There are two studies that provide the data for this project. The study based on the Honolulu Asia Aging Study is designed as a nested case control study and all cases of dementia identified in exams 4 and 5 of the Honolulu Asia Aging Study, cases of mild cognitive impairment (defined as a drop in CASI score of >4pts per year), a random set of controls frequency matched in 5-year strata to the cases. The second study is the Age Gene/Environment Susceptibility - Reykjavik Study (AGES-RS)of men and women born between 1907 - 1935 in Reykjavik, Iceland. Together these studies have unique and rich data on brain function and structure. We are currently conducting association studies of candidate gene polymorphisms for inflammation and vascular disease in relation to the risk for dementia and other related outcomes in brain aging. The genotyping is the same in both studies. In addition to this candidate gene approach, we have completed a whole genome wide scans on 3600 individuals from the AGES-RS and are collaborating in consortia to pool data with studies that have similar phenotypes and genotypes. In addition to studying brain phenotypes, we are also studying the association of geneotype to phenotypic factors that are associated with brain aging and pathology, such as blood pressure and other cardiovascular factor.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Investigator-Initiated Intramural Research Projects (ZIA)
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National Institute on Aging
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Sedaghat, Sanaz; Ding, Jie; Eiriksdottir, Gudny et al. (2018) The AGES-Reykjavik Study suggests that change in kidney measures is associated with subclinical brain pathology in older community-dwelling persons. Kidney Int 94:608-615
Ikram, M Arfan; Zonneveld, Hazel I; Roshchupkin, Gennady et al. (2018) Heritability and genome-wide associations studies of cerebral blood flow in the general population. J Cereb Blood Flow Metab 38:1598-1608
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Traylor, Matthew; Malik, Rainer; Nalls, Mike A et al. (2017) Genetic variation at 16q24.2 is associated with small vessel stroke. Ann Neurol 81:383-394
Sims, Rebecca (see original citation for additional authors) (2017) Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nat Genet 49:1373-1384
Ben-Avraham, Dan; Karasik, David; Verghese, Joe et al. (2017) The complex genetics of gait speed: genome-wide meta-analysis approach. Aging (Albany NY) 9:209-246
Hibar, Derrek P (see original citation for additional authors) (2017) Novel genetic loci associated with hippocampal volume. Nat Commun 8:13624
Day, Felix R (see original citation for additional authors) (2017) Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk. Nat Genet 49:834-841
(2017) 19th Workshop of the International Stroke Genetics Consortium, April 28-29, 2016, Boston, Massachusetts, USA: 2016.001 MRI-defined cerebrovascular genomics-The CHARGE consortium. Neurol Genet 3:S2-S11

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