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.