Laura B. Zahodne - US grants

PROJECT SUMMARY/ABSTRACT Identifying potential targets for interventions to reduce age-related cognitive morbidity in diverse elders is of critical importance to the rapidly expanding aging population in the U.S. Substantial evidence from observational studies suggest that modifiable positive psychosocial factors (i.e., well-being, self-efficacy, social support) are associated with better cognitive functioning among older adults. These effects are independent of negative affect (e.g., depression). However, little attention has been given to subgroups of older adults who are particularly vulnerable to age-related cognitive morbidity: African Americans, Hispanics, and individuals with mild cognitive impairment (MCI). In addition, it is unclear whether these positive psychosocial factors buffer against the negative cognitive effects of brain pathology, as measured with structural magnetic resonance imaging. This K99/R00 proposal lays the foundation for an independent research career focused on characterizing the mechanisms underlying psychosocial factors that protect against age-related cognitive morbidity among a diverse population. Together, the research and training plans will provide the applicant (1) supplementary training in modeling neuroimaging biomarker data in an aged population, (2) broader experience with psychosocial variables in aging, and (3) a strong foundation in cross-cultural neuropsychology. These experiences will supplement the applicant's strong existing background in geriatric neuropsychology and quantitative methods. The research plan expands an existing community-based longitudinal study of multi-ethnic older adults at Columbia University. This diverse population is followed every 18-24 months with cognitive testing, medical evaluation, health measures, and consensus diagnoses of MCI/dementia. A subset receive structural neuroimaging. This proposal adds well-validated, computer-based measures of psychosocial functioning and cognition from the NIH Toolbox. Cross-sectional and longitudinal structural equation models (SEM) will test relationships between positive psychosocial factors, cognition, and quantitated measures of hippocampal volume, regional cortical thickness, white matter hyperintensity volume, and infarcts. The primary goal is to characterize the role of positive psychosocial factors in late-life cognitive decline and to determine whether they reduce the impact of structural MRI markers of brain pathology on cognitive functioning.

The overall aim of this longitudinal study is to identify new, modifiable mechanisms of racial/ethnic disparities in Alzheimer's disease (AD) among a multi-ethnic cohort of approximately 2,000 older adults. The incidence of AD is higher for African Americans and Hispanics, compared to non-Hispanic Whites, even after controlling for the ?usual suspects? in disparities research: traditional socioeconomic indicators and vascular health. Persistent and unexplained disparities suggest two possibilities that have not been well-examined: (1) known AD risk factors exhibit differential impact across race/ethnicity and/or (2) yet unmeasured factors increase AD risk for minorities. Our research team has identified multiple factors that have stronger cognitive impact among older African Americans or Hispanics, including depressive symptoms and MRI markers of brain pathology. These variables, along with poor vascular health and lower education/income, may be less impactful among Whites because membership in a majority group is associated with social-environmental resources that promote resilience. In the current proposal, resilience is conceptualized as better-than-expected outcomes given level of AD risk factors or brain pathology. This study will examine how resources that differ across race/ethnicity in our cohort (e.g., perceived social status, quality of education, and the perception that life outcomes are controllable) promote resilience at multiple points in the AD pathogenic pathway using repeat MRI and cognitive assessments across three time points. Because racial/ethnic minorities face unique stressors (e.g., acculturative stress, racial discrimination), we will also test whether these experiences influence the progression of MRI markers of brain pathology, cognitive decline, and incident AD. Our overarching hypothesis is that AD disparities persist because racial/ethnic minorities have depleted resources to adapt to known AD risk factors and brain pathology and/or unique, yet unmeasured AD risk factors. Specific aims are to (1) identify risk factors relevant to minority populations and examine whether they predict advancing brain pathology, cognitive decline, and incident AD among African Americans or Hispanics, (2) determine which resources explain racial/ethnic differences in the impact of known AD risk factors on advancing brain pathology (i.e., brain resilience), and (3) determine which resources explain racial/ethnic differences in the impact of advancing brain pathology on cognitive decline and incident AD (i.e., cognitive resilience).

Michigan Center for Contextual Factors in Alzheimer's Disease (MCCFAD) aims to foster and enhance innovative research in Alzheimer's disease and related dementias (ADRD) with the long term goals to 1) advance ADRD-relevant social and behavioral science research in underserved and underrepresented communities while; 2) diversify the research workforce dedicated to healthy aging. This center will build on the existing deep infrastructure and research strengths in dementia and aging research at the University of Michigan (UM). The MCCFAD will emphasize research in three priority areas of: epidemiology, health economics, and culturally sensitive care. The rationale for these three areas is directly related to the current lack of a comprehensive understanding of the contextual complexities inherent in ADRD disparities, the need to enhance diversity in the professional research workforce addressing the brain and cognitive health of older adults, as well as dynamic changes in the demographic and multi-cultural composition of the U.S. population. The MCCFAD will promote diversifying the research workforce dedicated to healthy aging through collaborations with other NIA-sponsored Centers and programs and via connections with R1, R2 and R3 universities in Michigan. The Center will focus on the contexts in which ADRD is experienced. Knowledge concerning the contexts of ADRD is quite limited but has been shown to be critical for elucidating sociocultural, economic and behavioral contributors to and consequences of health disparities generally and ADRD disparities specifically. The Center's four Cores are: Administrative (AC), Research and Education (REC), Analytic (AnC), Community Liaison and Recruitment (CLRC) with the following specific aims: Aim 1: Advance ADRD-relevant disparities research in epidemiology, health economics, and culturally-sensitive care; Aim 2: Recruit and mentor 15 AD-RCMAR Scientists (RS) from the pilot-study investigator stage through professional publications and independent research applications and funding; Aim 3: Connect with African American, Arab American and Latino communities to broaden understanding of intra- and inter-cultural factors affecting participation in ADRD research. The Center profits from the groundbreaking, successful work of their extensive network of experienced mentors and experts. These resources, along with planned structure and activities will ensure that, upon receiving NIA designation as an AD-RCMAR, the MCCFAD will have a significant impact in diversifying the research workforce dedicated to healthy aging while enhancing research to better understand AD and related forms of dementia across various contexts.