GBA and APOE Impact Cognitive Decline in Parkinson's Disease: A 10-Year Population-Based Study.

Background: Common genetic variance in apolipoprotein E (APOE), β-glucocerebrosidase (GBA), microtubule-associated protein tau (MAPT), and α-synuclein (SNCA) has been linked to cognitive decline in Parkinson's disease (PD), although studies have yielded mixed results.

Objectives: To evaluate the effect of genetic variants in APOE, GBA, MAPT, and SNCA on cognitive decline and risk of dementia in a pooled analysis of six longitudinal, non-selective, population-based cohorts of newly diagnosed PD patients.

Methods: 1002 PD patients, followed for up to 10 years (median 7.

Motor complications in Parkinson's disease: 13-year follow-up of the CamPaIGN cohort.

Background: Long-term population-representative data on motor fluctuations and levodopa-induced dyskinesias in Parkinson's disease is lacking.

Methods: The Cambridgeshire Parkinson's Incidence from GP to Neurologist (CamPaIGN) cohort comprises incident PD cases followed for up to 13 years (n = 141). Cumulative incidence of motor fluctuations and levodopa-induced dyskinesias and risk factors were assessed using Kaplan-Meyer and Cox regression analyses.

Prediction of cognition in Parkinson's disease with a clinical-genetic score: a longitudinal analysis of nine cohorts.

Background: Cognitive decline is a debilitating manifestation of disease progression in Parkinson's disease. We aimed to develop a clinical-genetic score to predict global cognitive impairment in patients with the disease.

Methods: In this longitudinal analysis, we built a prediction algorithm for global cognitive impairment (defined as Mini Mental State Examination [MMSE] ≤25) using data from nine cohorts of patients with Parkinson's disease from North America and Europe assessed between 1986 and 2016.

Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's.

Objective: We hypothesized that specific mutations in the β-glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non-neuropathic GD mutations confer intermediate progression rates.

Methods: A total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.

The role of tau in the pathological process and clinical expression of Huntington's disease.

Huntington's disease is a neurodegenerative disorder caused by an abnormal CAG repeat expansion within exon 1 of the huntingtin gene HTT. While several genetic modifiers, distinct from the Huntington's disease locus itself, have been identified as being linked to the clinical expression and progression of Huntington's disease, the exact molecular mechanisms driving its pathogenic cascade and clinical features, especially the dementia, are not fully understood. Recently the microtubule associated protein tau, MAPT, which is associated with several neurodegenerative disorders, has been implicated in Huntington's disease.

Association between MAPT haplotype and memory function in patients with Parkinson's disease and healthy aging individuals.

Genetic variation is associated with differences in the function of the brain as well as its susceptibility to disease. The common H1 haplotypic variant of the microtubule-associated protein tau gene (MAPT) has been related to an increased risk for Parkinson's disease (PD). Furthermore, among PD patients, H1 homozygotes have an accelerated progression to dementia.

Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study.

Parkinson's disease is associated with multiple cognitive impairments and increased risk of dementia, but the extent of these deficits varies widely among patients. The ICICLE-PD study was established to define the characteristics and prevalence of cognitive change soon after diagnosis, in a representative cohort of patients, using a multimodal approach. Specifically, we tested the 'Dual Syndrome' hypothesis for cognitive impairment in Parkinson's disease, which distinguishes an executive syndrome (affecting the frontostriatal regions due to dopaminergic deficits) from a posterior cortical syndrome (affecting visuospatial, mnemonic and semantic functions related to Lewy body pathology and secondary cholinergic loss).

Characterizing mild cognitive impairment in incident Parkinson disease: the ICICLE-PD study.

Objective: To describe the frequency of mild cognitive impairment (MCI) in Parkinson disease (PD) in a cohort of newly diagnosed incident PD cases and the associations with a panel of biomarkers.

Methods: Between June 2009 and December 2011, 219 subjects with PD and 99 age-matched controls participated in clinical and neuropsychological assessments as part of a longitudinal observational study. Consenting individuals underwent structural MRI, lumbar puncture, and genotyping for common variants of COMT, MAPT, SNCA, BuChE, EGF, and APOE.

Two-stage association study and meta-analysis of mitochondrial DNA variants in Parkinson disease.

Objectives: Previous associations between mitochondrial DNA (mtDNA) and idiopathic Parkinson disease (PD) have been inconsistent and contradictory. Our aim was to resolve these inconsistencies and determine whether mtDNA has a significant role in the risk of developing PD.

Methods: Two-stage genetic association study of 138 common mtDNA variants in 3,074 PD cases and 5,659 ethnically matched controls followed by meta-analysis of 6,140 PD cases and 13,280 controls.

Glucocerebrosidase mutations influence the natural history of Parkinson's disease in a community-based incident cohort.

Carriers of mutations in the glucocerebrosidase gene (GBA) are at increased risk of developing Parkinson's disease. The frequency of GBA mutations in unselected Parkinson's disease populations has not been established. Furthermore, no previous studies have investigated the influence of GBA mutations on the natural history of Parkinson's disease using prospective follow-up.

Genetic and pathological links between Parkinson's disease and the lysosomal disorder Sanfilippo syndrome.

Background: Parkinson's disease (PD) is a common neurodegenerative disorder of unknown etiology. The characteristic α-synuclein aggregation of PD is also a feature of Sanfilippo syndrome, a storage disorder caused by α-N-acetylglucosaminidase (NAGLU) gene mutations. We explored genetic links between these disorders and studied the pathology of Sanfilippo syndrome to investigate a common pathway toward α-synuclein aggregation.

Translational approaches to frontostriatal dysfunction in attention-deficit/hyperactivity disorder using a computerized neuropsychological battery.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent condition associated with cognitive dysfunction. The Cambridge Neuropsychological Test Automated Battery is a computerized set of tests that has been widely used in ADHD and in translation/back-translation. Following a survey of translational research relevant to ADHD in experimental animals, a comprehensive literature review was conducted of studies that had used core Cambridge Neuropsychological Test Automated Battery tests 1) to evaluate cognitive dysfunction in ADHD and 2) to evaluate effects of salient drugs in patients and in volunteers.