# Health of the Cholinergic System and Risk for Alzheimer's Disease in Postmenopausal Women

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2020 · $1,483,342

## Abstract

Women are at increased risk for Alzheimer’s disease (AD). Notably at menopause, some women experience
a change in cognition. However, not all women experience negative effects of menopause on cognition. The
cognitive changes that occur at menopause have not yet been connected to late life risk for pathological aging
including AD. Thus, understanding the neurobiological factors related to individual differences in cognition at
menopause is critical for understanding normal cognitive aging and for determining risk for pathological aging.
The challenge in understanding the role of estrogen loss on the risk for AD is the long lag time between the
hormonal changes at menopause and the clinical manifestations of AD. Thus, identifying how the hormone
changes after menopause are related to AD risk will alter the risk calculus for postmenopausal women in the
future.
 The novel study proposed here will examine an established AD-related neurotransmitter-based mechanism
that may also underlie cognitive changes after menopause. We propose that the change in the hormonal milieu
at menopause interacts with the cholinergic system and other brain pathologies to influence a woman’s risk for
cognitive decline. Preclinical studies have shown that estrogen is necessary for normal cholinergic functioning
and its withdrawal leads to cholinergic dysfunction and cognitive impairment. It is important to determine whether
menopause-related cognitive changes correlate with both cholinergic functional integrity and established AD
biomarkers that portend increased risk for late-life cognitive impairment or dementia. This study will examine
brain functioning following cholinergic blockade to separate individuals into those who are able to compensate
for the hormone change after menopause and those who are not. We hypothesize women with poor
compensation have increased sensitivity to cholinergic blockade by showing poor performance on a cognitive
task, altered brain activation, and decreased basal forebrain cholinergic system (BFCS) volume. These
cholinergic markers will be related to menopausal factors associated with poor cognition and biomarkers of AD.
 Specific Aim 1 is to examine cholinergic functional “integrity” by measuring working memory performance,
functional brain activation, and BFCS structure in postmenopausal women. Specific Aim 2 will examine whether
individual differences in menopause-relevant symptoms and known AD biomarkers are related to cognition and
brain activation after anticholinergic challenge.
 The public health significance of this study is that it will identify individual difference factors that are
associated with cognitive performance changes after menopause and their relationship to structural, functional,
and biomarker evidence of risk for later life cognitive dysfunction. Knowledge of these factors will serve to
advance personalized future risk-mitigation strategies for women including hormonal, medication, cognitive
remediation, etc. that will...

## Key facts

- **NIH application ID:** 10018632
- **Project number:** 5R01AG066159-02
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** JULIE A DUMAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,483,342
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018632

## Citation

> US National Institutes of Health, RePORTER application 10018632, Health of the Cholinergic System and Risk for Alzheimer's Disease in Postmenopausal Women (5R01AG066159-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10018632. Licensed CC0.

---

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