Striatal dopamine transporter imaging correlates with depressive symptoms and tower of London task performance in Parkinson's disease

We studied whether the ¹²³I‐FP‐CIT uptake in the striatum correlates with depressive symptoms and cognitive performance in patients with Parkinson's disease (PD). Twenty patients with PD without major depression and/or dementia (mean age 61.7 ± 12.7 years) underwent the ¹²³I‐FP‐CIT SPECT. Depressive symptoms and cognitive performance were assessed in the ON state. The ratios of striatal to occipital binding for the entire striatum, putamina, and putamen to the caudate (put/caud) index were calculated in the basal ganglia. The association between neuropsychiatric measures and dopamine transporter (DAT) availability was calculated; multiple regression analysis was used to assess association with age and disease duration. We found significant correlations between Montgomery and Asberg Depression Rating Scale (MARDS) and Tower of London (TOL) task scores and ¹²³I‐FP‐CIT uptake in various striatal ROIs. Multiple regression analysis confirmed the significant relationship between TOL performance and put/caud ratio (P = 0.001) and to age (P = 0.001), and between MADRS and left striatal (P = 0.005) and putaminal DAT availability (P = 0.003). Our pilot study results demonstrate that imaging with ¹²³I‐FP‐CIT SPECT appears to be sensitive for detecting dopaminergic deficit associated with mild depressive symptoms and specific cognitive dysfunction in patients with PD, yet without a current depressive episode and/or dementia. © 2008 Movement Disorder Society     

Head‐to‐head comparison of 18F‐FP‐CIT and 123I‐FP‐CIT for dopamine transporter imaging in patients with Parkinson's disease: A preliminary study

¹²³I‐FP‐CIT and ¹⁸F‐FP‐CIT are radiotracers which are widely used to diagnose Parkinson's disease (PD). However, to our knowledge, no studies to date have made head‐to‐head comparisons between ¹²³I‐FP‐CIT and ¹⁸F‐FP‐CIT. Therefore, in this study, ¹²³I‐FP‐CIT SPECT/CT was compared with ¹⁸F‐FP‐CIT PET/CT in the same cohort of subjects. Patients with PD and essential tremor (ET) underwent ¹²³I‐FP‐CIT SPECT/CT and ¹⁸F‐FP‐CIT PET/CT. Visual and semiquantitative analyses were conducted. The specific binding ratio (SBR) and putamen to caudate ratio (PCR) were compared between subjects who underwent ¹²³I‐FP‐CIT SPECT/CT and ¹⁸F‐FP‐CIT PET/CT. Visual analysis showed that the striatal uptake of both radiotracers was decreased in the PD group, whereas striatal uptake was intact in the ET group. The SBR between ¹²³I‐FP‐CIT SPECT/CT and ¹⁸F‐FP‐CIT PET/CT showed a positive correlation (r = .78, p < .01). However, the mean SBRs on ¹⁸F‐FP‐CIT PET/CT were higher than those on ¹²³I‐FP‐CIT SPECT/CT (2.19 ± .87 and 1.22 ± .49, respectively; p < .01). The PCRs in these two modalities were correlated with each other (r = .71, p < .01). The mean PCRs on ¹⁸F‐FP‐CIT PET/CT were not significantly higher than those on ¹²³I‐FP‐CIT SPECT/CT (1.31 ± .19 and 0.98 ± .06, respectively; p = .06). These preliminary results indicate that the uptake of both ¹²³I‐FP‐CIT and ¹⁸F‐FP‐CIT was decreased in the PD group when compared with the ET controls. Visual analyses using both methods did not affect the diagnostic accuracy in this study. However, semiquantitative analysis indicated a better contrast of ¹⁸F‐FP‐CIT PET/CT relative to ¹²³I‐FP‐CIT SPECT/CT.     

