Abstract:
Alzheimer's disease and related dementias (ADRD) are age-related neurodegenerative disorders that are
rapidly increasing as US population age and disproportionately affecting ethnic/racial minorities. Latinos are
the largest and fastest growing ethnic/racial minority in the United States and will account for 20% of the US
senior population by year 2050. Additionally, average life expectancy at birth for Latinos (81.8y) exceeds that
of Whites (78.8y) by 3-years in spite of SES disadvantages and disparately high levels of chronic disorders
morbidity (e.g., diabetes).4-8 A growing US Latino senior population with excess risk for ADRD, including longer
life expectancy is a significant problem for US public health. Lastly, there are critical gaps in scientific
knowledge about ADRD and aging among diverse Latinos. In particular, the molecular determinants of
neurocognitive aging and Latino longevity are largely unknown. DNA methylation (DNAm), which regulates
gene expression, represents one of the biological processes by which the interplay of genes and
environmental/lifestyle exposures may have profound and sustained effects on aging, cognitive decline and
ADRD. The proposed project will leverage the unique data and resources of the Hispanic Community Health
Study/Study of Latinos (SOL; baseline n=16,415) and Study of Latinos-Investigation of Neurocognitive Aging
(SOL-INCA baseline n=9,652). SOL provides rich sociocultural, cardiometabolic risk factors and genetic
information, while SOL-INCA provides neurocognitive aging and MCI phenotypes measured at two visits.
Specifically, we will (1) investigate blood DNAm signatures of biological aging and their relationship to cognitive
decline and MCI at midlife; (2) identify blood DNAm signatures of neurocognitive decline and MCI and examine
whether they differ in the context of the APOE genotype, ancestry, and acculturation; (3) leverage available
biomarkers and genome-wide genetic data and use multi-omic integrative approaches and Mendelian
randomization analyses to identify functional gene networks and biological exposures that influence blood
DNAm signatures of neurocognitive aging and MCI. The project will efficiently fill gaps in scientific knowledge
about Latino longevity and neurocognitive aging and disorders.