The effect of directional social cues on saccadic eye movements in Parkinson's disease.

There is growing interest in how social processes and behaviour might be affected in Parkinson's disease. A task which has been widely used to assess how people orient attention in response to social cues is the spatial cueing task. Socially relevant directional cues, such as a picture of someone gazing or pointing to the left or the right have been shown to cause orienting of visual attention in the cued direction. The basal ganglia may play a role in responding to such directional cues, but no studies to date have examined whether similar social cueing effects are seen in people with Parkinson's disease. In this study, patients and healthy controls completed a prosaccade (Experiment 1) and an antisaccade task (Experiment 2) in which the target was preceded by arrow, eye gaze or pointing finger cues. Patients showed increased errors and response times for antisaccades but not prosaccades. Healthy participants made most anticipatory errors on pointing finger cue trials, but Parkinson's patients were equally affected by arrow, eye gaze and pointing cues. It is concluded that Parkinson's patients have a reduced ability to suppress responding to directional cues, but this effect is not specific to social cues.

Clinical and laboratory measures of balance and comparison of balance performances according to postural instability and gait disorders in individuals with Parkinson's disease.

PURPOSE/AIM: Primary aim was to investigate the association between laboratory measures of balance and clinical balance tests in individuals with Parkinson's disease (PD). The secondary aim was to compare the balance performances according to postural instability and gait disorders (PIGD). MATERIALS AND METHODS: Sixty-four individuals with PD were included in the study. Clinical data were investigated using modified Hoehn and Yahr Scale and Unified Parkinson's Disease Rating Scale (UPDRS). Berg Balance Scale (BBS), Timed Up&Go Test (TUG), Five Times Sit-to-Stand Test (FTSST) were used for clinical measures of balance. Laboratory measures of balance were evaluated by Balance Master System including the modified Clinical Test of Sensory Interaction of Balance (mCTSIB), Limits of Stability Test (LOS), Sit to Stand Test (STS), and Tandem Walk Test (TW). The relationship between clinical and laboratory measures of balance was determined. After participants were divided into two groups based on UPDRS: patients with and without PIGD, their balance performance was compared. RESULTS: There were significant correlations between BBS and mCTSIB, LOS-Movement Velocity, and LOS-Endpoint Excursion. FTSST was correlated with STS-Weight Transfer and STS-Rising Index, and TUG was correlated with TW-Speed. Patients with PIGD had worse scores of balance assessments including FTSST, LOS-Movement Velocity, STS-Rising Index. CONCLUSION: Laboratory measures are associated with clinical balance tests and they may reflect clinical balance outcome measures. Furthermore, PIGD may negatively affect balance performance in patients with PD.

Determinants of 6-minute walk test in people with Parkinson's disease.

BACKGROUND: Most of the previous studies, investigating determinants of 6-minute walk test (6MWT), were conducted on small sample sizes and/or have not explored different aspects such as freezing of gait, physical activity, gender, dual-task cost, and/or have not been able to explain large portion of variation in 6MWT in people with Parkinson's disease. AIMS: This study aimed to investigate the determinants of 6MWT, including aspects that previous studies have not explored. METHODS: In this descriptive cross-sectional study, 6MWT determinants were investigated upon 42 people with Parkinson's disease. After recording participants' demographic data, walking capacity, disease stage, severity of motor symptoms, freezing of gait, balance, physical activity, fear of falling, functional balance, and dual-task cost values were evaluated and grouped into modifiable and unmodifiable variables to investigate possible therapeutic benefits aiming improvement in walking capacity. RESULTS: The mean distance for 6MWT was 401.7 ± 92.7 m. Significant differences between women and men were found for height, walking capacity and speed, fear of falling, and functional balance (p<0.05). Hierarchical regression analysis showed that gender, age, and time since diagnosis significantly explained 52.4% of the variance in 6MWT and disease stage, freezing of gait, dual-task cost, and functional balance added an extra 35.6% to the explained variance. CONCLUSIONS: These results showed that gender, age, disease stage, freezing of gait, dual-task cost, and functional balance values are significant contributors to the variance in 6MWT. Therefore, while planning rehabilitation strategies to improve walking capacity, one should focus on these aspects in people with Parkinson's disease.

Impact of the COVID-19 pandemic on physical activity, anxiety, and depression in patients with Parkinson's disease.

The coronavirus disease 2019 pandemic has yielded containment measures with detrimental effects on the physical and mental health of the general population. The impacts of lockdown on clinical features in Parkinson's disease are not well known. We aimed to compare the physical activity, anxiety-depression levels between Parkinson's disease patients and controls during lockdown. Forty-five Parkinson's disease patients and 43 controls were evaluated with the Physical Activity Scale for the Elderly (PASE) and Hospital Anxiety and Depression Scale (HADS) via telephone interview. The patients' disease-related symptoms were worsened during lockdown though regular Parkinson's disease medication use. The PASE scores were low in both groups. The HADS scores of groups were below the cutoff point of anxiety-depression presence. Pandemic restrictions could lead to worsening of the motor and nonmotor symptoms in Parkinson's disease.

