Non-educational sources of later-life cognitive reserve and resilience among older adults with and without formal education in India

PROJECT SUMMARY By 2050, over 75% of cases of Alzheimer’s disease and related dementias (ADRD) are expected to occur in low- and middle-income countries (LMICs), such as India, which is world’s most populous country with a population of >1.4 billion. Education is the strongest known modifiable protective factor for ADRD, yet ~50% of adults aged

≥45 in India have no formal education and will carry a heavy share of the future global dementia burden. Education is thought to protect against ADRD by promoting cognitive reserve, a theoretical construct representing between-person differences in the susceptibility of cognitive function to brain pathology. The

determinants of cognitive reserve in older adults who lack formal education are unknown. There is a critical need to identify modifiable factors that promote later-life cognitive reserve in older adults across a range of educational backgrounds. Our overarching goal is to empirically characterize cognitive reserve in a diverse population that

largely lacks formal education and identify the roles of life course employment, social relationships, and social engagement as modifiable factors that may promote cognitive reserve, slow cognitive decline, and reduce ADRD risk, among older adults with and without formal education. To achieve our goal, we will use data on general and

domain-specific cognitive function from the Harmonized Cognitive Assessment Protocol (HCAP), MRI and blood- based AD biomarker measures of brain pathology, and in-person interviews in the NIA-funded, nationally representative “Longitudinal Study of Aging in India: Diagnostic Assessment of Dementia” (LASI-DAD) Waves 1

and 2 (2017-20 to 2022-24). We will operationalize cognitive reserve as the variance in general and domain- specific cognitive function that is not explained by MRI and blood-based AD biomarker measures of brain pathology. Indeed, our preliminary data show a robust operationalization of this approach that is consistent with

results from high-income, Western older populations, using data from an MRI pilot study at LASI-DAD Wave 1. We aim to 1) compare the contributions of comprehensive brain pathology measures to general and domain- specific cognition between older adults with and without formal education; 2) evaluate the roles of employment,

social relationships, and social engagement in promoting cognitive reserve among older adults with and without formal education; and, 3) compare the associations of employment, social relationships, and social engagement with cognitive change and ADRD incidence among older adults with and without formal education. This proposal

is a major innovation in ADRD research, as it will challenge the conventional use of formal education as the predominant contributor to cognitive reserve. It will identify modifiable non-educational pathways to later-life cognitive reserve. This proposal is significant because it represents a large share of the global population that

has no formal education due to a lack of opportunity and has high ADRD risk. Our results will advance scientific theory on resilience to aging-related brain pathology in the absence of formal education and support the identification of intervention targets to reduce the global ADRD burden for diverse older populations.