Disease-Cognitive Rating Scale Research Articles

Utility of the Parkinson's disease-Cognitive Rating Scale for the screening of global cognitive status in Huntington's disease.

Cognitive impairment is an essential feature of Huntington's disease (HD) and dementia is a predictable outcome in all patients. However, validated instruments to assess global cognitive performance in the field of HD are lacking. We aimed to explore the utility of the Parkinson's disease-Cognitive Rating Scale (PD-CRS) for the screening of global cognition in HD. A multicenter cohort of 132 HD patients at different disease stages and 33 matched healthy controls were classified as having preserved cognition, mild cognitive impairment (HD-MCI) or dementia (HD-Dem) according to the Clinical Dementia Rating and Functional Independence Score. The PD-CRS and the Mini-Mental State Examination were administered. Receiver operating characteristic curve analysis was used to determine optimal cutoffs to differentiate patients according to their cognitive status. A PD-CRS cutoff score ≤ 81/82 was optimal to detect HD-MCI (sensitivity = 93%; specificity = 80%; area under the curve (AUC) = 0.940), and ≤ 63/64 was optimal to detect HD-Dem (sensitivity = 90%; specificity = 87%; AUC = 0.933). MMSE scores failed to show robust psychometric properties in this context. The PD-CRS is a valid and reliable instrument to assess global cognition in HD in routine clinical care and clinical trials.

Subjective memory decline in Parkinson's disease patients with and without fatigue

IntroductionPrevious studies on Parkinson's disease (PD) have shown that memory complaints and fatigue co-occur since premotor stages of disease, but whether Subjective Memory Decline (SMD, defined as memory complaints with normal objective cognitive performance) and fatigue were associated in PD has not been explored yet. MethodsOne-hundred PD patients underwent measures of memory complaints (Multifactorial Memory Questionnaire, MMQ), neuropsychological test (Parkinson's Disease-Cognitive Rating Scale), and assessment of behavioural symptoms. Fatigue was diagnosed according to current diagnostic criteria. Mann-Whitney test or Pearson chi-square test were used to compare fatigued and nonfatigued patients for prevalence of SMD and for demographic, clinical, and behavioural features, memory complaint, and objective cognitive measures. The confounding effect of sample's features on results was controlled by logistic regression and Quade's rank analysis. ResultsTwenty-three patients were diagnosed as fatigued whereas 15 patients met SMD criteria. Fatigued patients showed higher levodopa equivalent daily dose and more marked behavioural symptoms than nonfatigued patients (ps< 0.01). The prevalence of SMD was higher in fatigued patients than in those nonfatigued (35% vs 9%, p < 0.01). After controlling for confounds, the patients with fatigue had an odds ratio for SMD 5.97 [CI 95%, 1.18–30.03] times higher and presented significantly lower scores on Contentment subscales of MMQ (p < 0.01) than those without fatigue. ConclusionFatigue in PD is associated with SMD mainly characterized by less contentment with one's own memory ability. These findings suggest possible shared pathogenic mechanisms underlying these two nonmotor manifestations and foster to identify potential phenotypes of patients requiring multistrategic therapeutic approaches.

B-25 Osteopathic Manipulative Treatment Improves Non-Motor Symptoms in Parkinson’s Disease: A Preliminary Study

