Significance of brain lesions in Parkinson disease dementia and Lewy body dementia.

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. Copyright (c) 2009 S. Karger AG, Basel.