Nonmotor and Dopamine Transporter Change in REM Sleep Behavior Disorder by Olfactory Impairment

OBJECTIVE: It is unclear whether the decline in dopamine transporters (DAT) differs among idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with different levels of olfactory impairment. This study aimed to characterize DAT changes in relation to nonmotor features in iRBD patients by olfactory loss. METHODS: This prospective cohort study consisted of three age-matched groups: 30 polysomnography-confirmed iRBD patients, 30 drug-naïve Parkinson's disease patients, and 19 healthy controls without olfactory impairment. The iRBD group was divided into two groups based on olfactory testing results. Participants were evaluated for reported prodromal markers and then underwent 18F-FP-CIT positron emission tomography and 3T MRI. Tracer uptakes were analyzed in the caudate, anterior and posterior putamen, substantia nigra, and raphe nuclei. RESULTS: Olfactory impairment was defined in 38.5% of iRBD patients. Mild parkinsonian signs and cognitive functions were not different between the two iRBD subgroups; however, additional prodromal features, constipation, and urinary and sexual dysfunctions were found in iRBD patients with olfactory impairment but not in those without. Tracer uptake showed significant group differences in all brain regions, except the raphe nuclei. The iRBD patients with olfactory impairment had uptake reductions in the anterior and posterior putamen, caudate, and substantia nigra (p < 0.016 in all, adjusted for age), which ranged from 0.6 to 0.8 of age-normative values. In contrast, those without olfactory impairment had insignificant changes in all regions ranging above 0.8. CONCLUSION: There was a clear distinction in DAT loss and nonmotor profiles by olfactory status in iRBD.

The Measurement of Sensitivity and Comparative Analysis of Simplified Quantitation Methods to Measure Dopamine Transporters Using I-123 IPT Pharmacokinetic Computer Simulations / 대한핵의학회잡지

Recently, [I-123]IPT SPECT has been used for early diagnosis of Parkinson's patients(PP) by imaging dopamine transporters. The dynamic time activity curves in basal ganglia(BG) and occipital cortex(OCC) without blood samples were obtained for 2 hours. These data were then used to measure dopamine transporters by operationally defined ratio methods of (BG-OCC)/OCC at 2 hrs, binding potential Rv=k3/k4 using graphic method or RA= (ABBG-ABOCC)/ABOCC for 2 hrs, where ABBG represents accumulated binding activity in basal ganglia(integral 0 120minBG(t)dt) and ABOCC represents accumulated binding activity in occipital cortex(integral 0 120minBG(t)dt). The purpose of this study was to examine the IPT pharmacokinetics and investigate the usefulness of simplified methods of (BG-OCC)/OCC, RA, and RA which are often assumed that these values reflect the true values of k3/k4. The rate constants K1, k2, k3 and k4 to be used for simulations were derived using [I-123]IPT SPECT and aterialized blood data with a standard three compartmental model. The sensitivities and time activity curves in BG and OCC were computed by changing K1 and k3(only BG) for every 5min over 2 hours. The values (BG-OCC)/OCC, RA, and Rv were then computed from the time activity curves and the linear regression analysis was used to measure the accuracies of these methods. The rate constants K1, k2, k3, k4 at BG and OCC were 1.26+/-5.41%, 0.044+/-19.58%, 0.031+/-24.36%, 0.008+/-22.78% and 1.36+/-4.76%, 0.170+/-6.89%, 0.007+/-23.89%, 0.007+/-45.09%, respectively. The Sensitivities for ((delta S/S)/(delta k3/k3)) and ((delta S/delta S)/(delta K1/K1)) at 30min and 120min were measured as (0.19, 0.50) and (0.61, 0.23), respectively. The correlation coefficients and slopes of ((BG-OCC)/OCC, RA, and Rv) with k3/k4 were (0.98, 1.00, 0.99) and (1.76, 0.47, 1.25), respectively. These simulation results indicate that a late [1-123]IPT SPECT image may represent the distribution of the dopamine transporters. Good correlations were shown between (BG-OCC)/OCC, RA or Rv and true k3/k4,, although the slopes between them were not unity. Pharmacokinetic computer simulations may be very useful technique in studying dopamine transpoter systems.