Background: Discrete clinical and pathological subtypes of Alzheimer’s disease (AD) with variable presentations and rates of progression are well known. These subtypes may have specific patterns of regional brain atr...Background: Discrete clinical and pathological subtypes of Alzheimer’s disease (AD) with variable presentations and rates of progression are well known. These subtypes may have specific patterns of regional brain atrophy, which are identifiable on MRI scans. Methods: To examine distinct regions which had distinct underlying patterns of cortical atrophy, factor analytic techniques applied to structural MRI volumetric data from cognitively normal (CN) (n = 202), amnestic mild cognitive impairment (aMCI) (n = 333) or mild AD (n = 146) subjects, in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database was applied. This revealed the existence of two neocortical (NeoC-1 and NeoC-2), and a limbic cluster of atrophic brain regions. The frequency and clinical correlates of these regional patterns of atrophy were evaluated among the three diagnostic groups, and the rates of progression from aMCI to AD, over 24 months were evaluated. Results: Discernable patterns of regional atrophy were observed in about 29% of CN, 55% of aMCI and 83% of AD subjects. Heterogeneity in clinical presentation and APOE ε4 frequency were associated with regional patterns of atrophy on MRI scans. The most rapid progression rates to dementia among aMCI subjects (n = 224), over a 24-month period, were in those with NeoC-1 regional impairment (68.2%), followed by the Limbic regional impairment (48.8%). The same pattern of results was observed when only aMCI amyloid positive subjects were examined. Conclusions: The neuroimaging results closely parallel findings described recently among AD patients with the hippocampal sparing and limbic subtypes of AD neuropathology at autopsy. We conclude that NeoC-1, Limbic and other patterns of MRI atrophy may be useful markers for predicting the rate of progression of aMCI to AD and could have utility selecting individuals at higher risk for progression in clinical trials.展开更多
文摘Background: Discrete clinical and pathological subtypes of Alzheimer’s disease (AD) with variable presentations and rates of progression are well known. These subtypes may have specific patterns of regional brain atrophy, which are identifiable on MRI scans. Methods: To examine distinct regions which had distinct underlying patterns of cortical atrophy, factor analytic techniques applied to structural MRI volumetric data from cognitively normal (CN) (n = 202), amnestic mild cognitive impairment (aMCI) (n = 333) or mild AD (n = 146) subjects, in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database was applied. This revealed the existence of two neocortical (NeoC-1 and NeoC-2), and a limbic cluster of atrophic brain regions. The frequency and clinical correlates of these regional patterns of atrophy were evaluated among the three diagnostic groups, and the rates of progression from aMCI to AD, over 24 months were evaluated. Results: Discernable patterns of regional atrophy were observed in about 29% of CN, 55% of aMCI and 83% of AD subjects. Heterogeneity in clinical presentation and APOE ε4 frequency were associated with regional patterns of atrophy on MRI scans. The most rapid progression rates to dementia among aMCI subjects (n = 224), over a 24-month period, were in those with NeoC-1 regional impairment (68.2%), followed by the Limbic regional impairment (48.8%). The same pattern of results was observed when only aMCI amyloid positive subjects were examined. Conclusions: The neuroimaging results closely parallel findings described recently among AD patients with the hippocampal sparing and limbic subtypes of AD neuropathology at autopsy. We conclude that NeoC-1, Limbic and other patterns of MRI atrophy may be useful markers for predicting the rate of progression of aMCI to AD and could have utility selecting individuals at higher risk for progression in clinical trials.
