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BACKGROUND: This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. METHODS: Placebo-controlled, parallel group, double-blind, randomized two-by-two factorial trial. We recruited adults aged?70years with sarcopenia, defined as low gait speed (

BACKGROUND: Cognitive impairment is common in Parkinson's disease (PD), with 80% cumulatively developing dementia (PDD). OBJECTIVE: We sought to identify tests that are sensitive to change over time above normal ageing so as to refine the neuropsychological tests predictive of PDD. METHODS: Participants with newly diagnosed PD (n = 211) and age-matched controls (n = 99) completed a range of clinical and neuropsychological tests as part of the ICICLE-PD study at 18-month intervals over 72 months. Impairments on tests were determined using control means (

BACKGROUND: Mild cognitive impairment (MCI) is common in early Parkinson's disease (PD). We evaluated the stability of PD-MCI over time to determine its clinical utility as a marker of disease.METHODS: 212 newly diagnosed participants with PD were recruited into a longitudinal study and reassessed after 18 and 36 months. Participants completed a range of clinical and neuropsychological assessments. PD-MCI was classified using Movement Disorders Society Task Force level I (Montreal Cognitive Assessment RESULTS: After 36 months, 75% of participants returned; 8% of patients had developed a dementia all of which were previously PD-MCI. Applying level I criteria, 70% were cognitively stable, 19% cognitively declined and 11% improved over 36 months. Applying level II criteria (1, 1.5 and 2SD), 25% were cognitively stable, 41% cognitively declined, 15% improved and 19% fluctuated over 36 months. 18% of participants reverted to normal cognition from PD-MCI.DISCUSSION: Cognitive impairment in PD is complex, with some individuals' function fluctuating over time and some reverting to normal cognition. PD-MCI level I criteria may have greater clinical convenience, but more comprehensive level II criteria with 2SD cut-offs may offer greater diagnostic certainty.

BACKGROUND: Cumulative dementia incidence in Parkinson's disease (PD) is significant, with major personal and socioeconomic impacts on individuals with PD and their carers. Early identification of dementia risk is vital to ensuring optimal intervention. Saccadic deficits often distinguish neurodegenerative disorders and cognitive impairment, but their ability to predict cognitive decline in PD has yet to be determined. The aims of this study were to (1) evaluate baseline (6.4 ± 6.1 months since PD diagnosis) differences in pro-saccadic metrics between those with early PD and healthy age-matched adults; and (2) assess the ability of baseline pro-saccades to predict subsequent cognitive decline over 4.5 years. METHODS: One hundred and forty-one PD and 90 age-matched participants recruited at diagnosis underwent saccadometric assessment of pro-saccades at baseline and had cognition assessed at baseline, 18, 36, and 54 months. Pro-saccadic characteristics included latency, duration, amplitude, peak, and average velocity. Cognitive assessment included executive function, attention, fluctuating attention, and memory. Linear mixed-effects models examined pro-saccadic metrics as predictors of cognitive decline over 54 months. RESULTS: Pro-saccades were significantly impaired at baseline in PD compared with controls. Pro-saccadic characteristics of latency, duration, peak, and average velocity predicted decline in global cognition, executive function, attention, and memory over 54 months in PD. In addition, only reduction in global cognition and attention were predicted by pro-saccadic metrics in age-matched adults, indicating that PD findings were not purely age related. CONCLUSIONS: Saccadic characteristics are impaired in early PD and are predictive of cognitive decline in several domains. Assessment of saccades may provide a useful non-invasive biomarker for long-term PD cognitive decline in early disease. © 2019 International Parkinson and Movement Disorder Society.

BACKGROUND: Visual hallucinations (VHs) are common in Parkinson's disease (PD), with prevalence ranging from 27-50% in cross-sectional cohorts of patients with well-established disease. However, minor hallucinations may occur earlier in the disease process than has been previously reported. OBJECTIVE: We sought to categorise VHs in a cohort of newly diagnosed PD patients and establish their relationship to other clinical features. METHODS: Newly diagnosed PD participants (n = 154) were recruited as part of the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in PD (ICICLE-PD) study. Participants completed the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS III), Montreal Cognitive Assessment (MoCA) and Parkinson's Disease Questionnaire (PDQ-39) to assess motor severity, cognition and quality of life (QoL), respectively. VHs were classified using the North East Visual Hallucinations Inventory. Hierarchical regression was used to build predictive models of motor severity, QoL and cognition. RESULTS: 22% (n = 34) of participants experienced recurrent VHs with minor VHs being most frequently reported (64.7% of hallucinators). Complex VHs were present in 32.4% of hallucinating participants. Linear regression showed VHs predicted poorer PDQ-39 and MoCA scores (β= 0.201, p = 0.006 and β= - 0.167, p = 0.01, respectively) but not motor severity (p > 0.05). CONCLUSIONS: Over a fifth of people with newly diagnosed PD reported recurrent VHs; minor hallucinations were the most common, although a small proportion reported complex VHs. Recurrent VHs were found to be a significant independent predictor of cognitive function and QoL but not motor severity. Our findings highlight the importance of screening for VHs at diagnosis.

Objective To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline.Methods FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA.Results PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (beta=0.38, p=0.001) and MoCA (beta=0.3, p=0.002) at 18 months controlling for baseline score.Conclusions Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia.

