and the utility of hormone replacement therapy (HRT) remains unclear. DESIGN/METHODS: Female subjects from two longitudinal studies of cognitive decline: Religious Orders Study (ROS), and Memory and Aging Project (MAP) with data on reproductive histories at baseline were included. Three types of cognition-related outcomes were assessed: (1) longitudinal measure of 5 cognitive domains and global cognition using a linear mixed effects model, (2) neuropathologic measures from brain samples obtained at death using a linear regression model and (3) clinical diagnosis of Alzheimer9s Disease (AD) according to NINCDS-ARDA criteria modeled using Cox proportional hazards regression. We examined the association between age at menarche and menopause, number of cycling years, and ever use and duration of HRT. All models were adjusted for age, education, smoking and study and stratified by surgical vs. natural menopause. RESULTS: A total of 1837 women were included. For women with surgically induced menopause (33% of cohort), early age at menopause was associated with faster decline in semantic memory (p=0.002), episodic memory and global cognition (ps CONCLUSIONS: Early age at surgical menopause was associated with longitudinal cognitive decline and neuropathologic outcomes in women with surgical menopause but not natural. Ongoing evaluation of the neuroprotective effects of HRT after early surgical menopause is warranted. Supported by: NIH 5T32AI074549 (RB). Disclosure: Dr. Bove has nothing to disclose. Dr. Secor has nothing to disclose. Dr. Chibnik has nothing to disclose. Dr. Barnes has nothing to disclose. Dr. Schneider has received personal compensation for activities with AVID Radiopharmaceuticals, Inc. and GE Healthcare. Dr. Bennett has received personal compensation for activities with Danone, Inc., GmbH & Co., KG Pharmaceuticals, and Eli Lilly & Company. Dr. Bennett has received research support from Danone, Inc. Dr. De Jager has received personal compensation for activities with Merck Serono, Teva Neuroscience, and Biogen Idec. Dr. De Jager has received research support from Biogen Idec.