# Impact of menopause associated adrenal aging on cognitive function and Alzheimer dementia neuroimaging biomarkers

> **NIH NIH R03** · MAYO CLINIC ROCHESTER · 2022 · $169,178

## Abstract

PROJECT SUMMARY
Aging is associated with both physical and cognitive decline. Endocrine-wise, impairment in the hypothalamic-
pituitary-adrenal axis has been reported, including elevated diurnal cortisol concentrations, abnormal
suppression of cortisol following dexamethasone administration, and increased salivary cortisol. Previous
studies reported association between higher cortisol concentrations and poor overall cognitive performance
and structural changes in the brain, with cortical and hippocampal atrophy, as well as Alzheimer Disease (AD)
development. However, these studies used suboptimal assessment of adrenal steroid metabolome, mainly
concentrating on cortisol (only 1% of steroid metabolome). As we show in our preliminary data, steroid
metabolome (as assessed by a novel steroid profiling assay) changes with age, differentially in women versus
men, with decreased androgens and increased glucocorticoid metabolites, increasing with age
glucocorticoid/androgen ratio, and steroid ratio changes suggestive of increased tissue exposure of cortisol.
Previous studies reported that menopause accelerates epigenetic aging of blood, and that later age of natural
menopause is associated with decreased mortality. Women undergoing bilateral salpingo-oophorectomy
(BSO) prior to the age of natural menopause experience a higher degree of accelerated aging with increased
rates of multiple morbidities, most notably cardiovascular disease, cognitive decline, and increased mortality.
As shown in our preliminary data, most significant change in steroid metabolome occurs in women after
menopause. We further show that abnormal steroid metabolome in menopausal women is associated with
decline in executive function, processing speed, and working memory. In our proposed research, our
hypothesis is that adrenal aging (as measured by the 24h urine steroid metabolome) is accelerated with
menopause; BSO accelerates adrenal aging which, in turn, impacts cognitive function and brain structures. In
our proposed research, we will take advantage of the ongoing study in the Mayo Clinic Specialized Center of
Research Excellence (SCORE) on sex differences to assess how abrupt loss of ovarian hormones caused by
BSO affects adrenal aging (Aim 1). In addition, through a machine learning analysis, we propose to determine
whether abnormal steroid metabolome is associated with cognitive decline and AD structural changes on brain
imaging (Aim 2).
This project will deliver the insight into BSO-related changes in steroid metabolome and will estimate the
impact of adrenal aging on cognitive changes and structural changes of AD on brain imaging. A specific steroid
signature will be identified to potentially serve as biomarker of aging and cognitive decline.

## Key facts

- **NIH application ID:** 10371283
- **Project number:** 1R03AG071934-01A1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Irina Bancos
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $169,178
- **Award type:** 1
- **Project period:** 2022-02-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371283

## Citation

> US National Institutes of Health, RePORTER application 10371283, Impact of menopause associated adrenal aging on cognitive function and Alzheimer dementia neuroimaging biomarkers (1R03AG071934-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10371283. Licensed CC0.

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