Grant Overview
Innovative Research on Cognitive Decline and ADRD
The science in this program takes advantage of the unique scientific opportunity created by the coronavirus pandemic, to study the interactions between the exposure to the virus and genomic variation on cognitive decline and Alzheimer’s disease and related dementias (ADRD) in large cohorts of older adults from underrepresented minorities in the USA and ancestral groups in Africa and South America. The investigators leading the program have extensive experience in directing international consortia and longitudinal cohorts, including the creation and follow up of an Amerindian cohort in the Andes region for longer than a decade.
This study investigates the interactions between whole genome sequence genetic variations and COVID-19 infection/disease on the risk of cognitive decline and risk of ADRD in 4,300 individuals as part of newly recruited cohorts in Texas, New York, Washington State, Ibadan (Nigeria), and Jujuy (Argentina). Participant assessments include neurological, cognitive, imaging, and blood- and cerebrospinal fluid (CSF)-based biomarker evaluations at 3 time points: initial visit, and 18 and 36 month afterwards. We propose to answer this complex research question with 4 highly integrated Projects supported by equally integrated Administrative, Clinical, Neuroimaging, Biomarker, and Data Management/Statistics Cores.
Consortium Partners
Collaborative Resources and Expertise
Resources and study expertise are tightly coordinated across the multiple sites and Cores, and integrated to the National Institute of Aging Alzheimer’s Disease Sequencing Project (ADSP) and National Alzheimer’s Coordinating Center which will help ensure optimal sharing of both the data and knowledge.
Overall Aims
Risk of Cognitive Decline
Determine whether cognitive/neuropsychiatric sequelae of SARS-CoV-2 infection place individuals (particularly older adults) at increased risk of Alzheimer’s disease or related dementias (ADRD), earlier onset, or a faster course of illness.
Predictors of Risk and Resilience
Explore environmental, genetic, clinical, and neuroimaging predictors of risk and resilience in order to design secondary prevention and treatment strategies.
Longitudinal Course
Describe the longitudinal course, epidemiological risk/resiliency factors, and environmental interactions predictive of cognitive decline and progress to cognitive decline or ADRD following SARS-CoV-2 infection in adults over 65 years of age from ancestral and admixed populations.
Gene x Environment Interactions
Assess gene x environment interactions predictive of risk and resilience to cognitive decline and progression to ADRD in ancestral and admixed populations, using whole genome sequencing from Amerindian, African, and US-based admixed (Hispanic and African American) newly recruited cohorts.
Neural Signatures of COVID-19
Describe the neural signatures of COVID-19 on neuroimaging networks associated with neurological symptoms (anosmia and cognitive impairment) as predictors of progression to cognitive decline or ADRD in ancestral and admixed populations.
Pathophysiology and Prevention
Deepen the understanding of the pathophysiology of both long-term sequelae of COVID-19 and ADRD and thus lead to novel and successful preventative strategies for both diseases and for syndemic interactions between them.
Data Collected All Over the World
The sites span both urban and rural populations. All of the sites leverage majority populations (or very significant minority in the case of Seattle) of groups that are under-represented in existing genetic and clinical databases of aging adults with or without dementia. Self-reporting is used to document racial/ethnic status, but for all analyses, we use quantitative ancestry indices derived from genetic data to determine ethnicity (see Project 2).
RESEARCH
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