Parkinson's Disease Participants Research Articles

Optimal Feature Selection and Classification for Parkinson’s Disease Using Deep Learning and Dynamic Bag of Features Optimization

Parkinson’s Disease (PD) is a neurological condition that worsens with time and is characterized bysymptoms such as cognitive impairment andbradykinesia, stiffness, and tremors. Parkinson’s is attributed to the interference of brain cells responsible for dopamine production, a substance regulating communication between brain cells. The brain cells involved in dopamine generation handle adaptation and control, and smooth movement. Convolutional Neural Networks are used to extract distinctive visual characteristics from numerous graphomotor sample representations generated by both PD and control participants. The proposed method presents an optimal feature selection technique based on Deep Learning (DL) and the Dynamic Bag of Features Optimization Technique (DBOFOT). Our method combines neural network-based feature extraction with a strong optimization technique to dynamically choose the most relevant characteristics from biological data. Advanced DL architectures are then used to classify the chosen features, guaranteeing excellent computational efficiency and accuracy. The framework’s adaptability to different datasets further highlights its versatility and potential for further medical applications. With a high accuracy of 0.93, the model accurately identifies 93% of the cases that are categorized as Parkinson’s. Additionally, it has a recall of 0.89, which means that 89% of real Parkinson’s patients are accurately identified. While the recall for Class 0 (Healthy) is 0.75, meaning that 75% of the real healthy cases are properly categorized, the precision decreases to 0.64 for this class, indicating a larger false positive rate.

The Prevalence of Depressive Symptoms in Patients with Idiopathic Parkinson's Disease: Cross-Sectional Study from Somalia.

Depression is one of the most common non-motor symptom of Parkinson's disease (PD), with an increasing prevalence in recent years. It causes significant psychological consequences that affect the disease course, overall quality of life, and functioning. The objective of this study was to determine the prevalence of depression in outpatients with Parkinson's disease evaluated in the neurology clinic at tertiary hospital in Mogadishu, Somalia. A cross-sectional study was conducted among 50 PD patients without dementia to determine the prevalence of depression at the neurology clinic of the Mogadishu Somalia Türkiye Training and Research Hospital between February and November 2022. All eligible participants were interviewed by a team of doctors using a structured questionnaire that consisted of sociodemographics and clinical characteristics, the Beck Depression Inventory-II (BDI-II) for depression assessment, and the Modified Hoehn and Yahr Scale for PD staging. Of the 50 PD participants, 60% were male and 58% were older than 60 years. 20% of them had a family history of PD and HTN as comorbid conditions. The prevalence of depression among the participants was 46% (95% CI 31.8-60.7). Of the patients with depression, 22% and 24% had mild and moderate depressive symptoms, respectively. The Mann-Whitney U-test revealed a statistically significant association between depression symptoms and the presence of comorbidity (χ2 = 136.50, p<0.01). The Kruskal-Wallis test revealed a statistically significant association between depression symptoms and a longer duration of PD (χ2 (2) = 18.21, p<0.01) and advanced stages of PD (χ2 (2) = 13.74, p<0.01). This is the first study conducted on patients with PD in Somalia and found that a significant proportion of these patients experienced depressive symptoms. We also highlighted that factors such the presence of medical comorbidities, high monthly income, advanced PD stage, longer duration of PD, and use of multiple medications for PD were significantly associated with the presence of depressive symptoms.

Evaluating the Effects of Frequency of Subthalamic Nucleus Deep Brain Stimulation on Postural Control in Parkinson's Disease: A Case-Series Study.