Physical activity in patients with Parkinson's disease: A holistic approach based on the ICF model.

OBJECTIVES: The International Classification of Functioning, Disability and Health (ICF) is a framework providing information on disability and health. Physical activity's behavior is complex and affected by various factors. We aimed to examine the ICF domains in Parkinson's disease (PD) patients; to compare them in sedentary and non-sedentary PD patients and their association with activity level. PATIENTS AND METHODS: Sixty PD patients (25 sedentary PD group, 35 non-sedentary PD group) were included in this retrospective study. Functional disability was evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale. The physical activity level was measured by the SenseWear Arm Band activity monitor. Patients' cognitive function, severity of depression and anxiety, the functional impact of fatigue, balance performance (NeuroCom Balance Master System), functional mobility (Timed Up and Go Test, TUG), walking capacity (Six-Minute Walk Test, 6MWT), fear of falling, health-related quality of life are also analyzed. RESULTS: Sedentary PD patients had worse scores in NeuroCom Balance Master System parameters, TUG score, and 6MWT distance in activities domains of the ICF model as a guide than non-sedentary group (p < 0.05). No statistically significant differences were found in the body structures and function, participation, personal and environmental domains of the ICF model between sedentary and non-sedentary PD groups (p > 0.05). There was no correlation between steps taken per day and NeuroCom Balance Master System parameters, TUG score, and 6MWT distance in both groups (p > 0.05). CONCLUSION: Patients with sedentary lifestyle had worse scores in postural control/balance, sit-to-stand and walking performance. However, deteriorated dynamic balance may not lead to sedentary lifestyle. Physiotherapy programs should be including the behavior change interventions and motivational strategies to promote activity level in PD.

Does the postural stability of patients with Parkinson's disease affect the physical activity?

Postural instability is one of the cardinal features in Idiopathic Parkinson's disease. It is a significant factor of disability in Parkinson's disease. We aimed to examine the physical activity levels in patients with Parkinson's disease comparing with healthy subjects and their association with the postural stability. Fifty-six Parkinson's disease patients and 58 healthy subjects were involved. The disease-specific disability of patients was determined by using Modified Hoehn and Yahr Scale and Movement Disorder Society Unified Parkinson's Disease Rating Scale. The physical activity levels of participants were evaluated using SenseWear Arm Band activity monitor. The participants used the activity monitor for seven consecutive days. The postural stability was assessed using NeuroCom Balance Master system. The Parkinson's disease group was found to take fewer steps and to have shorter duration of sleep and sedentary behavior but a higher level of energy expenditure than the healthy control group (P < 0.05). In Parkinson's disease group, the data obtained from the activity monitor were found to be in correlation with disease-specific disability and the parameters of NeuroCom Balance Master system (P < 0.05). We found that the physical activity levels of patients with a mild or moderate stage of Parkinson's disease were lower compared to healthy subjects and were affected by the disease-specific symptoms, dynamic postural instability, and walking function. To increase the activity level in Parkinson's disease, these factors should be aimed to improve, as well as designing the personalized physiotherapy programs starting from the early-mid stage.

Timed Up and Go Test With a Cognitive Task: Correlations With Neuropsychological Measures in People With Parkinson's Disease.

Background The Timed Up and Go (TUG) test is a simple and widely used clinical test for the assessment of lower extremity function, balance, mobility, and fall risk in various populations. The TUG has been found as a valid and reliable measure in people with Parkinson's disease (PD). Besides, the addition of a cognitive task to the TUG (TUG-cognitive) enhances predictive validity related to fall risk in people with PD. However, further investigation is needed about the correlations of the TUG-cognitive test with neuropsychological measures in people with PD. Methods Thirty-three people with PD [modified Hoehn and Yahr scale, median (min-max)=2.5 (1.0-3.0)] participated in this cross-sectional study. The TUG was administered in the traditional way and with a cognitive task (counting backward by three from any number between 20 and 100). Neuropsychological measures included the Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT), and the Simple Reaction Time (SRT) test for stepping. The self-reported number of falls in the last six months was also recorded. Results The TUG-cognitive [13.1 (SD=8.5) seconds] was significantly longer than the TUG-traditional [12.2 (SD=8.1) seconds] (p<0.01). The TUG-cognitive significantly correlated with the MoCA [(rho=-0.712), TMT part A (TMT-A; rho=0.722), TMT part B (TMT-B; rho=0.694), SRT (rho=0.794), and number of falls (rho=0.960)] (p<0.01). The TUG-traditional also significantly correlated with the MoCA (rho=-0.682), TMT-A (rho=0.684), TMT-B (rho=0.746), SRT (rho=0.755), and number of falls (rho=0.702) (p<0.01). Conclusion Both the TUG-cognitive and TUG-traditional strongly correlated with neuropsychological measures; while the correlations were slightly stronger for the TUG-cognitive, the difference was not significant. The TUG-cognitive can be used in the clinical practice as a simple and more informative alternative to the TUG-traditional in people with PD.

