Striatal DAT and extrastriatal SERT binding in early-stage Parkinson's disease and dementia with Lewy bodies, compared with healthy controls: An (123)I-FP-CIT SPECT study.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are thought to be part of a spectrum: both have a clinical profile including symptoms associated with dopaminergic and serotonergic loss, yet few imaging studies have focused on serotonergic neurodegeneration in both disorders. We aimed to study degeneration of terminals with dopamine and serotonin transporter (DAT and SERT, respectively) in patients with early-stage PD and DLB relative to healthy controls, using 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) single photon emission computed tomography (SPECT). We conducted region of interest (ROI) and voxel-based analyses on 123I-FP-CIT SPECT scans. Using the cerebellum as a reference region, we determined binding ratios (BRs) for bilateral ROIs in the DAT-rich striatum (head of the caudate nucleus and posterior putamen) and SERT-rich extrastriatal brain regions (thalamus, hypothalamus and hippocampus). We compared BRs in PD and DLB patients with BRs in healthy controls (all groups: n = 16). Both PD and DLB patients had lower striatal 123I-FP-CIT BRs than healthy controls for the bilateral caudate head (PD-left: F(1,29) = 28.778, P < .001, ω2 = 0.35; right: F(1,29) = 35.338, P < .001, ω2 = 0.42; DLB-left: F(1,29) = 28.241, P < .001, ω2 = 0.31; right: F(1,29) = 18.811, P < .001, ω2 = 0.26) and bilateral posterior putamen (PD-left: F(1,29) = 107.531, P < .001, ω2 = 0.77; right: F(1,29) = 87.525, P < .001, ω2 = 0.72; DLB-left: F(1,29) = 39.910, P < .001, ω2 = 0.48; right: F(1,29) = 26.882, P < .001, ω2 = 0.38). DLB patients had lower hypothalamic 123I-FP-CIT BRs than healthy controls (F(1,29) = 6.059, P = .020, ω2 = 0.12). In the voxel-based analysis, PD and DLB patients had significantly lower striatal binding than healthy controls. Both PD patients in the early disease stages and DLB patients have reduced availability of striatal DAT, and DLB patients lower hypothalamic SERT compared with healthy controls. These observations add to the growing body of evidence that PD and DLB are not merely dopaminergic diseases, thereby providing additional clinicopathological insights.

Joling M ，Vriend C ，Raijmakers PGHM ，van der Zande JJ ，Lemstra AW ，Berendse HW ，Booij J ，van den Heuvel OA ... -  《NeuroImage-Clinical》

Serotonergic deficits in dementia with Lewy bodies with concomitant Alzheimer's disease pathology: An (123)I-FP-CIT SPECT study.

To study the influence of concomitant Alzheimer's disease (AD) pathology in dementia with Lewy bodies (DLB) on dopamine transporter (DAT) and serotonin transporter (SERT) availability, using 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (123I-FP-CIT) single photon emission computed tomography (SPECT). Based on their cerebrospinal fluid biomarker profile, fifty-two patients with probable DLB were divided in a group with (DLB/AD+, N = 15) and without concomitant AD-pathology (DLB/AD-, N = 37). We conducted atrophy-corrected region of interest (ROI) analyses comparing binding ratios (BRs) in the DAT-rich striatal and SERT-rich extrastriatal brain areas (amygdala, hippocampus, thalamus, midbrain and pons). DLB/AD+ patients had significantly lower 123I-FP-CIT BRs in the left amygdala, and a trend was seen in the right hippocampus. Groups did not differ significantly in striatal 123I-FP-CIT BRs, neuropsychiatric or motor symptoms. Motor symptoms correlated negatively with striatal DAT BRs. DLB/AD+ patients may have lower SERT binding in limbic brain regions than DLB/AD- patients, possibly indicating faster neurodegeneration in mixed pathology.

van der Zande JJ ，Joling M ，Happach IG ，Vriend C ，Scheltens P ，Booij J ，Lemstra AW ... -  《NeuroImage-Clinical》

Lower (123)I-FP-CIT binding to the striatal dopamine transporter, but not to the extrastriatal serotonin transporter, in Parkinson's disease compared with dementia with Lewy bodies.

Joling M ，Vriend C ，van der Zande JJ ，Lemstra AW ，van den Heuvel OA ，Booij J ，Berendse HW ... -  《NeuroImage-Clinical》

Analysis of Extrastriatal (123)I-FP-CIT Binding Contributes to the Differential Diagnosis of Parkinsonian Diseases.

123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) SPECT can visualize and quantify striatal dopamine transporter (DAT) binding in vivo. In addition, 123I-FP-CIT has modest affinity for the serotonin transporter (SERT), predominantly represented in extrastriatal binding. On the basis of previous imaging studies that have suggested more pronounced degeneration of other monoaminergic systems in multiple-system atrophy (MSA) and progressive supranuclear palsy (PSP) than in Parkinson disease (PD), we hypothesized that, in addition to striatal DAT binding, there would be differences in extrastriatal 123I-FP-CIT SPECT binding to SERT between MSA, PSP, and PD. Methods: We included patients with parkinsonian type MSA (multiple-system atrophy with predominantly parkinsonism [MSA-P], n = 9), cerebellar type MSA (MSA-C, n = 7), PSP (n = 13), and PD (n = 30). 123I-FP-CIT binding was analyzed using region-of-interest (ROI)- as well as voxel-based methods in both the DAT-rich striatum (caudate nucleus and putamen) and the SERT-rich extrastriatal brain regions (thalamus, hypothalamus, and pons). For SERT analysis, patients on selective serotonin reuptake inhibitor were excluded (n = 48 remained). Results: In the ROI analyses, extrastriatal 123I-FP-CIT binding ratios in the hypothalamus were significantly lower in PSP than in MSA-C patients, and we observed significantly lower striatal 123I-FP-CIT binding ratios in the caudate nucleus of PSP patients than in that of both PD and MSA-C patients. In the posterior putamen, binding ratios were significantly lower in MSA-P, PSP, and PD than MSA-C patients. Striatal ROI outcomes were confirmed by the voxel-based analyses that additionally showed a significantly lower hypothalamic binding in PSP and MSA-P than PD. Conclusion: Striatal 123I-FP-CIT binding to DAT and hypothalamic 123I-FP-CIT binding to SERT are significantly lower in MSA-P and PSP than in PD and MSA-C patients and might therefore be of interest for differential diagnosis.

Joling M ，Vriend C ，van den Heuvel OA ，Raijmakers PGHM ，Jones PA ，Berendse HW ，Booij J ... -  《-》

Extrastriatal dopaminergic and serotonergic pathways in Parkinson's disease and in dementia with Lewy bodies: a (123)I-FP-CIT SPECT study.

Pilotto A ，Schiano di Cola F ，Premi E ，Grasso R ，Turrone R ，Gipponi S ，Scalvini A ，Cottini E ，Paghera B ，Garibotto V ，Rizzetti MC ，Bonanni L ，Borroni B ，Morbelli S ，Nobili F ，Guerra UP ，Perani D ，Padovani A ... -  《-》