Longitudinal cognitive decline characterizes the profile of non-PD-manifest GBA1 mutation carriers.

With disease-modifying treatment for Parkinson's disease (PD) associated with variants in the glucocerebrosidase gene (GBA1) under way, the challenge to design clinical trials with non-PD-manifest GBA mutation carriers (GBA1NMC) comes within close reach. To delineate trajectories of motor and non-motor markers as well as serum neurofilament light (sNfL) levels and to evaluate clinical endpoints as outcomes for clinical trials in GBA1NMC, longitudinal data of 56 GBA1NMC carriers and 112 age- and sex-matched GBA1 wildtype participants (GBA1wildtype) with up to 9 years of follow-up was analyzed using linear mixed-effects models (LMEM) and Kaplan-Meier survival analysis of clinical endpoints for motor and cognitive function. GBA1NMC showed worse performance in Pegboard, 20 m fast walking, global cognition as well as in executive and memory function at baseline. Longitudinally, LMEM revealed a higher annual increase of the MDS-UPDRS III bradykinesia subscore in GBA1NMC compared to GBA1wildtype, but comparable trajectories of all other motor and non-motor markers as well as sNfL. Kaplan-Meier survival analysis showed a significantly earlier progression to clinical endpoints of cognitive decline in GBA1NMC. Incidence of PD was significantly higher in GBA1NMC. In conclusion, our study extends data on GBA1NMC indicating early cognitive decline as a potentially characteristic feature. Comprehensive longitudinal assessments of cognitive function are crucial to delineate the evolution of early changes in GBA1NMC enabling a more accurate stratification and allow for a more precise definition of trial design and sample size.

CSF α-synuclein seed amplification kinetic profiles are associated with cognitive decline in Parkinson's disease.

Seed amplification assays have been implemented in Parkinson's disease to reveal disease-specific misfolded alpha-synuclein aggregates in biospecimens. While the assays' qualitative dichotomous seeding response is valuable to stratify and enrich cohorts for alpha-synuclein pathology in general, more quantitative parameters that are associated with clinical dynamics of disease progression and that might potentially serve as exploratory outcome measures in clinical trials targeting alpha-synuclein would add important information. To evaluate whether the seeding kinetic parameters time required to reach the seeding threshold (LAG phase), the peak of fluorescence response (Imax), and the area under the curve (AUC) are associated with clinical trajectories, we analyzed LAG, Imax, and AUC in relation to the development of cognitive decline in a longitudinal cohort of 199 people with Parkinson's disease with positive CSF alpha-synuclein seeding status. Patients were stratified into tertiles based on their individual CSF alpha-synuclein seeding kinetic properties. The effect of the kinetic parameters on longitudinal development of cognitive impairment defined by MoCA ≤25 was analyzed by Cox-Regression. Patients with a higher number of positive seeding replicates and tertile groups of shorter LAG, higher Imax, and higher AUC showed a higher prevalence of and a shorter duration until cognitive impairment longitudinally (3, 6, and 3 years earlier with p ≤ 0.001, respectively). Results remained similar in separate subgroup analyses of patients with and without GBA mutation. We conclude that a more prominent alpha-synuclein seeding kinetic profile translates into a more rapid development of cognitive decline.

Resting state EEG as biomarker of cognitive training and physical activity's joint effect in Parkinson's patients with mild cognitive impairment.