Background/Objectives: Subthalamic nucleus deep brain stimulation (STN-DBS) is a standard treatment for motor complications in Parkinson's disease (PD). Its impact on axial symptoms is still not fully understood. This study aimed to quantitatively evaluate the effect of frequency changes within the therapeutic window on postural control performances of individuals with PD who underwent bilateral STN-DBS. Methods: Postural control was assessed using Computerized Dynamic Posturography with randomized DBS frequency parameters, low (60 Hz), high (130 Hz), and very high (180 Hz), across six sensory organization test (SOT) conditions. Results: Twenty PD participants with a mean age of 61.2 ± 10.1 years were included. There were no differences in equilibrium scores of SOT conditions between 60, 130, and 180 Hz frequencies (p > 0.05), except the SOT6 score (p = 0.003), where 60 Hz showed better equilibrium performance in SOT6, indicating an advantage in postural control when visual cues are disturbed. Discussion: Low-frequency settings (60 Hz) in STN-DBS may benefit those who rely heavily on visual cues while ineffectively using somatosensory and vestibular inputs. Conclusions: A tailored approach to the DBS frequency setting could optimize postural stability and reduce fall risk in these patients. Future research is needed to explore these mechanisms to enhance therapeutic strategies.

Advancing Parkinson's Disease Research in Canada: The Canadian Open Parkinson Network (C-OPN) Cohort.

Enhancing the interactions between study participants, clinicians, and investigators is imperative for advancing Parkinson's disease (PD) research. The Canadian Open Parkinson Network (C-OPN) stands as a nationwide endeavor, connecting the PD community with ten accredited universities and movement disorders research centers spanning, at the time of this analysis, British Columbia, Alberta, Ontario, and Quebec. Our aim is to showcase C-OPN as a paradigm for bolstering national collaboration to accelerate PD research and to provide an initial overview of already collected data sets. The C-OPN database comprises de-identified data concerning demographics, symptoms and signs, treatment approaches, and standardized assessments. Additionally, it collects venous blood-derived biomaterials, such as for analyses of DNA, peripheral blood mononuclear cells (PBMC), and serum. Accessible to researchers, C-OPN resources are available through web-based data management systems for multi-center studies, including REDCap. As of November 2023, the C-OPN had enrolled 1,505 PD participants. The male-to-female ratio was 1.77:1, with 83% (n = 1098) residing in urban areas and 82% (n = 1084) having pursued post-secondary education. The average age at diagnosis was 60.2±10.3 years. Herein, our analysis of the C-OPN PD cohort encompasses environmental factors, motor and non-motor symptoms, disease management, and regional differences among provinces. As of April 2024, 32 research projects have utilized C-OPN resources. C-OPN represents a national platform promoting multidisciplinary and multisite research that focuses on PD to promote innovation, exploration of care models, and collaboration among Canadian scientists.

Boostering motor imagery processing to improve gait in patients with Parkinson disease and freezing of gait: A pilot study

BackgroundGiven that patients with Parkinson's Disease (PD) and Freezing of Gait (FoG) may lack the cognitive resources necessary to activate the motor imagery (MI) process, investigating how to boost MI vividness and accuracy could be a valuable therapeutic strategy in MI Practice (MIP). ObjectiveWe aim to evaluate the priming effect of visual, or auditory, or attentional stimuli in enhancing MI ability by using quantitative data on gait and turning performance. MethodsNineteen PD participants with FoG underwent four one-week sessions of MIP, with pre and post clinical assessments. Each session included MI alone or one of three booster MI tasks (Attentional, Action observation, or Auditory) before imagining and executing walking straight and performing a 180° turn. Gait and turning performances were evaluated using six inertial sensors before and after each session. ResultsOur findings showed that both MI and boosted MI induced similar improvement in gait (speed and stride length) and 180° (step number and velocity) and 360° turning (velocity, angle) parameters compared to baseline. When differences among “booster” tasks were analyzed, results showed that Auditory and Attentional boosted MI were superior to MI alone in some gait and turning parameters. At the end of the 4 sessions, MI ability measured by means of Kinesthetic and Visual Imagery Questionnaire and Gait Imagery Questionnaire and FoG symptoms were also improved. ConclusionOur preliminary results suggest that boosting MI is a feasible strategy for enhancing MI ability and addressing FoG symptoms. Auditory and Attentional conditions appear to enhance the priming effect of MI on gait and turning performance more effectively.

