In vivo assessment of pathology in Parkinson’s disease with Positron Emission Tomography

Abstract

Twenty-one non-demented Parkinson’s disease (PD) subjects had [11C]-(R)-PK11195, [11C]-PIB and [18F]-FDG PET scans to evaluate activated microglia, amyloid and cerebral metabolism, respectively; of these, 19 underwent repeat scanning at a mean interval of 21.4 months. Motor, cognitive and non-motor clinical assessments were conducted. 7 subjects with PD dementia had [11C]-PIB and [18F]-FDG scans. 8 [11C]-(R)-PK11195, 9 [11C]-PIB, and 8 [18F]-FDG control scans were obtained. [11C]-(R)-PK11195 uptake correlated with multiple motor and cognitive deficits and other non-motor clinical symptoms, suggesting that neuroinflammation associated with microglial activation is relevant to the clinical phenotypic expression from early disease onwards. Higher activated microglia burden was associated with greater cognitive deterioration, and may constitute a biomarker for risk of PD dementia. [11C]-PIB uptake was elevated throughout the neocortex and in the striatum in the non-demented PD group compared to controls, with a predilection for posterior cortical structures. [11C]-PIB uptake had increased in the non-demented PD group at interval scanning. [11C]-PIB retention in the PD dementia group was higher than in the non-demented PD group, with a relative excess of anterior cortical [11C]-PIB binding. Striatal [11C]-PIB retention correlated inversely with verbal fluency. Subjective motor disability, impaired verbal fluency, and communication difficulties were associated with frontal lobe [11C]-PIB uptake in the non-demented PD group, suggesting that amyloid may contribute to frontal lobe dysfunction in PD before the onset of dementia.

In a separate study, 47 [18F]-FDG PET scans with comprehensive gait analysis data were acquired. Brain metabolic deficits, detected with [18F]-FDG PET, were associated with abnormalities in gait pace and variability. Reduced gait velocity correlated with hypometabolism in the brainstem, putamen, globus pallidus, cingulate and anterior neocortex. The same pattern of metabolic derangement was related to increased gait variability, but spared the brainstem. It is conceived that brainstem locomotor structure contribute to pace, a more rudimentary component of gait function, whilst excess variability is a consequence of impaired supratentorial control of brainstem locomotion structures. Excess gait variability in PD may represent failure of compensatory mechanisms localising to the basal ganglia and anterior neocortex, due to progressive intrinsic PD pathology in these structures.