Cerebral glucose metabolism and cognition in newly diagnosed Parkinson's disease: ICICLE-PD study

Abstract

Objective To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline. Methods FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA. Results PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (β=0.38, p=0.001) and MoCA (β=0.3, p=0.002) at 18 months controlling for baseline score. Conclusions Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia.

18F-FDG PET in Parkinsonism: Differential Diagnosis and Evaluation of Cognitive Impairment

“…Interestingly, hypometabolism on 18 F-FDG PET preceded spatially matching atrophic changes on MRI (103). Across the entire group of patients with PD, PD-MCI, or PDD, regional glucose metabolism correlated with memory and visuospatial functions in the posterior temporal and parietal regions and also with attentional, executive, and language functions in the frontal regions (88,98). Several additional clinical observations support the strong negative prognostic value of posterior cortical hypometabolism.…”

“…Patients with MCI typically exhibit decreased temporoparietal, occipital, precuneal, and frontal metabolism when compared with healthy controls and, to a lesser extent, PD patients without MCI (88,91,98,101,102). These changes were more pronounced in multidomain than single-domain MCI (91,102).…”

“…These changes were more pronounced in multidomain than single-domain MCI (91,102). Recent studies using the current diagnostic criteria for PD-MCI demonstrated that the overall pattern of hypometabolism gradually develops from smaller clusters of mainly parietal and occipital (and sometimes frontal) hypometabolism in cognitively normal PD patients, to more widespread parietal, occipital, frontal, and (to a lesser extent) posterior temporal clusters in PD-MCI, and then to extensive parietal, occipital, frontal, and temporal hypometabolism in PDD (88,98,103). Interestingly, hypometabolism on 18 F-FDG PET preceded spatially matching atrophic changes on MRI (103).…”

Long reaction times are associated with delayed brain activity in lewy body dementia

“…These results suggest that the increased RT in the LBD group is a result of delayed onset of task related cognitive activity, and hence slower processing. These regions are all affected in LBD, with metabolic reductions in the occipital and parietal lobes (Firbank et al, ; Kantarci et al, ), reports of reduced grey matter in the insula (Blanc et al, ; Xu et al, ) and cholinergic (Mazère et al, ) and dopaminergic (O'Brien et al, ) alterations in the BG.…”

Molecular imaging to track Parkinson's disease and atypical parkinsonisms: New imaging frontiers

“…Imaging biomarker studies of cognitive impairment in PD have targeted neurotransmitter systems, pathological protein deposits, and glucose metabolic or perfusion changes. Prospective evaluation of glucose metabolic changes have shown that incident dementia initially may present as a predominant hypometabolic posterior cortical pathology involving the visual association cortex, inferior parietal and temporal regions, the posterior cingulum, and precuneus in PD . Subsequent progression to dementia is associated with mixed subcortical, including the thalamus and caudate nuclei, and widespread cortical changes that involve the anterior cortices as well .…”