TY - JOUR
T1 - Rates of cerebral atrophy differ in different degenerative pathologies
AU - Whitwell, Jennifer L.
AU - Jack, Clifford R.
AU - Parisi, Joseph E.
AU - Knopman, David S.
AU - Boeve, Bradley F.
AU - Petersen, Ronald C.
AU - Ferman, Tanis J.
AU - Dickson, Dennis W.
AU - Josephs, Keith A.
N1 - Funding Information:
This study was supported by the NIH Roadmap Multidisciplinary Clinical Research Career Development Award Grant (K12/NICHD)-HD49078, by grants P50 AG16574, U01 AG06786, R01 AG15866 and R01 AG11378 from the National Institute on Aging, Bethesda, MD, NIRG-03-4842 from the Alzheimer’s Association, and the generous support of the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation, USA. D.S.K. has been a consultant to GE HealthCare, GlaxoSmithKline and Myriad Pharmaceuticals, has served on a Data Safety Monitoring Board for Neurochem Pharmaceuticals, and is an investigator in a clinical trial sponsored by Elan Pharmaceuticals. R.C.P. has been a consultant to GE Healthcare and an investigator in a clinical trial sponsored by Elan Pharmaceuticals. We would like to thank Vernon Shane Pankratz, PhD and Stephen Weigand, MS, for their statistical help and advice, and acknowledge Professor Nick Fox at the Dementia Research Centre, London, UK, for providing the MIDAS image analysis software.
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Dementia with Lewy bodies
KW - Frontotemporal lobar degeneration
KW - Magnetic resonance imaging
KW - Progressive supranuclear palsy
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U2 - 10.1093/brain/awm021
DO - 10.1093/brain/awm021
M3 - Article
C2 - 17347250
AN - SCOPUS:34249749823
SN - 0006-8950
VL - 130
SP - 1148
EP - 1158
JO - Brain
JF - Brain
IS - 4
ER -