BACKGROUND: Cognitive decline is a major factor for the deterioration of the quality of life in patients suffering from Parkinson's disease (PD). Recently, it was reported that cognitive training (CT) in PD patients with mild cognitive impairment (PD-MCI) led to an increase of physical activity (PA) accompanied by improved executive function (EF). Moreover, PA has been shown to alter positively brain function and cognitive abilities in PD. Both observations suggest an interaction between CT and PA. OBJECTIVES: A previous multicenter (MC) study was slightly significant when considering independent effects of interventions (CT and PA) on EF. Here, we use MC constituent single center data that showed no effect of interventions on EF. Thus, this exploratory study considers pooling data from both interventions to gain insight into a recently reported interaction between CT and PA and provide a proof of principle for the usefulness of resting state EEG as a neurophysiological biomarker of joint intervention's effect on EF and attention in PD-MCI. METHODS: Pre- and post-intervention resting state EEG and neuropsychological scores (EF and attention) were obtained from 19 PD-MCI patients (10 (CT) and 9 (PA)). We focused our EEG analysis on frontal cortical areas due to their relevance on cognitive function. RESULTS: We found a significant joint effect of interventions on EF and a trend on attention, as well as trends for the negative correlation between attention and theta power (pre), the positive correlation between EF and alpha power (post) and a significant negative relationship between attention and theta power over time (post-pre). CONCLUSIONS: Our results support the role of theta and alpha power at frontal areas as a biomarker for the therapeutic joint effect of interventions.

Multidomain cognitive training increases physical activity in people with Parkinson's disease with mild cognitive impairment.

INTRODUCTION: Cognitive impairment in Parkinson's disease (PD), especially in patients with mild cognitive impairment (PD-MCI), coincides with less physical activity. Cognitive trainings (CT) have been found to promote laboratory environment-based movement. Knowledge about their effect in natural home-based environment, reflecting everyday function, is sparse. This explorative study investigated short-term effects of CT on physical activity assessed by home-based accelerometry, and its relation to change of cognitive function over time and non-cognitive outcomes in patients with PD-MCI. Cognitive and non-cognitive correlates of movement parameters at pretest were evaluated as well. METHODS: Eighteen patients with PD-MCI of the TrainParC study were analyzed. Those patients received either a 6-week multidomain group CT or physical training (PT). Physical activity and sedentary behavior were assessed with wearable accelerometers worn up to seven days pre- and post-training. RESULTS: Patients in the CT group displayed significantly greater increases in active periods after training than patients assigned to PT. In the CT group, increases in executive functioning were associated with increases in active periods and decreases in active mean bout length after training. At pretest, reduced working memory correlated with longer sedentary mean bout length, and impairment in activities of daily living (ADL) correlated with a higher number of sedentary periods. CONCLUSION: Study data revealed that CT can increase physical activity in patients with PD-MCI, possibly due to effects on executive functions, which needs further investigation in larger sample sizes. Lower working memory performance and ADL impairment might be associated with a more inactive lifestyle in patients with PD-MCI.

Characteristics of behavioural addiction in Parkinson's disease patients with self-reported impulse control disorder and controls matched for levodopa equivalent dose: a matched case-control study.

Impulse control disorders (ICD) in Parkinson's disease (PD) frequently occur, not always as a direct consequence of dopaminergic medication. This study investigated premorbid personality traits and behavioural characteristics in non-demented PD patients with self-reported symptoms of ICD (PD-srICD). From a total of 200 non-demented PD patients who filled out questionnaires assessing symptoms and severity of ICD, those were classified as PD-srICD (n = 32) who reported current occurrence of at least one compulsive behaviour (gambling, sexual behaviour, buying behaviour, or eating). As a control group, 32 patients with no self-reported ICD symptoms were matched for levodopa equivalent daily dose. The demographic, clinical, and premorbid personality profiles were compared between both groups. Frequency of psychological characteristics indicating substance use disorder was evaluated in patients with PD-srICD. Patients with PD-srICD were more frequently male, younger at examination, had earlier PD onset, more depression, higher non-motor burden, less quality of life (p < 0.05, respectively), and more frequently reported premorbid sensation seeking/novelty orientation (p = 0.03) and joyful experience of stress (p = 0.04) than patients in the control group. Of patients with PD-srICD, 90.6% reported at least one behavioural characteristic of substance use disorder, most frequently positive expectations following ICD behaviour and illusional beliefs about its behavioural control. Signs of addiction were common among patients with PD-srICD. Therefore, the profile of psychological characteristics in patients with PD-srICD resembled that of patients with substance use disorder. It can be concluded that dopamine replacement therapy (DRT) alone does not account for PD-srICD and that thorough psychological diagnostics are recommended.

