India ENIGMA Initiative for Global Aging & Mental Health

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ABSTRACT Our revised proposal launches the India ENIGMA Initiative for Global Aging & Mental Health - a globally coordinated study of brain aging and Alzheimer's disease (AD), created response to the NIH FOA: Global Brain and Nervous System Disorders Research Across the Lifespan (R01; PAR-18-834; https://grants.nih.gov/grants/guide/pa-files/PAR-18-835.html). Our overall goal is to identify predictive markers in the blood, genome, and epigenome that influence brain aging in India, to better understand prognosis, and to support personalized risk evaluations on each continent. We plan to identify etiological pathways to resilience using the rich biobanking strategy developed by our partners at NIMHANS in India. To do this, we will leverage our global consortium, ENIGMA (http://enigma.ini.usc.edu), to partner with dementia research pioneers in India, creating new links between international biobanks, and building research capacity. By 2020, 70% of the world's population over age 60 will live in developing countries, with 14% in India (Mathuranath 2012). Recently, attention has been drawn to a “diversity” crisis in brain research, as most brain research is conducted in Caucasian populations from relatively wealthy backgrounds (LeWinn 2017). This lack of ethnic diversity means that: (1) we do not know if predictors of health (and disease) generalize to other ethnic groups, and (2) we fail to collect vital data that could teach us how AD progresses in populations with different genetic and environmental backgrounds. Our coordinated analyses in US/EU and Indian biobanks will help identify brain aging predictors specific to India and those that are universal. Specifically, we will: Aim 1. Create Lifespan Charts of brain aging Trajectories in India using MRI, DWI and Resting State Functional MRI. Aim 2. Identify Blood and Epigenetic Markers that Predict Brain Aging and AD in India. Aim 3. Using a combination of multimodal imaging, blood markers, and clinical data to predict clinical decline in India. We test structural equation models that hypothesize how brain aging depends on lifestyle and psychosocial factors (diet, family support, drug abuse, literacy, sleep, and depression), as well as sex, education, and AD genetic risk. With novel machine learning methods, will analyze blood markers and plasma proteomic analytes, to define processes that are harmful to brain aging. In Capacity Building Aims, we will leverage ENIGMA's successful strategies to train emerging and established scientists in India to analyze their data with high quality control and precision, with targeted biostatistical and imaging workshops to bolster capacity. This collaborative India-US initiative will enable future science initiatives, and equip the NIMHANS team with the necessary tools to train new scientists and independently conduct high impact research bridging efforts into numerous international partnerships.