Abstract
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Objectives Cognitive impairment is frequent in Parkinson disease (PD) and can be observed at all stages. The aim was to examine the effect of cortical cholinergic degeneration on cognitive performance in PD patients while taking into account the degree of striatal dopaminergic denervation and possible modulating effects of cortical β-amyloid (Aβ) depositions.
Methods PD subjects (N=38, 8F/30M), 69.1±5.6 years, motor disease duration 7.0±4.7 years, Hoehn and Yahr stage 2.6±0.5 underwent cognitive assessment and [11C]-DTBZ VMAT2, [11C]-PMP AChE, and [11C]-PiB Aβ PET imaging. Cortical cholinergic degeneration in PD patients was characterized by dichotomizing into normal or below-normal range [11C]-PMP AChE hydrolysis rate (k3) based on a normative group of non-PD elderly. ANCOVA’s were performed to assess the independent effect of dichotomized cortical [11C]-PMP k3 on different cognitive domains (verbal learning, executive, visuospatial, attention, and global composite z-score) while covarying for striatal [11C]-DTBZ Distribution Volume Ratio (DVR) and cortical [11C]-PiB DVR.
Results The results of the ANCOVA’s are tabulated in Table 1.
Conclusions Both cortical cholinergic denervation and cortical Aβ plaques independently contribute to broad cognitive impairments in PD patients. The absence of a striatal dopaminergic effect on cognition may reflect severe dopaminergic denervation resulting in a statistical ‘floor’ effect. Progressive decline of cognitive function in PD patients could be prevented by cholinergic treatment and prevention of amyloid plaques.