Parkinson Disease With Dementia

Abstract

Subjects with Parkinson's disease (PD) frequently develop dementia with greater than one-third meeting neuropathologic diagnostic criteria for Alzheimer's disease (AD). The objective is to identify clinical and neuropathological differences between PDD (PD with dementia) subjects, with and without coexistent AD pathology. Neuropathologic examination was available on subjects diagnosed by clinicopathologic criteria with PDD-AD (N = 23) and PDD+AD (N = 28). A small subset of subjects with PDD-AD and PDD+AD had received at least one standardized neuropsychological assessment. PDD+AD subjects were significantly older at age of PD onset and death, progressed to onset of dementia in less time, and had a shorter duration of PD symptoms prior to the onset of dementia. Education, responsiveness of L-Dopa and dopaminergic medications, presence of cognitive fluctuations and hallucinations, mean MMSE, GDS, FAST and UPDRS scores did not differ significantly between the two groups. The PDD+AD group had significantly greater total plaques, neuritic plaques, total tangles, and Braak stages compared to PDD-AD. This study suggests that it is difficult to distinguish PDD+AD and PDD-AD on the basis of movement, clinical, and neuropsychological assessment. PDD-AD and PDD+AD have similar degrees of dementia and approximately half of PDD subjects have enough AD pathology to attain a neuropathological diagnosis of AD. PDD can develop in the absence of significant Alzheimer pathology.

Cognitive status correlates with white matter alteration in Parkinson's disease

“…Although the role of cortical Lewy pathologies and/or Alzheimer's disease-type pathologies has been suggested in many studies, there remains a discrepancy in the results [Braak et al, 2005;Colosimo et al, 2003;Mattila et al, 2000;Sabbagh et al, 2009]. As far as we know, there have been no neuropathological studies investigating the relationship between white matter damage and cognitive status in Lewy body disease.…”

“…While cortical Lewy bodies, Alzheimer's disease-type pathologies such as neurofibrillary tangles, amyloid plaque deposition, and degeneration of nucleus basalis of Meynert are suggested to play roles, there remains a discrepancy in the results [Braak et al, 2005;Colosimo et al, 2003;Mattila et al, 2000;Sabbagh et al, 2009]. Among cerebral structures, the white matter is particularly vulnerable to the postmortem effect because it contains abundant protease such as calcium-activated neutral proteinases.…”

Parkinson's disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies

“…PDD+AD. 40, 75, 81, 87, 90, 91 Thus, AD neuropathology, especially Aβ plaque pathology, appears to play an important role in the pathogenesis of PDD for a significant proportion of patients.…”

Challenges in the Neuropathological Diagnosis of Dementias

“…DLB cases had more severe Aβ load than PDD; but no differences in neuritic and αSyn scores, while others reported higher Aβ load in cortical and subcortical areas (Compta et al, 2011;Kalaitzakis et al, 2011), the Aβ load being similar to that in AD (Dugger et al, 2012;Gomperts et al, 2012). Between 10 and 50% of PDD brains had enough AD lesions to attain the pathological diagnosis of definite AD (Sabbagh et al, 2009), but cognitive impairment may also be related to higher Braak LB stages in the absence of significant AD pathology (Braak et al, 2005). A recent clinico-pathological study showed that cortical LB/LN pathology is the most significant correlate of dementia in PD, while AD pathology, being abundant in a subset of patients, may modify the clinical phenotype (Irwin et al, 2012).…”