NEUROINFLAMMATION IN PARKINSON’S DISEASE: A STUDY WITH [11C]PBR28 PET AND CEREBROSPINAL FLUID MARKERS

ObjectiveTo investigate neuroinflammation in Parkinson’s disease (PD) with [11C]PBR28 positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers, and the relationship to dopaminergic functioning measured with 6-[18F]-fluoro-L-dopa ([18F]FDOPA) PET. MethodsThe clinical cohort consisted of 20 subjects with PD and 51 healthy controls (HC). All HC and 15 PD participants underwent [11C]PBR28 High Resolution Research Tomograph (HRRT) PET for the quantitative assessment of cerebral binding to the translocator protein (TSPO), a neuroinflammation marker. CSF samples were available from 17 subjects with PD and 21 HC and were examined for soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase 3-like 1 protein (YKL-40), neurogranin (NG), alpha-synuclein (aSyn) and oligo-alpha-synuclein. All subjects with PD underwent [18F]FDOPA HRRT PET. ResultsWhile the subjects with PD and HC did not differ in the total volume of distribution (VT) of [11C]PBR28 in any studied brain regions, higher levels of neuroinflammation and neurodegeneration CSF biomarkers sTREM2 and NG, respectively were associated with more severe motor symptoms evaluated by The Unified Parkinson’s Disease Rating Scale motor part (UPDRS-III) (r = 0.52, p=0.041 and r = 0.59, p=0.016 respectively). Additionally, in the PD group increased [11C]PBR28 VT in the basal ganglia and substantia nigra (SN) was related to higher levels of neuroinflammation biomarker YKL-40 (p <0.01). ConclusionAssociations between CSF biomarkers, motor disability and [11C]PBR28 VT in the striatum and SN may support a role for neuroinflammation in PD.

Efficacy and long-term effects of the intervention of Zhan Zhuang Qigong on Pisa syndrome in Parkinson's disease: the study protocol for a randomised control trial.

Pisa syndrome (PS) is a postural abnormality that frequently manifests in various neurological disorders. In recent years, the dangers associated with Parkinson's disease (PD) and PS have been increasingly acknowledged, leading to heightened research efforts directed toward the treatment of PS. Nevertheless, the underlying causes of PS remain complex, and no clinically effective treatments have been established. While several studies have demonstrated the significant effects of Qigong in treating PD, there is currently no evidence to support the efficacy of Qigong in the treatment of PS. To assess the immediate and long-term effects of Zhan Zhuang Qigong on PS in participants with PD using a rigorous randomised, parallel-control design with assignment concealment and evaluator-blinding methodologies. 60 PD participants meeting the inclusion criteria will be recruited and randomly assigned to one of two groups: conventional treatment (n=30) or Zhan Zhuang Qigong (n=30). The conventional treatment group will receive standard medications and physical therapy. The Zhan Zhuang Qigong group will receive conventional medicine plus 30 min of Zhan Zhuang Qigong practiced five times per week. The long-term effects of Qigong on PS will be evaluated after 6 months and 1 year of follow-up. Assessment tools will include the NeuroPostureApp, the B-PHY(A model of a balance testing system) balance check training system, the Unified Parkinson's Disease Rating Scale and the Parkinson's Disease Quality of Life Questionnaire, which will measure total camptocormia, upper hump degree, Pisa angles, plantar pressure distribution, motor function and quality of life in participants with PD. The local ethics committee approved this study (approval number: 2023-K068). The committee will oversee the study throughout its duration and will be notified of any protocol modifications. The results of the study will be disseminated through publication in an international journal or presentation at a conference. ChiCTR2400079696.

Parkinson's disease is characterized by vitamin B6-dependent inflammatory kynurenine pathway dysfunction.

