Arithmetic Errors in Financial Contexts in Parkinson's Disease.

Research on dyscalculia in neurodegenerative diseases is still scarce, despite high impact on patients' independence and activities of daily living function. Most studies address Alzheimer's Disease; however, patients with Parkinson's Disease (PD) also have a higher risk for cognitive impairment while the relation to arithmetic deficits in financial contexts has rarely been studied. Therefore, the current exploratory study investigates deficits in two simple arithmetic tasks in financial contexts administered within the Clinical Dementia Rating in a sample of 100 PD patients. Patients were classified as cognitively normal (PD-NC) or mildly impaired (PD-MCI) according to Level I consensus criteria, and assessed using a comprehensive neuropsychological test battery, neurological motor examination, and sociodemographic and clinical questionnaires. In total, 18% showed arithmetic deficits: they were predominately female, had longer disease duration, more impaired global cognition, but minor signs of depression compared to PD patients without arithmetic deficits. When correcting for clinical and sociodemographic confounders, greater impairments in attention and visuo-spatial/constructional domains predicted occurrence of arithmetic deficits. The type of deficit did not seem to be arbitrary but seemed to involve impaired place × value processing frequently. Our results argue for the importance of further systematic investigations of arithmetic deficits in PD with sensitive tests to confirm the results of our exploratory study that a specific subgroup of PD patients present themselves with dyscalculia.

Effects of Levodopa on quality of sleep and nocturnal movements in Parkinson's Disease.

BACKGROUND: Sleep disturbances are common in Parkinson's Disease (PD), with nocturnal akinesia being one of the most burdensome. Levodopa is frequently used in clinical routine to improve nocturnal akinesia, although evidence is not well proven. METHODS: We assessed associations of Levodopa intake with quality of sleep and perception of nocturnal akinesia in three PD cohorts, using the Parkinson's Disease Sleep Scale (PDSS-2) in two cohorts and a question on nocturnal immobility in one cohort. In one cohort also objective assessment of mobility during sleep was performed, using mobile health technology. RESULTS: In an independent analysis of all three cohorts (in total n = 1124 PD patients), patients taking Levodopa CR reported a significantly higher burden by nocturnal akinesia than patients without Levodopa. Higher Levodopa intake and MDS-UPDRS part IV scores (indicating motor fluctuations) predicted worse PDSS-2 and higher subjective nocturnal immobility scores, while disease duration and severity were not predictive. Levodopa intake was not associated with objectively changed mobility during sleep. CONCLUSION: Our results showed an association of higher Levodopa intake with perception of worse quality of sleep and nocturnal immobility in PD, indicating that Levodopa alone might not be suitable to improve subjective feeling of nocturnal akinesia in PD. In contrast, Levodopa intake was not relevantly associated with objectively measured mobility during sleep. PD patients with motor fluctuations may be particularly affected by subjective perception of nocturnal mobility. This study should motivate further pathophysiological and clinical investigations on the cause of perception of immobility during sleep in PD.

Association of cognitive activities of daily living (ADL) function and nonmotor burden in nondemented Parkinson's disease patients.

OBJECTIVE: In Parkinson's disease (PD), nonmotor symptoms (NMS) considerably influence disease progression and cognitive decline. Depression, anxiety, sleep disturbances, and hallucinations (DASH), may indicate a risk for dementia (PDD). Mild impairments in activities of daily living (ADL) caused by cognitive dysfunction are also present in the prodromal stage of PDD. The association of both factors has been sparsely investigated. Aim was to evaluate these specific NMS in a large nondemented PD cohort and their co-occurrence with cognitive dysfunction and ADL impairments. METHOD: Data of 226 PD patients was analyzed. Using corresponding items, two DASH scores were constructed from the NMS-Scale and Parkinson's disease Questionnaire (PDQ-39). Correlations between DASH scores and PDD risk factors were examined. PD patients with mild cognitive impairment (PD-MCI) were additionally split into patients with low and high DASH burden, the latter group additionally stratified by presence of cognitive-driven ADL impairment. RESULTS: DASH-NMS scores differed significantly between PD-MCI and cognitively normal (PD-CN) patients (p = .04), while the DASH-PDQ did not (p = .73). The only significant predictor of the DASH-NMS score was cognitive-driven ADL (p = .01). PD-MCI patients with a high DASH burden and more cognitive ADL impairment presented with worse global cognition than patients with a low burden (p = .045). CONCLUSION: Our results show that the DASH-NMS is superior to the DASH-PDQ score, related to the severity of cognitive impairment, and strongly influenced by cognitive-driven ADL impairment. Presence of DASH symptoms and cognitive-ADL in PD-MCI patients may define a risk group for PDD conversion. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Assessment of cognitive-driven activity of daily living impairment in non-demented Parkinson's patients.