Dopaminergic deficit is not the rule in orthostatic tremor

Involvement of the dopaminergic system in orthostatic tremor is controversial. The aim of this study was to detect possible dopaminergic denervation in primary orthostatic tremor (OT). Twelve consecutive patients with a firm diagnosis of primary orthostatic tremor were compared with age‐matched normal controls. All the patients had a neurological examination, surface polymyography, and quantification of striatal dopamine transporters with ¹²³I‐FP‐CIT SPECT imaging. There was no significant difference in ¹²³I‐FP‐CIT SPECT findings between controls and patients with OT. Longstanding primary orthostatic tremor is not necessarily associated with ¹²³I‐FP‐CIT SPECT abnormalities, as 8 of our patients had more than a 10‐year history of OT. Primary orthostatic tremor without dopaminergic denervation remains a valid entity, although representing only a subtype of high‐frequency OT. A new role may emerge for ¹²³I‐FP‐CIT SPECT in distinguishing between patients whose symptoms will be restricted to OT throughout the disease course and patients at an increased risk of developing PD. © 2008 Movement Disorder Society     

Midbrain serotonin transporters in de novo and L‐DOPA‐treated patients with early Parkinson’s disease – a [123I]‐ADAM SPECT study

Background: Dopaminergic availability is known to linearly decline in Parkinson’s disease (PD). In contrast, temporal characteristics of serotonergic markers like the serotonin transporter (SERT) in relation to clinical staging of PD and dopaminergic cell loss are less clear. This study investigated SERT availability using [¹²³I]‐ADAM and single‐photon emission tomography (SPECT) in drug‐naive, de novo patients, i.e., in a PD stage where dopaminergic decline starts to lead to the occurence of the characteristic motor symptoms. Methods: Nine de novo patients with PD and 9 age‐matched healthy controls were studied. Measurements were repeated after 3 months of levodopa treatment in patients with PD, and dopaminergic transporter (DAT) binding was examined at baseline using [¹²³I]‐FP‐CIT SPECT. Results: No alterations of SERT availability were found between groups, and neither correlation between SERT and DAT nor effects of levodopa treatment on SERT was found in patients with PD. Conclusions: These preliminary findings indicate that midbrain SERT is preserved in unmedicated patients at this early stage of PD, supporting the view that serotonergic decline temporally follows dopaminergic cell loss.     

[123I] FP‐CIT spect study in vascular parkinsonism and Parkinson's disease

There is substantial evidence to support a role for small vessel disease (SVD) as a cause for vascular parkinsonism (VP). Using [¹²³I] FP‐CIT SPECT (single photon emission computed tomography), we have tried to determine whether VP patients have pre‐synaptic dopaminergic function similar to PD patients, and whether the severity of parkinsonian symptoms as well as the levodopa response in VP patients are correlated with pre‐synaptic dopaminergic dysfunction. Thirteen patients fulfilling operational clinical criteria for VP had [¹²³I] FP‐CIT scans. Mean [¹²³I] FP‐CIT uptake in the basal ganglia was significantly lower in VP patients than in healthy controls, and the asymmetry index was not significantly different between these groups. In contrast, compared with the PD group, only the mean asymmetry index was significantly lower in VP patients. None of the parameters measured was significantly different between VP patients who had an insidious onset of parkinsonism (VPi) and those who had an acute onset (VPa). There was a significant correlation between the bilateral basal ganglia FP‐CIT uptake reduction in the VP patients and UPDRS motor scores, but not with the mean % reduction in motor UPDRS after levodopa. We suggest that in the majority of VP patients, pre‐synaptic dopaminergic function is reduced. The presence of a rather symmetrical FP‐CIT uptake in the basal ganglia may help to distinguish VP from PD and could therefore be used as a criterion for the clinical diagnosis of VP. © 2007 Movement Disorder Society     

Striatal dopamine transporter levels correlate with apathy in neurodegenerative diseases A SPECT study with partial volume effect correction

OBJECTIVES: The aim of the present study was to stress the relationship between neuropsychiatric symptoms and most particularly apathy and striatal dopamine uptake in patients with Alzheimer's disease (AD) or dementia with Lewy body (DLB). PATIENTS AND METHODS: Twenty-two patients (AD n=14; DLB n=8) were included. All patients had neuropsychological and behavioral examination including Mini Mental Test Examination (MMSE), Neuropsychiatric Inventory (NPI), and UPDRS for the motor activity assessment. Apathy dimensions, emotional blunting, lack of initiative and lack of interest were assessed using the Apathy Inventory (AI). Dopamine transporter (DAT) striatal uptake was assessed using (123)I-FP-CIT (DaTSCAN) SPECT. Quantitative measurements were obtained in 3D using a method which compensates for physical detection biases including partial volume effect. RESULTS: We observed a correlation between DAT uptake and NPI's domains only for apathy. More specifically using the AI, lack of initiative significantly correlated with bilateral putamen DAT uptake. Using partial correlation coefficients controlling for the UPDRS score, the correlation remained significant between lack of initiative and right and left putamen DAT uptake. CONCLUSION: These results demonstrate a relationship between apathy and DAT levels independent from motor activity. They suggest that the patients with neurodegenerative diseases presenting with apathy are characterized by some degree of dopaminergic neuronal loss.     

