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Older individuals often face disabilities or diseases that lower their quality of life (QoL). While inpatient rehabilitation can initially enhance QoL, there is often a lack of continuation at home. Virtual coaches (VCs) as specific embodied conversational agents promise appropriate support for home rehabilitation. They emerge as complementary digital aids to ensure care continuity. This paper presents the results of implementing a full-featured VC for older patients' home rehabilitation in a multi-stage study, summarizing the main results regarding QoL outcomes and user experience tests. The study confirms the intervention as an engaging means for rehabilitation (mostly above user experience thresholds) and improvements of QoL (>10% between experimental and control groups).
Subject(s)
Home Care Services , Mentoring , Quality of Life , Humans , Aged , Male , Female , User-Computer Interface , TelerehabilitationABSTRACT
The heterogeneity of protein-rich inclusions and its significance in neurodegeneration is poorly understood. Standard patient-derived iPSC models develop inclusions neither reproducibly nor in a reasonable time frame. Here, we developed screenable iPSC "inclusionopathy" models utilizing piggyBac or targeted transgenes to rapidly induce CNS cells that express aggregation-prone proteins at brain-like levels. Inclusions and their effects on cell survival were trackable at single-inclusion resolution. Exemplar cortical neuron α-synuclein inclusionopathy models were engineered through transgenic expression of α-synuclein mutant forms or exogenous seeding with fibrils. We identified multiple inclusion classes, including neuroprotective p62-positive inclusions versus dynamic and neurotoxic lipid-rich inclusions, both identified in patient brains. Fusion events between these inclusion subtypes altered neuronal survival. Proteome-scale α-synuclein genetic- and physical-interaction screens pinpointed candidate RNA-processing and actin-cytoskeleton-modulator proteins like RhoA whose sequestration into inclusions could enhance toxicity. These tractable CNS models should prove useful in functional genomic analysis and drug development for proteinopathies.
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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder characterized by heterogeneous symptoms, which lack specific biomarkers for its diagnosis. This study aimed to investigate plasma neurofilament light chain (NfL) levels as a potential biomarker for ME/CFS and explore associations with cognitive, autonomic, and neuropathic symptoms. Here, 67 ME/CFS patients and 43 healthy controls (HCs) underwent comprehensive assessments, including neuropsychological evaluation, autonomic nervous system (ANS) testing, and plasma NfL level analysis. ME/CFS patients exhibited significantly higher plasma NfL levels compared to HC (F = 4.30, p < 0.05). Correlations were observed between NfL levels and cognitive impairment, particularly in visuospatial perception (r = -0.42; p ≤ 0.001), verbal memory (r = -0.35, p ≤ 0.005), and visual memory (r = -0.26; p < 0.05) in ME/CFS. Additionally, higher NfL levels were associated with worsened autonomic dysfunction in these patients, specifically in parasympathetic function (F = 9.48, p ≤ 0.003). In ME/CFS patients, NfL levels explained up to 17.2% of the results in cognitive tests. Unlike ME/CFS, in HC, NfL levels did not predict cognitive performance. Elevated plasma NfL levels in ME/CFS patients reflect neuroaxonal damage, contributing to cognitive dysfunction and autonomic impairment. These findings support the potential role of NfL as a biomarker for neurological dysfunction in ME/CFS. Further research is warranted to elucidate underlying mechanisms and clinical implications.
