title: Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns.
abstract: We systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20-90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (P<0.05), anti-hypertensive (P<0.05), anti-diabetic drug use (men P<0.05, women P=0.06) and waist circumference for the male cohort (P<0.05), after adjusting for age. Subjects with ABA had spatially extensive gray matter loss in the frontal, parietal and temporal lobes (false-discovery-rate-corrected q<0.001). ABA patterns of atrophy were partially overlapping with, but notably deviating from those typically found in AD. Subjects with ABA had higher SPARE-AD values; largely due to the partial spatial overlap of associated patterns in temporal regions. The AD polygenic risk score was significantly associated with SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely characterized by pathophysiologic mechanisms that are distinct from, or only partially overlapping with those of AD.
authors.affiliation: Institute for Community Medicine, University of Greifswald, Greifswald, Germany.|Department of Radiology, Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA.|Department of Psychiatry, University of Greifswald, Greifswald, Germany.
authors.forename: M
authors.identifier: http://orcid.org/0000-0001-9447-5805
authors.initials: M
authors.lastname: Habes
authors.affiliation: Department of Psychiatry, University of Greifswald, Greifswald, Germany.
authors.forename: D
authors.identifier: http://orcid.org/0000-0003-4324-9298
authors.initials: D
authors.lastname: Janowitz
authors.affiliation: Department of Radiology, Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Erus
authors.affiliation: Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Toledo
authors.affiliation: Laboratory of Behavioral Neuroscience, Biomedical Research Center, National Institute on Aging, Baltimore, MD, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Resnick
authors.affiliation: Department of Radiology, Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Doshi
authors.affiliation: Department of Psychiatry, University of Greifswald, Greifswald, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Van der Auwera
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Greifswald, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Wittfeld
authors.affiliation: Department of Radiology, University of Greifswald, Greifswald, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Hegenscheid
authors.affiliation: Department of Radiology, University of Greifswald, Greifswald, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Hosten
authors.affiliation: Department of Dentistry, University of Greifswald, Greifswald, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Biffar
authors.affiliation: Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Homuth
authors.affiliation: Institute for Community Medicine, University of Greifswald, Greifswald, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Völzke
authors.affiliation: Department of Psychiatry, University of Greifswald, Greifswald, Germany.|German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Greifswald, Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Grabe
authors.affiliation: Institute for Community Medicine, University of Greifswald, Greifswald, Germany.|German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Greifswald, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Hoffmann
authors.affiliation: Department of Radiology, Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Davatzikos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000473:pathology*; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D001284:Atrophy; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D001931:Brain Mapping / Q000379:methods; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012307:Risk Factors; D017678:Sex Distribution; D055815:Young Adult