Gray matter correlates of dopaminergic degeneration in Parkinson's disease: A hybrid PET/MR study using 18F‐FP‐CIT

Dopaminergic degeneration is a hallmark of Parkinson's disease (PD), which causes various symptoms affected by corticostriatal circuits. So far, the relationship between cortical changes and dopamine loss in the striatum is unclear. Here, we evaluate the gray matter (GM) changes in accordance with striatal dopaminergic degeneration in PD using hybrid PET/MR. Sixteen patients with idiopathic PD underwent ¹⁸F‐FP‐CIT PET/MR. To measure dopaminergic degeneration in PD, binding ratio (BR) of dopamine transporter in striatum was evaluated by ¹⁸F‐FP‐CIT. Voxel‐based morphometry (VBM) was used to evaluate GM density. We obtained voxelwise correlation maps of GM density according to the striatal BR. Voxel‐by‐voxel correlation between BR maps and GM density maps was done to evaluate region‐specific correlation of striatal dopaminergic degeneration. There was a trend of positive correlation between striatal BR and GM density in the cerebellum, parahippocampal gyri, and frontal cortex. A trend of negative correlation between striatal BR and GM density in the medial occipital cortex was found. Voxel‐by‐voxel correlation revealed that the positive correlation was mainly dependent on anterior striatal BR, while posterior striatal BR mostly showed negative correlation with GM density in occipital and temporal cortices. Decreased GM density related to anterior striatal dopaminergic degeneration might demonstrate degeneration of dopaminergic nonmotor circuits. Furthermore, the negative correlation could be related to the motor circuits of posterior striatum. Our integrated PET/MR study suggests that the widespread structural progressive changes in PD could denote the cortical functional correlates of the degeneration of striatal dopaminergic circuits. Hum Brain Mapp 37:1710–1721, 2016. © 2016 Wiley Periodicals, Inc .     

Application of feedback‐controlled bolus plus infusion (FC‐B/I) method for quantitative PET imaging of dopamine transporters with [18F]β‐CFT‐FE in conscious monkey brain

The competitive inhibition of dopamine transporters (DAT) with cocaine, a specific DAT inhibitor, was evaluated with a feedback‐controlled bolus plus infusion (FC‐B/I) method using animal positron emission tomography (PET) in the living brain of conscious monkey. 2β‐Carbomethoxy‐3β‐(4‐fluorophenyl)‐8‐(2‐[¹⁸F]fluoroethyl) nortropane ([¹⁸F]β‐CFT‐FE; Harada et al. [2004] Synapse 54:37–45) was used for this study because it provided specific, fast, and reversible kinetic properties to DAT in the striatum. In FC‐B/I method, the real‐time image reconstruction was started just after intravenous bolus injection of [¹⁸F]β‐CFT‐FE to generate a time‐activity curve in the striatum, and the infusion rate was adjusted to achieve an equilibrium state of the striatal radioactivity concentrations by means of a feedback‐control algorithm. The first equilibrium state in the brain was reached within 20 min after the infusion start. Intravenous administration of cocaine at the doses of 0.02, 0.1, and 0.5 mg/kg shifted the equilibrium radioactivity level to the second equilibrium state in a dose‐dependent manner, while no significant alterations was observed in the cerebellum. The present results demonstrated that the combined use of FC‐B/I method and PET probe with fast kinetics like [¹⁸F]β‐CFT‐FE could be useful to assess the occupancy of drugs in the living brain with PET. Synapse, 2013. © 2012 Wiley Periodicals, Inc.     