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Retinal thickness may serve as a biomarker in Parkinson's disease (PD). In this prospective longitudinal study, we aimed to determine if PD patients present accelerated thinning rate in the parafoveal ganglion cell-inner plexiform layer (pfGCIPL) and peripapillary retinal nerve fiber layer (pRNFL) compared to controls. Additionally, we evaluated the relationship between retinal neurodegeneration and clinical progression in PD. A cohort of 156 PD patients and 72 controls underwent retinal optical coherence tomography, visual, and cognitive assessments between February 2015 and December 2021 in two Spanish tertiary hospitals. The pfGCIPL thinning rate was twice as high in PD (ß [SE] = -0.58 [0.06]) than in controls (ß [SE] = -0.29 [0.06], p < 0.001). In PD, the progression pattern of pfGCIPL atrophy depended on baseline thickness, with slower thinning rates observed in PD patients with pfGCIPL below 89.8 µm. This result was validated with an external dataset from Moorfields Eye Hospital NHS Foundation Trust (AlzEye study). Slow pfGCIPL progressors, characterized by older at baseline, longer disease duration, and worse cognitive and disease stage scores, showed a threefold increase in the rate of cognitive decline (ß [SE] = -0.45 [0.19] points/year, p = 0.021) compared to faster progressors. Furthermore, temporal sector pRNFL thinning was accelerated in PD (ßtime x group [SE] = -0.67 [0.26] µm/year, p = 0.009), demonstrating a close association with cognitive score changes (ß [SE] = 0.11 [0.05], p = 0.052). This study suggests that a slower pattern of pfGCIPL tissue loss in PD is linked to more rapid cognitive decline, whereas changes in temporal pRNFL could track cognitive deterioration.
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BACKGROUND: Falls represent a critical concern in Parkinson's disease (PD), contributing to increased morbidity and reduced quality of life. PURPOSE: We conducted a systematic review to assess the prognostic factors associated with falls in PD, aiming to provide a comprehensive overview of relevant demographic and clinical parameters, and aid neurologists in identifying subsets of PD patients most susceptible to falls and associated injuries. METHODS: PubMed and Web of Science databases were searched for prospective studies assessing factors associated with falls in ambulatory PD patients across different settings, from inception to August 2023. Data extraction was conducted using CHARMS-PF checklist and risk of bias was assessed with QUIPS tool. PRISMA guidelines were followed. RESULTS: The initial search yielded 155 references. Thirty-four studies, involving a total of 3454 PD patients, were included in the final analysis. The mean pooled age was 67.6 years, and 45.1% were women. PD patients presented mild motor impairment (UPDRS III score 27.8) with mean pooled disease duration of 5.7 years. Gait and balance disorders and history of prior falls emerged as the most consistent predictors of falls across studies. Disease duration, disease severity, dysautonomic symptoms, freezing of gait, frontal cognitive functions, and PD medication dosages yielded inconsistent findings. Conversely, dyskinesias, age, sex, and depression were unrelated to future falls in PD. Logistic regression models were most commonly employed to identify factors significantly associated with falls in PD. Substantial heterogeneity prevailed in the inclusion of confounding factors. CONCLUSION: The evidence suggests that previous history of falls, gait disorders, and poor balance are robust prognostic markers for falls in PD.
Subject(s)
Gait Disorders, Neurologic , Parkinson Disease , Humans , Female , Aged , Male , Parkinson Disease/complications , Prospective Studies , Prognosis , Quality of LifeABSTRACT
BACKGROUND: Cognitive decline has been reported in premanifest and manifest Huntington's disease but reliable biomarkers are lacking. Inner retinal layer thickness seems to be a good biomarker of cognition in other neurodegenerative diseases. OBJECTIVE: To explore the relationship between optical coherence tomography-derived metrics and global cognition in Huntington's Disease. METHODS: Thirty-six patients with Huntington's disease (16 premanifest and 20 manifest) and 36 controls matched by age, sex, smoking status, and hypertension status underwent macular volumetric and peripapillary optical coherence tomography scans. Disease duration, motor status, global cognition and CAG repeats were recorded in patients. Group differences in imaging parameters and their association with clinical outcomes were analyzed using linear mixed-effect models. RESULTS: Premanifest and manifest Huntington's disease patients presented thinner retinal external limiting membrane-Bruch's membrane complex, and manifest patients had thinner temporal peripapillary retinal nerve fiber layer compared to controls. In manifest Huntington's disease, macular thickness was significantly associated with MoCA scores, inner nuclear layer showing the largest regression coefficients. This relationship was consistent after adjusting for age, sex, and education and p-value correction with False Discovery Rate. None of the retinal variables were related to Unified Huntington's Disease Rating Scale score, disease duration, or disease burden. Premanifest patients did not show a significant association between OCT-derived parameters and clinical outcomes in corrected models. CONCLUSIONS: In line with other neurodegenerative diseases, OCT is a potential biomarker of cognitive status in manifest HD. Future prospective studies are needed to evaluate OCT as a potential surrogate marker of cognitive decline in HD.
