Sex differences in episodic memory in early midlife: impact of reproductive aging.
Few have characterized cognitive changes with age as a function of menopausal stage relative to men, or sex differences in components of memory in early midlife. The study aim was to investigate variation in memory function in early midlife as a function of sex, sex steroid hormones, and reproductive status.



A total of 212 men and women aged 45 to 55 were selected for this cross-sectional study from a prenatal cohort of pregnancies whose mothers were originally recruited in 1959 to 1966. They underwent clinical and cognitive testing and hormonal assessments of menopause status. Multivariate general linear models for multiple memory outcomes were used to test hypotheses controlling for potential confounders. Episodic memory, executive function, semantic processing, and estimated verbal intelligence were assessed. Associative memory and episodic verbal memory were assessed using Face-Name Associative Memory Exam (FNAME) and Selective Reminding Test (SRT), given increased sensitivity to detecting early cognitive decline. Impacts of sex and reproductive stage on performance were tested.



Women outperformed men on all memory measures including FNAME (β = -0.30, P < 0.0001) and SRT (β = -0.29, P < 0.0001). Furthermore, premenopausal and perimenopausal women outperformed postmenopausal women on FNAME (initial learning, β= 0.32, P = 0.01) and SRT (recall, β= 2.39, P = 0.02). Across all women, higher estradiol was associated with better SRT performance (recall, β = 1.96, P = 0.01) and marginally associated with FNAME (initial learning, β = 0.19, P = 0.06).



This study demonstrated that, in early midlife, women outperformed age-matched men across all memory measures, but sex differences were attenuated for postmenopausal women. Initial learning and memory retrieval were particularly vulnerable, whereas memory consolidation and storage were preserved. Findings underscore the significance of the decline in ovarian estradiol production in midlife and its role in shaping memory function.
1Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 2Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 3Connors Center for Women's Health and Gender Biology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 4Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 5Departments of Psychiatry and Medicine, Harvard Medical School, Boston, MA.
Dorene M
DM
Rentz
Blair K
BK
Weiss
Emily G
EG
Jacobs
Sara
S
Cherkerzian
Anne
A
Klibanski
Anne
A
Remington
Harlyn
H
Aizley
Jill M
JM
Goldstein
D000375:Aging / Q000523:psychology*; D000544:Alzheimer Disease / Q000235:genetics; D003430:Cross-Sectional Studies; D003704:Dementia / Q000235:genetics; D004958:Estradiol / Q000097:blood; D056344:Executive Function; D005260:Female; D006801:Humans; D007858:Learning / Q000502:physiology; D008297:Male; D061212:Memory, Episodic; D008593:Menopause / Q000523:psychology*; D011939:Mental Recall / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D017698:Postmenopause / Q000523:psychology; D011581:Psychological Tests; D012737:Sex Factors
D004958:Estradiol