Cholinesterase inhibitor use does not significantly influence the ability of 123I-FP-CIT imaging to distinguish Alzheimer's disease from dementia with Lewy bodies

Background

¹²³I‐labelled 2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐fluoropropyl) nortropane (¹²³I‐FP‐CIT) imaging is a diagnostic tool to help differentiate dementia with Lewy bodies (DLB) from Alzheimer''s disease (AD). However, in animals, cholinesterase inhibitors (ChEi) have been reported to reduce radioligand binding to the striatal dopamine transporter. As ChEi are frequently used in people with dementia, it is important to determine whether their use affects ¹²³I‐FP‐CIT uptake in the striatum.

Objective

To clarify whether chronic ChEi therapy modulates striatal dopamine transporter binding measured by ¹²³I‐FP‐CIT in patients with AD, DLB and Parkinson''s disease with dementia (PDD).

Design

Cross sectional study in 99 patients with AD (nine on ChEi, 25 not on ChEi), DLB (nine on ChEi, 19 not on ChEi) and PDD (six on ChEi, 31 not on ChEi) comparing ¹²³I‐FP‐CIT striatal binding (caudate, anterior and posterior putamen) in patients receiving compared with those not receiving ChEi, correcting for key clinical variables including diagnosis, age, sex, Mini‐Mental State Examination score, severity of parkinsonism and concurrent antidepressant use.

Results

As previously described, ¹²³I‐FP‐CIT striatal uptake was lower in DLB and PDD subjects compared with those with AD. Median duration of ChEi use was 180 days. ¹²³I‐FP‐CIT uptake was not significantly reduced in subjects receiving ChEi compared those not receiving ChEi (mean percentage reduction: AD 4.3%; DLB 0.7%; PDD 6.1%; p = 0.40). ChEi use did not differentially affect striatal ¹²³FP‐CIT uptake between patient groups (p = 0.83).

Conclusions

Use of ChEi does not significantly influence the ability of ¹²³I‐FP‐CIT imaging to distinguish AD from DLB.Single photon emission computed tomography (SPECT) with the ligand ¹²³I‐labelled 2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐fluoropropyl) nortropane (¹²³I‐FP‐CIT), which binds to the dopamine transporter (DAT), has been shown to be useful in discriminating dementia with Lewy bodies (DLB) from Alzheimer''s dementia (AD).^1,2However, the utility of ¹²³I‐FP‐CIT imaging may be undermined if individuals are taking medications that affect the striatal binding of ¹²³I‐FP‐CIT, particularly if such agents differentially influence ¹²³I‐FP‐CIT striatal binding between DLB and AD. A significant class of drugs which might impact on ¹²³I‐FP‐CIT binding in these patient groups are cholinesterase inhibitors (ChEi). In the monkey, DAT availability, assessed by [¹¹C] β‐CFT positron emission tomography (PET), was reported to be acutely suppressed in a dose dependent manner by the ChEi donepezil.³ Direct evidence that cholinesterase inhibition modulates DAT function in humans is currently lacking.To determine whether chronic ChEi therapy influences striatal DAT binding by ¹²³I‐FP‐CIT in humans, we compared ¹²³I‐FP‐CIT striatal binding in patients with AD, DLB and Parkinson''s disease with dementia (PDD) treated with ChEi with those not receiving these agents.     

Differences in nigro‐striatal impairment in clinical variants of early Parkinson’s disease: evidence from a FP‐CIT SPECT study

Introduction: In idiopathic Parkinson’s disease (PD), two different clinical phenotypes are usually distinguished: a tremor dominant variant (TD) and an akinetic‐rigid type (ART). TD patients are characterized by a slower disease progression and a minor cognitive impairment. Striatal density of DAT, as quantified by FP‐CIT SPECT, has been reported to correlate with rigidity and akinesia but not with tremor. Objective: To evaluate FP‐CIT uptake in TD and ART phenotypes. Methods: We retrospectively evaluated from our database the pre‐synaptic nigro‐striatal function of 24 patients with TD‐PD and 38 patients with ART‐PD who underwent a FP‐CIT SPECT within 1 year from disease onset. Results: Disease duration, age at the time of SPECT scan and disease severity as measured with Unified Parkinson’s Disease Rating scale part III (UPDRS III) were not statistically different between the two groups. Putamen contralateral to the most clinically affected side showed a lower FP‐CIT uptake in ART patients compared to TD patients. No statistically significant differences emerged when considering bilateral caudate and ipsilateral putaminal uptake, as well as asymmetry indices and caudate/putamen ratios. FP‐CIT contralateral putaminal uptake correlated with the severity of rigidity and hypokinesia but not with tremor. Conclusions: These data suggest that other neurotransmitter systems apart from the nigro‐striatal dopaminergic system are involved in the generation of Parkinsonian tremor, and they are consistent with previous evidence of a lack of correlation between tremor severity and FP‐CIT uptake. Putaminal relative sparing in TD patients could partially explain the slower disease progression reported in this PD phenotype.     