Subject(s)
Cognitive Dysfunction , Huntington Disease , Humans , Huntington Disease/complications , Huntington Disease/diagnostic imaging , Retina/diagnostic imaging , Biomarkers , Cognitive Dysfunction/etiology , Cognitive Dysfunction/complications , Tomography, Optical Coherence/methodsABSTRACT
BACKGROUND: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD). OBJECTIVE: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity. METHODS: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort fromJanuary 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL:1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8). RESULTS: Four hundred and thirty-nine PD patients (62.05±7.84 years old; 59% males) were included. MNCD stage was:stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advancedMNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p< 0.0001) and EUROHIS-QOL8 (p< 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages. CONCLUSION: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD.
Subject(s)
Parkinson Disease , Male , Humans , Middle Aged , Aged , Female , Parkinson Disease/diagnosis , Parkinson Disease/complications , Quality of Life , Activities of Daily Living , Severity of Illness Index , Patient AcuityABSTRACT
BACKGROUND: We aimed to characterize subtypes of synucleinopathies using a clustering approach based on cognitive and other nonmotor data and to explore structural and functional magnetic resonance imaging (MRI) brain differences between identified clusters. METHODS: Sixty-two patients (n = 6 E46K-SNCA, n = 8 dementia with Lewy bodies (DLB) and n = 48 idiopathic Parkinson's disease (PD)) and 37 normal controls underwent nonmotor evaluation with extensive cognitive assessment. Hierarchical cluster analysis (HCA) was performed on patients' samples based on nonmotor variables. T1, diffusion-weighted, and resting-state functional MRI data were acquired. Whole-brain comparisons were performed. RESULTS: HCA revealed two subtypes, the mild subtype (n = 29) and the severe subtype (n = 33). The mild subtype patients were slightly impaired in some nonmotor domains (fatigue, depression, olfaction, and orthostatic hypotension) with no detectable cognitive impairment; the severe subtype patients (PD patients, all DLB, and the symptomatic E46K-SNCA carriers) were severely impaired in motor and nonmotor domains with marked cognitive, visual and bradykinesia alterations. Multimodal MRI analyses suggested that the severe subtype exhibits widespread brain alterations in both structure and function, whereas the mild subtype shows relatively mild disruptions in occipital brain structure and function. CONCLUSIONS: These findings support the potential value of incorporating an extensive nonmotor evaluation to characterize specific clinical patterns and brain degeneration patterns of synucleinopathies.
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Visual hallucinations (VH) are present in up to 75% of Parkinson's disease (PD) patients. However, their neural bases and participation of the visual system in VH are not well-understood in PD. Seventy-four participants, 12 PD with VH (PDVH), 35 PD without VH (PDnoVH) and 27 controls underwent a battery of primary visual function and visual cognition tests, retinal optical coherence tomography and structural and resting-state functional brain MRI. We quantified cortical thickness with Freesurfer and functional connectivity (FC) of Visual (VIS), Fronto-Parietal (FP), Ventral Attention (VAN) and Dorsal Attention (DAN) networks with CONN toolbox. Group comparisons were performed with MANCOVA. Area Under the Curve (AUC) was computed to assess the ability of visual variables to differentiate PDVH and PDnoVH. There were no significant PDVH vs PDnoVH differences in disease duration, motor manifestations, general cognition or dopamine agonist therapy (DA) use. Compared to PDnoVH and HC, and regardless of DA use, PDVH showed significantly reduced contrast sensitivity, visuoperceptive and visuospatial abilities, increased retina photoreceptor layer thickness, reduced cortical thickness mostly in right visual associative areas, decreased between-network VIS-VAN and VAN-DAN connectivity and increased within-network DAN connectivity. The combination of clinical and imaging variables that best discriminated PDVH and PDnoVH (highest AUC), where within-network DAN FC, photoreceptor layer thickness and cube analysis test from Visual Object and Space Perception Battery (accuracy of 81.8%). Compared to PDnoVH, PDVH have specific functional and structural abnormalities within the visual system, which can be quantified non-invasively and could potentially constitute biomarkers for VH in PD.