Parkinson's disease (PD) is a complex multisystem disorder clinically characterized by motor, non-motor, and premotor manifestations. Pathologically, PD involves neuronal loss in the substantia nigra, striatal dopamine deficiency, and accumulation of intracellular inclusions containing aggregates of α-synuclein. Recent studies demonstrate that PD is associated with dysregulated metabolic flux through the kynurenine pathway (KP), in which tryptophan is converted to kynurenine (KYN), and KYN is subsequently metabolized to neuroactive compounds quinolinic acid (QA) and kynurenic acid (KA). This multicenter study used highly sensitive liquid chromatography-tandem mass-spectrometry to compare blood and cerebral spinal fluid (CSF) KP metabolites between 158 unimpaired older adults and 177 participants with PD. Results indicate that increased neuroexcitatory QA/KA ratio in both plasma and CSF of PD participants associated with peripheral and cerebral inflammation and vitamin B6 deficiency. Furthermore, increased QA tracked with CSF tau and severity of both motor and non-motor PD clinical dysfunction. Importantly, plasma and CSF kynurenine metabolites classified PD participants with a high degree of accuracy (AUC = 0.897). Finally, analysis of metabolite data revealed subgroups with distinct KP profiles, and these were subsequently found to display distinct PD clinical features. Together, these data further support the hypothesis that the KP serves as a site of brain and periphery crosstalk, integrating B-vitamin status, inflammation and metabolism to ultimately influence PD clinical manifestation.

Intravenous arachnoid granulation hypertrophy in patients with Parkinson disease

Intravenous arachnoid granulations (AGs) are protrusions of the arachnoid membrane into the venous lumen and function as contributors to the cerebrospinal fluid (CSF) flow circuit. Patients with Parkinson disease (PD) often present with accumulation of alpha synuclein. Previous works have provided evidence for neurofluid circulation dysfunction in neurodegenerative diseases associated with changes in CSF egress, which may have implications regarding AG morphology. The present study aims to investigate group differences in AG volumetrics between healthy and PD participants, as well as relationships between AG characteristics and clinical assessments. Generalized linear models revealed significant increases in AG volumetrics and number in PD compared to healthy controls. Partial Spearman-rank correlation analyses demonstrated significant relationships between AG metrics and motor and cognitive assessments. Finally, AG volumetrics were positively correlated with objective actigraphy measures of sleep dysfunction, but not self-report sleep symptoms.

Assessment of verbal memory in Parkinson's disease utilizing a virtual reality-based Rey Auditory Verbal Learning Test

The Rey Auditory Verbal Learning Test (RAVLT) is a commonly used tool for evaluating verbal learning and memory in neuropsychological assessments. In recent years, we developed a Virtual Reality (VR) adaptation of the RAVLT (VR-RVLT), aiming for increased ecological validity compared to the traditional pen and paper gold standard (GS-RAVLT). Following validation in healthy cohorts, the VR-RAVLT was validated with thirty individuals with Parkinson's Disease (PD) that completed both the GS-RAVLT and the VR- RAVLT. Validity of the VR-RAVLT was evaluated by assessing its construct and discriminant validity, and test–retest reliability, in comparison to the GS-RAVLT. Results of the PD participants were compared to those of 46 previously recruited healthy participants with comparable age and level of education. Main outcome measures derived from the remembered items on the test lists, exhibited significant and comparable correlations between VR-RAVLT and GS-RAVLT, both among healthy participants and PD participants. Likewise, serial position effects were similar for both formats amog the PD participants. Additionally, both formats showed similar discriminatory ability between healthy controls and PD participants, as well as comparable test–retest reliability measures. Taken together, the results suggest that the VR-based RAVLT is equally effective in measuring verbal memory capabilities in individuals with PD as compared to the GS-RAVLT. Certain results indicate that the virtual reality version has the capability to encompass additional factors that might impact memory performance, thereby suggesting an enhanced ecological validity.

Long-Term Dementia Risk in Parkinson Disease.