The core criterion for Parkinson's disease dementia (PDD) is the impairment in activities of daily living (ADL) function primarily caused by cognitive, not motor symptoms. There is evidence to assume that mild ADL impairments in mild cognitive impairment (PD-MCI) characterize those patients at high risk for dementia. Data of 216 Parkinson's disease (PD) patients assessed with comprehensive motor and neuropsychological assessments were analysed. Based on linear regression models, subscores of the Functional Activities Questionnaire (FAQ) primarily reflecting patients' global cognitive status (FAQC ) or PD-related motor severity (FAQM ) were developed. A quotient (FAQQ ) of both scores was calculated, with values >1 indicating more cognitive- compared to motor-driven ADL impairment. Both FAQC and FAQM scores were higher in PD-MCI than cognitively normal (PD-CN) patients, indicating more severe cognitive- and motor-driven ADL impairments in this group. One third (31.6%) of the PD-MCI group had a FAQQ score >1, which was significantly different from patients with PD-CN (p = .02). PD-MCI patients with an FAQQ score >1 were more impaired on tests assessing attention (p = .019) and language (p = .033) compared to PD-MCI patients with lower FAQQ values. The differentiation between cognitive- and motor-driven ADL is important, as the loss of functional capacity is the defining factor for a diagnosis of PDD. We were able to differentiate the cognitive-driven from the motor-driven ADL impairments for the FAQ. PD-MCI patients with more cognitive- compared to motor-driven ADL impairments may pose a risk group for conversion to PDD and can be targeted for early treatments.

Dual vs. Single Tasking During Circular Walking: What Better Reflects Progression in Parkinson's Disease?

Background and Aim: Reliable, valid and sensitive measures of dual-task-associated impairments in patients with Parkinson's disease (PD) may reveal progressive deficits unnoticed under single-task walking. The aim of this study was to quantitatively identify markers of progressive gait deficits in idiopathic PD while walking over a circular trajectory condition in single-task walking and in different dual-task conditions: (1) circular walking while checking boxes on a paper sheet as fast as possible and (2) circular walking while performing subtraction of 7 as fast as possible. In addition, we aimed to study the added value of dual-tasking assessment over single (circular) walking task assessment in the study of PD progression. Methods: The assessments were performed every 6 months over a (up to) 5 years period for 22 patients in early-stage PD, 27 patients in middle-stage PD and 25 healthy controls (HC). Longitudinal changes of 27 gait features extracted from accelerometry were compared between PD groups and HCs using generalized estimating equations analysis, accounting for gait speed, age, and levodopa medication state confounders when required. In addition, dual-task-interference with gait and cognitive performance was assessed, as well as their combination. Results: The results support the validity and robustness of some of the gait features already identified in our previous work as progression markers of the disease in single-task circular walking. However, fewer gait features from dual-task than from single-task assessments were identified as markers of progression in PD. Moreover, we did not clearly identify progressive worsening of dual-task-interference in patients with PD, although some group differences between early and middle stages of PD vs. the control group were observed for dual-task interference with the gait task and with the concurrent tasks. Conclusions: Overall, the results showed that dual-tasking did not have added value in the study of PD progression from circular gait assessments. Our analyses suggest that, while single-task walking might be sensitive enough, dual-tasking may introduce additional (error) variance to the data and may represent complex composite measures of cognitive and motor performance.

Progressive Gait Deficits in Parkinson's Disease: A Wearable-Based Biannual 5-Year Prospective Study.