Subject(s)
Parkinson Disease , Humans , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Hallucinations/diagnostic imaging , Hallucinations/etiology , Brain , Attention/physiology , Magnetic Resonance Imaging , BiomarkersABSTRACT
Characterizing the effect of age and sex on macular retinal layer thicknesses and foveal pit morphology is crucial to differentiating between natural and disease-related changes. We applied advanced image analysis techniques to optical coherence tomography (OCT) to: 1) enhance the spatial description of age and sex effects, and 2) create a detailed open database of normative retinal layer thickness maps and foveal pit shapes. The maculae of 444 healthy subjects (age range 21-88) were imaged with OCT. Using computational spatial data analysis, thickness maps were obtained for retinal layers and averaged into 400 (20 x 20) sectors. Additionally, the geometry of the foveal pit was radially analyzed by computing the central foveal thickness, rim height, rim radius, and mean slope. The effect of age and sex on these parameters was analyzed with multiple regression mixed-effects models. We observed that the overall age-related decrease of the total retinal thickness (TRT) (-1.1% per 10 years) was mainly driven by the ganglion cell-inner plexiform layer (GCIPL) (-2.4% per 10 years). Both TRT and GCIPL thinning patterns were homogeneous across the macula when using percentual measurements. Although the male retina was 4.1 µm thicker on average, the greatest differences were mainly present for the inner retinal layers in the inner macular ring (up to 4% higher TRT than in the central macula). There was an age-related decrease in the rim height (1.0% per 10 years) and males had a higher rim height, shorter rim radius, and steeper mean slope. Importantly, the radial analysis revealed that these changes are present and relatively uniform across angular directions. These findings demonstrate the capacity of advanced analysis of OCT images to enhance the description of the macula. This, together with the created dataset, could aid the development of more accurate diagnosis models for macular pathologies.
Subject(s)
Macula Lutea , Nerve Fibers , Male , Humans , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Child , Nerve Fibers/pathology , Retinal Ganglion Cells/pathology , Fovea Centralis/diagnostic imaging , Macula Lutea/diagnostic imaging , Macula Lutea/pathology , Tomography, Optical Coherence/methodsABSTRACT
Introduction: Telerehabilitation in neurological and cardiological diseases is an alternative rehabilitation that improves the quality of life and health conditions of patients and enhances the accessibility to health care. However, despite the reported benefits of telerehabilitation, it is necessary to study its impact on the healthcare system. Methods: The systematic review aims to investigate the costs and results of telerehabilitation in neurological and cardiological diseases. MEDLINE and EMBASE databases were searched from 2005 to 2021, for studies that assess the costs and results of telerehabilitation compared to traditional rehabilitation (center-based programs) in neurological and cardiological diseases. A narrative synthesis of results was carried out. Results: A total of 8 studies (865 participants) of 430 records were included. Three studies were related to the costs and results of telerehabilitation in neurological diseases (specifically in stroke). In total, five studies assessed telerehabilitation in cardiological diseases (chronic heart failure, coronary heart disease, acute coronary syndrome, and cardiovascular diseases). The duration of the telerehabilitation ranged from 6 to 48 weeks. The studies included cost-analysis, cost-benefit, cost-effectiveness, or cost-utility. In total, four studies found significant cost/savings per person between $565.66 and $2,352.00 (p < 0.05). In contrast, most studies found differences in costs and clinical effects between the telerehabilitation performed and the rehabilitation performed at the clinic. Just one study found quality-adjusted life years (QALY) significant differences between groups [Incremental cost-effectiveness ratio (ICER) per QALY ($-21,666.41/QALY). Discussion: Telerehabilitation is an excellent alternative to traditional center rehabilitation, which increases the accessibility to rehabilitation to more people, either due to the geographical situation of the patients or the limitations of the health systems. Telerehabilitation seems to be as clinical and cost-effective as traditional rehabilitation, even if, generally, telerehabilitation is less costly. More research is needed to evaluate health-related quality of life and cost-effectiveness in other neurological diseases. Systematic review registration: [https://figshare.com/articles/journal_ contribution/Review_Protocol_Costs_and_effects_of_Telerehabilitation_in_ Neurological_and_Cardiological_Diseases_A_Systematic_Review/19619838], identifier [19619838].
