Enhancing Alzheimer's-related research in rural South Africa with portable MRI - PROJECT SUMMARY This project will incorporate portable, low-field brain magnetic resonance imaging (MRI) into a population- representative study of Alzheimer’s disease (AD) and related dementias (ADRD) in rural South Africa, transforming the ability to assess ADRD-related brain atrophy and cerebrovascular disease in low- and middle- income country (LMIC) settings. Increasing incidence and prevalence of ADRD represent a global health crisis that disproportionately affects LMICs, including South Africa. The study of ADRD risk, pathogenesis, and course has been revolutionized by the development of accessible fluidic biomarkers that capture the amyloid and tau components of AD-related pathophysiology, but direct measurement of neurodegeneration and cerebrovascular disease - - primary drivers of cognitive outcomes and clinical progression - - is limited in rural areas and LMICs because of the cost, infrastructure, technological access, and expertise required to conduct MRI research. Newly developed portable MRI scanners coupled with advances in data post-processing now provide the possibility to conduct high-fidelity, high-throughput brain imaging studies in rural settings. The proposed study will enhance the research infrastructure and resources for studies of ADRD neuroscience relevant to Africa by being the first to establish and incorporate portable brain MRI for the study of ADRD in rural South Africa. The proposed work leverages the robust infrastructure, cohort, and resources available through the Health, Aging and Dementia in South Africa: A Longitudinal Study (HAALSI; P01 AG041710), an ongoing population-representative study that addresses core issues in dementia epidemiology in older South Africans. HAALSI has completed three waves of longitudinal dementia survey data in over 5,000 participants over aged 40 within a population-representative cohort in Agincourt (“HAALSI Agincourt”). Two additional waves of intensive dementia data collection have been completed under the Harmonized Cognitive Assessment Protocol (HCAP) among more than 600 HAALSI participants over age 50 (“HAALSI Agincourt-HCAP”; R01 AG054066). Over 300 structural MRI scans at 1.5T field strength have been acquired in these participants. During the UG3 phase of the proposed study, we will install a low-field portable MRI scanner in a community health facility in Agincourt; establish acquisition, data transfer, and analytic pipelines; and collect portable MRI data among 350 Agincourt-HCAP participants with available 1.5T MRI scans, biomarker, and clinical data. During the UH3 phase, we will conduct the largest portable MRI ADRD study in a LMIC to date, acquiring 3500 MRI scans (including 300 repeat scans) in HAALSI Agincourt participants to examine associations of atrophy and cerebrovascular disease with ADRD fluidic biomarkers, cognition, vascular factors, and social determinants. Consistent with RFA-AG-24-027, we will transform collaborations between US and African scientists; enhance research infrastructure and resources to study ADRD in South Africa; and conduct preliminary studies that will inform future ADRD research in Africa.
