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

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.

Grant Number: 3U19AG063720-04S2
NIH Institute/Center: NIH
Principal Investigator: Maria Brooks