Subjective cognitive decline as a risk for Alzheimer's disease and vascular cognitive impairment across diverse groups

Alzheimer’s disease (AD) and related causes of dementia including cerebrovascular disease (inclusively referred to here as AD/ADRD) are major public health problems with high personal and societal burden. Individuals from ethnic and racial groups are disproportionally affected, with Black older adults having twice the risk, and Latino older adults 1.5 times the risk of dementia as White Americans. Given growing support for prevention strategies and disease modifying treatments, there is a critical need for sensitive and scalable approaches to identifying those at increased risk for AD/ADRD. Accumulating evidence supports subjective cognitive decline (SCD), self-perceived cognitive decline in the context of normal cognition on testing, as a potential early sign of preclinical AD/ADRD. Older adults with SCD are at double the risk of developing mild cognitive impairment or dementia. Emerging evidence also suggests SCD may be associated with increased likelihood of abnormal AD/ADRD biomarkers including neurodegeneration, elevated amyloid levels, and markers of cerebrovascular disease. However, not all older adults with SCD go on to develop objective cognitive impairment, which highlights the importance of better defining for whom SCD is a risk or under what conditions. A major limitation of existing research on SCD has been a focus on predominantly White older adults. This is a critical knowledge gap due to potentially meaningful differences across cultural, racial and ethnic groups in how SCD is expressed and how it relates to disease outcomes. Various characteristics of SCD have been proposed to enhance the likelihood that it is an early manifestation of AD/ADRD, but these features have not been well studied in diverse populations; such features include SCD-associated worry and consistent/worsening SCD complaints over time (perhaps both signaling a more pronounced or pervasive problem). While most previous work has focused on memory complaints, less is known about the impact of other types of SCD (e.g., executive) complaints on predicting clinical outcomes or their association with disease mechanisms. This project will leverage four large cohorts (N=4000+), comprised of racially and ethnically diverse older adults across four groups: Black, Latino, Asian and White older adults. All participants complete a harmonized measure of SCD that characterizes not only severity but type of complaint and presence of worry, as well as harmonized measures of objective cognition, mood and social determinants of health, and receive a syndromic diagnosis at each follow up research visit. A subsample also has imaging biomarkers associated with AD (amyloid PET, hippocampal and cortical atrophy) and cerebrovascular disease (imaging measures of white matter integrity). We will utilize a prospective longitudinal design to address four aims: (1) the relationship between SCD and biomarkers of AD and cerebrovascular disease (2) the associations between SCD and cognitive decline and incident MCI/dementia, (3) the contributions of mood/affect and social determinants of health to SCD and its impact on cognitive/diagnostic outcomes, and (4) the relationship between of longitudinal change in SCD on cognitive/diagnostic outcomes. This project will advance our understanding of the potential utility of SCD as a cost-effective tool for screening and early detection among a diverse range of older adults, thereby helping redress disparities in cognitive and brain aging. Project Number: 1R01AG094076-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: SARAH TOMASZEWSKI-FARIAS | Institution: UNIVERSITY OF CALIFORNIA AT DAVIS, DAVIS, CA | Award Amount: $690,934 | Activity Code: R01 | Study Section: Neurological, Mental and Behavioral Health Study Section[NMBH] View on NIH RePORTER: https://reporter.nih.gov/project-details/11144052