Correlation of striatal dopamine transporter binding with substantia nigra cell counts

WCN 2013 No: 951 Topic: 2—Movement Disorders A phase I single and repeated dose pharmacokinetic study of oral V81444, a selective non-xanthine adenosine A2A receptor antagonist S. Pawsey, K. Donaldson, S. Warrington, E. Tranter. Vernalis (RD Jade Consultants, Cambridge, UK; Hammersmith Medicines Research, London, UK Background: V81444 is a selective non-xanthine adenosine A2A receptor antagonist of potential utility in neurological disorders. Objectives: This study evaluated its pharmacokinetics (PK) after first administration to man. Methods: In a double-blind, randomised, placebo-controlled study, 18 healthy men in 2 alternating cohorts each received 2 single oral doses of V81444 and 1 of placebo. Doses were 30, 100, 200 and 300 mg. Thereafter, 31 healthy men received placebo or 50, 100 or 200 mg once daily orally, for 14 days. V18444 was assayed in plasma and urine, and PK parameters derived by non-compartmental analysis. Safety variables were also assessed. Results: V81444 was absorbed promptly (lag time≤ 0.5 h) after single doses. The maximum observed concentration was ≤4 h after dosing. V81444 exposurewas less than proportional to dose (slope for area under curve (AUC) extrapolated to infinity: 0.88 [90% confidence interval: 0.81– 0.95]). Geometric mean terminal elimination half-life was about 5–7 h (range: 3.29–11.4 h). After repeated dosing, steady-state was reached by Day 3 with little accumulation (accumulation ratio for AUC over the dose interval 1.19 [1.05–1.35]). The elimination half-life was somewhat longer (7–10 h). Less than 0.12% of the dose was excreted in urine. V81444 was well tolerated with no safety concerns at the doses studied. Conclusion: Orally administered V81444 was rapidly absorbed with little drug accumulation at steady-state, a half-life compatible with twice daily dosing, and minimal urinary excretion. doi:10.1016/j.jns.2013.07.450 Abstract—WCN 2013 No: 874 Topic: 2—Movement Disorders Correlation of striatal dopamine transporter binding with substantia nigra cell countsWCN 2013 No: 874 Topic: 2—Movement Disorders Correlation of striatal dopamine transporter binding with substantia nigra cell counts J. Kraemmer, G.G. Kovacs, L. Perju-Dumbrava, T. Traub-Weidinger, W. Pirker. Department of Neurology, Medical University of Vienna, Vienna, Austria; Neurological Institute, Medical University of Vienna, Vienna, Austria; Department of Nuclear Medicine, Medical University of Vienna, Vienna, Austria Background: Dopamine transporter (DAT) imaging is widely used for the differential diagnosis of parkinsonism. However, only limited data is available on the relationship between striatal DAT binding and dopaminergic cell loss in the substantia nigra (SN). Objective: We retrospectively analyzed SN cell counts in patients who had ante mortem undergone DAT single photon emission computerized tomography (SPECT). Patients and methods: Pathological diagnoses included Parkinson's disease (n= 1), dementia with Lewy bodies (n= 2), multiple system atrophy (n= 1), corticobasal degeneration (n= 2), atypical parkinsonism with multiple pathology (n= 1), Alzheimer's disease (AD, n = 1) and Creutzfeldt Jacob disease (CJD, n = 1). DAT SPECT with [I]β-CIT was performed using a standardized protocol on the same triple-head gammacamera. The density of neuromelanin-containing SN neurons/mmwas evaluated bymorphometricmethods using paraffinembedded tissue sections. Results: Mean disease duration at the time of DAT imaging was 2.3 years, followed by a mean interval of 29.3 months (range: 4– 68 months) until death. Visual analysis of DAT images showed reduced striatal uptake in all 7 patients with neurodegenerative parkinsonism, but not in AD and CJD cases. Averaged (left + right / 2) striatal uptake was highly correlated with averaged SN cell counts (Spearman's rho 0.98; p b .0005). Similar high correlations were found in separate analyses for the right and left nigrostriatal system. Conclusion: The present study shows a high correlation of striatal DAT binding in vivo with post mortem SN cell counts and confirms the validity of DAT imaging as an excellent in-vivo marker of nigrostriatal dopaminergic degeneration. doi:10.1016/j.jns.2013.07.451 Abstract—WCN 2013 No: 853 Topic: 2—Movement Disorders Impaired cognitive performance and Hippocampal atrophy in Parkinson's diseaseWCN 2013 No: 853 Topic: 2—Movement Disorders Impaired cognitive performance and Hippocampal atrophy in Parkinson's disease D. Yildiz, S. Erer Ozbek, M. Zarifoglu, B. Hakyemez, M. Bakar, N. Karli, N. Usca, N. Buyukkoyuncu Pekel, F. Tufan. Neurology, Şevket Yilmaz Training and Research Hospital, Turkey; Uludag University, Turkey; Şevket Yilmaz Training and Research Hospital, Bursa, Turkey Introduction: Since MRI has been used, hippocampalatrophy has been shown in demented and non-demented patients with PD. We aimed to assess the level of cognitive decline and the severity of hippocampalatrophy by measuring bilateral hippocampal volume in patients with PD. Methods: Thirty three patients with idiopathic PD and 16 healthy subjects were enrolled to our study. All of these patients were under follow-up in movement disorders outpatient clinic, Department of Neurology, Uludag University School of Medicine. Cognitive functions were tested with mini-mental state examination (MSE). The patients were classified as having normal cognitive function (PD-NC) or mild cognitive impairment (PD-MCI). Glucose, hemoglobin, TSH, total cholesterol, homocystein, vitamin B12, and folic acid levels were tested. Absence of depression was confirmed by Beck depression test. The cases were also evaluated with modified Wechsler memory scale, Luria draw test, Paven's test (RSPM), Stroop test, RUFF shape fluency test and KAS word fluency test, Trails A and B, forward and backward number repeating tests. Hippocampal volumes were calculated using Leonardo workstation. Abstracts / Journal of the Neurological Sciences 333 (2013) e109–e151 e135