Abstract Parkinson’s disease (PD) is a neurodegenerative disease characterized by debilitating motor and non-motor symptoms. Osteopathic Manipulative Treatment (OMT) has been shown to alleviate stress, mood, and sleep in musculoskeletal conditions and older adults, as well as improve gait and balance in PD and elderly patients, respectively. Research on the efficacy of OMT in reducing PD symptoms is lacking. Therefore, the aim of this preliminary study was to evaluate changes in mood, cognitive, and motor symptoms in a sample of non-demented PD patients following 6-weeks of OMT. Sixteen non-demented individuals with PD received 6 weekly 30-minute OMT by an osteopathic physician. Participants were administered measures of cognition (Parkinson’s Disease-Cognitive Rating Scale; PD-CRS), anxiety (Geriatric Anxiety Inventory; GAI), sleep quality (Pittsburgh Sleep Quality Index; PSQI), stress (Perceived Stress Scale; PSS), and motor function (Unified Parkinson’s Disease Rating Scale-Part 3) before and after treatment. Paired-samples t-tests were used to examine changes in symptoms pre and post-OMT. Results revealed significant improvement in cognition (PD-CRS; p = .015) and perceived stress (PSS; p = .02) from pre- to post-intervention. There was a trend towards improvement in anxiety (GAI; p = .064) and sleep quality (PSQI; p = .08). There was no change in motor symptoms from pre- to post-OMT (p = .56). Findings suggest that OMT may improve non-motor symptoms – particularly cognition and stress - in PD. Future research is needed to determine if these effects can be replicated within a randomized-control-trial and maintained over time. With further research, OMT may prove to be a beneficial non-invasive treatment for non-motor symptoms in PD.

Auditory and vestibular dysfunction in patients with Parkinson\u2019s disease

BackgroundMotor dysfunction in patients with Parkinson disease (PD) is just the tip of the iceberg. Auditory and vestibular dysfunction in patients with PD gained much attention owing to them being one of the nonmotor symptoms.AimTo explore abnormalities of pure tone audiometry (PTA), brainstem auditory evoked potentials (BAEPs), vestibular evoked myogenic potential (VEMP), and videonystagmography (VNG) in patients with PD and their correlation with motor and cognitive dysfunction.Patients and methodsThe study was conducted on 20 patients with PD and 15 controls. Selected patients were subjected to evaluation of motor symptoms using Unified Parkinson’s Disease Rating Scale (UPDRS) and cognitive function using Parkinson disease-Cognitive Rating Scale (PD-CRS). PTA, BAEPs, cervical VEMPs, and VNG were carried out for all patients and controls.ResultsPatients with PD show higher mean hearing thresholds at all PTA frequencies in both ears than controls. Analysis of BAEP demonstrated that patients with PD have significantly prolonged absolute latencies of wave III and wave V and interpeak latencies of I–III and I–V in both ears than controls. VEMP findings revealed that patients have significantly delayed P13 and N23 latencies and smaller P13–N23 amplitude in both ears than controls. VNG findings showed canal paresis in 60% of patients with PD and nystagmus in 60% of patients with PD. Correlative results revealed statistically significant correlations between VEMP parameters and UPDRS as well as PD-CRS, but there were no statistically significant correlations between PTA frequencies or BAEP latencies and UPDRS or PD-CRS.ConclusionAuditory and vestibular dysfunction is common in PD but cannot be totally correlated with the motor and cognitive symptoms.

Source activity during emotion processing and its relationship to cognitive impairment in Parkinson's disease

BackgroundNeural mechanisms contributing to an underlying cognitive impairment in Parkinson's disease (PD) are poorly understood. An effective method to probe cognitive processing deficits in PD is the examination of brain activity during emotional processes, particularly in explicit language emotion recognition contexts. MethodsThe present study utilised cortical source imaging of event related potentials (ERP) from electroencephalography (EEG) to evaluate valence judgements on negative and neutral target words in an automatic affective priming paradigm. Fifty non-demented PD patients, unmedicated for depression or anxiety, completed affective priming tasks during EEG monitoring. Cognitive impairment was measured using the validated Parkinson's Disease-Cognitive Rating Scale (PD-CRS). ResultsResults reveal that compared to healthy age-matched controls, PD patients demonstrate a reduced N400 activation during affective priming tasks in bilateral regions of the middle frontal gyrus (MFG), inferior parietal lobule (IPL) and, notably, have a late wave ERP component (LPP) in left MFG, present between 600 and 800 ms, following family-wise error correction (pFWE < 0.05). LPP in PD patients were significantly associated with PD-CRS scores. LimitationsAlthough affective priming paradigms are an effective means for various domains of cognition, it is not a focused cognitive behavioural test for cognitive dysfunction. Our study is thus limited to a surrogate measure of cognitive dysfunction via examination of emotional word processing cues. ConclusionsThese findings suggest that source imaging methods with ERP paradigms in PD are effective in identifying delayed cognitive processes in PD.