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Wilson disease (WD) is a genetic disorder of copper metabolism caused by variants in the ATP7B gene, which are inherited in an autosomal recessive pattern. Despite all the advances made on pathogenesis, cellular biology, and genetics, to date, WD remains a diagnostic and therapeutic challenge. With this series of cases, we aim to illustrate the main challenges that clinicians may encounter when dealing with patients with WD: the difficulties with clinical diagnosis, the therapeutic management of WD and the indication for advanced therapies, management during pregnancy, and genotype-phenotype correlations.
Subject(s)
Hepatolenticular Degeneration , Alleles , Copper/metabolism , Copper-Transporting ATPases/genetics , Genetic Association Studies , Hepatolenticular Degeneration/diagnosis , Hepatolenticular Degeneration/genetics , Hepatolenticular Degeneration/therapy , Humans , Mutation/geneticsABSTRACT
PURPOSE: This study aimed to determine predictors of health-related quality of life (HRQoL) in Parkinson's disease (PD) and to explore their predictive value before and after controlling overlapping items between HRQoL and clinical variables. METHODS: One hundred and eight PD patients underwent motor, anxiety, depression, apathy, fatigue, and neurocognition assessment. HRQoL was assessed by the Parkinson's Disease Questionnaire-39 (PDQ-39). In order to determine predictors of HRQoL in PD, stepwise multiple regression analyses were performed in two ways: before and after removing the emotional well-being dimension from PDQ-39 to control the overlap between depression and anxiety, and HRQoL. RESULTS: HRQoL total index was predicted by anxiety, fatigue, motor symptoms, and depression, explaining 26.9%, 7.2%, 2.8%, and 1.9% of the variance. However, after removing overlapping items, HRQoL total index was predicted by fatigue (16.5%), anxiety (6.1%), motor symptoms (3.9%), and neurocognition (2.5%), but not depression. Regarding HRQoL dimensions, mobility and activities of daily living were predicted by fatigue (19.7% and 5%) and UPDRS-III (4% and 10.2%); emotional well-being by fatigue (7.9%); social support by anxiety (12.2%) and UPDRS-III (8.6%); communication by neurocognition (5.3%) and UPDRS-III (3.4%); cognition by anxiety (10.6%) and bodily discomfort by anxiety (23%) and fatigue (4.1%). CONCLUSION: These findings showed the importance of identifying and controlling overlapping items of HRQoL and clinical measures to perform an accurate interpretation. HRQoL dimensions showed different predictors before and after controlling the overlap. Based on these results fatigue, anxiety, motor symptoms, and neurocognition, but not depression are the main predictors of HRQoL in PD patients.
Subject(s)
Apathy , Parkinson Disease , Activities of Daily Living , Fatigue/psychology , Humans , Parkinson Disease/psychology , Quality of Life/psychology , Severity of Illness Index , Surveys and QuestionnairesABSTRACT
Introduction: On March 11, 2020, the World Health Organization sounded the COVID-19 pandemic alarm. While efforts in the first few months focused on reducing the mortality of infected patients, there is increasing data on the effects of long-term infection (Post-COVID-19 condition). Among the different symptoms described after acute infection, those derived from autonomic dysfunction are especially frequent and limiting. Objective: To conduct a narrative review synthesizing current evidence of the signs and symptoms of dysautonomia in patients diagnosed with COVID-19, together with a compilation of available treatment guidelines. Results: Autonomic dysfunction associated with SARS-CoV-2 infection occurs at different temporal stages. Some of the proposed pathophysiological mechanisms include direct tissue damage, immune dysregulation, hormonal disturbances, elevated cytokine levels, and persistent low-grade infection. Acute autonomic dysfunction has a direct impact on the mortality risk, given its repercussions on the respiratory, cardiovascular, and neurological systems. Iatrogenic autonomic dysfunction is a side effect caused by the drugs used and/or admission to the intensive care unit. Finally, late dysautonomia occurs in 2.5% of patients with Post-COVID-19 condition. While orthostatic hypotension and neurally-mediated syncope should be considered, postural orthostatic tachycardia syndrome (POTS) appears to be the most common autonomic phenotype among these patients. A review of diagnostic and treatment guidelines focused on each type of dysautonomic condition was done. Conclusion: Symptoms deriving from autonomic dysfunction involvement are common in those affected by COVID-19. These symptoms have a great impact on the quality of life both in the short and medium to long term. A better understanding of the pathophysiological mechanisms of Post-COVID manifestations that affect the autonomic nervous system, and targeted therapeutic management could help reduce the sequelae of COVID-19, especially if we act in the earliest phases of the disease.
