The cohort was established in 1967 by the Icelandic Heart Association; participants were followed up to six times. Baseline enrollment of 5764 men and women ran from 2002-2006; from 2007-2011 a follow-up exam was completed in 3,411 participants. Follow-up continues for hospitalizations, nursing home and home care assessments, and deaths. To study risk factors, prognosis, cause of death; and, uniquely, examine trajectories of health status and disease from middle to old age, this study of longitudinal change into old age has defined phenotypes for epidemiologic, genomic, and other omics analyses. A rich image and bio-repository has been developed for specimens that can be used for future novel research questions, thus maintaining the opportunities to test new hypotheses as they emerge. Together, these data provide a life-course perspective of disease and will enhance understanding of how health is maintained and disease develops over the lifetime. To date we have published widely on genetic and environmental risk factors for a range of common subclinical diseases in older persons, for example: atherosclerosis, coronary disease, and heart failure; osteoporosis, fractures and rheumatologic disease; obesity and glucose abnormalities; prevalence and risk factors for hearing and vision loss; brain structure and function, ADRD, and cerebral small vessel disease; and life style factors such as physical activity actigraphy and diet. We have also looked at cross associations among various systems, and shared underlying mechanisms such as inflammation, systemic vascular disease and metabolic dysregulation. Overall, the study has made important contributions to our understanding of the complexity and interrelationships amongst biologic systems in the trajectory towards old age. Our findings emphasize the need for a more systems-based approaches both to the study of, and clinical care for health and disease in old age. Specifically, for brain disease, this study has made important contributions to understanding the role of small vessel disease as both a consequence of cardiovascular risk factors and a substrate for cognitive impairment, dementia and depression. Work on the heart-brain and kidney-brain axes, which are all connected through small vessel disease, is in progress, as is continued research on the hemodynamic contribution to brain pathology. Data on the Off-spring of AD cases in AGES-RS is currently being analyzed to understand the genetic basis of the relation between AD and cardiovascular risk factors. This study has made a major contribution to understanding the genetic basis of a wide range of phenotypes, in the context of several international consortia. It also contributes to a NINDS sponsored consortia on plasma based biomarkers for vascular cognitive impairment, and to many other international consortia.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG007380-13
Application #
9986417
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2019
Total Cost
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
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
Emilsson, Valur; Ilkov, Marjan; Lamb, John R et al. (2018) Co-regulatory networks of human serum proteins link genetics to disease. Science 361:769-773
Forsberg, Lars; Sigurdsson, Sigurdur; Fredriksson, Jesper et al. (2017) The AGES-Reykjavik study atlases: Non-linear multi-spectral template and atlases for studies of the ageing brain. Med Image Anal 39:133-144
Sobrin, Lucia; Chong, Yong He; Fan, Qiao et al. (2017) Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study. Diabetes 66:3130-3141
Veronese, Nicola; Sigeirsdottir, Kristin; Eiriksdottir, Gudny et al. (2017) Frailty and Risk of Cardiovascular Diseases in Older Persons: The Age, Gene/Environment Susceptibility-Reykjavik Study. Rejuvenation Res :
Ding, Jie; Sigurðsson, Sigurður; Jónsson, Pálmi V et al. (2017) Space and location of cerebral microbleeds, cognitive decline, and dementia in the community. Neurology 88:2089-2097
Ding, Jie; Sigurðsson, Sigurður; Jónsson, Pálmi V et al. (2017) Large Perivascular Spaces Visible on Magnetic Resonance Imaging, Cerebral Small Vessel Disease Progression, and Risk of Dementia: The Age, Gene/Environment Susceptibility-Reykjavik Study. JAMA Neurol 74:1105-1112
Graff, Mariaelisa (see original citation for additional authors) (2017) Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults. PLoS Genet 13:e1006528
Li, Man; Li, Yong; Weeks, Olivia et al. (2017) SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function. J Am Soc Nephrol 28:981-994
Justice, Anne E (see original citation for additional authors) (2017) Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat Commun 8:14977

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