Ambroxol as a novel disease-modifying treatment for Parkinson\u2019s disease dementia: protocol for a single-centre, randomized, double-blind, placebo-controlled trial

BackgroundCurrently there are no disease-modifying treatments for Parkinson’s disease dementia (PDD), a condition linked to aggregation of the protein α-synuclein in subcortical and cortical brain areas. One of the leading genetic risk factors for Parkinson's disease is being a carrier in the gene for β-Glucocerebrosidase (GCase; gene name GBA1). Studies in cell culture and animal models have shown that raising the levels of GCase can decrease levels of α-synuclein. Ambroxol is a pharmacological chaperone for GCase and is able to raise the levels of GCase and could therefore be a disease-modifying treatment for PDD. The aims of this trial are to determine if Ambroxol is safe and well-tolerated by individuals with PDD and if Ambroxol affects cognitive, biochemical, and neuroimaging measures.MethodsThis is a phase II, single-centre, double-blind, randomized placebo-controlled trial involving 75 individuals with mild to moderate PDD. Participants will be randomized into Ambroxol high-dose (1050 mg/day), low-dose (525 mg/day), or placebo treatment arms. Assessments will be undertaken at baseline, 6-months, and 12-months follow up times. Primary outcome measures will be the Alzheimer’s disease Assessment Scale-cognitive subscale (ADAS-Cog) and the ADCS Clinician’s Global Impression of Change (CGIC). Secondary measures will include the Parkinson’s disease Cognitive Rating Scale, Clinical Dementia Rating, Trail Making Test, Stroop Test, Unified Parkinson’s disease Rating Scale, Purdue Pegboard, Timed Up and Go, and gait kinematics. Markers of neurodegeneration will include MRI and CSF measures. Pharmacokinetics and pharmacodynamics of Ambroxol will be examined through plasma levels during dose titration phase and evaluation of GCase activity in lymphocytes.DiscussionIf found effective and safe, Ambroxol will be one of the first disease-modifying treatments for PDD.Trial registrationClinicalTrials.gov NCT02914366, 26 Sep 2016/retrospectively registered.

Multifocal alterations of white matter accompany the transition from normal cognition to dementia in Parkinson's disease patients.

The purpose of the present study was to investigate the pattern of white matter (WM) changes associated with Parkinson's disease (PD)-related cognitive impairment by using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) measures. Diffusion Tensor Imaging (DTI) was performed in 21 PD-patients with dementia (PDD) and in an age-matched control group including 40 PD-patients without dementia (PD-CTRL). The Parkinson's disease-Cognitive Rating Scale (PD-CRS) was used for patients' neuropsychological assessment. Local microstructural WM differences associated with the presence of cognitive impairment were tested using tract-based spatial statistics analysis. Multiple regression models investigated the association of DTI indices with total PD-CRS score, PD-CRS raw items and other clinical measures across the whole study sample. Significant FA decreases were found in PDD compared to PD-CTRL patients mainly in the body of corpus callosum, corona radiata and cingulum. Lower PD-CRS score was significantly associated with decreased FA, MD and AD values in multiple WM tracts primarily located in prefrontal and limbic areas as well as across the corpus callosum. Lower performance in specific PD-CRS raw items was also associated with FA decreases in major WM tracts. The results suggest that multifocal microstructural changes of WM accompany the transition from normal to demented cognitive state in PD-patients. The corpus callosum, the corona radiata and the cingulum are among the regions mostly affected during this course. A progressive axonal degeneration is proposed as a key underlying mechanism.

Accuracy of Two Cognitive Screening Tools to Detect Mild Cognitive Impairment in Parkinson's Disease.

