Cognitive Reserve in Early Manifest Huntington Disease Patients: Leisure Time Is Associated with Lower Cognitive and Functional Impairment

We focused on Cognitive Reserve (CR) in patients with early Huntington Disease (HD) and investigated whether clinical outcomes might be influenced by lifetime intellectual enrichment over time. CR was evaluated by means of the Cognitive Reserve Index questionnaire (CRIq), an internationally validated scale which includes three sections: education, working activity, and leisure time. The clinical HD variables were quantified at three different time points (baseline-t0, 1 year follow up-t1 and 2 years follow up-t2) as per the Unified Huntington’s Disease Rating Scale (UHDRS), an internationally standardized and validated scale including motor, cognitive, functional and behavioral assays. Our sample consisted of 75 early manifest patients, withclinical stage scored according to the Total Functional Capacity (TFC) scale. Our correlational analysis highlighted a significant inverse association between CRIq leisure time (CRIq_LA) and longitudinal functional impairment (namely, the differential TFC score between t2 and t0 or ΔTFC) (p < 0.05), and the multidimensional progression of HD as measured by the composite UHDRS (cUHDRS, p < 0.01). CRIq_LA was significantly and positively associated with better cognitive performances at all time points (p < 0.05). Our results suggest that higher is the CRIq_LA, milder is the progression of HD in terms of functional, multidimensional and cognitive outcome.

Remote Evaluation of Parkinson's Disease Using a Conventional Webcam and Artificial Intelligence

Objective: This study aimed to prove the concept of a new optical video-based system to measure Parkinson's disease (PD) remotely using an accessible standard webcam.Methods: We consecutively enrolled a cohort of 42 patients with PD and healthy subjects (HSs). The participants were recorded performing MDS-UPDRS III bradykinesia upper limb tasks with a computer webcam. The video frames were processed using the artificial intelligence algorithms tracking the movements of the hands. The video extracted features were correlated with clinical rating using the Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale and inertial measurement units (IMUs). The developed classifiers were validated on an independent dataset.Results: We found significant differences in the motor performance of the patients with PD and HSs in all the bradykinesia upper limb motor tasks. The best performing classifiers were unilateral finger tapping and hand movement speed. The model correlated both with the IMUs for quantitative assessment of motor function and the clinical scales, hence demonstrating concurrent validity with the existing methods.Conclusions: We present here the proof-of-concept of a novel webcam-based technology to remotely detect the parkinsonian features using artificial intelligence. This method has preliminarily achieved a very high diagnostic accuracy and could be easily expanded to other disease manifestations to support PD management.

Factors predicting fear of falling avoidance behavior in parkinsonisms

BACKGROUND: Fear of falling avoidance behavior (FFAB) is common in parkinsonisms and results in potentially mitigable downstream consequences. OBJECTIVE: Determine the characteristics of individuals with parkinsonisms most associated with FFAB. METHODS: A retrospective, cross-sectional study was conducted from medical records data of 142 patients with parkinsonisms. These data included: demographics (age, sex), disease severity (Movement Disorders Society –Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III), years since diagnosis), fall history (number of fall injuries in previous year), and gait and balance function (five times sit to stand, MiniBESTest, Timed Up and Go (TUG), dual-task TUG, ten-meter walk test (10MWT), observed freezing of gait (FOG) (MDS-UPDRS III item 11)). RESULTS: 10MWT (p < .001) and MDS-UPDRS III item 11 (p < .014) were significantly associated with FFAB above and beyond disease severity, which also contributed significantly to the overall model (ps < .046). Fall history was not associated with FFAB. CONCLUSION: Our findings suggest that the largest portion of variability in FFAB is explained by gait velocity and FOG; however, disease severity also explains a significant portion of the variability of FFAB. Further investigation into factors predictive of FFAB and mitigation of downstream consequences, using more robust designs, is warranted.

Diplopia Is Frequent and Associated with Motor and Non-Motor Severity in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up

Background and objective: Diplopia is relatively common in Parkinson’s disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it. Patients and Methods: PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as “with diplopia” or “without diplopia” according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls. Results: The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269–4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012–1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson’s Disease Rating Scale–III (OR = 1.039; 95%CI, 1.023–1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001–1.057; p = 0.049) scores were independent factors associated with diplopia (R2 = 0.25; Hosmer and Lemeshow test, p = 0.716). Conclusions: Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity.

