Mitochondrial Complex 1, Sigma 1, and Synaptic Vesicle 2A in Early Drug-Naive Parkinson's Disease.

Background: Dysfunction of mitochondrial energy generation may contribute to neurodegeneration, leading to synaptic loss in Parkinson's disease (PD). The objective of this study was to find cross-sectional and longitudinal changes in PET markers of synaptic vesicle protein 2A, sigma 1 receptor, and mitochondrial complex 1 in drug-naive PD patients.

Methods: Twelve early drug-naive PD patients and 16 healthy controls underwent a 3-Tesla MRI and PET imaging to quantify volume of distribution of [ C]UCB-J, [ C]SA-4503, and [ F]BCPP-EF for synaptic vesicle protein 2A, sigma 1 receptor, and mitochondrial complex 1, respectively.

Predict cognitive decline with clinical markers in Parkinson's disease (PRECODE-1).

Over the course of the disease, about 80% of Parkinson's disease patients will develop cognitive impairment. However, predictive factors associated with cognitive decline are still under investigation. Here, we investigated which clinically available markers are predictive of cognitive impairment in a cohort of early drug-naïve Parkinson's disease patients.

[F]Florbetapir PET/MR imaging to assess demyelination in multiple sclerosis.

Purpose: We evaluated myelin changes throughout the central nervous system in Multiple Sclerosis (MS) patients by using hybrid [F]florbetapir PET-MR imaging.

Methods: We included 18 relapsing-remitting MS patients and 12 healthy controls. Each subject performed a hybrid [F]florbetapir PET-MR and both a clinical and cognitive assessment.

Imidazoline 2 binding sites reflecting astroglia pathology in Parkinson's disease: an in vivo11C-BU99008 PET study.

Astroglia are multifunctional cells that regulate neuroinflammation and maintain homeostasis within the brain. Astroglial α-synuclein-positive cytoplasmic accumulations have been shown post-mortem in patients with Parkinson's disease and therefore astroglia may play an important role in the initiation and progression of Parkinson's disease. Imidazoline 2 binding sites are expressed on activated astroglia in the cortex, hippocampus, basal ganglia and brainstem; therefore, by measuring imidazoline 2 binding site levels we can indirectly evaluate astrogliosis in patients with Parkinson's disease.

Dysphagia is associated with presynaptic dopaminergic dysfunction and greater non-motor symptom burden in early drug-naïve Parkinson's patients.

Background: The underlying pathophysiology of dysphagia is multifactorial and evidence clarifying the precise mechanisms are scarce. Dysfunction in dopamine-related and non-dopamine-related pathways, changes in cortical networks related with swallowing and peripheral mechanisms have been implicated in the pathogenesis of dysphagia. We aimed at investigating whether dysphagia is associated with presynaptic dopaminergic deficits, faster motor symptom progression and cognitive decline in a population of early drug-naïve patients with Parkinson's disease.

Serotonergic pathology and disease burden in the premotor and motor phase of A53T α-synuclein parkinsonism: a cross-sectional study.

Background: Because of the highly penetrant gene mutation and clinical features consistent with idiopathic Parkinson's disease, carriers of the autosomal dominant Ala53Thr (A53T; 209G→A) point mutation in the α-synuclein (SNCA) gene are an ideal population to study the premotor phase and evolution of Parkinson's pathology. Given the known neurochemical changes in the serotonergic system and their association with symptoms of Parkinson's disease, we hypothesised that carriers of the A53T SNCA mutation might show abnormalities in the serotonergic neurotransmitter system before the diagnosis of Parkinson's disease, and that this pathology might be associated with measures of Parkinson's burden.

Methods: In this cross-sectional study, we recruited carriers of the A53T SNCA mutation from specialist Movement Disorders clinics in Athens, Greece, and Salerno, Italy, and a cohort of healthy controls with no personal or family history of neurological or psychiatric disorders from London, UK (recruited via public advertisement) who were age matched to the A53T SNCA carriers.

Speech difficulties in early de novo patients with Parkinson's disease.

Introduction: Speech difficulties are a common debilitating feature of Parkinson's disease and we aimed to investigate whether speech difficulties are associated with striatal dopaminergic deficits and faster disease progression.

Methods: Using the Parkinson's Progression Markers Initiative database, 143 early de novo Parkinson's disease patients with speech difficulties were identified and matched 1:1 with 143 Parkinson's disease patients without speech difficulties for age, disease duration and motor symptom severity. We investigated differences in clinical features and striatal [I]FP-CIT single photon emission computed tomography (SPECT) uptake in Parkinson's disease patients with and without speech difficulties.

Diabetes mellitus and Parkinson disease.

Objective: To investigate whether diabetes mellitus is associated with Parkinson-like pathology in people without Parkinson disease and to evaluate the effect of diabetes mellitus on markers of Parkinson pathology and clinical progression in drug-naive patients with early-stage Parkinson disease.

Methods: We compared 25 patients with Parkinson disease and diabetes mellitus to 25 without diabetes mellitus, and 14 patients with diabetes mellitus and no Parkinson disease to 14 healthy controls (people with no diabetes mellitus or Parkinson disease). The clinical diagnosis of diabetes mellitus was confirmed by 2 consecutive fasting measurements of serum glucose levels >126 mL/dL.

Parkinson's Disease, Diabetes and Cognitive Impairment.

Background: Parkinson's disease is a chronic neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. The pathophysiological mechanisms underlying Parkinson's are still unknown. Mitochondrial dysfunction, abnormal protein aggregation, increased neuroinflammation and impairment of brain glucose metabolism are shared processes among insulinresistance, diabetes and neurodegeneration and have been suggested as key mechanisms in development of Parkinson's and cognitive impairment.