Cognitive-Driven Activities of Daily Living Impairment as a Predictor for Dementia in Parkinson Disease: A Longitudinal Cohort Study.

OBJECTIVES: One-third of Parkinson's disease (PD) patients with mild cognitive impairment (PD-MCI) convert to dementia within a few years. Markers with a high prognostic value for dementia conversion are needed. Loss of everyday function primarily caused by cognitive dysfunction is the core criterion for the diagnosis of PD dementia, with an onset of more complex instrumental activities of daily living (IADL) dysfunction in the prodromal stage. This study evaluated the phenotype associated with cognitive IADL impairment and its predictive value for defining a high-risk group for PD dementia. METHODS: An observational longitudinal study using cognitive and clinical scores in addition to genetic and CSF biomarkers was conducted. The Functional Activities Questionnaire (FAQ) quotient (cut-off ≥1), indicating more cognitive than motor-driven IADL impairment, defined cognitive IADL impairment status at baseline. Hazard ratios (HR) were used to compare the impact of baseline classifications on dementia conversion. RESULTS: Of 268 patients with PD assessed at baseline, 108 (40.3%) had PD-MCI. After a period of 3.78±0.84 years, 164 (61.2%) patients were re-assessed. At follow-up, 93 (56.7%) patients had no cognitive impairment, 54 (32.9%) fulfilled PD-MCI criteria, and 17 (10.4%) had developed dementia. The HR of baseline cognitive IADL impairment (n=37) for dementia conversion was descriptively higher than for PD-MCI, but highest in patients with both markers (HR=12.01, 95%-CI 4.47-32.22, p<0.001). In the follow-up sample, nearly half of patients (n=10, 47.6%) with baseline classification of cognitive IADL impairment and PD-MCI converted to dementia. Baseline status of cognitive IADL impairment was associated with higher non-motor burden, worse cognitive performance, and more severe IADL progression over the study period. CONCLUSION: The importance of differentiating between cognitive and motor aspects on ADL function in PD and monitoring cognitive ADL impairment in the prodromal stage of dementia is paramount. Patients with PD-MCI and cognitive IADL impairment may be a valuable target group for clinical trials aiming to slow down development of dementia. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT03687203. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that impairment of cognitive activities of daily living is associated with progression from mild cognitive impairment to dementia among patients with Parkinson's disease.

Evaluation of the Dementia Apraxia Test in Parkinson's Disease Patients.

INTRODUCTION: Ideomotor apraxia, a disorder of skilled movements affecting limbs and/or face, can be seen in patients with Parkinson's disease (PD), yet tests of apraxia in PD are rare. The aim of this project was to evaluate the psychometric properties and validity of the Dementia Apraxia Test (DATE) in a PD sample. METHODS: 118 PD patients were included. Besides DATE performance, motor and non-motor burden, cognition, and activity of daily living (ADL) function were assessed. Patients were classified as cognitively impaired (n = 41) or non-cognitively impaired (n = 77). RESULTS: Interrater reliability of the DATE (sub-)scores between video ratings and on-site ratings by the investigator was good (0.81 ≤ rk ≤ 0.87). Items were mostly easy to perform, especially the buccofacial apraxia items, which had also low discriminatory power. DATE scores were associated with cognition and ADL function. DATE performance was confounded by motor impairment and patients' age; however, when analysed for both cognitive groups separately, the correlation between DATE and motor performance was not significant. DISCUSSION/CONCLUSION: The DATE seems to be an objective and predominantly valid apraxia screening tool for PD patients, with a few items needing revision. Due to the potential effect of motor impairment and age, standardized scores adjusting for these confounders are needed.

Exploration of whether socioeconomic factors affect the results of priority setting partnerships: updating the top 10 research priorities for the management of Parkinson's in an international setting.