Effect of Probiotics on Parkinson's Disease Rating, Selected Gastrointestinal Measurements and Oxidative Stress Parameters in Parkinson’s Disease: A Systematic Review of Randomized Controlled Trials

Introduction: Parkinson's disease is the world's second most prevalent neurological disease. In Parkinson’s disease intracytoplasmic neuronal inclusions are observed in enteric neurons in the gastrointestinal tract, and the composition of the intestinal microbiome is altered. These changes correlate with the motor phenotype. A systematic review was conducted to determine the effect of probiotics with individuals with Parkinson’s disease. Methods: Scopus, PubMed, Web of Science, The Cochrane Library, Science Direct and OVID-LWW were searched until April 2021 and total 27.395 records were reached according to inclusion and exclusion criteria with the following outcomes: Parkinson's disease rating; oxidative stress, and gastrointestinal system markers. Data searches, article selection and data extraction assessments were performed according to the PRISMA guidelines. The Jadad scale was used to rate the evidence's quality. Results: The information gathered from 5 randomized controlled trials involving 350 individuals with Parkinson’s disease receiving probiotic supplements. Parkinson’s disease rating and non-motor symptoms test were performed. Oxidative stress (Glutathione, malondialdehyde) and gastrointestinal system symptoms (bowel opening frequency, gut transit time, complete bowel movement, spontaneous bowel movements) were evaulated for 4-12 weeks of usage. Conclusion: While all high-quality studies demonstrate progress, there is currently insufficient data to recommend the use of probiotics for people with Parkinson's disease in clinical practice.

Mild Parkinsonian Signs Are Related to Lower Cortico-Striatal Connectivity in Executive Networks

Mild Parkinsonian signs (MPS) affect up to 24% of community-dwelling older adults. We hypothesize that MPS are associated with Parkinson’s-like alterations of functional connectivity (FC) in sensorimotor, executive, and reward cortico-striatal networks. Participants (N=266; mean age=83; 57% female) without Parkinson’s completed resting-state fMRI and Unified Parkinsonian Disease Rating Scale (UPDRS). FC between striatum and cortex was measured within each network. Logistic regression tested associations of each network’s FC with MPS (UPDRS&gt;0), adjusted for MPS risk factors, then including white matter hyperintensities (WMH). MPS was associated with lower cortical-striatal FC in the left executive cortico-striatal network (OR [95%CI]: 0.188 [0.043,0.824]). Association survived adjusting for risk factors (0.162 [0.030,0.874]) but was attenuated after including WMH (0.209 [0.036, 1.200]). In stratified analyses, left executive cortico-striatal FC was associated with MPS only for those with higher WMH (0.077 [0.010,0.599]). Future work should examine whether higher FC protects against the influence of WMH on MPS.

Progression of Self-Perceived Speech and Swallowing Impairment in Early Stage Parkinson's Disease: Longitudinal Analysis of the Unified Parkinson's Disease Rating Scale

Purpose: The purpose of this study was to investigate the presence and progression of self-perceived speech and swallowing impairments in newly diagnosed people with Parkinson's disease (PD) longitudinally across 6 years. Method: Longitudinal data from the Parkinson's Progression Markers Initiative were analyzed across six consecutive years in a cohort of 269 newly diagnosed people with PD, and a subset of those ( n = 211) who were assessed at every time point across the 6 years. Dependent variables included self-perceived ratings of speech and swallowing impairment severity from the Unified Parkinson's Disease Rating Scale. Patient-centered factors of age at diagnosis and motor phenotype were also assessed to determine if they were related to the change in self-perceived speech and swallowing impairments. Results: Overall, self-perceived speech and swallowing impairments were present in newly diagnosed people with PD, although over time, the degree of severity for both remained in the mild range. However, the rate of change over time was significant for perceived speech impairment, F (5.5, 1158.8) = 21.1, p < .001), and perceived swallowing impairment, F (5.2, 1082.6) = 8.6, p < .001. Changes for speech and swallowing impairment were both in the direction of progressive severity. There were no effects of age at diagnosis or motor phenotype on the degree of change for either speech or swallowing. Conclusions: Self-perceptions of speech and swallowing impairment changed significantly over time in newly diagnosed people with PD (PWPD). Consistent with existing literature, self-perceptions of speech impairment were rated as more severe than those of swallowing impairment. These findings reveal that even in the early years postdiagnoses, PWPD are experiencing changes to speech and swallowing function, albeit within the mildly severe range. The presence of self-perceived mild speech and swallowing impairments in the initial years postdiagnosis may support the need for intervention to improve and or sustain function over time.