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BACKGROUND: Reliable biomarkers for Parkinson's disease (PD) diagnosis are urgently needed. Alpha-synuclein (α-syn) and its proteoforms play a key role in PD pathology but in vivo measurements have raised conflicting results, and whether α-syn in blood could distinguish PD patients from healthy controls is still controversial. METHODS: A systematic literature search yielded 35 eligible studies for meta-analysis reporting the concentration of total, oligomeric or phosphorylated α-syn in plasma and/or serum of PD patients and healthy controls. Standardized mean differences (SMD) were pooled using multivariate/multilevel linear mixed-effects models. Meta-regression analyses were conducted to investigate possible modifiers. RESULTS: A meta-analysis of 32 articles involving 2683 PD patients and 1838 controls showed a significant overall effect of PD on total α-syn levels (SMD = 0.85, p = 0.004). Meta-regression showed that increased SMD of total α-syn in PD was significantly associated with lower age, shorter disease duration, mild motor impairment, and Immunomagnetic Reduction assay for protein quantification. In contrast, no significant differences were observed for oligomeric or phosphorylated α-syn between PD and controls but increased oligomeric α-syn was significantly associated with shorter disease duration. The heterogeneity among studies was high (>98%). CONCLUSIONS: These findings suggest that increased total plasma/serum α-syn levels in PD primarily occur in early phases of the disease. The evidence obtained from a small number of studies measuring plasma/serum concentrations of oligomeric and phosphorylated species of α-syn shows no difference. The clinical applicability of measuring plasma or serum α-syn species for differentiating PD from healthy control warrants further studies with better clinical profiling of PD patients.
Subject(s)
Parkinson Disease , alpha-Synuclein , Biomarkers , Humans , Parkinson Disease/metabolism , alpha-Synuclein/metabolismABSTRACT
Heart rate variability (HRV) abnormalities are potential early biomarkers in Parkinson's disease (PD) but their relationship with central autonomic network (CAN) activity is not fully understood. We analyzed the synchronization between HRV and brain activity in 31 PD patients and 21 age-matched healthy controls using blood-oxygen-level-dependent (BOLD) signals from resting-state functional brain MRI and HRV metrics from finger plethysmography recorded for 7.40 min. We additionally quantified autonomic symptoms (SCOPA-AUT) and objective autonomic cardiovascular parameters (blood pressure and heart rate) during deep breathing, Valsalva, and head-up tilt, which were used to classify the clinical severity of dysautonomia. We evaluated HRV and BOLD signals synchronization (HRV-BOLD-sync) with Pearson lagged cross-correlations and Fisher's statistics for combining window-length-dependent HRV-BOLD-Sync Maps and assessed their association with clinical dysautonomia. HRV-BOLD-sync was lower significantly in PD than in controls in various brain regions within CAN or in networks involved in autonomic modulation. Moreover, heart-brain synchronization index (HBSI), which quantifies heart-brain synchronization at a single-subject level, showed an inverse exposure-response relationship with dysautonomia severity, finding the lowest HBSI in patients with severe dysautonomia, followed by moderate, mild, and, lastly, controls. Importantly, HBSI was associated in PD, but not in controls, with Valsalva pressure recovery time (sympathetic), deep breathing E/I ratio (cardiovagal), and SCOPA-AUT. Our findings support the existence of heart-brain de-synchronization in PD with an impact on clinically relevant autonomic outcomes.
