Amyloid deposition in Parkinson's disease and cognitive impairment: a systematic review

Abstract

Background: Varying degrees of cortical amyloid deposition are reported in the setting of Parkinsonism with cognitive impairment. We performed a systematic review to estimate the prevalence of Alzheimer disease (AD) range cortical amyloid deposition among patients with Parkinson's disease with dementia (PDD), Parkinson's disease with mild cognitive impairment (PD-MCI) and dementia with Lewy bodies (DLB). We included amyloid positron emission tomography (PET) imaging studies using Pittsburgh Compound B (PiB).

Methods: We searched the databases Ovid MEDLINE, PubMed, Embase, Scopus, and Web of Science for articles pertaining to amyloid imaging in Parkinsonism and impaired cognition. We identified 11 articles using PiB imaging to quantify cortical amyloid. We used the metan module in Stata, version 11.0, to calculate point prevalence estimates of patients with "PiB-positive" studies, that is, patients showing AD range cortical Aβ-amyloid deposition. Heterogeneity was assessed. A scatterplot was used to assess publication bias.

Results: Overall pooled prevalence of "PiB-positive" studies across all three entities along the spectrum of Parkinson's disease and impaired cognition (specifically PDD, PD-MCI, and DLB) was 0.41 (95% confidence interval [CI], 0.24-0.57). Prevalence of "PiB-positive" studies was 0.68 (95% CI, 0.55-0.82) in the DLB group, 0.34 (95% CI, 0.13-0.56) in the PDD group, and 0.05 (95% CI, -0.07-0.17) in the PD-MCI group.

Conclusions: Substantial variability occurs in the prevalence of "PiB-positive" studies in subjects with Parkinsonism and cognitive impairment. Higher prevalence of PiB-positive studies was encountered among subjects with DLB as opposed to subjects with PDD. The PD-MCI subjects showed overall lower prevalence of PiB-positive studies than reported findings in non-PD-related MCI. © 2015 International Parkinson and Movement Disorder Society.

Keywords: DLB; MCI; PDD; Parkinson's disease; systematic review.

Figure 1. Flowchart illustrates the selection of studies

PiB = Pittsburgh compound B, PET = positron emission tomography, PDD = Parkinson disease with dementia, DLB = dementia with Lewy bodies, PD-MCI = Parkinson disease with mild cognitive impairment.

Figure 2

Forest plot of point prevalence of PiB positive studies among the three entities encompassed by parkinsonism and cognitive impairment, specifically PDD, DLB and PD-MCI. The center point represents the estimated point prevalence for the respective study and the horizontal line, the 95% confidence interval for the respective study. The vertical broken line represents the pooled point prevalence and the boundaries of the hollow diamond represents the 95% CI of the pooled results. PDD = Parkinson disease with dementia, DLB = dementia with Lewy bodies, PD-MCI = Parkinson disease with mild cognitive impairment, n+ = number of subjects positive for amyloid, npat = total number of patients in each study.

Figure 3

Study Quality Scores. Graph illustrates study quality based on QUADAS criteria, expressed as a percent of studies meeting each criterion.

Figure 4

Assessing Publication Bias. The funnel plot horizontal axis expresses treatment effect, in this instance, measured by point prevalence. The vertical axis expresses study size, as measured by standard error (S.E.). Studies with larger standard errors have a wider confidence interval (CI) due to smaller sample size. The graphed vertical line represents the point prevalence and the dashed lines represent the 95% confidence limits for the expected distribution for published studies. The points represent the observed distribution of the published studies. Visual inspection of the plot demonstrates the presence of publication bias, with many studies outside the 95% confidence limits.