Dopaminergic and Serotonergic Degeneration and Cortical [¹⁸F]Fluorodeoxyglucose Positron Emission Tomography in De Novo Parkinson's Disease

Abstract

A BS TRACT: Background: Degeneration of the nigrostriatal dopaminergic (DA) and the raphe-thalamic serotonergic (SE) systems is among the earliest changes observed in Parkinson's disease (PD). The consequences of those changes on brain metabolism, especially regarding their impact on the cortex, are poorly understood. Objectives: Using multi-tracer molecular imaging, we assessed in a cohort of drug-naive PD patients the association between cortical metabolism and DA and SE system deafferentation of either striatum or thalamus, and we explored whether this association was mediated by either striatum or thalamus metabolism. Methods: We recruited 96 drug-naive PD patients (aged 71.9 AE 7.5 years) who underwent [ 123 I]ioflupane single-photon emission computed tomography ([ 123 I] FP-CIT-SPECT) and brain [ 18 F]fluorodeoxyglucose positron emission tomography ([ 18 F]FDG-PET). We used a voxel-wise analysis of [ 18 F]FDG-PET images to correlate regional metabolism with striatal DA and thalamic SE innervation as assessed using [ 123 I]FP-CIT-SPECT.Results: We found that [ 123 I]FP-CIT specific to nondisplaceable binding ratio (SBR) and glucose metabolism positively correlated with one another in the deep gray matter (thalamus: P = 0.001, r = 0.541; caudate P = 0.001, r = 0.331; putamen P = 0.001, r = 0.423). We then observed a direct correlation between temporoparietal metabolism and caudate DA innervation, as well as a direct correlation between prefrontal metabolism and thalamus SE innervation. The effect of caudate [ 123 I]FP-CIT SBR values on temporoparietal metabolism was mediated by caudate metabolic values (percentage mediated: 89%, P-value = 0.008), and the effect of thalamus [ 123 I]FP-CIT SBR values on prefrontal metabolism was fully mediated by thalamus metabolic values (P < 0.001). Conclusions: These data suggest that the impact of deep gray matter monoaminergic deafferentation on cortical function is mediated by striatal and thalamic metabolism in drug-naive PD.

Metabolic correlates of olfactory dysfunction in COVID-19 and Parkinson’s disease (PD) do not overlap

“…Bohnen and colleagues demonstrated by means of acetylcholinesterase (AChE) PET that cholinergic denervation is a more robust determinant of hyposmia than nigrostriatal dopaminergic denervation in PD [ 46 ]. The typical posterior PD hypometabolic pattern that we have here identified is in line with these findings as, in PD patients, hypometabolism in these regions has been previously linked to cholinergic dysfunction as well as to the risk of developing clinically significant cognitive impairment [ 29 ]. Accordingly, the present findings are in keeping with the hypothesis that olfactory judgement/interpretation and, not only olfactory perception, is altered in PD patients.…”

“…Between January 2015 and May 2021, we examined 123 consecutive drug-naïve PD patients who underwent a full neuropsychological assessment and [ 123 I]FP-CIT-SPECT imaging [ 29 ]. Inclusion criteria for the present study were availability of a brain [ 18 F]-FDG PET within 3 months following clinical diagnosis (mainly due to their inclusion in previous prospective studies in our center) and presence of hyposmia as documented by means of olfaction test (see below).…”

SUN11602, a bFGF mimetic, modulated neuroinflammation, apoptosis and calcium-binding proteins in an in vivo model of MPTP-induced nigrostriatal degeneration

“…PD is a progressive neurodegenerative disease whose pathological characteristic is the degeneration of the nigrostriatal dopaminergic system [ 32 ]. Current therapeutic approaches of Parkinsonian patients aimed to attenuate clinical symptoms through the administration of levodopa and monoamine oxidase B (MAO-B) inhibitors [ 33 , 34 ].…”

Investigating the aspect of asymmetry in brain-first versus body-first Parkinson’s disease

“…In this retrospective study, we gathered and analyzed clinical and imaging data previously obtained for PD and iRBD patients. These data were collected within the framework of clinical practice (PD) and other specific studies (iRBD) 44 , 45 .…”