Background: Gait changes occur during all Parkinson's disease (PD) stages and wearable sensor-derived gait parameters may quantify PD progression. However, key aspects that may qualify quantitative gait parameters as progression markers in PD remain elusive. Objectives: Longitudinal changes in gait parameters from a lower-back sensor under convenient and challenging walking conditions in early- and mid-stage PD patients (E-PD, M-PD) compared to controls were investigated. Methods: Normal- and fast-pace parameters (step: number, time, velocity, variability) were assessed every 6 months for up to 5 years in 22 E-PD (<4 years baseline disease duration), 18 M-PD (>5 years) and 24 controls. Parameter trajectories and associations with MDS-UPDRS-III were tested using generalized estimating equations. Results: Normal-pace step number (annual change in E-PD: 2.1%, Time∗Group: p = 0.001) and step time variability (8.5%, p < 0.05) longitudinally increased in E-PD compared to controls (0.7%, -12%). For fast pace, no significant progression differences between groups were observed. Longitudinal changes in M-PD did not differ significantly from controls. MDS-UPDRS-III was largely associated with normal-pace parameters in M-PD. Conclusion: Wearables can quantify progressive gait deficits indicated by increasing step number and step time variability in E-PD. In M-PD, and for fast-pace, gait parameters possess limited potential as PD progression markers.

Potential Markers of Progression in Idiopathic Parkinson's Disease Derived From Assessment of Circular Gait With a Single Body-Fixed-Sensor: A 5 Year Longitudinal Study.

Background and Aim: Development of objective, reliable and easy-to-use methods to obtain progression markers of Parkinson's disease (PD) is required to evaluate interventions and to advance research in PD. This study aimed to provide quantitative markers of progression in idiopathic PD from the assessment of circular gait (walking in circles) with a single body-fixed inertial sensor placed on the lower back. Methods: The assessments were performed every 6 months over a (up to) 5 years period for 22 patients in early-stage PD, 27 patients in middle-stage PD and 25 healthy controls (HC). Longitudinal changes of 24 gait features extracted from accelerometry were compared between PD groups and HCs with generalized estimating equations (GEE) analysis, accounting for gait speed, age and levodopa medication state confounders when required. Results: Five gait features indicated progressive worsening in early stages of PD: number of steps, total duration and harmonic ratios calculated from vertical (VT), medio-lateral (ML), and anterior-posterior (AP) accelerations. For middle stages of PD, three gait features were identified as potential progression markers: stride time variability, and stride regularity from VT and AP acceleration. Conclusion: Faster progressive worsening of gait features in early and middle stages of PD relative to healthy controls over 5 years confirmed the potential of accelerometry-based assessments as quantitative progression markers in early and middle stages of the disease. The difference in significant parameters between both PD groups suggests that distinct domains of gait deteriorate in these PD stages. We conclude that instrumented circular walking assessment is a practical and useful tool in the assessment of PD progression that may have relevant potential to be implemented in clinical trials and even clinical routine, particularly in a developing digital era.

Arm swing asymmetry in overground walking.

Treadmill experiments suggest that left-dominant arm swing is common in healthy walking adults and is modulated by cognitive dual-tasking. Little is known about arm swing asymmetry in overground walking. We report directional (dASI) and non-directional arm swing symmetry indices (ndASI) from 334 adults (mean age 68.6 ± 5.9 y) walking overground at comfortable (NW) and fast (FW) speeds and while completing a serial subtraction task (DT). dASI and ndASI were calculated from sagittal shoulder range of motion data generated by inertial measurement units affixed to the wrist. Most (91%) participants were right-handed. Group mean arm swing amplitude was significantly larger on the left in all walking conditions. During NW, ndASI was 39.5 ± 21.8, with a dASI of 21.9 ± 39.5. Distribution of dASI was bimodal with an approximately 2:1 ratio of left:right-dominant arm swing. There were no differences in ndASI between conditions but dASI was smaller during DT compared to FW (15.2 vs 24.6; p = 0.009). Handedness was unrelated to ndASI, dASI or the change in ASI metrics under DT. Left-dominant arm swing is the norm in healthy human walking irrespective of walking condition or handedness. As disease markers, ndASI and dASI may have different and complementary roles.

Effect of Fear of Falling on Turning Performance in Parkinson's Disease in the Lab and at Home.

