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Pallido-nigro-luysial atrophy (PNLA) is a rare disorder that in many cases has histopathological features similar to progressive supranuclear palsy (PSP). In a pathological series of over 400 cases of PSP, eight cases were noted to have features similar to those described in PNLA, including severe atrophy and neuronal loss in the globus pallidus, substantia nigra and subthalamic nucleus, in addition to many axonal spheroids in the globus pallidus and substantia nigra. These eight cases of PSP–PNLA were compared to 11 typical PSP cases with quantitative neuropathologic indices and assessment of demographics, clinical features and the timing of clinical features. PSP–PNLA cases were younger, had longer disease duration and more often were not initially diagnosed with PSP; in the end, they did not differ from PSP with respect to any major clinical feature. The clinical course of PSP–PNLA, however, was different, with earlier gait abnormalities and difficulty with handwriting, but later falls, rigidity and dysphagia than PSP. Pathologically, the same types of lesions were detected in both PSP and PSP–PNLA, but there were differences in the distribution and density of tau-pathology, with less tau-pathology in motor cortex, striatum, pontine nuclei and cerebellum in PSP–PNLA. These clinical and pathological findings suggest that PSP–PNLA should be considered a variant of PSP. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 Alzheimers disease, dementia with Lewy bodies (DLB), mixed Alzheimers 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 Alzheimers disease, mixed Alzheimers 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 Alzheimers disease/DLB, Alzheimers 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 Alzheimers disease, mixed Alzheimers 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 Alzheimers disease from cases with mixed Alzheimers disease/DLB pathology, they demonstrate important pathophysiological differences between DLB and those with mixed Alzheimers disease/DLB and Alzheimers disease pathology, and between those with CBD and PSP pathology. [ABSTRACT FROM AUTHOR]