Residual striatal dopaminergic nerve terminals in very long‐standing Parkinson's disease: A single photon emission computed tomography imaging study

Molecular imaging studies of Parkinson's disease (PD) progression mostly focus on the first 5 years after disease onset, demonstrating rapid initial nigrostriatal neuronal loss. The fate of residual functional dopaminergic nerve terminals in patients with long‐standing PD has not yet been specifically explored. Therefore, we performed [¹²³I]‐FP‐CIT single photon emission computed tomography (SPECT) in 15 patients with very long‐standing PD (mean disease duration 20.6 ± 6.3 years). Measurable uptake of [¹²³I]‐FP‐CIT was still detected in the striata of all patients. As seen in early stages, reduction of tracer uptake in the putamen was more prominent than in the caudate nucleus. Asymmetry in tracer uptake between the two putamen and caudate nuclei was preserved. These findings indicate that degeneration of dopaminergic neurons in PD is not total even after many years of illness. Data should be considered in exploring underlying causes of progressive loss of nigrostriatal dopaminergic neurons and development of future novel dopaminergic therapeutic strategies in PD. © 2010 Movement Disorder Society     

123I‐Ioflupane SPECT in the diagnosis of suspected psychogenic Parkinsonism

Psychogenic Parkinsonism (PsyP) can be clinically difficult to differentiate from Parkinson's disease (PD). Striatal dopamine transporter (DAT) imaging could be helpful in differentiating them. We performed ¹²³I‐Ioflupane single‐photon emission computed tomography (SPECT) in 9 patients with suspected PsyP. In 1 patient, ¹²³I‐Ioflupane SPECT disclosed bilateral decrease of striatal tracer uptake that indicated nigrostriatal degeneration. In this patient, a parkin gene mutation was detected. In the other 8 patients, ¹²³I‐Ioflupane SPECT was normal and supported the initial suspicion of PsyP. Normal DAT imaging supports the diagnosis of PsyP, whereas reduced striatal tracer uptake suggests an underlying neurodegenerative Parkinsonism and should encourage the search for additional causes for the syndrome. © 2006 Movement Disorder Society     

[123I]FP‐CIT SPET imaging in drug‐induced Parkinsonism

We assessed the status of dopamine nerve terminals in patients treated with dopamine receptor blocking agents (DRBAs) who had developed drug‐induced parkinsonism (DIP). We performed [¹²³I]FP‐CIT SPET in 32 consecutive patients who were on DRBAs for at least 6 months and developed extrapyramidal signs. The UPDRS‐III was used to assess clinical severity. Twenty‐six age‐ and sex‐matched healthy subjects served as control group. Putamen [¹²³I]FP‐CIT SPET binding was reduced in 14 and normal in the remaining 18 patients. There was no difference between the two groups for age, duration of DRBAs treatment, UPDRS III, tremor, rigidity, and bradykinesia subscores for upper and lower limbs. Conversely, symmetry of parkinsonian signs and presence bucco‐linguo‐masticatory dyskinesias were more frequent in individuals with normal tracer binding. Imaging of the dopamine transporter may help to identify subjects with DIP secondary to a loss of dopamine nerve terminals. © 2008 Movement Disorder Society     

Dopamine transporter imaging is associated with long‐term outcomes in Parkinson's disease

