Kan Z Gianattasio1, Erin E Bennett1, Jingkai Wei1, Megha L Mehrotra2, Thomas Mosley3, Rebecca F Gottesman4, Dean F Wong5, Elizabeth A Stuart6, Michael E Griswold7, David Couper8, M Maria Glymour2, Melinda C Power1. 1. Department of Epidemiology, George Washington University, Washington, District of Columbia, USA. 2. Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California, USA. 3. Department of Neurology, University of Mississippi Medical Center, Jackson, Mississippi, USA. 4. Departments of Neurology and Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA. 5. Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri, USA. 6. Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. 7. Department of Biostatistics, University of Mississippi Medical Center, Jackson, Mississippi, USA. 8. Department of Biostatistics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
Abstract
INTRODUCTION: Clinic-based study samples, including the Alzheimer's Disease Neuroimaging Initiative (ADNI), offer rich data, but findings may not generalize to community-based settings. We compared associations in ADNI to those in the Atherosclerosis Risk in Communities (ARIC) study to assess generalizability across the two settings. METHODS: We estimated cohort-specific associations among risk factors, cognitive test scores, and neuroimaging outcomes to identify and quantify the extent of significant and substantively meaningful differences in associations between cohorts. We explored whether using more homogenous samples improved comparability in effect estimates. RESULTS: The proportion of associations that differed significantly between cohorts ranged from 27% to 34% across sample subsets. Many differences were substantively meaningful (e.g., odds ratios [OR] for apolipoprotein E ε4 on amyloid positivity in ARIC: OR = 2.8, in ADNI: OR = 8.6). DISCUSSION: A higher proportion of associations differed significantly and substantively than would be expected by chance. Findings in clinical samples should be confirmed in more representative samples.
INTRODUCTION: Clinic-based study samples, including the Alzheimer's Disease Neuroimaging Initiative (ADNI), offer rich data, but findings may not generalize to community-based settings. We compared associations in ADNI to those in the Atherosclerosis Risk in Communities (ARIC) study to assess generalizability across the two settings. METHODS: We estimated cohort-specific associations among risk factors, cognitive test scores, and neuroimaging outcomes to identify and quantify the extent of significant and substantively meaningful differences in associations between cohorts. We explored whether using more homogenous samples improved comparability in effect estimates. RESULTS: The proportion of associations that differed significantly between cohorts ranged from 27% to 34% across sample subsets. Many differences were substantively meaningful (e.g., odds ratios [OR] for apolipoprotein E ε4 on amyloid positivity in ARIC: OR = 2.8, in ADNI: OR = 8.6). DISCUSSION: A higher proportion of associations differed significantly and substantively than would be expected by chance. Findings in clinical samples should be confirmed in more representative samples.
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