OBJECTIVES: Explore whether socioeconomic differences of patients affect the prioritisation of pre-existing research questions and explore the agreement between healthcare professionals (HCP) and patients in priority setting partnerships (PSPs). DESIGN AND SETTING: Prospective, three centre survey across UK (400 participants), Tuebingen (176 participants) and Luxembourg (303 participants). People with Parkinson's (PwP), research participants, relatives and HCP associated with three Parkinson's cohort studies were invited to participate, along with linked centres (clinical care settings, research groups, charities). Responders were encouraged to pass on the survey to friends/families/carers. METHODS: The survey involved rating the importance of research questions on a Likert scale, allowing for the generation of one new question participants felt was particularly important. Collection of demographic information allowed for comparisons of priorities across a range of socioeconomic variables; the top 10 research priorities for each group were then compared. Questions added by participants were subject to a thematic analysis. RESULTS: 879 participants completed the survey (58% PwP, 22% family/friends, 13% HCP, 4% carers). Finding the best form of physiotherapy for PwP was the number one priority across the majority of analyses. HCP were the only subgroup not to place physiotherapy in the top 10. Factors most likely to affect prioritisation in PwP included educational level, presence of carer support and disease duration. There was little difference between other socioeconomic categories. CONCLUSIONS: Socioeconomic factors modestly influenced some research priority ratings but did not significantly affect the top priority in most comparisons. Future studies must ensure patients from a range of socioeconomic backgrounds are recruited, ensuring results generalisable to the public while also identifying any key disparities in prioritisation. PSP should also take care that HCP do not skew results during prioritisation of questions, as in this study the most important priority to patients was not identified by professionals.

Cognition in prodromal Parkinson's disease.

One characteristic of Parkinson's disease (PD) is a prodromal phase, lasting many years during which both pre-clinical motor and non-motor symptoms occur. Around one-fifth of patients with PD manifest mild cognitive impairment at time of clinical diagnosis. Thus, important challenges are to define the time of onset of cognitive dysfunction in the prodromal phase of PD, and to define its co-occurrence with other specific characteristics. Evidence for cognitive change in prodromal PD comes from various study designs, including both longitudinal and cross-sectional approaches with different target groups. These studies support the concept that changes in global cognitive function and alterations in executive functions occur, and that these changes may be present up to 6 years before clinical PD diagnosis. Notably, this evidence led to including global cognitive impairment as an independent prodromal marker in the recently updated research criteria of the Movement Disorder Society for prodromal PD. Knowledge in this field, however, is still at its beginning, and evidence is sparse about many aspects of this topic. Further longitudinal studies including standardized assessments of global and domain-specific cognitive functions are needed to gain further knowledge about the first appearance, the course, and the interaction of cognitive deficits with other non-motor symptoms in prodromal stage PD. Treatment approaches, including non-pharmacological interventions, in individuals with prodromal PD might help to prevent or delay cognitive dysfunction in early PD.

Divergence Between Informant and Self-Ratings of Activities of Daily Living Impairments in Parkinson's Disease.