It is widely cited that dementia occurs in up to 80% of patients with Parkinson disease (PD), but studies reporting such high rates were published over two decades ago, had relatively small samples, and had other limitations. We aimed to determine long-term dementia risk in PD using data from two large, ongoing, prospective, observational studies. Participants from the Parkinson's Progression Markers Initiative (PPMI), a multisite international study, and a long-standing PD research cohort at the University of Pennsylvania (Penn), a single site study at a tertiary movement disorders center, were recruited. PPMI enrolled de novo, untreated PD participants and Penn a convenience cohort from a large clinical center. For PPMI, a cognitive battery is administered annually, and a site investigator makes a cognitive diagnosis. At Penn, a comprehensive cognitive battery is administered either annually or biennially, and a cognitive diagnosis is made by expert consensus. Interval-censored survival curves were fit for time from PD diagnosis to stable dementia diagnosis for each cohort, using cognitive diagnosis of dementia as the primary end point and Montreal Cognitive Assessment (MoCA) score <21 and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I cognition score ≥3 as secondary end points for PPMI. In addition, estimated dementia probability by PD disease duration was tabulated for each study and end point. For the PPMI cohort, 417 participants with PD (mean age 61.6 years, 65% male) were followed, with an estimated probability of dementia at year 10 disease duration of 9% (site investigator diagnosis), 15% (MoCA), or 12% (MDS-UPDRS Part I cognition). For the Penn cohort, 389 participants with PD (mean age 69.3 years, 67% male) were followed, with 184 participants (47% of cohort) eventually diagnosed with dementia. The interval-censored curve for the Penn cohort had a median time to dementia of 15 years (95% CI 13-15); the estimated probability of dementia was 27% at 10 years of disease duration, 50% at 15 years, and 74% at 20 years. Results from two large, prospective studies suggest that dementia in PD occurs less frequently, or later in the disease course, than previous research studies have reported.

Lower-Limb Exoskeletons for Gait Training in Parkinson's Disease: The State of the Art and Future Perspectives.

Gait dysfunction (GD) is a common impairment of Parkinson's disease (PD), which negatively impacts patients' quality of life. Among the most recent rehabilitation technologies, a lower-limb powered exoskeleton (LLEXO) arises as a useful instrument for gait training in several neurological conditions, including PD. However, some questions relating to methods of use, achievable results, and usefulness compared to traditional rehabilitation methodologies still require clear answers. Therefore, in this review, we aim to summarise and analyse all the studies that have applied an LLEXO to train gait in PD patients. Literature research on PubMed and Scopus retrieved five articles, comprising 46 PD participants stable on medications (age: 71.7 ± 3.7 years, 24 males, Hoehn and Yahr: 2.1 ± 0.6). Compared to traditional rehabilitation, low-profile lower-limb exoskeleton (lp-LLEXO) training brought major improvements towards walking capacity and gait speed, while there are no clear major benefits regarding the dual-task gait cost index and freezing of gait symptoms. Importantly, the results suggest that lp-LLEXO training is more beneficial for patients with an intermediate-to-severe level of disease severity (Hoehn and Yahr > 2.5). This review could provide a novel framework for implementing LLEXO in clinical practise, highlighting its benefits and limitations towards gait training.

Clinical symptoms and neuroanatomical substrates of daytime sleepiness in Parkinson’s disease

Clinical and neuroanatomical correlates of daytime sleepiness in Parkinson’s disease (PD) remain inconsistent in the literature. Two studies were conducted here. The first evaluated the interrelation between non-motor and motor symptoms, using a principal component analysis, associated with daytime sleepiness in PD. The second identified the neuroanatomical substrates associated with daytime sleepiness in PD using magnetic resonance imaging (MRI). In the first study, 77 participants with PD completed an extensive clinical, cognitive testing and a polysomnographic recording. In the second study, 29 PD participants also underwent MRI acquisition of T1-weighted images. Vertex-based cortical and subcortical surface analysis, deformation-based morphometry, and voxel-based morphometry were performed to assess the association between daytime sleepiness severity and structural brain changes in participants. In both studies, the severity of daytime sleepiness and the presence of excessive daytime sleepiness (EDS; total score >10) were measured using the Epworth Sleepiness Scale. We found that individuals with EDS had a higher score on a component including higher dosage of dopamine receptor agonists, motor symptoms severity, shorter sleep latency, and greater sleep efficiency. Moreover, increased daytime sleepiness severity was associated with a larger surface area in the right insula, contracted surfaces in the right putamen and right lateral amygdala, and a larger surface in the right posterior amygdala. Hence, daytime sleepiness in PD was associated with dopaminergic receptor agonists dosage, motor impairment, and objective sleep measures. Moreover, neuroanatomical changes in cortical and subcortical regions related to vigilance, motor, and emotional states were associated with more severe daytime sleepiness.

