Byun, Min Soo; Kim, Song E; Park, Jinsick; Yi, Dahyun; Choe, Young Min; Sohn, Bo Kyung; Choi, Hyo Jung; Baek, Hyewon; Han, Ji Young; Woo, Jong Inn; Lee, Dong Young
PloS one
2015NA ; 10 ( 11 ) :e0142756.
PMID : 26618360
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Byun, Min Soo - Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
Kim, Song E - Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
Park, Jinsick - Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea.
Yi, Dahyun - Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
Choe, Young Min - Department of Neuropsychiatry, Ulsan University Hospital, Ulsan, Republic of Korea.
Sohn, Bo Kyung - Department of Neuropsychiatry, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea.
Choi, Hyo Jung - Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
Baek, Hyewon - Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
Han, Ji Young - Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
Woo, Jong Inn - Neuroscience Research Institute, Medical Research Center Seoul National University, Seoul, Republic of Korea.
Lee, Dong Young - Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea. CN - Alzheimer's Disease Neuroimaging Initiative
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.
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