OBJECTIVE: To examine the agreement between self- and informant-reported activities of daily living (ADL) deficits in Parkinson's Disease (PD) patients, and to examine factors influencing ADL ratings. BACKGROUND: In PD, the loss of functional independence is an important outcome of disease progression. The valid assessment of ADL function in PD is essential, but it is unclear to what extent informants' and patients' perceptions of their daily functions concur, and how other factors may influence both ratings. METHODS: Data of 150 PD patients who underwent cognitive and motor testing, as well as their informants were analyzed. The 10-item Functional Activities Questionnaire (FAQ), completed separately by patients (FAQ-S) and their informants (FAQ-I), assessed ADL function. Weighted κ statistics summarized level of agreement, and a discrepancy score (FAQ-I - FAQ-S) quantified agreement. Correlation analyses between FAQ total scores, patient and informant characteristics, and cognitive scores were conducted, with post hoc regressions to determine the associations between both FAQ scores and cognition, independent of patient characteristics. RESULTS: The sample included 87 patients with normal cognition, 50 with mild cognitive impairment, and 13 with dementia. Overall, there was fair to moderate agreement between patients and informants on individual FAQ items (0.27 ≤ κ ≤ 0.61, p < 0.004), with greater discrepancies with increasing cognitive impairment. Patients' age, motor severity, non-motor burden, and depression also affected both ratings (0.27 ≤ r ≤ 0.50, p < 0.001), with motor severity showing the greatest influence on both ratings. Both the FAQ-I and FAQ-S were correlated with almost all cognitive domains. Post hoc regression analyses controlling for patient characteristics showed that the attention domain was a significant predictor of both the FAQ-S and FAQ-I scores, and memory was also a significant predictor of the FAQ-I score. Only 29.3% of patients agreed perfectly with informants on the FAQ total score, with informants most commonly rating ADL impairments as more severe than patients. CONCLUSIONS: Patient and informant ratings of ADL function using FAQ items showed moderate agreement, with only few items reaching substantial agreement. Ratings of both were associated with patient cognitive status, but also other characteristics. In addition to patient and informant reports, objective measures are needed to accurately classify ADL deficits in PD.

Long-Term Cognitive Decline Related to the Motor Phenotype in Parkinson's Disease.

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 follow-up 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 were present and we found differences for motor phenotypes in attention (ß= -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.

Effects of exergaming on hippocampal volume and brain-derived neurotrophic factor levels in Parkinson's disease.

BACKGROUND AND OBJECTIVE: Cognitive impairment is among the most burdensome non-motor symptoms in Parkinson's disease (PD) and has been associated with hippocampal atrophy. Exercise has been reported to enhance neuroplasticity in the hippocampus in correlation with an improvement of cognitive function. We present data from the Training-PD study, which was designed to evaluate effects of an "" training protocol on neuronal plasticity in PD. METHODS: We initiated a 6-week exergaming training program, combining visually stimulating computer games with physical exercise in 17 PD patients and 18 matched healthy controls. Volumetric segmentation of hippocampal subfields on T1- and T2-weighted magnetic resonance imaging and brain-derived neurotrophic factor (BDNF) serum levels were analyzed before and after the training protocol. RESULTS: The PD group showed a group-dependent significant volume increase of the left hippocampal subfields CA1, CA4/dentate gyrus (DG) and subiculum after the 6-week training protocol. The effect was most pronounced in the left DG of PD patients, who showed a significantly smaller percentage volume compared to healthy controls at baseline, but not at follow-up. Both groups had a significant increase in serum BDNF levels after training. CONCLUSIONS: The results of the present study indicate that exergaming might be a suitable approach to induce hippocampal volume changes in PD patients. Further and larger studies are needed to verify our findings.

Brain age and Alzheimer's-like atrophy are domain-specific predictors of cognitive impairment in Parkinson's disease.

Recently, it was shown that patients with Parkinson's disease (PD) who exhibit an "Alzheimer's disease (AD)-like" pattern of brain atrophy are at greater risk for future cognitive decline. This study aimed to investigate whether this association is domain-specific and whether atrophy associated with brain aging also relates to cognitive impairment in PD. SPARE-AD, an MRI index capturing AD-like atrophy, and atrophy-based estimates of brain age were computed from longitudinal structural imaging data of 178 PD patients and 84 healthy subjects from the LANDSCAPE cohort. All patients underwent an extensive neuropsychological test battery. Patients diagnosed with mild cognitive impairment or dementia were found to have higher SPARE-AD scores as compared to patients with normal cognition and healthy controls. All patient groups showed increased brain age. SPARE-AD predicted impairment in memory, language and executive functions, whereas advanced brain age was associated with deficits in attention and working memory. Data suggest that SPARE-AD and brain age are differentially related to domain-specific cognitive decline in PD. The underlying pathomechanisms remain to be determined.

Quantifying activities of daily living impairment in Parkinson's disease using the Functional Activities Questionnaire.

