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IC‐03‐07: A voxel‐based morphometry study correlating MRI with Braak neurofibrillary tangle stage at autopsy
Author(s) -
Whitwell Jennifer L.,
Josephs Keith A.,
Kantarci Kejal,
Przybelski Scott A.,
Weigand Stephen D.,
Senjem Matthew L.,
Parisi Joseph E.,
Knopman David S.,
Boeve Bradley F.,
Petersen Ronald C.,
Dickson Dennis W.,
Jack Clifford R.
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.012
Subject(s) - grey matter , pathology , neurofibrillary tangle , atrophy , temporal lobe , voxel based morphometry , psychology , alzheimer's disease , medicine , magnetic resonance imaging , neuroscience , white matter , senile plaques , disease , radiology , epilepsy
Background: Neurofibrillary tangles (NFT) and amyloid plaques are the pathological hallmarks of Alzheimer’s disease (AD). The topographic distribution and progression of NFT pathology has been described by the Braak NFT staging scheme. While region-of-interest measures of individual structures such as the hippocampus have been correlated with Braak NFT stage, no studies have evaluated the correlation between pathologically determined disease severity and the full 3 dimensional pattern of atrophy on MRI throughout the brain. This study aimed to determine whether grey matter atrophy patterns from antemortem MRI correlate with the Braak NFT staging scheme. Methods: Eighty-five subjects with Braak NFT stage III-VI (III 16; IV 11; V 31; VI 27), a pathological diagnosis of low, intermediate or high probability AD according to NIA Reagan criteria, and MRI within four years of death were identified. Voxel-based morphometry was used to assess grey matter atrophy in each Braak NFT stage compared to 19 pathological control subjects (Braak stage 0-II). Regression analyses identified regions of loss that correlated with Braak NFT stage, MiniMental State Examination and Clinical Dementia Rating score. Results: Grey matter loss in medial and inferior temporal, temporoparietal, posterior cingulate and frontal regions correlated with Braak NFT stage. In pair-wise comparisons with controls a graded response was observed across Braak stages V and VI (Figure). While both groups showed loss in medial temporal lobe, temporoparietal neocortex and posterior cingulate, the most severe and widespread pattern of loss was identified in these regions at Braak stage VI with additional involvement of striatum and primary visual cortex. No regions of loss were identified in Braak NFT stage III or IV compared with the control group (Figure). However, the sub-set of these subjects that were demented showed medial temporal lobe loss. Loss in medial and inferior temporal, temporoparietal, posterior cingulate and frontal regions also correlated to minimental state examination and clinical dementia rating scores. Conclusions: The distribution of NFT pathology correlates with patterns of grey matter loss, although in a nonlinear fashion with greater changes occurring between high Braak NFT stages than lower stages. These results validate the use of MRI as a biomarker of neurofibrillary pathology in AD. SATURDAY, JULY 26, 2008 ALZHEIMER’S IMAGING CONSORTIUM IC-P1 POSTER PRESENTATIONS