Mild cognitive impairment (MCI) is prevalent in 15%-40% of Parkinson's disease (PD) patients at diagnosis. In this investigation, we study brain intra- and inter-network alterations in resting state functional magnetic resonance imaging (rs-fMRI) in recently diagnosed PD patients and characterise them as either cognitive normal (PD-NC) or with MCI (PD-MCI). Patients were divided into two groups, PD-NC (N = 62) and PD-MCI (N = 37) and for comparison, healthy controls (HC, N = 30) were also included. Intra- and inter-network connectivity were investigated from participants' rs-fMRIs in 26 resting state networks (RSNs). Intra-network differences were found between both patient groups and HCs for networks associated with motor control (motor cortex), spatial attention and visual perception. When comparing both PD-NC and PD-MCI, intra-network alterations were found in RSNs related to attention, executive function and motor control (cerebellum). The inter-network analysis revealed a hyper-synchronisation between the basal ganglia network and the motor cortex in PD-NC compared with HCs. When both patient groups were compared, intra-network alterations in RSNs related to attention, motor control, visual perception and executive function were found. We also detected disease-driven negative synchronisations and synchronisation shifts from positive to negative and vice versa in both patient groups compared with HCs. The hyper-synchronisation between basal ganglia and motor cortical RSNs in PD and its synchronisation shift from negative to positive compared with HCs, suggest a compensatory response to basal dysfunction and altered basal-cortical motor control in the resting state brain of PD patients. Hum Brain Mapp 38:1702-1715, 2017. © 2016 Wiley Periodicals, Inc.

INTRODUCTION: Anxiety and mild cognitive impairment (MCI) are prevalent non-motor manifestations of Parkinson's disease (PD). While few studies have demonstrated a possible link between cognitive dysfunction and anxiety in PD, to our knowledge, no studies have directly examined the association between them. This study investigated the association between anxiety and cognitive deficits in newly diagnosed PD patients. METHODS: Patients with newly diagnosed PD (N = 185) were recruited from community and outpatient clinics. Anxiety was assessed using the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) clinician rated anxiety item, which has previously been validated against a standardized criteria for the diagnosis of anxiety disorders in PD. Participants scoring ≥2 were classified as anxious. A threshold of 1 SD below normative values (obtained from controls) was used to define cognitive impairment. Impairments in specific cognitive domains were identified as being >1 SD below controls in ≥1 test per domain. RESULTS: After controlling for age, education and motor severity, patients with anxiety were three times more likely to have cognitive impairment compared to those without anxiety (OR = 3.0, 95% CI = 1.2-7.3, p < 0.05). Patients with anxiety were more than twice as likely to be classified as having cognitive impairment due to impairment in the memory domain compared with PD without anxiety (OR = 2.3, 95% CI = 1.0-5.1, p < 0.05), whilst no associations were found between anxiety and performance on other cognitive domains. CONCLUSION: This study shows an association between anxiety and cognitive impairment (specifically memory impairment). Examining the neural basis of this association warrants future research in this developing field.

BACKGROUND: The immune system is a promising therapeutic target for disease modification in Parkinson's disease (PD), but appropriate immune-related biomarkers must be identified to allow patient stratification for trials and tracking of therapeutic effects. The objective of this study was to investigate whether immune markers in peripheral blood are candidate prognostic biomarkers through determining their relationship with disease progression in PD. METHODS: Serum samples were collected in incident PD cases and age-matched controls. Subjects were clinically evaluated at baseline and 18 and 36 months. Ten cytokines and C-reactive protein were measured, with data reduction using principal-component analysis, and relationships between component scores and motor (MDS Unified Parkinson's Disease Rating Scale - part 3) and cognitive (Mini Mental State Examination [MMSE]) measures of disease severity/progression were investigated. RESULTS: TNF-α, IL1-β, IL-2, and IL-10 were higher in PD (n = 230) than in controls (n = 93), P ≤ 0.001). Principal-component analysis of log-transformed data resulted in a 3-component solution explaining 51% of the variance. Higher "proinflammatory" and lower "anti-inflammatory" component scores were associated with more rapid motor progression over 36 months (P

INTRODUCTION: Parkinson's disease dementia (PDD) is associated with poorer quality of life (QoL). Prior to the onset of PDD, many patients experience progressive cognitive impairment. There is a paucity of longitudinal studies investigating the effects of cognitive decline on QoL. This study aimed to determine the longitudinal impact of cognitive change on QoL in an incident PD cohort. METHODS: Recently diagnosed patients with PD (n = 212) completed a schedule of neuropsychological assessments and QoL measures; these were repeated after 18 (n = 190) and 36 months (n = 158). Mild cognitive impairment (PD-MCI) was classified with reference to the Movement Disorder Society criteria. Principal component analysis was used to reduce 10 neuropsychological tests to three cognitive factors: attention, memory/executive function, and global cognition. RESULTS: Baseline PD-MCI was a significant contributor to QoL (β = 0.2, p < 0.01). For those subjects (9%) who developed dementia, cognitive function had a much greater impact on QoL (β = 10.3, p < 0.05). Multivariate modelling showed attentional deficits had the strongest predictive power (β = -2.3, p < 0.01); brief global tests only modestly predicted decline in QoL (β = -0.4, p < 0.01). CONCLUSIONS: PD-MCI was associated with poorer QoL over three years follow up. Cognitive impairment had a greater impact on QoL in individuals who developed dementia over follow-up. Impaired attention was a significant determinant of QoL in PD. Interventions which improve concentration and attention in those with PD could potentially improve QoL.