Energy Decline May Predict Mild Parkinsonian Signs in Community-Dwelling Older Adults

Mild Parkinsonian Signs (MPS) are common in older adults without overt neurological disease. MPS are often progressive and predict disability and dementia, yet little is known about predictors for MPS. Low self-reported energy is associated with mobility impairment, which is a hallmark of MPS. Yet whether self-reported energy relates to MPS is unknown. We explored the association of changes in self-reported energy with MPS in 293 participants (aged 83 ± 2.8 years, 58% women, 61% White) free of dementia and Parkinson’s Disease in the Health, Aging and Body Composition Study. Self-reported energy was assessed on a 0-10 scale annually between Year 2 and Year 10 (mean follow-up: 8 years) and its slope was estimated via linear mixed effects models. MPS were evaluated at Year 10 based on the Unified Parkinson Disease Rating Scale motor component. On average, self-reported energy declined 0.06 points per year. In a linear regression model adjusted for age, fatigue, and comorbidities, those with MPS had steeper SEL decline (β [Standard Error] = -0.358 [0.119]) in the prior eight years than those without MPS. Thus, declining self-reported energy may be a risk factor for MPS. Self-reported energy is easily evaluated in routine clinic visits, and may be a modifiable risk factor that can be targeted to reduce the incidence of MPS.

The Association of Olfactory Dysfunction With Depression, Cognition, and Disease Severity in Parkinson's Disease

Background: Non-motor subtypes of Parkinson's disease (PD) include the limbic, cognitive, and brainstem phenotype, which may have different pathological pathways with olfaction. In this work, we aim to clarify the association between olfactory dysfunction, depression, cognition, and disease severity in PD.Methods: A total of 105 PD subjects were included and divided into anosmia and non-anosmic groups, using the University of Pennsylvania Smell Identification Test (UPSIT). All patients were evaluated with the movement disorder society unified Parkinson's disease rating scale (MDS-UPDRS), the Beck depression inventory (BDI)-II, and the Montreal cognitive assessment (MoCA).Results: The BDI-II and UPSIT scores had a trend of reverse correlation without statistical significance (β-coefficient −0.12, p = 0.232). However, the odds ratio (OR) in anosmia was 2.74 (95% CI 1.01–7.46) for depression and 2.58 (95% CI 1.06–6.29) for cognitive impairment. For the MDS-UPDRS total and Part 3 score, the anosmia had a β-coefficient of 12.26 (95% CI 5.69–18.82) and 8.07 (95% CI 3.46–12.67), respectively. Neither depression nor cognitive impairment is associated with motor symptoms.Conclusion: More severe olfactory dysfunction in PD is associated with cognitive impairment and greater disease severity. Depression in PD may involve complex pathways, causing relatively weak association with olfactory dysfunction.

Automated Assessment of the Substantia Nigra Pars Compacta in Parkinson’s Disease: A Diffusion Tensor Imaging Study

The substantia nigra (SN) pars compacta (SNpc) and pars reticulata (SNpr) are differentially affected in Parkinson’s disease (PD). Separating the SNpc and SNpr is challenging with standard magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) allows for the characterization of SN microstructure in a non-invasive manner. In this study, 29 PD patients and 28 healthy controls (HCs) were imaged with 1.5T MRI for DTI. Images were nonlinearly registered to standard space and SNpc and SNpr DTI parameters were measured. ANCOVA and receiver operator characteristic (ROC) analyses were performed. Clinical associations were assessed with Spearman correlations. Multiple corrections were controlled for false discovery rate. PD patients presented with significantly increased SNpc axial diffusivity (AD) (1.207 ± 0.068 versus 1.156 ± 0.045, p = 0.024), with ROC analysis yielding an under the curve of 0.736. Trends with Unified Parkinson’s Disease Rating Scale (UPDRS) III scores were identified for SNpc MD (rs = 0.449), AD (rs = 0.388), and radial diffusivity (rs = 0.391) (all p < 0.1). A trend between baseline SNpr MD and H&Y change (rs = 0.563, p = 0.081) over 2.9 years of follow-up was identified (n = 14). In conclusion, SN microstructure shows robust, clinically meaningful associations in PD.