OBJECTIVE: Cognitive-driven activity of daily living (ADL) impairment in Parkinson's disease (PD) is increasingly discussed as prodromal marker for dementia. Diagnostic properties of assessments for this specific ADL impairment are sparsely investigated in PD. The ability of the Functional Activities Questionnaire (FAQ) for differentiating between PD patients with normal cognition and with mild cognitive impairment (PD-MCI), according to informant and self-reports, was examined. Global cognitive function in groups with and without mild ADL impairment was compared according to different cut-offs. METHODS: Multicenter data of 589 patients of an international cohort (CENTRE-PD) were analyzed. Analyses were run separately for informant-rated and self-rated FAQ. Receiver operating characteristic (ROC) analysis was conducted to define the optimal FAQ cut-off for PD-MCI (≥ 1), and groups were additionally split according to reported FAQ cut-offs for PD-MCI in the literature (≥ 3, ≥ 5). Binary logistic regressions examined the effect of the Montreal Cognitive Assessment (MoCA) score in PD patients with and without mild ADL impairment. RESULTS: Two hundred and twenty-five (38.2%) patients were classified as PD-MCI. For all three cut-off values, sensitivity was moderate to low (< 0.55), but specificity was moderately high (> 0.54) with a tendency of higher values for self-reported deficits. For the self-report, the cut-off ≥ 3 showed a significant effect of the MoCA (B = - 0.31, p = 0.003), where FAQ ≥ 3 patients had worse cognition. No effect for group differences based on informant ratings was detected. CONCLUSION: Our data argue that self-reported ADL impairments assessed by the FAQ show a relation to the severity of cognitive impairment in PD.

Effect of Fear of Falling on Mobility Measured During Lab and Daily Activity Assessments in Parkinson's Disease.

In chronic disorders such as Parkinson's disease (PD), fear of falling (FOF) is associated with falls and reduced quality of life. With inertial measurement units (IMUs) and dedicated algorithms, different aspects of mobility can be obtained during supervised tests in the lab and also during daily activities. To our best knowledge, the effect of FOF on mobility has not been investigated in both of these settings simultaneously. Our goal was to evaluate the effect of FOF on the mobility of 26 patients with PD during clinical assessments and 14 days of daily activity monitoring. Parameters related to gait, sit-to-stand transitions, and turns were extracted from IMU signals on the lower back. Fear of falling was assessed using the Falls Efficacy Scale-International (FES-I) and the patients were grouped as with (PD-FOF+) and without FOF (PD-FOF-). Mobility parameters between groups were compared using logistic regression as well as the effect size values obtained using the Wilcoxon rank-sum test. The peak angular velocity of the turn-to-sit transition of the timed-up-and-go (TUG) test had the highest discriminative power between PD-FOF+ and PD-FOF- (r-value of effect size = 0.61). Moreover, PD-FOF+ had a tendency toward lower gait speed at home and a lower amount of walking bouts, especially for shorter walking bouts. The combination of lab and daily activity parameters reached a higher discriminative power [area under the curve (AUC) = 0.75] than each setting alone (AUC = 0.68 in the lab, AUC = 0.54 at home). Comparing the gait speed between the two assessments, the PD-FOF+ showed higher gait speeds in the capacity area compared with their TUG test in the lab. The mobility parameters extracted from both lab and home-based assessments contribute to the detection of FOF in PD. This study adds further evidence to the usefulness of mobility assessments that include different environments and assessment strategies. Although this study was limited in the sample size, it still provides a helpful method to consider the daily activity measurement of the patients with PD into clinical evaluation. The obtained results can help the clinicians with a more accurate prevention and treatment strategy.

Cognitive profiles of patients with mild cognitive impairment due to Alzheimer's versus Parkinson's disease defined using a base rate approach: Implications for neuropsychological assessments.

