Brain Advance Access originally published online on March 8, 2007
Brain 2007 130(4):1148-1158; doi:10.1093/brain/awm021
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Rates of cerebral atrophy differ in different degenerative pathologies
Departments of 1Radiology, 2Laboratory Medicine and Pathology and 3Neurology (Behavioral Neurology), Mayo Clinic Rochester, Rochester, MN and Departments of 4Psychiatry and Psychology 5Neuroscience (Neuropathology), Mayo Clinic Jacksonville, Jacksonville, FL, USA
Correspondence to: Keith A. Josephs MST, MD, Department of Neurology, Divisions of Movement Disorders & Behavioral Neurology, Mayo Clinic, Rochester, MN 55905, USA E-mail: josephs.keith{at}mayo.edu
Neurodegenerative disorders are pathologically characterized by the deposition of abnormal proteins in the brain. It is likely that future treatment trials will target the underlying protein biochemistry and it is therefore increasingly important to be able to distinguish between different pathologies during life. The aim of this study was to determine whether rates of brain atrophy differ in neurodegenerative dementias that vary by pathological diagnoses and characteristic protein biochemistry. Fifty-six autopsied subjects were identified with a clinical diagnosis of dementia and two serial head MRI. Subjects were subdivided based on pathological diagnoses into Alzheimer's disease, dementia with Lewy bodies (DLB), mixed Alzheimer's disease/DLB, frontotemporal lobar degeneration with ubiquitin-only-immunoreactive changes (FTLD-U), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). Twenty-five controls were matched by age, gender and scan interval, to the study cohort. The boundary-shift integral was used to calculate change over time in whole brain (BBSI) and ventricular volume (VBSI). All BSI results were annualized by adjusting for scan interval. The rates of whole brain atrophy and ventricular expansion were significantly increased compared to controls in the Alzheimer's disease, mixed Alzheimer's disease/DLB, FTLD-U, CBD and PSP groups. However, atrophy rates in the DLB group were not significantly different from control rates of atrophy. The largest rates of atrophy were observed in the CBD group which had a BBSI of 2.3% and VBSI of 16.2%. The CBD group had significantly greater rates of BBSI and VBSI than the DLB, mixed Alzheimer's disease/DLB, Alzheimer's disease and PSP groups, with a similar trend observed when compared to the FTLD-U group. The FTLD-U group showed the next largest rates with a BBSI of 1.7% and VBSI of 9.6% which were both significantly greater than the DLB group. There was no significant difference in the rates of atrophy between the Alzheimer's disease, mixed Alzheimer's disease/DLB and PSP groups, which all showed similar rates of atrophy; BBSI of 1.1, 1.3 and 1.0% and VBSI of 8.3, 7.2 and 10.9%, respectively. Rates of atrophy therefore differ according to the pathological diagnoses and underlying protein biochemistry. While rates are unlikely to be useful in differentiating Alzheimer's disease from cases with mixed Alzheimer's disease/DLB pathology, they demonstrate important pathophysiological differences between DLB and those with mixed Alzheimer's disease/DLB and Alzheimer's disease pathology, and between those with CBD and PSP pathology.
Key Words: magnetic resonance imaging; Alzheimer's disease; dementia with Lewy bodies; frontotemporal lobar degeneration; progressive supranuclear palsy
Abbreviations: BSI, boundary shift integral; CBD, corticobasal degeneration; CDR, Clinical Dementia Rating; DLB, dementia with Lewy bodies; FTLD-U, frontotemporal lobar degeneration with ubiquitin-only-immunoreactive changes; MMSE, Mini-Mental State Examination; PiD, Pick disease; PSP, progressive supranuclear palsy
Received October 31, 2006. Revised January 21, 2007. Accepted January 23, 2007.
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