Patients with Parkinson's disease (PD) who have mild cognitive impairment (PD-MCI) are at increased risk of developing PD dementia (PDD). Therefore, it is important to identify PD-MCI in a reliable way. We evaluated the accuracy of the Parkinson's Disease-Cognitive Rating Scale (PD-CRS) and the Mattis Dementia Rating Scale-2 (MDRS-2) for detecting PD-MCI. Data from healthy subjects were used to correct for demographic influences. We compared the accuracy of the two instruments using ROC analysis. The gold standard was level II diagnosis of PD-MCI according to consensus criteria of the International Parkinson and Movement Disorder Society. Seventy-five healthy subjects and 125 PD patients were included. Education level, age and sex correlated with the PD-CRS, but only age correlated with the MDRS-2. Twenty-seven percent of the patients had PD-MCI. Areas under the curve (AUCs) for raw scores of PD-CRS and MDRS-2 were 0.83 and 0.81, respectively. At the optimal cut-off for the PD-CRS (101/102), sensitivity was 88% and specificity was 64%. For the MDRS-2 (139/140) sensitivity and specificity were 68% and 79%, respectively.AUCs for demographically corrected scores of PD-CRS and for age-corrected scores of MDRS-2 were 0.80 and 0.78, respectively. At the optimal cut-off for the PD-CRS, sensitivity was 79% and specificity was 72%, while for the MDRS-2 these were 77% and 67%, respectively. Both cognitive screening tools are suitable for distinguishing PD-MCI patients from cognitively intact PD patients. Demographical correction of scores did not improve sensitivity and specificity.

Apolipoprotein Eε4: A Biomarker for Executive Dysfunction among Parkinson's Disease Patients with Mild Cognitive Impairment.

Background: Cognitive impairment is prevalent in Parkinson's disease (PD), affecting 15–20% of patients at diagnosis. α-synuclein expression and genetic polymorphisms of Apolipoprotein E (ApoE) have been associated with the presence of cognitive impairment in PD although data have been inconsistent.Objectives: To determine the prevalence of cognitive impairment in patients with PD using Montreal Cognitive Assessment (MoCA), Comprehensive Trail Making Test (CTMT) and Parkinson's disease-cognitive rating scale (PDCRS), and its association with plasma α-synuclein and ApoE genetic polymorphisms.Methods: This was across-sectional study involving 46 PD patients. Patients were evaluated using Montreal cognitive assessment test (MoCA), and detailed neuropsychological tests. The Parkinson's disease cognitive rating scale (PDCRS) was used for cognitive function and comprehensive trail making test (CTMT) for executive function. Blood was drawn for plasma α-synuclein measurements and ApoE genetic analysis. ApoE polymorphism was detected using MutaGELAPoE from ImmunDiagnostik. Plasma α-synuclein was detected using the ELISA Technique (USCN Life Science Inc.) according to the standard protocol.Results: Based on MoCA, 26 (56.5%) patients had mild cognitive impairment (PD-MCI) and 20 (43.5%) had normal cognition (PD-NC). Based on the PDCRS, 18 (39.1%) had normal cognition (PDCRS-NC), 17 (37%) had mild cognitive impairment (PDCRS-MCI), and 11 (23.9%) had dementia (PDCRS-PDD). In the PDCRS-MCI group, 5 (25%) patients were from PD-NC group and all PDCRS-PDD patients were from PD-MCI group. CTMT scores were significantly different between patients with MCI and normal cognition on MoCA (p = 0.003). Twenty one patients (72.4%) with executive dysfunction were from the PD-MCI group; 17 (77.3%) with severe executive dysfunction and 4 (57.1%) had mild to moderate executive dysfunction. There were no differences in the plasma α-synuclein concentration between the presence or types of cognitive impairment based on MoCA, PDCRS, and CTMT. TheApoEe4 allele carrier frequency was significantly higher in patients with executive dysfunction (p = 0.014).Conclusion: MCI was prevalent in our PD population. PDCRS appeared to be more discriminatory in detecting MCI and PDD than MoCA. Plasma α-synuclein level was not associated with presence nor type of cognitive impairment, but the ApoEe4 allele carrier status was significantly associated with executive dysfunction in PD.

Global scales for cognitive screening in Parkinson's disease: Critique and recommendations.