INTRODUCTION: Large studies on cognitive profiles of patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD-MCI) compared to Parkinson's disease (PD-MCI) are rare. METHODS: Data from two multicenter cohort studies in AD and PD were merged using a unified base rate approach for the MCI diagnosis. Cognitive profiles were compared using scores derived from the Consortium to Establish a Registry for Alzheimer's Disease battery. RESULTS: Patients with AD-MCI showed lower standardized scores on all memory test scores and a language test. Patients with PD-MCI showed lower standardized scores in a set-shifting measure as an executive task. A cross-validated logistic regression with test scores as predictors was able to classify 72% of patients correctly to AD-MCI versus PD-MCI. DISCUSSION: The applied test battery successfully discriminated between AD-MCI and PD-MCI. Neuropsychological test batteries in clinical practice should always include a broad spectrum of cognitive domains to capture any cognitive changes.

A new CERAD total score with equally weighted z-scores and additional executive and non-amnestic "CERAD-Plus" tests enhances cognitive diagnosis in patients with Parkinson's disease: Evidence from the LANDSCAPE study.

INTRODUCTION: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) is a renowned cognitive test battery, which has been extended in its German version to the CERAD-Plus including tests of executive functions and processing speed. The most commonly used total score (TS) is based on the restricted CERAD version and reflects the sum of selected raw-values (Chandler et al., 2005). The CERAD-Plus extensions might be of particular diagnostic utility for cognitive assessments in Parkinson's Disease (PD), as executive functions and processing speed belong to the most vulnerable domains in PD. OBJECTIVE: The aim was to develop a CERAD-TS based on the extended CERAD-Plus' age-, gender-, and education-corrected z-scores and to evaluate its diagnostic accuracy compared to the established CERAD-Chandler-TS. METHODS: Baseline data of n = 679 patients with PD (69% male, n = 277 PD without cognitive impairment, n = 307 PD-MCI, n = 95 PD-D) from the multicenter, prospective DEMPARK/LANDSCAPE study were analyzed. ROC-analyses were conducted for four different TS that were either based on the original CERAD or CERAD-Plus, on raw-values or z-scores, and equally-weighted or based on factor scores. AUC-comparisons were conducted to determine the best yet most parsimonious TS. RESULTS: The newly designed CERAD-Plus-TS based on equally-weighted z-scores outperformed both the CERAD-Chandler-TS and cognitive screening instruments when differentiating between individuals with PD of varying cognitive impairment (0.78 ≤ AUC ≤ 0.98). CONCLUSION: Results suggest a high relevance of non-amnestic subscales for the cognitive assessment in PD populations. The proposed CERAD-Plus-TS needs further validation. The extensions might offer diagnostic potential for non-PD populations as well.

Deficits in or preservation of basic number processing in Parkinson's disease? A registered report.

Neurodegenerative diseases such as Parkinson's disease (PD) have a huge impact on patients, caregivers, and the health-care system. To date, the diagnosis of mild cognitive impairments in PD has been established based on domain-general functions such as executive functions, attention, or working memory. However, specific numerical deficits observed in clinical practice have not yet been systematically investigated. PD-immanent deterioration of domain-general functions and domain-specific numerical areas suggests the mechanisms of both primary and secondary dyscalculia. The current study will systematically investigate basic number processing performance in PD patients for the first time, targeting domain-specific cognitive representations of numerosity and the influence of domain-general factors. The overall sample consists of patients with a diagnosis of PD, according to consensus guidelines, and healthy controls. PD patients will be stratified into patients with normal cognition or mild cognitive impairment (level I-PD-MCI based on cognitive screening). Basic number processing will be assessed using transcoding, number line estimation, and (non)symbolic number magnitude comparison tasks. Discriminant analysis will be employed to assess whether basic number processing tasks can differentiate between a healthy control group and both PD groups. All participants will be subjected to a comprehensive numerical and a neuropsychological test battery, as well as sociodemographic and clinical measures. Study results will give the first broad insight into the extent of basic numerical deficits in different PD patient groups and will help us to understand the underlying mechanisms of the numerical deficits faced by PD patients in daily life.