Dopamine (DA) transporter (DAT) imaging has been studied as a diagnostic tool for degenerative parkinsonism. Our aim was to measure the prognostic value of imaging for motor and nonmotor outcomes in Parkinson's disease (PD). We prospectively evaluated a Parkinson's cohort after enrollment in a de novo clinical trial with a battery of motor (UPDRS), cognitive (Montreal Cognitive Assessment), and behavioral measures. DAT imaging with [¹²³I][β]‐CIT and single‐photon emission computerized tomography (SPECT) was performed at baseline and after 22 months. In total, 491 (91%) of the 537 subjects had evidence of DA deficiency on their baseline scan, consistent with PD, and were included in the analyses. The cohort was followed for 5.5 (0.8) years, with a mean duration of diagnosis of 6.3 (1.2). Lower striatal binding at baseline was independently associated with higher risk for clinical milestones and measures of disease severity, including motor‐related disability, falling and postural instability, cognitive impairment, psychosis, and clinically important depressive symptoms. Subjects in the bottom quartile for striatal binding, compared to the top quartile, had an odds ratio (95% confidence interval) of 3.3 (1.7, 6.7) for cognitive impairment and 12.9 (2.6, 62.4) for psychosis. Change from baseline in imaging after 22 months was also independently associated with motor, cognitive, and behavioral outcomes. DAT imaging with [¹²³I][β]‐CIT and SPECT, shortly after the diagnosis of PD, was independently associated with clinically important long‐term motor and nonmotor outcomes. These results should be treated as hypothesis generating and require confirmation. © 2012 Movement Disorder Society     

6‐hydroxydopamine‐induced Parkinson's disease‐like degeneration generates acute microgliosis and astrogliosis in the nigrostriatal system but no bioluminescence imaging‐detectable alteration in adult neurogenesis

Parkinson's disease is a slowly progressing neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra (SN), leading to severe impairment in motor and non‐motor functions. Endogenous subventricular zone (SVZ) neural stem cells constantly give birth to new cells that might serve as a possible source for regeneration in the adult brain. However, neurodegeneration is accompanied by neuroinflammation and dopamine depletion, potentially compromising regeneration. We therefore employed in vivo imaging methods to study striatal deafferentation (N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐[¹²³I]iodophenyl)nortropane single photon emission computed tomography, DaTscan^™) and neuroinflammation in the SN and striatum (N,N‐diethyl‐2‐(2‐(4‐(2‐[¹⁸F]fluoroethoxy)phenyl)‐5,7‐dimethylpyrazolo[1,5‐a]pyrimidin‐3‐yl)acetamide positron emission tomography, [¹⁸F]DPA‐714 PET) in the intranigral 6‐hydroxydopamine Parkinson's disease mouse model. Additionally, we transduced cells in the SVZ with a lentivirus encoding firefly luciferase and followed migration of progenitor cells in the SVZ–olfactory bulb axis via bioluminescence imaging under disease and control conditions. We found that activation of microglia in the SN is an acute process accompanying the degeneration of dopaminergic cell bodies in the SN. Dopaminergic deafferentation of the striatum does not influence the generation of doublecortin‐positive neuroblasts in the SVZ, but generates chronic astrogliosis in the nigrostriatal system.     

Cognitive executive impairment and dopaminergic deficits in de novo Parkinson's disease

Cognitive impairment in Parkinson's disease (PD) is common and does directly impact patients' everyday functioning. However, the underlying mechanisms of early cognitive decline are not known. This study explored the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug‐naïve PD patients and tested the hypothesis that executive dysfunction in PD is associated with striatal dopaminergic depletion. A cross‐sectional multicenter cohort of 339 PD patients and 158 healthy controls from the Parkinson's Progression Markers Initiative study was analyzed. Each individual underwent cerebral single‐photon emission CT (SPECT) and a standardized neuropsychological assessment with tests of memory as well as visuospatial and executive function. SPECT imaging was performed with [¹²³I]FP‐CIT, and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios, cognitive domain scores, and age was analyzed using Pearson's correlations, partial correlation, and conditional process analysis. A small, but significant, positive association between total striatal dopamine transporter binding and the attention/executive domain was found (r = 0.141; P = 0.009) in PD, but this was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with PD were mediated by an age‐moderated striatal dopaminergic deficit. Our findings support the hypothesis that nigrostriatal dopaminergic deficit is associated with executive impairment, but not to memory or visuospatial impairment, in early PD. © 2014 International Parkinson and Movement Disorder Society     

Functional brain imaging in pure akinesia with gait freezing: [18F] FDG PET and [18F] FP‐CIT PET analyses

