Imaging biomarkers of cortical neurodegeneration underlying cognitive impairment in Parkinson's disease.

Purpose: Imaging biomarkers bear great promise for improving the diagnosis and prognosis of cognitive impairment in Parkinson's disease (PD). We compared the ability of three commonly used neuroimaging modalities to detect cortical changes in PD patients with mild cognitive impairment (PD-MCI) and dementia (PDD).

Methods: 53 cognitively normal PD patients (PD-CN), 32 PD-MCI, and 35 PDD underwent concurrent structural MRI (sMRI), diffusion-weighted MRI (dMRI), and [F]FDG PET.

Perspectives of Implementation of Closed-Loop Deep Brain Stimulation: From Neurological to Psychiatric Disorders.

Background: Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy to alleviate symptoms and improve quality of life in movement disorders such as Parkinson's disease, essential tremor, and dystonia, which is also being applied in several psychiatric disorders, such as obsessive-compulsive disorder and depression, when they are otherwise resistant to therapy.

Summary: At present, DBS is clinically applied in the so-called open-loop approach, with fixed stimulation parameters, irrespective of the patients' clinical state(s). This approach ignores the brain states or feedback from the central nervous system or peripheral recordings, thus potentially limiting its efficacy and inducing side effects by stimulation of the targeted networks below or above the therapeutic level.

Peripheral Inflammation Is Associated with Dopaminergic Degeneration in Parkinson's Disease.

Background: Peripheral inflammatory immune responses are suggested to play a major role in dopaminergic degeneration in Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR) is a well-established biomarker of systemic inflammation in PD. Degeneration of the nigrostriatal dopaminergic system can be assessed in vivo using [ I]FP-CIT single photon emission computed tomography imaging of striatal dopamine transporter (DAT) density.

Peripheral inflammatory immune response differs among sporadic and familial Parkinson's disease.

Peripheral inflammatory immune responses are thought to play a major role in the pathogenesis of Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a biomarker of systemic inflammation, has been reported to be higher in patients with PD than in healthy controls (HCs). The present study was aimed at determining if the peripheral inflammatory immune response could be influenced by the genetic background of patients with PD.

Homocysteine levels, genetic background, and cognitive impairment in Parkinson's disease.

Background: Hyperhomocysteinemia is considered an independent risk factor for cognitive impairment.

Objective: To study the correlation between homocysteine levels and cognitive impairment in patients with PD.

Methods: We conducted a case-control study that included 246 patients with PD, of whom 32 were cognitively impaired.

Heterogeneity of prodromal Parkinson symptoms in siblings of Parkinson disease patients.

A prodromal phase of Parkinson's disease (PD) may precede motor manifestations by decades. PD patients' siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort.

Natural History of Polymerase Gamma-Related Ataxia.

Background: Mutations in the mitochondrial DNA polymerase gamma are causing a wide phenotypic spectrum including ataxia as one of the most common presentations.

Objective: The objective of this study was to determine the course of disease of polymerase gamma-related ataxia.

Methods: In a prospective natural history study, we assessed 24 adult ataxia patients with biallelic polymerase gamma mutations for (1) severity of cerebellar dysfunction using the Scale for the Assessment and Rating of Ataxia score, (2) presence of nonataxia signs using the Inventory of Non-Ataxia Symptoms, (3) gray- and white-matter changes in brain MRI, and (4) findings in nerve conduction studies.

Association of PICALM with Cognitive Impairment in Parkinson's Disease.

Background: Cognitive impairment is one of the most disabling nonmotor symptoms in Parkinson's disease (PD). Recently, a genome-wide association study in Alzheimer's disease has identified the PICALM rs3851179 polymorphism as one of the most significant susceptibility genes for Alzheimer's disease after APOE. The aim of this study was to determine the potential role of PICALM and its genetic interaction with APOE in the development of cognitive decline in PD.

Analysis of p.Tyr307Asn variant in the LRP10 gene in Parkinson's disease in southern Spain.

Lipoprotein receptor-related protein 10 (LRP10) has been proposed as a novel causative gene for autosomal dominant Parkinson's disease (PD), and the c.919T>A (p.Tyr307Asn) variant has been identified as possibly involved in the development of familial PD and PD with dementia.

A replication study of GWAS-genetic risk variants associated with Parkinson's disease in a Spanish population.

Recently, 5 previously Parkinson's disease (PD)-related loci: ACMSD/TMEM163, STK39, MIR4697, SREBF1/RAI1PD and MAPT, have been associated to PD in a Southern Spanish population. However, due to the small sample size of the cohort, this association did not reach genome wide significance. Our aim was to investigate the robustness of this association in a larger and independent cohort from the South of Spain.