PROJECT SUMMARY/ABSTRACT
Every 65 seconds someone in the US is diagnosed with Alzheimer's Disease and Related Dementias (ADRD).
American Indian (AI) adults have greater burden of cerebrovascular and ADRD-related comorbidities than
their non-Hispanic white counterparts. AI adults also suffer disproportionate stress and trauma, and
concomitant high rates of depression. Relatedly, AI adults also have high rates of substance misuse compared
to other racial/ethnic groups. These public health problems become exacerbated as a population ages, since
stress, depression and substance use have been linked to cognitive impairment later in life. Fortunately,
improvements to health-related quality of life (HRQoL) and community connectedness may ameliorate these
negative impacts, although none of these associations have been fully evaluated in AI adults. As impaired
cognitive performance precedes development of ADRD, we will determine risk and protective factors of
cognitive performance in AI adults to inform prevention strategies to potentially circumvent later development
of ADRD. Longitudinal relationships between psychological risk factors and cognitive impairment need to be
directly evaluated to examine the temporal sequence of clinical changes that occur with aging. Additionally,
research testing the longitudinal relationship with cognitive performance and dementia in AI adults is missing.
Established, longitudinal cohort studies offer opportunity to assess modifiable risk and protective factors in
aging adults, with multiple data collections. Given these gaps in knowledge, our objectives are to test the
longitudinal relationship among stress, depression, and substance use (alcohol, tobacco, prescription opioids)
with cognitive performance in AI adults, and whether HRQoL and community connectedness moderate these
relationships. Our central hypothesis is that higher stress results in higher depression, more substance use
and especially misuse, and that all three are associated with lower cognitive scores, whereas better HRQoL
and better community connectedness moderate these deleterious effects. Using the psychometrically-robust
NIH Toolbox, we will also test and develop normative standards for the AI community, making it possible for
the first time to directly compare AI cognitive data with non-Hispanic white, Asian, African-American, and
Hispanic adults. Our proposed study is in partnership with the Strong Heart Study, a 30-year cohort of aging
AI adults. We propose to collect these psychological and cognitive data in a follow-up examination (N=3,000).
Defining associations among stress, depression, substance misuse, HRQoL, and community; and defining
cognitive standards in a commonly used, established platform will inform future public health prevention and
treatment strategies for this underserved, overburdened population.