Pure akinesia with gait freezing (PAGF) has characteristic features, including freezing of gait and prominent speech disturbance without rigidity or tremor. The purpose of this study was to investigate changes in brain glucose metabolism and presynaptic dopaminergic function in PAGF. By using [¹⁸F] fluorodeoxyglucose (FDG) PET, 11 patients with PAGF were compared with 14 patients with probable progressive supranuclear palsy (PSP), 13 patients with Parkinson's disease (PD), and 11 normal controls. [¹⁸F] N‐(3‐fluoropropyl)‐2β‐carbon ethoxy‐3β‐(4‐iodophenyl) nortropane (FP‐CIT) PET was performed in 11 patients with PAGF and with 10 normal controls. The PAGF patients showed decreased glucose metabolism in the midbrain when compared with normal controls. PSP patients showed a similar topographic distribution of glucose hypometabolism with additional areas, including the frontal cortex, when compared with normal controls. The FP‐CIT PET findings in patients with PAGF revealed severely decreased uptake bilaterally in the basal ganglia. These findings suggest that both PAGF and PSP may be part of the same pathophysiologic spectrum of disease. However, the reason why PAGF manifests clinically in a different manner needs to be further elucidated. © 2008 Movement Disorder Society     

Dopamine transporter binding in Gilles de la Tourette syndrome: a [123I]FP-CIT/SPECT study

Objective: To investigate dopamine transporter binding in Gilles de la Tourette syndrome (GTS) with SPECT and [¹²³I]FP‐CIT. Method: Ten neuroleptic naïve/free patients with GTS, and 10 age‐ and gender‐matched normal volunteers were studied. Subjects were clinically evaluated. GTS severity and affective symptoms were measured and the presence of GTS‐related behaviours were recorded. Results: The GTS group showed significantly higher binding in both caudate and putamen nuclei than the controls. No associations were found between striatal binding ratios and measures of affect or GTS‐related behaviours. Conclusion: Patients with GTS show higher striatal binding of FP‐CIT to the striatum in comparison with age‐ and gender‐matched control subjects, indicating that dopamine transporter abnormalities are involved in the pathophysiology of GTS. These abnormalities appear to be distributed across both caudate and putamen.     

Subthalamic deep brain stimulation differently alters striatal dopaminergic receptor levels in rats

High‐frequency stimulation (HFS) of the subthalamic nucleus (STN) is recognized as an effective treatment for the motor symptoms of Parkinson's disease (PD), but its mechanisms, particularly as concern dopaminergic transmission, remain unclear. The aim of this study was to evaluate changes in the expression of dopaminergic receptors (D₁, D₂, and D₃ receptors) after prolonged (4 h) unilateral STN‐HFS in anesthetized intact rats and rats with total dopaminergic denervation. We used [³H]SCH 23390, [¹²⁵I]iodosulpride, and [¹²⁵I]OH‐PIPAT to assess the densities of D₁R, D₂R, and D₃R, respectively, within different areas of the striatum—a major input structure of the basal ganglia—including the nucleus accumbens. We found that STN‐HFS increased D₁R levels in almost all of the striatal areas examined, in both intact and denervated rats. By contrast, STN‐HFS led to a large decrease in D₂R and D₃R levels, limited to the nucleus accumbens and independent of the dopaminergic state of the animals. These data suggest that the influence of STN‐HFS on striatal D₁R expression may contribute to its therapeutic effects on motor symptoms, whereas its impact on D₂R/D₃R levels in the nucleus accumbens may account for the neuropsychiatric side effects often observed in stimulated PD patients, such as postoperative apathy. © 2015 International Parkinson and Movement Disorder Society     

Neuropsychiatric aspects of dementia with lewy bodies

Neuropsychiatric symptoms are prominent clinical features of dementia with Lewy bodies (DLB). Visual hallucinations have been reported to be particularly common. Auditory hallucinations, delusions, and depression also may be characteristic to DLB. Misidentification delusions may be more common than with other types of delusional syndromes. Supersensitivity to neuroleptic drugs is common, making treatment of these symptoms difficult, and newer, atypical compounds have been recommended. However, supersensitive reactions to these medicines have been reported. Patients with DLB, especially those with visual hallucinations, are reported to have a marked cholinergic deficit, and cholinergic drugs may be beneficial in reducing the neuropsychiatric symptoms.