Impact of sex and reproductive status on the default mode network in early midlife: implications for aging of memory circuitry and function

Author:

Spets Dylan S1234ORCID,Cohen Justine E123,Konishi Kyoko1234,Aroner Sarah123,Misra Madhusmita567,Lee Hang358,Goldstein Jill M12345

Affiliation:

1. Clinical Neuroscience Laboratory for Sex Differences in the Brain , Department of Psychiatry, , 149 13th Street, Boston, MA 02129 , USA

2. Massachusetts General Hospital , Department of Psychiatry, , 149 13th Street, Boston, MA 02129 , USA

3. Innovation Center on Sex Differences in Medicine, Massachusetts General Hospital , 185 Cambridge Street, Boston, MA 02114 , USA

4. Department of Psychiatry, Harvard Medical School , 401 Park Drive, Boston, MA 02215 , USA

5. Department of Medicine, Harvard Medical School , 25 Shattuck Street, Boston, MA 02115 , USA

6. Department of Pediatrics , Division of Pediatric Endocrinology, , 55 Fruit Street Boston, MA 02114 , USA

7. Massachusetts General Hospital , Division of Pediatric Endocrinology, , 55 Fruit Street Boston, MA 02114 , USA

8. Biostatistics Center, Massachusetts General Hospital , 500 Staniford Street, Boston, MA 02114 , USA

Abstract

Abstract Alterations to the resting-state default mode network (rsDMN) are early indicators of memory decline and Alzheimer’s disease (AD). Brain regions shared by the rsDMN and memory circuitry are highly sexually dimorphic. However, data are limited regarding the impact of sex and reproductive status on rsDMN connectivity and memory circuitry and function. In the current investigation, rsDMN connectivity was assessed in 180 early midlife adults aged 45 to 55 by sex and reproductive status (87 women; 93 men). Associations between left and right hippocampal connectivity of rsDMN and verbal memory encoding circuitry were examined using linear mixed models, controlled for age and parental socioeconomic status, testing interactions by sex and reproductive status. Relative to men, women exhibited greater rsDMN connectivity between the left and right hippocampus. In relation to rsDMN-memory encoding connectivity, sex differences were revealed across the menopausal transition, such that only postmenopausal women exhibited loss of the ability to decrease rsDMN left–right hippocampal connectivity during memory encoding associated with poorer memory performance. Results demonstrate that sex and reproductive status play an important role in aging of the rsDMN and interactions with memory circuitry/function. This suggests the critical importance of sex and reproductive status when studying early midlife indicators of memory decline and AD risk.

Funder

National Institute of Mental Health

National Institute on Aging

Stuart T. Hauser Clinical Research Training Program

ORWH-NICHD

NIA

Publisher

Oxford University Press (OUP)

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