2327 Delirium predicts poor outcomes in Parkinson's disease

Abstract Introduction Reported delirium prevalence in inpatients with Parkinson’s disease (PD) varies widely across the literature and is often underreported. Delirium is associated with an increased risk of institutionalisation, dementia, and mortality, but to date there are no comprehensive prospective studies in PD. We aimed to determine delirium prevalence in PD compared to older adults and its associated risk with adverse outcomes. Method Participants from the ‘Defining Delirium and its Impact in Parkinson’s Disease’ (DELIRIUM-PD) and the ‘Delirium and Cognitive Impact in Dementia’ (DECIDE) studies were included. People with PD (DELIRIUM-PD) or older adults from the Cognitive Function and Ageing Study II – Newcastle cohort (DECIDE) admitted to hospitals in Newcastle were approached to take part. Delirium was assessed prospectively using the Diagnostic and Statistical Manual of Mental Disorders – 5th Edition criteria. Outcomes were determined by medical note reviews and home visits 12 months post discharge. Cox regression or binary logistic regression were used to evaluate the effect of delirium on institutionalisation, dementia, and mortality, independent of covariates. Results Delirium developed in 66.9% (n = 81/121) of PD participants compared to 38.7% (n = 77/199) of controls (p &amp;lt; 0.001). Delirium was associated with a significant increased risk of developing dementia in one year in PD (OR = 6.1 (1.3–29.5), p = 0.024) and in controls (OR = 13.4 (2.5–72.6), p = 0.003). However, in only PD participants, delirium was associated with a significantly higher risk of institutionalisation (OR = 10.7 (2.1–54.6), 0.004) and mortality (HR = 3.3 [95% CI 1.3–8.6], p = 0.014). Conclusion This is the first comprehensive prospective study of delirium in PD, showing that over two-thirds develop delirium during hospitalisation compared to a third of older adults. Delirium in PD is associated with a significant risk of dementia, institutionalisation, and death in one year. Furthermore, this is the first study to show that PD increases the risk of mortality and institutionalisation over and above a delirium in older adults.

Effects of DLPFC tDCS Followed by Treadmill Training on Dual-Task Gait and Cortical Excitability in Parkinson’s Disease: A Randomized Controlled Trial

Background Gait disturbances are exacerbated in people with Parkinson’s disease (PD) during dual-task walking (DTW). Transcranial direct current stimulation (tDCS) has been shown to exert beneficial effects on gait performance and cortical excitability in PD; however, its combined effects with treadmill training (TT) remain undetermined. Objective To investigate the effects of tDCS followed by TT on DTW performance and cortical excitability in individuals with PD. Methods Thirty-four PD participants were randomized to dorsal lateral prefrontal cortex (DLPFC) tDCS and TT group (DLPFC tDCS + TT group) or sham tDCS and TT group (sham tDCS + TT group) for 50 minutes per session (20 minutes tDCS followed by 30 minutes TT), 12 sessions within 5 weeks (2-3 sessions each week). Outcome measures included cognitive dual-task walking (CDTW), motor dual-task walking (MDTW), usual walking performance, cortical excitability, functional mobility, cognitive function, and quality of life. Results The DLPFC tDCS + TT group exerted significantly greater improvement in CDTW velocity (P = .046), cadence (P = .043), and stride time (P = .041) compared to sham tDCS + TT group. In addition, DLPFC tDCS + TT group demonstrated a significant increase in resting motor threshold of stimulated hemisphere compared with sham tDCS + TT group (P = .026). However, no significant differences between groups were found in MDTW performance and other outcomes. Conclusion Twelve-session DLPFC tDCS followed by TT significantly improved CDTW performance and decreased cortical excitability more than TT alone in individuals with PD. Applying DLPFC tDCS prior to TT could be suggested for gait rehabilitation in individuals with PD. Clinical trial registration number: Australian New Zealand Clinical Trials Registry ACTRN12622000101785

Simplification of Mobility Tests and Data Processing to Increase Applicability of Wearable Sensors as Diagnostic Tools for Parkinson's Disease.