Background: Parkinson's disease (PD) is a neurodegenerative movement disorder associated with gait and balance problems and a substantially increased risk of falling. Falls occur often during complex movements, such as turns. Both fear of falling (FOF) and previous falls are relevant risk factors for future falls. Based on recent studies indicating that lab-based and home assessment of similar movements show different results, we hypothesized that FOF and a positive fall history would influence the quantitative turning parameters differently in the laboratory and home. Methods: Fifty-five PD patients (43 underwent a standardized lab assessment; 40 were assessed over a mean of 12 days at home with approximately 10,000 turns per participant; and 28 contributed to both assessments) were classified regarding FOF and previous falls as "vigorous" (no FOF, negative fall history), "anxious" (FOF, negative fall history), "stoic" (no FOF, positive fall history) and "aware" (FOF, positive fall history). During the assessments, each participant wore a sensor on the lower back. Results: In the lab assessment, FOF was associated with a longer turning duration and lowered maximum and middle angular velocities of turns. In the home evaluations, a lack of FOF was associated with lowered maximum and average angular velocities of turns. Positive falls history was not significantly associated with turning parameters, neither in the lab nor in the home. Conclusion: FOF but not a positive fall history influences turning metrics in PD patients in both supervised and unsupervised environments, and this association is different between lab and home assessments. Our findings underline the relevance of comprehensive assessments including home-based data collection strategies for fall risk evaluation.

Less Is More - Estimation of the Number of Strides Required to Assess Gait Variability in Spatially Confined Settings.

Background: Gait variability is an established marker of gait function that can be assessed using sensor-based approaches. In clinical settings, spatial constraints and patient condition impede the execution of longer distance walks for the recording of gait parameters. Turning paradigms are often used to overcome these constraints and commercial gait analysis systems algorithmically exclude turns for gait parameters calculations. We investigated the effect of turns in sensor-based assessment of gait variability. Methods: Continuous recordings from 31 patients with movement disorders (ataxia, essential tremor and Parkinson's disease) and 162 healthy elderly (HE) performing level walks including 180° turns were obtained using an inertial sensor system. Accuracy of the manufacturer's algorithm of turn-detection was verified by plotting stride time series. Strides before and after turn events were extracted and compared to respective average of all strides. Coefficient of variation (CoV) of stride length and stride time was calculated for entire set of strides, segments between turns and as cumulative values. Their variance and congruency was used to estimate the number of strides required to reliably assess the magnitude of stride variability. Results: Non-detection of turns in 5.8% of HE lead to falsely increased CoV for these individuals. Even after exclusion of these, strides before/after turns tended to be spatially shorter and temporally longer in all groups, contributing to an increase of CoV at group level and widening of confidence margins with increasing numbers of strides. This could be attenuated by a more generous turn excision as an alternative approach. Correlation analyses revealed excellent consistency for CoVs after at most 20 strides in all groups. Respective stride counts were even lower in patients using a more generous turn excision. Conclusion: Including turns to increase continuous walking distance in spatially confined settings does not necessarily improve the validity and reliability of gait variability measures. Specifically with gait pathology, perturbations of stride characteristics before/after algorithmically excised turns were observed that may increase gait variability with this paradigm. We conclude that shorter distance walks of around 15 strides suffice for reliable and valid recordings of gait variability in the groups studied here.

Quantitative Timed-Up-and-Go Parameters in Relation to Cognitive Parameters and Health-Related Quality of Life in Mild-to-Moderate Parkinson's Disease.

