Aβ-amyloid deposition in patients with Parkinson disease at risk for development of dementia

Abstract

Objective: The aim of our study was to examine the relationship between corticostriatal Aβ-amyloid deposition and cognitive dysfunction in a cohort of patients with Parkinson disease (PD) at risk for dementia.

Methods: This was a cross-sectional study of 40 patients with PD with mild cognitive impairment (MCI) or other known dementia risk factors. Subjects underwent dynamic Aβ-amyloid and vesicular monoamine transporter 2 PET imaging using [(11)C] Pittsburgh compound B (PiB) and [(11)C]dihydrotetrabenazine (DTBZ), respectively, and neuropsychological assessment. PiB and DTBZ PET data were analyzed using the Logan graphical method to determine cerebral PiB deposition relative to the cerebellar hemispheres and striatal DTBZ binding relative to occipital neocortex. Component z scores were calculated for individual cognitive domains (memory, visuospatial processing, working memory/attention, and executive function) and combined linearly for global estimation of cognition. Correlation of cognitive function and cortical PiB binding was investigated.

Results: Elevated cerebral PiB binding at levels seen in patients with AD was infrequent (6 of 40 subjects). Mean cortical PiB binding in the entire cohort was 1.16 ± 0.16 (distribution volume ratio; range 0.96-1.78). A significant correlation was noted between cortical PiB binding and global composite cognitive function (r = -0.55, p < 0.005) as well as the Wechsler Adult Intelligence Scale score (r = -0.54, p = 0.0004).

Conclusion: Elevated cerebral Aβ-amyloid deposition at levels seen in Alzheimer disease is uncommon in subjects with PD at risk for dementia. In our sample, the prevalence of markedly elevated PiB binding was significantly lower than that found in prior studies of cognitively normal elderly individuals. Neocortical PiB binding correlated robustly with measures of cognitive impairment in our cohort.

Figure 1. Representative surface maps of Pittsburgh compound B (PiB) distribution volume ratio (DVR) in Parkinson disease (PD)

Shown are surface projection representations of ¹¹C-PiB DVRs in representative subjects with PD (rows). Images are in pseudocolor according to the key at the bottom right, ranging from a minimum DVR of 0 to a maximum DVR of 3. The top 2 rows depict subjects classified as having mild dementia (DEM) after neuropsychometric evaluation. The next 2 rows depict subjects classified as having mild cognitive impairment (MCI). The bottom row depicts a subject with normal-range neuropsychological abilities (NML). Subjects in the top 3 rows were classified as PiB-positive by qualitative assessment of these projection images as well as in transaxial assessments of frontal cortical/subcortical white matter PiB DVR. Note a similar pattern of regional cortical PiB DVRs, with the most conspicuous elevations above cerebellar background in the frontal and temporal lobes and in the posterior cingulate cortex. This pattern may also be present, albeit at low intensity, even in the subjects classified as PiB-negative in the bottom 2 rows.

Figure 2. Relationship of global cognition to neocortical Pittsburgh compound B (PiB) binding (A) and relationship of Wechsler Adult Intelligence Scale (WAIS) score to neocortical PiB binding (B)

(A) r = −0.55; p = 0.0006. (B) r = −0.54; p = 0.0004. DVR = distribution volume ratio.