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Objective: To determine the relative contributions of individual pathologic protein deposits associated with dementia in patients with Parkinson disease (PD). Design: Autopsied patients were analyzed from February 24, 2005, through July 25, 2010, to determine the distribution and severity of individual pathologic protein deposits (α-synuclein, Aβ, and tau) using routine protocols for histologic and immunohistochemical analysis and established neuropathologic staging criteria. Clinical data were extracted from an electronic medical record system used for all patients with PD. Patients: Thirty-two consecutive autopsied patients treated at the Washington University Movement Disorders Center who had neuropathologic confirmation of PD and a history of dementia, regardless of the timing of the onset of dementia with respect to motor symptoms. Results: Three pathologic subgroups of dementia associated with PD were identified: (1) predominant synucleinopathy (Braak Lewy body stages 5-6) (12 [38%]), (2) predominant synucleinopathy with Aβ deposition (Braak amyloid stages B-C) but minimal or no cortical tau deposition (19 [59%]), and (3) synucleinopathy and Aβ depositionwith at least moderate neocortical tauopathy (Braak tau stages 5-6; 1 [3%]). Kaplan-Meier and Cox regression analyses revealed that patients with synucleinopathy plus Aβdeposition had significantly shorter survival (years from PD onset until death and years from dementia onset until death) than patients with synucleinopathy only. Conclusions: Dementia associated with PD has 2 major pathologic subgroups: neocortical synucleinopathy and neocortical synucleinopathy with Aβ deposition. Alzheimer disease with neocortical Aβ and tau deposition does not commonly cause dementia with PD. Furthermore, accumulation of Aβ is associated with lower survival rates in PD patients with dementia. Additional studies are needed to prospectively determine the association between α-synuclein and Aβ accumulation and the role of Aβ in the development and progression of cognitive impairment in PD. [ABSTRACT FROM AUTHOR]

Objective: To determine the life expectancy of patients with Parkinson disease (PD) in the United States and identify demographic, geographic, and clinical factors that influence survival. Design: Retrospective cohort study of 138 000 Medicare beneficiaries with incident PD who were identified in 2002 and followed up through 2008. Main Outcome Measures: Confounder-adjusted 6-year risk of death as influenced by 3 groups of factors: (1) race, sex, and age at diagnosis; (2) geography and environmental factors; and (3) clinical conditions. We examined hospitalization diagnoses in patients with terminal PD and compared PD mortality with that of other common diseases. Results: Thirty-five percent of patients with PD lived more than 6 years. Sex and race significantly predicted survival; patients who were female (HR [hazard ratio], 0.74; 95% CI, 0.73-0.75), Hispanic (HR, 0.72; 95% CI, 0.65-0.80), or Asian (HR, 0.86; 95% CI, 0.82-0.91) had a lower adjusted risk of death than white men. Dementia, diagnosed in 69.6% of cases and most often in African American patients (78.2%) and women (71.5%), was associated with a greater likelihood of death (HR, 1.72; 95% CI, 1.69-1.75). Parkinson disease mortality was greater than that of many common life-threatening diseases. Patients with terminal PD were hospitalized frequently for cardiovascular disease (18.5%) and infection (20.9%) but rarely for PD (1.0%). Regional survival rates were similar but patients with PD living in urban high industrial metal emission areas had a slightly higher adjusted risk of death (HR, 1.19; 95% CI, 1.10-1.29). Conclusions: Demographic and clinical factors impact PD survival. Dementia is highly prevalent in patients with PD and is associated with a significant increase in mortality. More research is needed to understand whether environmental exposures influence PD course or survival. [ABSTRACT FROM AUTHOR]