Cerebral Small Vessel Disease and Brain Health in an Indigenous African Cohort (cSVD-IAC)

cSVD-IAC: Project Summary The overarching goal of cSVD- IAC is to characterize the burden of cerebral small vessel disease (SVD) [white matter hyperintensities (WMH), lacunar infarcts, enlarged perivascular spaces, microbleeds, cerebral atrophy, and total cSVD score] as defined by brain MRI in a population-based indigenous African cohort. We will test the relationship between MRI cSVD metrics and retinal imaging cSVD metrics (by fundal photography and optical coherence tomography-angiography) to determine thresholds for predicting and detecting cSVD with a more accessible and affordable approach in low - and middle - income countries and among underserved populations in the US. This will unravel the potential of retinal imaging for prediction and diagnosis of cSVD and cognitive impairment and dementia. Furthermore, we will unmask the modifiable, sex, genetic and blood-based biomarker determinants of cSVD and cognitive phenotypes in the cohort. To achieve this overall goal, we will recruit and characterize an additional 2000 participants to expand an existing cohort of > 1000 older Nigerians (50 yrs+) participating in the population-based Vascular heALth, fraiLty and cognItion in Ageing Nigerians sTudy [VALIANT]. We will undertake brain and retinal imaging and evaluate novel proteomic markers and assess transferability of genetic variants of cSVD among 1200 participants nested within the enlarged cohort (3000) and bank biological samples for future multi-omics and comparative studies with US and other global population-based aging cohorts. We will pursue these aims while training at least 5 African early career researchers (ECRs) and expanding stakeholder engagement. This project will consolidate and expand the growing African AD/ADRD research infrastructure by specifically characterizing cSVD in an under-represented African population. The novel data generated by this study will accelerate deeper understanding of cSVD biology in relation to cognitive impairment and dementia, identify lifestyles, and drug targets for prevention, disease modification and treatment, and ultimately enable the design of effective personalized strategies that will be of benefit to African, US and global populations in keeping with the priorities of the US National Dementia Plan and the recommendation of the National Academy of Medicine. We will accomplish this goal through an excellent partnership between experienced and leading US and African investigators.