Atypical brain FDG-PET patterns increase the risk of long-term cognitive and motor progression in Parkinson's disease

Introduction: Brain hypometabolism patterns have been previously associated with cognitive decline in Parkinson's disease (PD). Our aim is to evaluate the impact of single-subject fluorodeoxyglucose (FDG)-PET brain hypometabolism on long-term cognitive and motor outcomes in PD. Methods: Forty-nine non-demented PD patients with baseline brain FDG-PET data underwent an extensive clinical follow-up for 8 years. The ability of FDG-PET to predict long-term cognitive and motor progression was evaluated using Cox regression and mixed ANCOVA models. Results: Participants were classified according to FDG-PET pattern in PD with typical (n = 26) and atypical cortical metabolism (n = 23). Patients with atypical brain hypometabolic patterns showed higher incidence of dementia (60% vs 3%; HR = 18.3), hallucinations (56% vs 7%, HR = 7.3) and faster motor decline compared to typical pattern group. Conclusion: This study argues for specific patterns of FDG-PET cortical hypometabolism in PD as a prognostic marker for long term cognitive and motor outcomes at single-subject level

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

Purpose: The aim of the study was to evaluate extrastriatal dopaminergic and serotonergic pathways in patients with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) using 123I-FP-CIT SPECT imaging. Methods: The study groups comprised 56 PD patients without dementia, 41 DLB patients and 54 controls. Each patient underwent a standardized neurological examination and 123I-FP-CIT SPECT. Binding in nigrostriatal and extrastriatal regions of interest was calculated in each patient from spatially normalized images. The occipital-adjusted specific to nondisplaceable binding ratio (SBR) in the different regions was compared among the PD patients, DLB patients and controls adjusting for the effects of age, sex, disease duration and serotonergic/dopaminergic treatment. Covariance analysis was used to determine the correlates of local and long-distance regions with extrastriatal 123I-FP-CIT deficits. Results: Both PD and DLB patients showed lower 123I-FP-CIT SPECT SBR in several regions beyond the nigrostriatal system, especially the insula, cingulate and thalamus. DLB patients showed significantly lower 123I-FP-CIT SBR in the thalamus than controls and PD patients. Thalamic and cingulate 123I-FP-CIT SBR deficits were correlated, respectively, with limbic serotonergic and widespread cortical monoaminergic projections only in DLB patients but exhibited only local correlations in PD patients and controls. Conclusion: PD and DLB patients both showed insular dopamine deficits, whereas impairment of thalamic serotonergic pathways was specifically associated with DLB. Longitudinal studies are necessary to determine the clinical value of the assessment of extrastriatal 123I-FP-CIT SPECT

Italian Frontotemporal Dementia Network (FTD Group-SINDEM): sharing clinical and diagnostic procedures in Frontotemporal Dementia in Italy

In the prospect of improved disease management and future clinical trials in Frontotemporal Dementia, it is desirable to share common diagnostic procedures. To this aim, the Italian FTD Network, under the aegis of the Italian Neurological Society for Dementia, has been established. Currently, 85 Italian Centers involved in dementia care are part of the network. Each Center completed a questionnaire on the local clinical procedures, focused on (1) clinical assessment, (2) use of neuroimaging and genetics; (3) support for patients and caregivers; (4) an opinion about the prevalence of FTD. The analyses of the results documented a comprehensive clinical and instrumental approach to FTD patients and their caregivers in Italy, with about 1,000 newly diagnosed cases per year and 2,500 patients currently followed by the participating Centers. In analogy to other European FTD consortia, future aims will be devoted to collect data on epidemiology of FTD and its subtypes and to provide harmonization of procedures among Centers

Italian Frontotemporal Dementia Network (FTD Group-SINDEM): sharing clinical and diagnostic procedures in Frontotemporal Dementia in Italy

In the prospect of improved disease management and future clinical trials in Frontotemporal Dementia, it is desirable to share common diagnostic procedures. To this aim, the Italian FTD Network, under the aegis of the Italian Neurological Society for Dementia, has been established. Currently, 85 Italian Centers involved in dementia care are part of the network. Each Center completed a questionnaire on the local clinical procedures, focused on (1) clinical assessment, (2) use of neuroimaging and genetics; (3) support for patients and caregivers; (4) an opinion about the prevalence of FTD. The analyses of the results documented a comprehensive clinical and instrumental approach to FTD patients and their caregivers in Italy, with about 1,000 newly diagnosed cases per year and 2,500 patients currently followed by the participating Centers. In analogy to other European FTD consortia, future aims will be devoted to collect data on epidemiology of FTD and its subtypes and to provide harmonization of procedures among Centers

Predictions of in vivo prolactin levels from in vitro k I values of d 2 receptor antagonists using an agonist-antagonist interaction model

Item does not contain fulltextProlactin elevation is a side effect of all currently available D2 receptor antagonists used in the treatment of schizophrenia. Prolactin elevation is the result of a direct antagonistic D2 effect blocking the tonic inhibition of prolactin release by dopamine. The aims of this work were to assess the correlation between in vitro estimates of D2 receptor affinity and pharmacokinetic-pharmacodynamic model-based estimates obtained from analysis of clinical data using an agonist-antagonist interaction (AAI) model and to assess the value of such a correlation in early prediction of full prolactin time profiles. A population model describing longitudinal prolactin data was fitted to clinical data from 16 clinical phases 1 and 3 trials including five different compounds. Pharmacokinetic data were modeled for each compound and the prolactin model was both fitted in per-compound fits as well as simultaneously to all prolactin data. Estimates of prolactin elevating potency were compared to corresponding in vitro values and their predictability was evaluated through model-based simulations. The model successfully described the prolactin time course for all compounds. Estimates derived from experimental preclinical data and the model fit of the clinical data were strongly correlated (p < 0.001), and simulations adequately predicted the prolactin elevation in five out of six compounds. The AAI model has the potential to be used in drug development to predict prolactin response for a given exposure of D2 antagonists using routinely produced preclinical data