R01AG090417

Menobrain: A longitudinal investigation of menopause and brain health.

All women who live into midlife will transition through the menopause, a critical midlife reproductive transition accompanied by widespread physiologic change.

Cohort studies have provided a broad view of changes in women’s health occurring over the menopause transition, including declines in memory.

However, knowledge of the neurobiological basis for these changes is limited.

These gaps in knowledge are due largely to the lack of targeted, mechanistically-rigorous longitudinal studies of women’s brain health during the menopause transition, particularly during the perimenopause, the most dynamic phase of the transition.

Addressing this gap is a major priority: it is during the perimenopause that women show the major changes in sex hormones, increases in menopausal symptoms such as vasomotor symptoms (VMS) and sleep problems, deteriorations in cardiovascular health, and declines in memory performance.

Critically, studies of sex differences in Alzheimer’s disease (AD) frequently implicate menopause as a key contributing factor, while acknowledging the lack of rigorous studies to support those claims.

To address these gaps, building on our related studies in the postmenopause, we will recruit 224 women in the late reproductive to early menopausal transition (i.e., perimenopause) stage for two assessments over a 5-year period.

At each assessment, we will conduct comprehensive assessments of brain structure and function, cognition, cardiovascular health, sex hormones, and menopausal symptoms (VMS, sleep) using state of the art 7T brain magnetic resonance imaging, peripheral vascular ultrasound imaging, mass spectrometry assessments of sex hormones, and wearable objective sleep and VMS measurements.

Our primary aim is to elucidate the brain and cognitive changes that occur during the perimenopause, and the factors contributing to these changes.

We hypothesize (A) alterations in whole brain and hippocampal functional connectivity at rest and during memory tasks, and decreases in hippocampal volumes and in regional cortical thicknesses and volumes; (B) decreases in cerebrovascular health (increases in white matter hyperintensities, in perivascular space enlargement, and in vessel tortuosity, and decreases in cerebral blood flow); and (C) declines in verbal memory.

Secondary aims will (1) determine the role of menopausal symptoms (VMS, sleep changes), cardiovascular health, and sex hormones in these changes and (2) test a modifying role of APOE Ɛ4 genotype.

This work has high public health significance, as midlife is a key window for preventive efforts to forestall adverse cognitive and brain outcomes with aging, including AD, which has no cure and disproportionately affects women.

University Of Pittsburgh - Of The Commonwealth System Of Higher Education

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

Pittsburgh, Pennsylvania 152221808 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 97% from $1,558,726 to $3,063,196.