M Habes1, J B Toledo2, S M Resnick3, J Doshi4, S Van der Auwera5, G Erus4, D Janowitz5, K Hegenscheid6, G Homuth7, H Völzke8, W Hoffmann9, H J Grabe10, C Davatzikos4. 1. From the Institute for Community Medicine (M.H., H.V., W.H.) Department of Psychiatry (M.H., S.V.d.A., D.J., H.J.G.) Center for Biomedical Image Computing and Analytics (M.H., J.D., G.E., C.D.), University of Pennsylvania, Philadelphia, Pennsylvania habesm@uphs.upenn.edu jtoledo@mail.med.upenn.edu. 2. Department of Pathology and Laboratory Medicine (J.B.T.), Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania habesm@uphs.upenn.edu jtoledo@mail.med.upenn.edu. 3. Laboratory of Behavioral Neuroscience (S.M.R), National Institute on Aging, Bethesda, Maryland. 4. Center for Biomedical Image Computing and Analytics (M.H., J.D., G.E., C.D.), University of Pennsylvania, Philadelphia, Pennsylvania. 5. Department of Psychiatry (M.H., S.V.d.A., D.J., H.J.G.). 6. Department of Radiology (K.H.). 7. Institute for Genetics and Functional Genomics (G.H.), University of Greifswald, Greifswald, Germany. 8. From the Institute for Community Medicine (M.H., H.V., W.H.). 9. From the Institute for Community Medicine (M.H., H.V., W.H.) German Center for Neurodegenerative Diseases (W.H., H.J.G.), Rostock/Greifswald, Germany. 10. Department of Psychiatry (M.H., S.V.d.A., D.J., H.J.G.) German Center for Neurodegenerative Diseases (W.H., H.J.G.), Rostock/Greifswald, Germany.
Abstract
BACKGROUND AND PURPOSE: The presence of the apolipoprotein E ε4 allele is the strongest sporadic Alzheimer disease genetic risk factor. We hypothesized that apolipoprotein E ε4 carriers and noncarriers may already differ in imaging patterns in midlife. We therefore sought to identify the effect of apolipoprotein E genotype on brain atrophy across almost the entire adult age span by using advanced MR imaging-based pattern analysis. MATERIALS AND METHODS: We analyzed MR imaging scans of 1472 participants from the Study of Health in Pomerania (22-90 years of age). We studied the association among age, apolipoprotein E ε4 carrier status, and brain atrophy, which was quantified by using 2 MR imaging-based indices: Spatial Pattern of Atrophy for Recognition of Brain Aging (summarizing age-related brain atrophy) and Spatial Pattern of Abnormality for Recognition of Early Alzheimer Disease (summarizing Alzheimer disease-like brain atrophy patterns), as well as the gray matter volumes in several Alzheimer disease- and apolipoprotein E-related ROIs (lateral frontal, lateral temporal, medial frontal, and hippocampus). RESULTS: No significant association was found between apolipoprotein E ε4 carrier status and the studied ROIs or the MR imaging-based indices in linear regression models adjusted for age, sex, and education, including an interaction term between apolipoprotein E and age. CONCLUSIONS: Our study indicates that measurable apolipoprotein E-related brain atrophy does not occur in early adulthood and midlife and suggests that such atrophy may only occur more proximal to the onset of clinical symptoms of dementia.
BACKGROUND AND PURPOSE: The presence of the apolipoprotein E ε4 allele is the strongest sporadic Alzheimer disease genetic risk factor. We hypothesized that apolipoprotein E ε4 carriers and noncarriers may already differ in imaging patterns in midlife. We therefore sought to identify the effect of apolipoprotein E genotype on brain atrophy across almost the entire adult age span by using advanced MR imaging-based pattern analysis. MATERIALS AND METHODS: We analyzed MR imaging scans of 1472 participants from the Study of Health in Pomerania (22-90 years of age). We studied the association among age, apolipoprotein E ε4 carrier status, and brain atrophy, which was quantified by using 2 MR imaging-based indices: Spatial Pattern of Atrophy for Recognition of Brain Aging (summarizing age-related brain atrophy) and Spatial Pattern of Abnormality for Recognition of Early Alzheimer Disease (summarizing Alzheimer disease-like brain atrophy patterns), as well as the gray matter volumes in several Alzheimer disease- and apolipoprotein E-related ROIs (lateral frontal, lateral temporal, medial frontal, and hippocampus). RESULTS: No significant association was found between apolipoprotein E ε4 carrier status and the studied ROIs or the MR imaging-based indices in linear regression models adjusted for age, sex, and education, including an interaction term between apolipoprotein E and age. CONCLUSIONS: Our study indicates that measurable apolipoprotein E-related brain atrophy does not occur in early adulthood and midlife and suggests that such atrophy may only occur more proximal to the onset of clinical symptoms of dementia.
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