Quantitative mobility analysis using wearable sensors, while promising as a diagnostic tool for Parkinson's disease (PD), is not commonly applied in clinical settings. Major obstacles include uncertainty regarding the best protocol for instrumented mobility testing and subsequent data processing, as well as the added workload and complexity of this multi-step process. To simplify sensor-based mobility testing in diagnosing PD, we analyzed data from 262 PD participants and 50 controls performing several motor tasks wearing a sensor on their lower back containing a triaxial accelerometer and a triaxial gyroscope. Using ensembles of heterogeneous machine learning models incorporating a range of classifiers trained on a set of sensor features, we show that our models effectively differentiate between participants with PD and controls, both for mixed-stage PD (92.6% accuracy) and a group selected for mild PD only (89.4% accuracy). Omitting algorithmic segmentation of complex mobility tasks decreased the diagnostic accuracy of our models, as did the inclusion of kinesiological features. Feature importance analysis revealed that Timed Up and Go (TUG) tasks to contribute the highest-yield predictive features, with only minor decreases in accuracy for models based on cognitive TUG as a single mobility task. Our machine learning approach facilitates major simplification of instrumented mobility testing without compromising predictive performance.

Cognitive reserve and executive functions in dual task gait performance in Parkinson’s disease

A higher level of education was correlated with less severe motor impairment in Parkinson’s Disease (PD). Nevertheless, there is limited evidence on the relationship between cognitive reserve and motor performance in complex situations in PD. To investigate the association between cognitive reserve and the dual-task gait effect in PD. Additionally, we examined the relationship between executive function, clinical and sociodemographic variables and, dual-task gait effects. We conducted a cross-sectional study with 44 PD participants. We evaluated dual-task effect on cadence, stride length, and gait velocity. Dual-task effects were correlated with neurophysiological factors, including cognitive reserve (Cognitive Reserve Index Questionnaire), overall cognitive performance of executive functions, a specific executive function domain (Trail Making Test), and the global cognitive status (Montreal Cognitive Assessment and Mini-Mental State Examination). Age, gender, and disease severity were considered as variables to be examined for correlation. We found that cognitive reserve did not influence gait performance under dual-task conditions in this sample. However, executive functions, age, and disease severity were associated with the dual-task effect on gait. The overall cognitive performance with respect to the Trail Making Test showed an inverse relationship in the dual-task gait effect on cadence. Our study’s findings have important implications for understanding the association between executive functions, age, and disease severity with the dual-task effect on gait in PD. Pre-life factors, such as education, occupation, and leisure activity, did not contribute to coping with complex gait situations in PD.

The Parkinson's Disease Composite of Executive Functioning: A Measure for Detecting Cognitive Decline in Clinical Trials.

