# EFFECTS OF MENOPAUSE TRANSITION ON BRAIN STRUCTURE, FUNCTION, AND COGNITION

> **NIH NIH U19** · WASHINGTON UNIVERSITY · 2021 · $178,886

## Abstract

ABSTRACT FOR PROJECT 3
Menopause is a universal experience among women living to midlife, yet our understanding of the immediate
and long-term influence of the menopause transition on brain health and cognition is limited. A key component
of the Human Connectome-Aging Project (HCP-Aging) has been the ability to collect brain and cognitive data
across menopause stages. An enriched sample of 210 women aged 40-59 years provides data on brain
structure, function and connectivity at two visits ~ 20 months apart. In the Aging Adult Brain Connectome (AABC)
we propose to greatly enhance this dataset by acquiring those same measures at two additional visits in 220
women, for up to 10 years of longitudinal data across all menopause stages. In the Aging Adult Brain
Connectome (AABC) we propose to greatly enhance this dataset by acquiring those same measures at two
additional visits, for up to 10 years of longitudinal data across all menopause stages. The AABC Menopause
Project reflects increased recognition of sex differences in cognitive aging and Alzheimer's disease and related
dementias (ADRD), and increased appreciation for the role of menopause and sex steroid hormones like
estradiol (E2) on brain health. Our focus is on longitudinal trajectories of change across menopause stages (Aim
1), the role of menopause symptoms (Aim 2), and the vulnerability/resilience factors that influence cognition and
brain health at this time in a woman's life (Aim 3). Based on longitudinal studies of cognitive changes across the
menopause, we focus on the perimenopause as a likely inflection point in women's brain health. We aim to
understand the neural basis of the well-documented memory declines that occur in the perimenopause, and to
understand the role of E2 and menopause symptoms on these changes. Recognizing the considerable variability
in cognitive complaints in the menopause transition, we also aim to determine the factors that confer vulnerability
and resilience to those changes. To this end, we propose to add new measures to AABC to: 1) stage menopause
not only using gold-standard bleeding criteria but also a new FDA-approved biomarker (anti-Müllerian hormone;
AMH) (Aim 1); 2) assess reported menopausal symptoms, as well as objective measures of vasomotor
symptoms (VMS) with ambulatory skin conductance monitors and sleep with actigraphy (Aim 2); and 3) work
with other projects and cores to examine vulnerability and resilience factors to influence cognition and brain
health (Aim 3). We will also provide key insights into how AD biomarkers change with menopause stage and
symptoms, and how AD genetic risk factors influence the trajectory of cognitive and brain changes at midlife. To
achieve these goals, we will follow 220 women age 40-59 years of age at two additional neuroimaging visits. We
will synergize with other projects and cores to meet the study aims in a cost-effective manner. The ultimate goal
of this work is to provide new understanding of how menopause ...

## Key facts

- **NIH application ID:** 10283070
- **Project number:** 1U19AG073585-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** PAULINE M MAKI
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $178,886
- **Award type:** 1
- **Project period:** 2021-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10283070

## Citation

> US National Institutes of Health, RePORTER application 10283070, EFFECTS OF MENOPAUSE TRANSITION ON BRAIN STRUCTURE, FUNCTION, AND COGNITION (1U19AG073585-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10283070. Licensed CC0.

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