Mild Cognitive Impairment: A Prospective Community Study

Mild Cognitive Impairment: A Prospective Community Study. Dementia is a leading cause of disability and death in older adults. Its incidence increases exponentially with age. Identifying independent risk factors and valid disease markers are critical steps towards prevention, improved diagnosis, and treatment. To enhance clinical and public health care, these factors must be identified in population settings. We seek to extend, for a further five years, a 20-year prospective population-based study of mild cognitive impairment (MCI) and dementia in a low SES-area of southwestern Pennsylvania. The original richly characterized cohort is now aged 85+, and at maximum risk for dementia; we have replenished the cohort and enhanced its ethnoracial diversity by recruiting additional participants from a predominantly African American community. Our objective remains to identify, at the population level, risk factors for clinically relevant adverse cognitive outcomes of MCI, cognitive decline, and progression to dementia. During the current award period we have assessed several plasma biomarkers of Alzheimer's disease and related disorders (ADRD), examined data from ultra-high-resolution (7 Tesla) brain MRI scans on cerebrovascular morphology and gray matter volume including hippocampal segments, and reported preliminary GWAS and RNA sequencing results. We have also examined social determinants of health (SDOH) in relation to MCI. Our aims for the next five years are to build on these discoveries. exploring (1) additional novel plasma ADRD biomarkers, (2) additional 7T brain imaging to examine neural markers of aging including arterial tortuosity and white matter volume, hippocampal volume (whole and subfields), neuroplasticity (synapse/dendrite density), (3) whole genome sequencing to (i) to characterize and fine- map the novel candidate loci identified in GWAS analyses, identify additional and full spectrum of common and low-frequency/rare variants influencing cognitive decline; (ii) to identify novel loci using genome-wide genotype and WGS data for new plasma biomarkers, (iii) to functionally characterize the identified significant variants using genomics and bioinformatics approaches; and (4) to examine the associations of plasma biomarkers, 7T imaging markers, and genomics with one another, and how these markers are distributed by race/ethnicity and by SDOH, using state-of-the-art statistical modeling. RELEVANCE (See instructions): This ongoing population-based epidemiologic study of mild cognitive impairment (MCI) is being conducted among older adults in an under-resourced, ethnoracially diverse, group of communities in a Rust Belt region of Pennsylvania. Our purpose is to identify risk factors for MCI and dementia, and biological markers that predict cognitive decline and progression to dementia, so that steps can be taken to lower these risks. Project Number: 4R37AG023651-21 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: MARY GANGULI (+2 co-PIs) | Institution: UNIVERSITY OF PITTSBURGH AT PITTSBURGH, PITTSBURGH, PA | Award Amount: $3,831,172 | Activity Code: R37 | Study Section: NSS View on NIH RePORTER: https://reporter.nih.gov/project-details/11324798