INTRODUCTION: The instrumented-Timed-Up-and-Go test (iTUG) provides detailed information about the following movement patterns: sit-to-walk (siwa), straight walking, turning and walk-to-sit (wasi). We were interested in the relative contributions of respective iTUG sub-phases to specific clinical deficits most relevant for daily life in Parkinson's disease (PD). More specifically, we investigated which condition-fast speed (FS) or convenient speed (CS)-differentiates best between mild- to moderate-stage PD patients and controls, which parameters of the iTUG sub-phases are significantly different between PD patients and controls, and how the iTUG parameters associate with cognitive parameters (with particular focus on cognitive flexibility and working memory) and Health-Related-Quality of Life (HRQoL). METHODS: Twenty-eight PD participants (65.1 ± 7.1 years, H&Y stage 1-3, medication OFF state) and 20 controls (66.1 ± 7.5 years) performed an iTUG (DynaPort®, McRoberts BV, The Netherlands) under CS and FS conditions. The PD Questionnaire 39 (PDQ-39) was employed to assess HRQoL. General cognitive and executive functions were assessed using the Montreal Cognitive Assessment and the Trail Making Test. RESULTS: The total iTUG duration and sub-phases durations under FS condition differentiated PD patients slightly better from controls, compared to the CS condition. The following sub-phases were responsible for the observed longer total duration PD patients needed to perform the iTUG: siwa, turn and wasi. None of the iTUG parameters correlated relevantly with general cognitive function. Turning duration and wasi maximum flexion velocity correlated strongest with executive function. Walking back duration correlated strongest with HRQoL. DISCUSSION: This study confirms that mild- to moderate-stage PD patients need more time to perform the iTUG than controls, and adds the following aspects to current literature: FS may be more powerful than CS to delineate subtle movement deficits in mild- to moderate-stage PD patients; correlation levels of intra-individual siwa and wasi parameters may be interesting surrogate markers for the level of automaticity of performed movements; and sub-phases and kinematic parameters of the iTUG may have the potential to reflect executive functioning and HRQoL aspects of PD patients.

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors.

INTRODUCTION: Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). MATERIALS AND METHODS: IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. RESULTS: PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. DISCUSSION: Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders.

Limited Effect of Dopaminergic Medication on Straight Walking and Turning in Early-to-Moderate Parkinson's Disease during Single and Dual Tasking.

BACKGROUND: In Parkinson's disease (PD), the effects of dopaminergic medication on straight walking and turning were mainly investigated under single tasking (ST) conditions. However, multitasking situations are considered more daily relevant. METHODS: Thirty-nine early-to-moderate PD patients performed the following standardized ST and dual tasks as fast as possible for 1 min during On- and Off-medication while wearing inertial sensors: straight walking and turning, checking boxes, and subtracting serial 7s. Quantitative gait parameters as well as velocity of the secondary tasks were analyzed. RESULTS: The following parameters improved significantly in On-medication during ST: gait velocity during straight walking (p = 0.03); step duration (p = 0.048) and peak velocity (p = 0.04) during turning; velocity of checking boxes during ST (p = 0.04) and DT (p = 0.04). Velocity of checking boxes was the only parameter that also improved during DT. CONCLUSION: These results suggest that dopaminergic medication does not relevantly influence straight walking and turning in early-to-moderate PD during DT.

Intravenous and oral levetiracetam in patients with a suspected primary brain tumor and symptomatic seizures undergoing neurosurgery: the HELLO trial.

BACKGROUND: Levetiracetam (LEV) is a newer anticonvulsant with a favorable safety profile. There seem to be no relevant drug interactions, and an intravenous formulation is available. Therefore, LEV might be a suitable drug for the perioperative anticonvulsive therapy of patients with suspected brain tumors undergoing neurosurgery. METHODS: In this prospective study (NCT00571155) patients with suspected primary brain tumors and tumor-related seizures were perioperatively treated with oral and intravenous LEV up to 4 weeks before and until 4 weeks after a planned neurosurgical procedure. FINDINGS: Thirty patients with brain tumor-related seizures and intended neurosurgery were included. Three patients did not undergo the scheduled surgery after enrollment, and two patients were lost to follow-up. Therefore, 25 patients were fully evaluable. After initiation of therapy with LEV, 100% of the patients were seizure-free in the pre-surgery phase (3 days up to 4 weeks before surgery), 88% in the 48 h post-surgery phase and 84% in the early follow-up phase (48 h to 4 weeks post surgery). Treatment failure even after dose escalation to 3,000 mg/day occurred in three patients. No serious adverse events related to the treatment with LEV occurred. CONCLUSION: Our data show the feasibility and safety of oral and intravenous LEV in the perioperative treatment of tumor-related seizures. Although this was a single arm study, the efficacy of LEV appears promising. Considering the side effects and interactions of other anticonvulsants, LEV seems to be a favorable option in the perioperative treatment of brain tumor-related seizures.