Mild cognitive impairment in Parkinson's disease is associated with decreased P300 amplitude and reduced putamen volume.

OBJECTIVE: Functional and structural brain alterations of cognitively normal Parkinson's disease (PD-CN) and Parkinson's disease mild cognitive impairment (PD-MCI) patients were investigated using event-related potentials (ERP) P300 and volumetric magnetic resonance imaging (MRI) parameters. METHODS: Twenty three patients with PD-CN, 21 with PD-MCI, and 23 demographically-matched healthy controls were included. EEGs were recorded using a visual oddball task and mean amplitude and peak latency values of P300 were measured. Gray matter volumes (GMV) of thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala and nucleus accumbens were obtained using FMRIB Integrated Registration and Segmentation Tool. Correlations among P300, subcortical GMV and cognitive performances were assessed. RESULTS: PD-CN patients demonstrated reduced P300 amplitudes compared to healthy controls. PD-MCI patients had lower P300 amplitudes than both PD-CN patients and controls and reduced volumes of the putamen compared to controls. Both putamen volumes and P300 amplitudes showed moderate associations with executive functions. CONCLUSIONS: Our findings support that P300 amplitude may be a useful marker for the detection of preclinical changes before the appearance of cognitive and structural deterioration in PD, as shown by decreased frontal P300 amplitudes in PD-CN. The reduction further spread to centro-parietal areas in PD-MCI patients, which was accompanied by lower putamen volumes. SIGNIFICANCE: This study is the first to report on changes in ERP P300 amplitude and subcortical volume in well-matched samples of PD-CN, PD-MCI and healthy controls.

A Novel and Mosaic WDR45 Nonsense Variant Causes Beta-Propeller Protein-Associated Neurodegeneration Identified Through Whole Exome Sequencing and X chromosome Heterozygosity Analysis.

Beta-propeller protein-associated neurodegeneration (BPAN) is an X-linked rare dominant disorder of autophagy. The role of WDR45 has been implicated in BPAN almost exclusively in females possibly due to male lethality. Characterization of distinctive clinical manifestations and potentially the complex genetic determinants in rare male patients remain crucial for deciphering BPAN and other X-linked dominant diseases. We performed whole exome sequencing (WES) followed by segregation analysis and identified a novel nonsense and mosaic variant in WDR45, namely NM_007075.3:c.873C>G; p.(Tyr291*) in an affected male at the age of 34. His biphasic medical history was compatible with BPAN, which was characterized by delayed psychomotor development, intellectual disability, and progression into dystonia parkinsonism in his twenties. The variant had an apparently mosaic pattern both in whole exome and Sanger sequencing findings. In order to figure out if mosaicism was restricted to this variant or related to a chromosomal level mosaicism, we used our in-house WES data from 129 unrelated individuals to calculate the threshold values of male and female X chromosome heterozygosity (XcHet) in WES data for our pipeline. A background level of heterozygous variants on X chromosome excluding the pseudoautosomal loci is an observed phenomenon in WES analysis and this level has been used as a quality measure. Herein, we suggest utilization of this measure for detection of digital anomalies of the X chromosome in males by potentially observing a higher XcHet value than the threshold value. This approach has revealed a variant level mosaicism in the affected male, which was further supported with cytogenetic analyses.

Decrease of Delta Oscillatory Responses in Cognitively Normal Parkinson's Disease.

Parkinson's disease (PD) is a common progressive neurodegenerative disorder. This study aims to compare sensory-evoked oscillations (SEOs) and event-related oscillations (EROs) of visual modality in cognitively normal PD patients and healthy controls. Sixteen PD and 16 age-, gender-, and education-matched healthy controls participated in the study. A simple flashlight was used for SEO and a classical visual oddball paradigm was used for target ERO. Oscillatory responses in the delta frequency range (0.5-3.5 Hz) were examined. Significantly lower delta ERO and SEO responses were found in PD patients than healthy controls. Delta ERO responses were decreased at all frontal, central and parietal locations, whereas delta SEO responses were decreased over mid and right central locations in PD. According to the notion that SEO reflects the activity of sensory networks and ERO reflects cognitive networks, these findings indicate that PD patients have impairments in both cognitive and sensory networks of visual modality. Decreased delta ERO responses indicate that the subliminal cognitive changes in PD can be detected by electrophysiological methods. These results demonstrate that brain oscillatory responses have the potential to be studied as a biomarker for visual cognitive and sensory networks in PD.