Metabolic Correlates of Dopaminergic Loss in Dementia with Lewy Bodies

Abstract

Background Striatal dopamine deficiency and metabolic changes are well‐known phenomena in dementia with Lewy bodies and can be quantified in vivo by 123I‐Ioflupane brain single‐photon emission computed tomography of dopamine transporter and 18F‐fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill‐understood. Objective We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region‐of‐interest–based and voxel‐based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter‐region coefficients stratified by dopamine deficiency and compared to healthy controls. Results There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Associations among education, age, and the dementia with Lewy bodies (DLB) metabolic pattern: A European‐DLB consortium project

“…In particular, in agreement with Morbelli et al 13 . and Huber et al., 40 we here confirmed the presence of a positive covariance between basal ganglia metabolism and education, suggesting that a relatively preserved metabolism in the basal ganglia should be expected, especially in highly educated DLB patients (already characterized by significantly reduced striatal dopamine availability) 40 . From the methodological point of view, one strength of the present analysis is its stability, which is due to the averaging over the many PCA‐driven atlases, combined with the small overlapping of volume of interest (VOIs) embedding the same voxel but belonging to different atlases.…”

Premotor and fronto-striatal mechanisms associated with presence hallucinations in dementia with Lewy bodies

“…Our findings of a negative correlation between vPMC (and striatal) 18 F-FDG metabolism and caudate nucleus 123 I-FP-CIT dopaminergic uptake seems puzzling, at first glance. However, similar findings were observed by Huber et al, where a more pronounced striatal dopaminergic deficit was correlated with a relative hypermetabolism in the caudate nucleus and limbic regions for DLB subjects ( Huber et al, 2020 ). Therefore, while we demonstrated a reduced metabolism in vPMC and a disruption in fronto-striatal connectivity for DLB subjects with PH, this does not preclude that, in this specific group, the patients with more marked reduction of striatal dopaminergic deficit have an up-regulation of frontal metabolism, possibly to compensate motor difficulties.…”

Longitudinal Changes in Isolated Rapid Eye Movement Sleep Behavior Disorder‐Related Metabolic Pattern Expression

“…Of note, our data suggest that putaminal metabolic increase is related to nigrostriatal dopaminergic degeneration in iRBD. Similarly, most PD 22,[28][29][30] and DLB 21,31 patients have been reported to show increased metabolic activity in the putamen. In these disorders, putaminal hypermetabolism is regarded to be due to a pacemaker center in the basal ganglia that compensates dopaminergic loss with increased neuronal firing rate and consequently increased metabolic activity.…”