The Study of Women's Health Across the Nation (SWAN): The Impact of Midlife and the Menopause Transition on Health and Functioning in Early Old Age

  • Brooks, Maria Mori (PI)
  • Burnett-bowie, Sherri-ann M. (CoPI)
  • Derby, Carol A. (CoPI)
  • Harlow, Siobán D. (CoPI)
  • Hedderson, Monique Marie (CoPI)
  • Janssen, Imke (CoPI)
  • Karlamangla, Arun S. (CoPI)
  • Karvonen-gutierrez, Carrie Anne (CoPI)
  • Mcconnell, Daniel (CoPI)
  • Thurston, Rebecca (CoPI)
  • Waetjen, Elaine L. (CoPI)

Project: Research project

Project Details

Description

PROJECT SUMMARY Plasma concentrations of biomarkers of Alzheimer's Disease and Related Dementias (ADRD) are strongly correlated with their levels in the cerebrospinal fluid (CSF) and with amyloid and tau burden in the brain on PET scans. Not surprisingly they have also been found to correlate with cognitive functioning in older adults, raising the possibility of early identification of sub-clinical ADRD pathology in midlife, and early intervention to stave off ADRD before potentially irreversible damage has set in. The midlife has a demonstrably huge influence on old age health and functioning, and cognitive function starts declining from peak levels in midlife. At least 2 studies have indeed found that blood-based biomarkers in midlife are associated with impaired cognition decades later, but it is not known if these biomarkers can predict who declines early and whether midlife changes in biomarkers impact future trajectories of cognitive functioning. Other open questions are whether there are Black-White differences in the strength of the association between blood-based ADRD biomarkers and measured cognition in midlife, and whether there are synergies between vascular risk and ADRD biomarkers in midlife. Race modification of associations with cognition and synergy with vascular risk are both seen with CSF-based biomarkers in older adults; whether these translate to blood-based biomarkers in midlife is not known. Accordingly, the objectives of this administrative supplement to the SWAN Aging U19 are to 1) quantify midlife change in plasma concentrations of the ratio of Aβ1-42 to Aβ1-40, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and pTau181 and serum levels of brain-derived neurotrophic factor (BDNF) from the 12th follow up SWAN visit (V12; median age 60) to 15th follow up (V15; median age 65); 2) estimate the association of these biomarkers (and 5-year within-woman change in biomarkers) with concurrently measured performance (and V12-to-V15 change in performance) on tests of cognitive processing speed, episodic memory, and working memory; 3) estimate Black-White differences in biomarker levels in midlife women, and if present, the degree to which they explain racial disparities in cognitive processing speed and memory and their rates of decline; and 4) explore whether the associations of blood-based biomarkers with scores on tests of cognition are modified by a) race (Black vs. White) and b) cardiovascular risk.
StatusActive
Effective start/end date9/30/202/28/25

Funding

  • National Institute on Aging: $10,998,003.00
  • National Institute on Aging: $315,983.00
  • National Institute on Aging: $11,145,077.00
  • National Institute on Aging: $196,732.00

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