Cognitive impairment is a common nonmotor manifestation of Parkinson's disease, with deficits ranging from mild cognitive difficulties in 1 or more of the cognitive domains to severe dementia. The International Parkinson and Movement Disorder Society commissioned the assessment of the clinimetric properties of cognitive rating scales measuring global cognitive performance in PD to make recommendations regarding their use. A systematic literature search was conducted to identify the scales used to assess global cognitive performance in PD, and the identified scales were reviewed and rated as "recommended," "recommended with caveats," "suggested," or "listed" by the panel using previously established criteria. A total of 12 cognitive scales were included in this review. Three scales, the Montreal Cognitive Assessment, the Mattis Dementia Rating Scale Second Edition, and the Parkinson's Disease-Cognitive Rating Scale, were classified as "recommended." Two scales were classified as "recommended with caveats": the Mini-Mental Parkinson, because of limited coverage of executive abilities, and the Scales for Outcomes in Parkinson's Disease-Cognition, which has limited data on sensitivity to change. Six other scales were classified as "suggested" and 1 scale as "listed." Because of the existence of "recommended" scales for assessment of global cognitive performance in PD, this task force suggests that the development of a new scale for this purpose is not needed at this time. However, global cognitive scales are not a substitute for comprehensive neuropsychological testing. © 2017 International Parkinson and Movement Disorder Society.

Reliability test of parkinson's disease cognitive rating scale (PD-CRS) modification in patients with parkinson disease at sanglah hospital Denpasar

Reliability test of parkinson's disease cognitive rating scale (PD-CRS) modification in patients with parkinson disease at sanglah hospital Denpasar

Development and validation of an alternative version of the Parkinson's Disease-Cognitive Rating Scale (PD-CRS)

IntroductionThe Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a valid and reliable instrument to screen for and diagnose mild cognitive impairment in PD (PD-MCI) and to monitor potential outcomes in clinical trials. Although this scale shows adequate sensitivity to change in non-demented PD patients, an alternative form (AF) with proven reliability could minimize practice effects associated with repeated testing. MethodsWe selected PD-CRS/AF items following the criteria proposed in the original PD-CRS. We assessed a prospective sample of 75 non-demented PD patients (normal cognition, n = 50; PD-MCI, n = 25) using both tools, administered on two consecutive days, in a randomized order. ResultsThe PD-CRS/AF showed a high internal consistency (Cronbach's α = 0.80). Differences between total mean scores were not significant. Floor/ceiling effects were acceptable. The discriminative power for MCI was high for both tools (area under the curve 0.91; 95% CI, 0.84–0.98 for PD-CRS; 0.88, 95% CI, 0.80–0.96 for PD-CRS/AF). Receiver operating curve analysis showed the optimal cut-off point of the two versions to discriminate PD-MCI from PD-normal cognition was ≤81 (PD-CRS = sensitivity 94%, specificity 73%; PD-CRS/AF = sensitivity 92%, specificity 73%). ConclusionsOur results suggest that the PD-CRS/AF is a valid and reliable instrument to complement the original PD-CRS as an analogous tool for serial cognitive testing for PD patients in clinical practice and cognitive trials.

Frontal-subcortical defects correlate with task switching deficits in Parkinson`s disease.

Objectives:To examine correlation between frontal-subcortical/ parietal-cortical functioning and task switching.Methods:An experimental study was designed to examine objectives with 80 participants (40 patients with idiopathic Parkinson’s disease (PD) and 40 healthy controls). Patients were recruited from February until September 2016 at Recep Tayyip Erdogan Hospital Pakistan, Muzaffargarh, Pakistan and healthy controls participated from community. Participants were administered Parkinson’s disease cognitive rating scale and Word-Digit categorization task switching experiment.Results:In contrast to healthy controls, (i) PD patients showed impaired cognitive performance on frontal-subcortical and posterior-cortical functions as assessed through PD cognitive rating scale (ii) PD patients showed task switching deficits. Frontal-subcortical defects correlated with task switching deficits. Lesser the scores on frontal-subcortical functions, larger switch costs will appear. Frontal-subcortical defects significantly predicted task switch costs.Conclusion:Frontal-subcortical not the posterior-cortical dysfunctions are significant marker of task switching deficits.

The Parkinson's Disease-Cognitive Rating Scale (PD-CRS): normative values from 268 healthy Italian individuals.

The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a cognitive screening battery that includes subtests to assess cortical and subcortical functions. It is a valid screening tool for mild cognitive impairment (MCI) in Parkinson's disease (PD) and is recommended for diagnosing PD-MCI-Level I. Until now, no study has provided population-based norms for the Italian population. The aim of the present study was to collect normative values in a sample of Italian healthy subjects. Two hundred and sixty-eight (125 men) participants of different ages (age range 30-79years) and educational levels (from primary school to university) underwent the PD-CRS. Regression-based norming was used to explore the influence of demographic variables (age, education level, and gender) on PD-CRS total score, frontal-subcortical and instrumental-cortical sub-scores, and score achieved on each task of the PD-CRS. Multiple linear regression analysis revealed that age and education significantly predicted the total score, the two sub-scores and the score on each task of the PD-CRS. No significant effect of gender was found. From the derived linear equations, a correction grid for raw scores was developed. Inferential cut-off scores, estimated using a non-parametric technique, were 71.25 for PD-CRS total score and 46.25 and 20.17 for frontal-subcortical and instrumental-cortical sub-score, respectively. Since the use of adjusted scores is more informative when they are standardized, we have converted adjusted scores into equivalent scores. The present study provides normative data for the PD-CRS, being useful and recommended by Movement Disorders Society task force to identify PD-MCI-Level I, at several stages of the disease.

Validation of the Parkinson's Disease-Cognitive Rating Scale Applying the Movement Disorder Society Task Force Criteria for Dementia Associated with Parkinson's Disease.

The authors studied the measurement properties of the Parkinson's Disease-Cognitive Rating Scale (PD-CRS) compared with Movement Disorders Society Task Force (MDS-TF) criteria for the diagnosis of dementia in patients with Parkinson's disease. The sample consisted of 223 patients who were diagnosed in accordance with the United Kingdom Parkinson's Disease Society Brain Bank who were assessed with both the MDS-TF and the PD-CRS criteria (in addition to other instruments) without the assessors' knowledge of previous results. Internal consistency was studied (homogeneity of the items and Guttmann's λ values were obtained) in addition to convergent, divergent, and discriminative validity. The receiver operating characteristic curve was obtained, and the cutoff point at which the PD-CRS had the greatest efficiency was analyzed. The internal consistency was shown to be adequate, with a λ value of 0.821. A floor effect was observed in 4 of the items (Sustained Attention, Working Memory, Immediate Verbal Memory, and Alternating Verbal Fluency), and 1 item showed a ceiling effect (Clock Copying). The scale adequately discriminated patients with and without dementia (Kruskal-Wallis; P≤0.000). The area under the curve was 0.899. With a cutoff score of 62 (from a possible score of 134), the scale achieved 94% sensitivity and 99% specificity. The PD-CRS has adequate measurement properties and is a valid tool for studying the presence of dementia in patients with Parkinson's disease.

COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), a global--clinical evaluations, serum biomarkers, genetic studies and neuroimaging--prospective, multicenter, non-interventional, long-term study on Parkinson's disease progression.

BackgroundParkinson’s disease (PD) is a progressive neurodegenerative disorder causing motor and non-motor symptoms that can affect independence, social adjustment and the quality of life (QoL) of both patients and caregivers. Studies designed to find diagnostic and/or progression biomarkers of PD are needed. We describe here the study protocol of COPPADIS-2015 (COhort of Patients with PArkinson’s DIsease in Spain, 2015), an integral PD project based on four aspects/concepts: 1) PD as a global disease (motor and non-motor symptoms); 2) QoL and caregiver issues; 3) Biomarkers; 4) Disease progression.Methods/designObservational, descriptive, non-interventional, 5-year follow-up, national (Spain), multicenter (45 centers from 15 autonomous communities), evaluation study. Specific goals: (1) detailed study (clinical evaluations, serum biomarkers, genetic studies and neuroimaging) of a population of PD patients from different areas of Spain, (2) comparison with a control group and (3) follow-up for 5 years. COPPADIS-2015 has been specifically designed to assess 17 proposed objectives. Study population: approximately 800 non-dementia PD patients, 600 principal caregivers and 400 control subjects. Study evaluations: (1) baseline includes motor assessment (e.g., Unified Parkinson’s Disease Rating Scale part III), non-motor symptoms (e.g., Non-Motor Symptoms Scale), cognition (e.g., Parkinson’s Disease Cognitive Rating Scale), mood and neuropsychiatric symptoms (e.g., Neuropsychiatric Inventory), disability, QoL (e.g., 39-item Parkinson’s disease Quality of Life Questionnaire Summary-Index) and caregiver status (e.g., Zarit Caregiver Burden Inventory); (2) follow-up includes annual (patients) or biannual (caregivers and controls) evaluations. Serum biomarkers (S-100b protein, TNF-α, IL-1, IL-2, IL-6, vitamin B12, methylmalonic acid, homocysteine, uric acid, C-reactive protein, ferritin, iron) and brain MRI (volumetry, tractography and MTAi [Medial Temporal Atrophy Index]), at baseline and at the end of follow-up, and genetic studies (DNA and RNA) at baseline will be performed in a subgroup of subjects (300 PD patients and 100 control subjects). Study periods: (1) recruitment period, from November, 2015 to February, 2017 (basal assessment); (2) follow-up period, 5 years; (3) closing date of clinical follow-up, May, 2022. Funding: Public/Private.DiscussionCOPPADIS-2015 is a challenging initiative. This project will provide important information on the natural history of PD and the value of various biomarkers.

Mild cognitive impairment in Parkinson's disease is improved by transcranial direct current stimulation combined with physical therapy.

Parkinson's disease (PD) is characterized by both motor and cognitive deficits. In PD, physical exercise has been found to improve physical functioning. Recent studies demonstrated that repeated sessions of transcranial direct current stimulation led to an increased performance in cognitive and motor tasks in patients with PD. The present study investigated the effects of anodal transcranial direct current stimulation applied over the dorsolateral prefrontal cortex and combined with physical therapy in PD patients. A total of 20 patients with PD were assigned to 1 of 2 study groups: group 1, anodal transcranial direct current stimulation plus physical therapy (n = 10) or group 2, placebo transcranial direct current stimulation plus physical therapy (n = 10). The 2 weeks of treatment consisted of daily direct current stimulation application for 25 minutes during physical therapy. Long-term effects of treatment were evaluated on clinical, neuropsychological, and motor task performance at 3-month follow-up. An improvement in motor abilities and a reduction of depressive symptoms were observed in both groups after the end of treatment and at 3-month follow-up. The Parkinson's Disease Cognitive Rating Scale and verbal fluency test performances increased only in the anodal direct current stimulation group with a stable effect at follow-up. The application of anodal transcranial direct current stimulation may be a relevant tool to improve cognitive abilities in PD and might be a novel therapeutic strategy for PD patients with mild cognitive impairment. © 2016 International Parkinson and Movement Disorder Society.

Alterations in Cerebral White Matter and Neuropsychology in Patients with Cirrhosis and Falls

Background & AimFalls are frequent in patients with cirrhosis but underlying mechanisms are unknown. The aim was to determine the neuropsychological, neurological and brain alterations using magnetic resonance-diffusion tensor imaging (MR-DTI) in cirrhotic patients with falls.Patients and methodsTwelve patients with cirrhosis and falls in the previous year were compared to 9 cirrhotic patients without falls. A comprehensive neuropsychological and neurological evaluation of variables that may predispose to falls included: the Mini-Mental State Examination, Psychometric Hepatic Encephalopathy Score (PHES), Parkinson’s Disease-Cognitive Rating Scale, specific tests to explore various cognitive domains, Unified Parkinson’s Disease Rating Scale to evaluate parkinsonism, scales for ataxia and muscular strength, and electroneurography. High-field MR (3T) including DTI and structural sequences was performed in all patients.ResultsThe main neuropsychological findings were impairment in PHES (p = 0.03), Parkinson’s Disease-Cognitive Rating Scale (p = 0.04) and in executive (p<0.05) and visuospatial-visuoconstructive functions (p<0.05) in patients with falls compared to those without. There were no statistical differences between the two groups in the neurological evaluation or in the visual assessment of MRI. MR-DTI showed alterations in white matter integrity in patients with falls compared to those without falls (p<0.05), with local maxima in the superior longitudinal fasciculus and corticospinal tract. These alterations were independent of PHES as a covariate and correlated with executive dysfunction (p<0.05).ConclusionsWith the limitation of the small sample size, our results suggest that patients with cirrhosis and falls present alterations in brain white matter tracts related to executive dysfunction. These alterations are independent of PHES impairment.

