# Impact of Reproductive Aging on the Functional and Structural Architecture of the Human Brain

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA SANTA BARBARA · 2021 · $38,420

## Abstract

Project Summary
Despite the over-representation of women in the Alzheimer’s disease population, the influence that sex and sex
steroid hormones have on the aging brain remains understudied. Over the last quarter century, the vast majority
of brain imaging studies have studied the neural basis of age-related cognitive decline in adults aged 65 and
older. This convention overlooks one of the most significant neuroendocrine changes in a woman’s life—the
transition to menopause—and leaves a gap in our understanding of the aging brain during the critical midlife
years. The menopausal transition is marked by a sweeping decline in the production of sex hormones—up to
90% in the case of 17-estradiol and progesterone. For many women, this endocrine change is accompanied
by self-reported decrements in memory and attention, or “menopause fog”. Animal studies provide powerful
evidence that estradiol and progesterone play a neuroprotective role in brain regions vulnerable to
neurodegeneration, including the prefrontal cortex and medial temporal lobes. The degree to which female
reproductive aging leads to changes in human macrostructural brain morphology, intrinsic brain network
connectivity, and the neural circuits underlying higher-order cognition represents a significant knowledge gap
that has yet to be adequately examined. This project will probe the effects of reproductive aging on the brain in
healthy midlife women (N=90, ages 45–55), investigating the endocrine basis of neural and cognitive aging in
midlife. The well-characterized sample is enriched to include a balanced distribution of pre, peri-, and post-
menopausal women across a limited age range in order to isolate the effects of reproductive aging from
chronological aging. This project will build on the existing menopause literature by applying state-of-the-art
computational techniques to extend beyond our current understanding of fairly coarse regional differences in
brain activity and morphology by menopause status. In Aim 1, I will determine how the depletion of sex hormones
in midlife alters large-scale functional brain networks using resting-state fMRI and computational approaches
from complex systems analysis. In Aim 2, I will use high-resolution anatomical imaging of the hippocampus and
surrounding medial temporal lobe to determine whether the depletion of sex hormones impacts specific
hippocampal subfields (CA1-3, dentate gyrus, subiculum) and entorhinal, perirhinal, and parahippocampal
cortices, regions enriched with sex hormone receptors. In Aim 3, I will determine the effects of reproductive aging
on neural mechanisms of selective attention, including the ability to suppress neural processing of irrelevant
information, with the goal of elucidating the neural underpinnings of common cognitive complaints during
menopause. This project will clarify the endocrine basis of age-related neural and cognitive changes, a severely
understudied area in cognitive neuroscience with clear implicati...

## Key facts

- **NIH application ID:** 10313384
- **Project number:** 1F31AG074634-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA BARBARA
- **Principal Investigator:** Laura Pritschet
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,420
- **Award type:** 1
- **Project period:** 2021-09-19 → 2022-09-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10313384

## Citation

> US National Institutes of Health, RePORTER application 10313384, Impact of Reproductive Aging on the Functional and Structural Architecture of the Human Brain (1F31AG074634-01). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10313384. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*