Imaging amyloid deposition in Lewy body diseases

Abstract

Background: Extrapyramidal motor symptoms precede dementia in Parkinson disease (PDD) by many years, whereas dementia occurs early in dementia with Lewy bodies (DLB). Despite this clinical distinction, the neuropsychological and neuropathologic features of these conditions overlap. In addition to widespread distribution of Lewy bodies, both diseases have variable burdens of neuritic plaques and neurofibrillary tangles characteristic of Alzheimer disease (AD).

Objectives: To determine whether amyloid deposition, as assessed by PET imaging with the beta-amyloid-binding compound Pittsburgh Compound B (PiB), can distinguish DLB from PDD, and to assess whether regional patterns of amyloid deposition correlate with specific motor or cognitive features.

Methods: Eight DLB, 7 PDD, 11 Parkinson disease (PD), 15 AD, and 37 normal control (NC) subjects underwent PiB-PET imaging and neuropsychological assessment. Amyloid burden was quantified using the PiB distribution volume ratio.

Results: Cortical amyloid burden was higher in the DLB group than in the PDD group, comparable to the AD group. Amyloid deposition in the PDD group was low, comparable to the PD and NC groups. Relative to global cortical retention, occipital PiB retention was lower in the AD group than in the other groups. For the DLB, PDD, and PD groups, amyloid deposition in the parietal (lateral and precuneus)/posterior cingulate region was related to visuospatial impairment. Striatal PiB retention in the DLB and PDD groups was associated with less impaired motor function.

Conclusions: Global cortical amyloid burden is high in dementia with Lewy bodies (DLB) but low in Parkinson disease dementia. These data suggest that beta-amyloid may contribute selectively to the cognitive impairment of DLB and may contribute to the timing of dementia relative to the motor signs of parkinsonism.

Figure 1 Representative PiB images Images from a 75-year-old normal control (NC) (upper left), a 79-year-old patient with Alzheimer disease (AD) (Mini-Mental State Examination [MMSE] score 25; upper right), a 65-year-old patient with Parkinson disease (PD) (MMSE score 27; lower left), a 69-year-old patient with PD dementia (PDD) (MMSE score 25; lower middle), and a 71-year-old patient with dementia with Lewy bodies (DLB) (MMSE score 8; lower right) are displayed. Note that Pittsburgh Compound B (PiB) retention is qualitatively increased in AD, PDD, and DLB compared with NC and PD. Note also the variation in the regional distribution of amyloid across the AD, PDD, and DLB images. DVR = distribution volume ratio.

Figure 2 Amyloid deposition in Lewy body diseases Global Pittsburgh Compound B (PiB) distribution volume ratio for Alzheimer disease (AD), dementia with Lewy bodies (DLB), Parkinson disease dementia (PDD), Parkinson disease (PD), and normal control (NC) groups. Each point represents a single subject. Cases with specific cortical uptake of PiB (i.e., “PiB positive”) are shown as closed circles; some subjects with small foci of PiB retention had low global averages. Cases with low, nonspecific binding are shown as open circles (i.e., “PiB negative”). Lines connect group means that do not significantly differ: the AD and DLB group means were not significantly different from each other, and the PD, PDD, and NC means were not significantly different from each other. All pairwise comparisons between these two clusters were significant (p ≤ 0.05, Tukey post hoc tests).