The subthalamic region is activated during valence-related emotional processing in patients with Parkinson's disease

Visual stimuli are judged for their emotional significance based on two fundamental dimensions, valence and arousal, and may lead to changes in neural and body functions like attention, affect, memory and heart rate. Alterations in behaviour and mood have been encountered in patients with Parkinson's disease (PD) undergoing functional neurosurgery, suggesting that electrical high-frequency stimulation of the subthalamic nucleus (STN) may interfere with emotional information processing. Here, we use the opportunity to directly record neuronal activity from the STN macroelectrodes in patients with PD during presentation of emotionally laden and neutral pictures taken from the International Affective Picture System (IAPS) to further elucidate the role of the STN in emotional processing. We found a significant event-related desynchronization of STN alpha activity with pleasant stimuli that correlated with the individual valence rating of the pictures. Our findings suggest involvement of the human STN in valence-related emotional information processing that can potentially be altered during high-frequency stimulation of the STN in PD leading to behavioural complications

Amyloid PET and MRI in Alzheimer's Disease and Mild Cognitive Impairment

The neurodegenerative disorder Alzheimer's disease (AD) is the most common form of dementia. It is characterized by progressive impairment of cognitive functions and behavior. To distinguish clinically AD from other forms of dementia is an ongoing challenge. In addition, although mild cognitive impairment (MCI) is recognized as a risk factor for dementia, it remains a challenge to predict on an individual level who will convert to become demented. Amyloid beta (A beta) is one of the crucial pathological findings in AD. Recently, amyloid tracers for PET imaging have been developed successfully which may offer the unique possibility for measuring fibrillar A beta load in the living brain. Therefore, in the near future positron emission tomography (PET) may become an important tool for in vivo amyloid imaging contributing to early (differential) diagnosis as well as evaluation of treatment response in AD. Moreover, A beta may play a role in prediction the conversion of MCI to AD. In this paper we review the recent development of the molecular imaging technique PET and its different radiopharmaceuticals on the trail for imaging amyloid in AD and the conversion of MCI to A

A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA) : Rationale, Design, and Baseline Data

Altres ajuts: F. Hoffmann-La Roche Ltd.Background: Currently available treatments for Parkinson's disease (PD) do not slow clinical progression nor target alpha-synuclein, a key protein associated with the disease. Objective: The study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD. Methods: The PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1,500 or 4,500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40-80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis ≤2 years; having bradykinesia plus one other cardinal sign of PD (e.g., resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naïve or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinson's Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naïve and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations. Results: Of the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. Mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naïve PASADENA cohorts (MDS-UPDRS sum of Parts I + II + III [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naïve and 36.4% on MAO-B inhibitor) showed a similar severity in MDS-UPDRS scores (e.g., MDS-UPDRS sum of Parts I + II + III [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve). Conclusions: The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD. Trial Registration: NCT03100149