Executive functioning is one of the first domains to be impaired in Parkinson disease (PD), and the majority of patients with PD eventually develop dementia. Thus, developing a cognitive endpoint measure specifically assessing executive functioning is critical for PD clinical trials. The objective of this study was to develop a cognitive composite measure that is sensitive to decline in executive functioning for use in PD clinical trials. We used cross-sectional and longitudinal follow-up data from PD participants enrolled in the PD Cognitive Genetics Consortium, a multicenter setting focused on PD. All PD participants with Trail Making Test, Digit Symbol, Letter-Number Sequencing, Semantic Fluency, and Phonemic Fluency neuropsychological data collected from March 2010 to February 2020 were included. Baseline executive functioning data were used to create the Parkinson's Disease Composite of Executive Functioning (PaCEF) through confirmatory factor analysis. We examined the changes in the PaCEF over time, how well baseline PaCEF predicts time to cognitive progression, and the required sample size estimates for PD clinical trials. PaCEF results were compared with the Montreal Cognitive Assessment (MoCA), individual tests forming the PaCEF, and tests of visuospatial, language, and memory functioning. A total of 841 participants (251 no cognitive impairment [NCI], 480 mild cognitive impairment [MCI], and 110 dementia) with baseline data were included, of which the mean (SD) age was 67.1 (8.9) years and 270 were women (32%). Five hundred forty five PD participants had longitudinal neuropsychological data spanning 9 years (mean [SD] 4.5 [2.2] years) and were included in analyses examining cognitive decline. A 1-factor model of executive functioning with excellent fit (comparative fit index = 0.993, Tucker-Lewis index = 0.989, and root mean square error of approximation = 0.044) was used to calculate the PaCEF. The average annual change in PaCEF ranged from 0.246 points per year for PD-NCI participants who remained cognitively unimpaired to -0.821 points per year for PD-MCI participants who progressed to dementia. For PD-MCI, baseline PaCEF, but not baseline MoCA, significantly predicted time to dementia. Sample size estimates were 69%-73% smaller for PD-NCI trials and 16%-19% smaller for PD-MCI trials when using the PaCEF rather than MoCA as the endpoint. The PaCEF is a sensitive measure of executive functioning decline in PD and will be especially beneficial for PD clinical trials.

Diffusion Tensor Imaging-Along the Perivascular-Space Index Is Associated with Disease Progression in Parkinson's Disease.

The glymphatic clearance pathway is a waste clearance system that allows for removal of soluble proteins such as amyloid β (Aβ) from the brain. Higher Aβ levels are associated with cognitive dysfunction in Parkinson's disease (PD). Diffusion tensor imaging-along the perivascular space (DTI-ALPS) is an imaging measure proposed to indirectly measure glymphatic function. Evaluate differences in DTI-ALPS-index between PD and healthy controls (HC) and characterize relationships between this proposed measure of glymphatic clearance, cognition, and disease severity in PD. PD (n = 32) and HC (n = 23) participants underwent brain imaging to assess DTI-ALPS. PD participants were classified as PD-normal cognition (PD-NC; n = 20) or PD-mild cognitive impairment (PD-MCI; n = 12) based on a Level II comprehensive cognitive assessment. A subgroup of PD participants (n = 21) returned for annual assessments for up to 4 years after baseline. Longitudinal outcomes included changes in performance on the comprehensive cognitive assessment and changes in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). PD participants had lower DTI-ALPS-index compared to HC. PD participants classified as PD-MCI had significantly lower DTI-ALPS-index compared to PD-NC. Lower DTI-ALPS-index at baseline was associated with longitudinal cognitive decline and worse longitudinal disease severity. Glymphatic clearance, as measured with DTI-ALPS, has potential to serve as a marker of longitudinal disease progression. Interventions targeting glymphatic function should be explored for potential to slow cognitive decline in PD. © 2024 International Parkinson and Movement Disorder Society.

Navigating Visual Challenges: How Parkinson's Disease Alters Cognitive Priorities in Visual Search.

Parkinson's disease (PD) hampers visual search tasks such as reading, driving, and navigation. We examined expectations from past experiences, guiding cognition and contextual priors, on visual search in PD. We compared eye movements as PD and healthy participants searched for a hidden object (target) in cluttered real-world scenes. PD participants prolonged fixation on high-probability (high-prior) locations for the target, consistent across expected and unexpected scenario. Such emphasis on contextual visual priors, evidenced by high fixation duration on high-probability areas, was beneficial when the target was at the expected location but presented challenges when the target was situated in an unlikely place. This study contributes to understanding how PD impacts visual search behavior and cognitive processing. The findings indicate that PD alters attention allocation and visual processing by affecting the utilization of contextual visual priors. It provides insights for potential interventions targeting visuo-cognitive deficits in PD patients. Published 2024. This article is a U.S. Government work and is in the public domain in the USA.