Significance of Brain Lesions in Parkinson Disease Dementia and Lewy Body Dementia

Institute of Clinical Neurobiology, Vienna, Austria.
Frontiers of neurology and neuroscience 02/2009; 24:114-25. DOI: 10.1159/000197890
Source: PubMed


Dementia is increasingly recognized as a common feature in patients with Parkinson disease (PD)and dementia with Lewy bodies (DLB), both sharing many clinical and morphological features and believed to form a continuum within the spectrum of Lewy body diseases. Based on a large autopsy series of parkinsonism (31-37% with dementia) and review of the recent literature, the pathological changes underlying cognitive impairment in PD with dementia (PDD) and DLB are discussed. PD cases with Lewy body stages 3-5, i.e. only mild to moderate cortical alpha-synuclein (alphaSyn) depositions,and no additional pathologies, are rarely associated with cognitive impairment, which is frequently seen in PD and DLB cases with considerable cortical and limbic alphaSyn load (increasing Lewy body densities) and/or associated widespread Alzheimer-type pathology. Clinicopathological studies show a negative relation between cognitive impairment and both cortical Lewy body pathology and Alzheimer type changes, suggesting that these either alone or in combination are major causes of cognitive dysfunction, while others related them to presynaptic alphaSyn aggregates. The neuropathology of PDD and DLB is similar, without significant differences between cortical and subcortical Lewy bodies and the pattern of synuclein pathology in the brainstem, but there are topographic differences in nigral lesions, more frequent affection of the hippocampal CA 2/3 subareas and more severe diffuse amyloid plaque load in the striatum of DLB. In conclusion, the pathology underlying cognitive impairment in PDD and DLB is heterogeneous, but there are some differences in the topography and severity of lesions between both phenotypes that need further evaluation.

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    • "The neuropathology of DLB is similar to that of PD but a more severe diffuse load of Lewy bodies (eosinophilic, neuronal inclusions, which can be stained by actin, neurofilament, ubiquitin and -synuclein), is present in brain stem, diencephalon, anterior cingulate, amygdala and cerebral cortex. Many cases have substantial AD pathology (amyloid plaque and neocortical tangle) and this could explain the reason why many cases with Lewy body pathology present with an insidious amnestic syndrome are more similar to AD. Cognitive impairment seems to correlate with the presence of an AD-like pathology along with cortical and limbic -synuclein load which is the main constituent of Lewy body both in PD and DLB [62]. The contribution of the AD pathology to the dementia has been debated but mixed cases are more demented than pure cases. "
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