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Brain Advance Access published online on January 31, 2007

Brain, doi:10.1093/brain/awl388
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial use License (http://creativecommons.org/lisences/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distributed, and reproduction in medium, provided the original work is properly cited.

Focal atrophy in dementia with Lewy bodies on MRI: a distinct pattern from Alzheimer's disease

Jennifer L. Whitwell1, Stephen D. Weigand3, Maria M. Shiung1, Bradley F. Boeve2, Tanis J. Ferman5, Glenn E. Smith4, David S. Knopman2, Ronald C. Petersen2, Eduardo E. Benarroch2, Keith A. Josephs2 and Clifford R. Jack, Jr1

1Departments of Radiology, 2Neurology (Behavioral Neurology), 3Biostatistics, 4Psychiatry and Psychology, Mayo Clinic, Rochester, MN and 5Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA

Correspondence to: Clifford R. Jack Jr, Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA E-mail: jack.clifford{at}mayo.edu

Dementia with Lewy bodies (DLB) is the second most common cause of degenerative dementia after Alzheimer's disease. However, unlike the latter, the patterns of cerebral atrophy associated with DLB have not been well established. The aim of this study was to identify a signature pattern of cerebral atrophy in DLB and to compare it with the pattern found in Alzheimer's disease. Seventy-two patients that fulfilled clinical criteria for probable DLB were age- and gender-matched to 72 patients with probable Alzheimer's disease and 72 controls. Voxel-based morphometry (VBM) was used to assess patterns of grey matter (GM) atrophy in the two patient groups, relative to controls, after correction for multiple comparisons (P < 0.05). Study-specific templates and prior probability maps were used to avoid normalization and segmentation bias. Region-of-interest (ROI) analyses were also performed comparing loss of the midbrain, substantia innominata (SI), temporoparietal cortex and hippocampus between the groups. The DLB group showed very little cortical involvement on VBM with regional GM loss observed primarily in the dorsal midbrain, SI and hypothalamus. In comparison, the Alzheimer's disease group showed a widespread pattern of GM loss involving the temporoparietal association cortices and the medial temporal lobes. The SI and dorsal midbrain were involved in Alzheimer's disease; however, they were not identified as a cluster of loss discrete from uninvolved surrounding areas, as observed in the DLB group. On direct comparison between the two groups, the Alzheimer's disease group showed greater loss in the medial temporal lobe and inferior temporal regions than the DLB group. The ROI analysis showed reduced SI and midbrain GM in both patient groups, with a trend for more reduction of SI GM in Alzheimer's disease than DLB, and more reduction of midbrain in DLB than Alzheimer's disease. Significantly greater loss in the hippocampus and temporo-parietal cortex was observed in the Alzheimer's disease patients when the two patient groups were compared. A pattern of relatively focused atrophy of the midbrain, hypothalamus and SI, with a relative sparing of the hippocampus and temporoparietal cortex is, therefore, suggestive of DLB and this may aid in the differentiation of DLB from Alzheimer's disease. These findings support recent pathological studies showing an ascending pattern of Lewy body progression from brainstem to basal areas of the brain. Damage to this network of structures in DLB may affect a number of different neurotransmitter systems which in turn may contribute to a number of the core clinical features of DLB.

Key Words: dementia with Lewy bodies; Alzheimer's disease; voxel-based morphometry; magnetic resonance imaging; neurotransmitter systems

Abbreviations: DLB, dementia with Lewy bodies; AD, Alzheimer's disease; GM, grey matter; ROI, region of interest; SI, substantia innominata; VBM, voxel-based morphometry; MRI, magnetic resonance imaging; MMSE, Mini-Mental Status Examination; CDR, Clinical Dementia Rating; RBD, REM sleep behaviour disorder; TIV, total intracranial volume; NBM, nucleus basalis of Meynert

Received September 19, 2006. Revised December 7, 2006. Accepted December 18, 2006.


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