Abstract
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. 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). 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. 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.
Highlights
MethodsWe analyzed MR imaging scans of 1472 participants from the Study of Health in Pomerania (22–90 years of age)
BACKGROUND AND PURPOSEThe presence of the apolipoprotein E 4 allele is the strongest sporadic Alzheimer disease genetic risk factor
No significant association was found between apolipoprotein E 4 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
Summary
We analyzed MR imaging scans of 1472 participants from the Study of Health in Pomerania (22–90 years of age). Participants from the Study of Health in Pomerania scanner (Magnetom Avanto; Siemens, Erlangen, Germany). We used only the T1-weighted axial MPRAGE images. The Study of Health in Pomerania (SHIP) is a prospective cohort for measuring regional patterns of AD-related brain atrophy. Image Processing An automated multiatlas segmentation method was applied on the T1-weighted image of each subject to calculate a brain mask, by removing extracranial material on the T1-weighted image.[20] Total intracranial volume was estimated by calculating the volume of a subject’s brain mask, which included the volumes of gray matter, white matter, ventricles, and the CSF that were contained within the outer brain boundary. Each brain mask was visually inspected for quality, by M.H., and all low-quality brain masks (including either under- or oversegmented brain) were excluded
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