title: Heterogeneity of Regional Brain Atrophy Patterns Associated with Distinct Progression Rates in Alzheimer's Disease.
abstract: We aimed to identify and characterize subtypes of Alzheimer's disease (AD) exhibiting different patterns of regional brain atrophy on MRI using age- and gender-specific norms of regional brain volumes. AD subjects included in the Alzheimer's Disease Neuroimaging Initiative study were classified into subtypes based on standardized values (Z-scores) of hippocampal and regional cortical volumes on MRI with reference to age- and gender-specific norms obtained from 222 cognitively normal (CN) subjects. Baseline and longitudinal changes of clinical characteristics over 2 years were compared across subtypes. Whole-brain-level gray matter (GM) atrophy pattern using voxel-based morphometry (VBM) and cerebrospinal fluid (CSF) biomarkers of the subtypes were also investigated. Of 163 AD subjects, 58.9% were classified as the "both impaired" subtype with the typical hippocampal and cortical atrophy pattern, whereas 41.1% were classified as the subtypes with atypical atrophy patterns: "hippocampal atrophy only" (19.0%), "cortical atrophy only" (11.7%), and "both spared" (10.4%). Voxel-based morphometric analysis demonstrated whole-brain-level differences in overall GM atrophy across the subtypes. These subtypes showed different progression rates over 2 years; and all subtypes had significantly lower CSF amyloid-β 1-42 levels compared to CN. In conclusion, we identified four AD subtypes exhibiting heterogeneous atrophy patterns on MRI with different progression rates after controlling the effects of aging and gender on atrophy with normative information. CSF biomarker analysis suggests the presence of Aβ neuropathology irrespective of subtypes. Such heterogeneity of MRI-based neuronal injury biomarker and related heterogeneous progression patterns should be considered in clinical trials and practice with AD patients.
authors.affiliation: Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Byun
authors.affiliation: Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Song E
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea.
authors.forename: Jinsick
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Dahyun
authors.initials: D
authors.lastname: Yi
authors.affiliation: Department of Neuropsychiatry, Ulsan University Hospital, Ulsan, Republic of Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Choe
authors.affiliation: Department of Neuropsychiatry, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea.
authors.forename: Bo Kyung
authors.initials: BK
authors.lastname: Sohn
authors.affiliation: Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Baek
authors.affiliation: Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Han
authors.affiliation: Neuroscience Research Institute, Medical Research Center Seoul National University, Seoul, Republic of Korea.
authors.forename: Jong Inn
authors.initials: JI
authors.lastname: Woo
authors.affiliation: Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Dong Young
authors.initials: DY
authors.lastname: Lee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000145:classification / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged