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Background: Parkinson's disease (PD) is associated with various non-motor symptoms, including cognitive deterioration. Objective: Here, we used data from the DEMPARK/LANDSCAPE cohort to describe the association between progression of cognitive profiles and the PD motor phenotypes: postural instability and gait disorder (PIGD), tremor-dominant (TR-D), and not-determined (ND). Methods: Demographic, clinical, and neuropsychological six-year longitudinal data of 711 PD-patients were included (age: M= 67.57; 67.4% males). We computed z-transformed composite scores for a priori defined cognitive domains. Analyses were controlled for age, gender, education, and disease duration. To minimize missing data and drop-outs, three-year followup data of 442 PD-patients was assessed with regard to the specific role of motor phenotype on cognitive decline using linear mixed modelling (age: M= 66.10; 68.6% males). Results: Our study showed that in the course of the disease motor symptoms increased while MMSE and PANDA remained stable in all subgroups. After three-year follow-up, significant decline of overall cognitive performance for PIGD-patients was present and we found differences for motor phenotypes in attention (beta = -0.08, SE = 0.003, p < 0.006) and memory functions showing that PIGD-patients deteriorate per months by -0.006 compared to the ND-group (SE = 0.003, p = 0.046). Furthermore, PIGD-patients experienced more often difficulties in daily living. Conclusion: Over a period of three years, we identified distinct neuropsychological progression patterns with respect to different PD motor phenotypes, with early executive deficits yielding to a more amnestic profile in the later course. Here, in particular PIGD-patients worsened over time compared to TR-D and ND-patients, highlighting the greater risk of dementia for this motor phenotype.

Background Presence of mild cognitive impairment is currently the best predictor for the development of Parkinson's disease dementia. Diagnostic criteria for both Parkinson's with mild cognitive impairment and Parkinson's disease dementia have been suggested by the Movement Disorder Society. However, not all cognitive tests recommended are available in the German language with proper standard values. Objectives To define evidence-based guidelines for neuropsychological assessment of patients with Parkinson's disease in German. Methods Two systematic literature searches were conducted. First, articles that presented international guidelines (consensus papers or reviews) for the application of standardized neuropsychological assessments for the diagnosis of cognitive impairment in Parkinson's disease were selected. Of those, only neuropsychological assessments in German language with normative values referring either to a German, Austrian, or Swiss population were considered. Second, articles comparing test performances of healthy controls vs. Parkinson's disease and/or different cognitive Parkinson's disease subtypes (e.g. no cognitive impairment, Parkinson's with mild cognitive impairment, Parkinson's disease dementia) were selected. Effect sizes for group differentiation were calculated. Results Out of 127 full-text articles reviewed, 48 tests were identified during the first literature search. In the second search, 1716 articles were reviewed and 23 papers selected. The strongest effect sizes for group discrimination were revealed for tests assessing executive function, attention, and visuo-cognitive abilities. Based on the results of the two literature searches, consensus guidelines were defined by the authors, allowing for Level-II diagnosis for Parkinson's with mild cognitive impairment and Parkinson's disease dementia. Conclusions: The presented guidelines may have the potential to standardize and improve the neuropsychological assessment of Parkinson's diseas

Objectives Parkinson's disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia. The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function. Methods Demographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration. Results Compared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p= 0.012), formallexical word fluency (p= 0.043), card sorting (p= 0.006), attention (Trail Making Test version A; p= 0.024) and visuospatial abilities (Leistungsprufungssystem test 9; p= 0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR= 3.198) and akinetic-rigid PD (OR= 2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR= 8.314). Conclusion The three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings.

Introduction: Cognitive impairment is a common and disabling non-motor symptom in Parkinson's disease (PD). The apolipoprotein E (APOE) allele epsilon 4 is a known risk factor for Alzheimer's disease and has also been suggested to be a risk factor for dementia in PD and even a predictor of impairment in certain cognitive domains. Methods: A total of 447 PD patients (PD patients without cognitive impairment: n = 187; PD patients with mild cognitive impairment: n = 188; PD patients with dementia: n = 72) were included from an ongoing observational German multicenter cohort study (LANDSCAPE study). All patients underwent an extensive neuropsychological test battery, including assessments of memory, visuospatial functioning, attention, language, and executive function. APOE genotype was determined by an allelic discrimination assay. Linear regression analysis was used to explore the associations between APOE-epsilon 4 and cognitive performance. Results: The APOE-epsilon 4 allele was not associated with a diagnosis of cognitive impairment in PD (PD with mild cognitive impairment and PD with dementia) or with deficits in specific neuropsychological domains in our study cohort. Conclusion: Our data question the relevance of the APOE-epsilon 4 allele as a predictor of cognitive impairment in PD. (C) 2016 Elsevier Ltd. All rights reserved.

Objective Inconsistent results exist regarding the cognitive profile in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). We aimed at providing data on this topic from a large cohort of patients with PD-MCI. Methods Sociodemographic, clinical and neuropsychological baseline data from patients with PD-MCI recruited in the multicentre, prospective, observational DEMPARK/LANDSCAPE study were analysed. Results 269 patients with PD-MCI (age 67.8 +/- 7.4, Unified Parkinson's Disease Rating Scale (UPDRS-III) scores 23.2 +/- 11.6) were included. PD-MCI subtypes were 39.4% non-amnestic single domain, 30.5% amnestic multiple domain, 23.4% non-amnestic multiple domain and 6.7% amnestic single domain. Executive functions were most frequently impaired. The most sensitive tests to detect cognitive dysfunctions were the Modified Card Sorting Test, digit span backwards and word list learning direct recall. Multiple stepwise regression analyses showed that global cognition, gender and age, but not education or disease-related parameters predicted PD-MCI subtypes. Conclusions This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia.

Objective. We examined the diagnostic value of subjective memory complaints (SMCs) assessed with a single item in a large cross-sectional cohort consisting of families with autosomal dominant Alzheimer's disease (ADAD) participating in the Dominantly Inherited Alzheimer Network (DIAN). Methods. The baseline sample of 183 mutation carriers (MCs) and 117 noncarriers (NCs) was divided according to Clinical Dementia Rating (CDR) scale into preclinical (CDR 0; MCs: n = 107; NCs: n = 109), early symptomatic (CDR 0.5; MCs: n = 48; NCs: n = 8), and dementia stage (CDR >= 1; MCs: n = 28; NCs: n = 0). These groups were subdivided by the presence or absence of SMCs. Results. At CDR 0, SMCs were present in 12.1% of MCs and 9.2% of NCs (p = 0.6). At CDR 0.5, SMCs were present in 66.7% of MCs and 62.5% of NCs (p = 1.0). At CDR >= 1, SMCs were present in 96.4% of MCs. SMCs inMCs were significantly associated with CDR, logical memory scores, Geriatric Depression Scale, education, and estimated years to onset. Conclusions. The present study shows that SMCs assessed by a single-item scale have no diagnostic value to identify preclinical ADAD in asymptomatic individuals. These results demonstrate the need of further improvement of SMCmeasures that should be examined in large clinical trials.