Validation of the Italian version of Parkinson’s Disease-Cognitive Rating Scale (PD-CRS)

Cognitive impairment (CI) is a frequent feature associated with both early and advanced stages of Parkinson's disease (PD). An evaluation of cognitive functions is relevant to identify those parkinsonians at risk of developing dementia. In the present study, the Italian version of Parkinson's Disease-Cognitive Rating Scale (PD-CRS) assessing fronto-subcortical and cortical cognitive functions in PD was validated in 387 parkinsonians and was used to test the empirical validity of the item 1.1 (cognitive impairment) of the Italian version of MDS-UPDRS as screening tool for CI in PD. PD-CRS was free from floor and ceiling effect. The mean PD-CRS score was 76.1 (mean cortical score, 24.5±4.6; mean subcortical score, 51.5±17.5). The internal consistency was satisfactory (α=0.89); corrected item-total correlation was 0.570 (naming) to 0.696 (working memory). The correlation between PD-CRS and part I-IV of MDS-UPDRS was weak. The low agreement between classification of PD sample into patients with mild cognitive impairment (PD-MCI), dementia (PD-D) and normal cognition (PD-NC) according to scores of item 1.1 and classification according to cutoff scores of PD-CRS for PD-MCI, PD-D and PD-NC indicated a poor empirical validity of item 1.1 of MDS-UPDRS as cognitive screening tool for CI in PD (Κ=0.114; weighted Κ=0.17; SE of Κ=0.038; 95% confidence interval from 0.040 to 0.1895). The Italian version of PD-CRS is an easy, consistent and valid tool for assessment of the cognitive cortical and subcortical impairments in PD.

Spectroscopic Changes Associated with Mild Cognitive Impairment and Dementia in Parkinson’s Disease

Frontal subcortical cognitive defects are predominant in Parkinson’s disease (PD). Temporal lobe dysfunction seems more relevant for progression to dementia. We aimed to study the relative importance of temporal lobe defects versus executive impairment in the progression to dementia in PD by using proton magnetic resonance spectroscopy (¹H-MRS). The ¹H-MRS features of PD patients with intact cognition (PD-CgInt; n = 16), mild cognitive impairment (MCI; n = 15) and dementia (PDD; n = 15) were compared, to delineate the metabolic alterations correlating with cognitive status. Metabolite concentrations were acquired from voxels localized to the hippocampus and dorsolateral prefrontal cortex (DL-PFC). Cognitive status was established following the Movement Disorder Society PDD criteria, administering the Clinical Dementia Rating Scale and Mattis Dementia Rating Scale. The Parkinson’s Disease Cognitive Rating Scale (PD-CRS) was used to correlate ¹H-MRS with neuropsychology. N-acetylaspartate (NAA) concentrations in the right DL-PFC were decreased in PD-MCI compared with PD-CgInt patients (p = 0.002), and correlated with frontal subcortical tasks. Decreased NAA concentrations in the left hippocampus in PDD compared to PD-MCI (p = 0.03) correlated with confrontation naming. The present findings support that executive impairment is related to dorsolateral prefrontal dysfunction from the early stages, while progression to dementia is linked to the additional impairment of temporal lobe structures. The PD-CRS was able to capture the differential impairment of prefrontal versus temporal cortical areas.