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BACKGROUND: Visual impairment is frequent and highly disabling in Parkinson's disease (PD); however, few studies have comprehensively evaluated its impact on vision-related quality of life. OBJECTIVE: To evaluate the relationship between visual function tests and the visual impairment perceived by PD patients in daily living activities. METHODS: We cross-sectionally evaluated 62 PD patients and 33 healthy controls (HC). Visual disability was measured with a comprehensive battery of primary visual function and visual cognition tests (visual outcomes), and vision-related quality of life was evaluated with the National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25). The relationship between visual outcomes and NEI VFQ-25 sub-scores was analyzed with Pearson's correlations and stepwise linear regression. RESULTS: In PD patients, and not in HC, most NEI VFQ-25 sub-scores were significantly correlated with Cube Analysis and Dot Counting from Visual Object and Space Perception (VOSP) battery (visual perception), Clock Drawing Test (visuoconstructive capacity) and Trail Making Test part-A (visual attention and processing speed) and to a lesser extent with high- and low-contrast visual acuity. Dot Counting (VOSP) was the test primarily associated with most NEI VFQ-25 sub-scores (5 out of 12). Roth-28 color test was the one that best explained the variance of Peripheral Vision (R2: 0.21) and Role Difficulties (R2: 0.36) sub-scores of NEI VFQ-25, while photopic contrast sensitivity explained 41% of Driving sub-score variance. CONCLUSION: Vision-related quality of life in PD is mainly influenced by alterations in visual perception, visuoconstructive capacity and visual attention and processing speed. Future studies are warranted to confirm and further extend our findings.
Subject(s)
Parkinson Disease , Quality of Life , Humans , Parkinson Disease/complications , Sickness Impact Profile , Surveys and Questionnaires , Vision Disorders/etiology , Visual AcuityABSTRACT
INTRODUCTION: Blood and cerebrospinal fluid represent emerging candidate fluids for biomarker identification in Parkinson's disease (PD). METHODS: We studied 8 individuals carrying the E46K-SNCA mutation (3 PD dementia (PDD), 1 tremor-dominant PD, 2 young rigid-akinetic PD and 2 asymptomatic) and 8 age- and sex-matched healthy controls. We quantified the levels of total alpha-synuclein (a-syn), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), Tau and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) with SiMoA (Quanterix) in cerebrospinal fluid (CSF) of mutation carriers and in serum of all participants. The correlation between the concentration of biofluid markers and clinical outcomes was evaluated. RESULTS: Although based on a small number of cases, CSF a-syn was decreased in symptomatic E46K-SNCA carriers compared to the asymptomatic ones. Asymptomatic carriers exhibited similar serum biomarker levels as compared to matched controls, except for serum a-syn, which was higher in asymptomatic individuals. Carriers with PDD diagnosis displayed increased levels of serum NfL and GFAP compared to matched controls. These findings highly correlated with cognitive and motor status of E46K-SNCA carriers, but not with disease duration. CONCLUSIONS: Patients with familial forms of neurodegenerative disease exhibit variable penetrance of the phenotype and are exceptionally valuable for delineating biomarkers. Serum and CSF molecular biomarkers in E46K-SNCA mutation carriers show that a-syn might be suitable to track the conversion from asymptomatic to PD, whereas NfL and GFAP might serve to foresee the progression to PD dementia. These findings should be interpreted with caution and need to be replicated in other genetic synucleinopathy cohorts.
Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Parkinson Disease , alpha-Synuclein , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Humans , Mutation , Neurodegenerative Diseases/blood , Neurodegenerative Diseases/cerebrospinal fluid , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/genetics , Parkinson Disease/blood , Parkinson Disease/cerebrospinal fluid , Parkinson Disease/diagnosis , Parkinson Disease/genetics , alpha-Synuclein/blood , alpha-Synuclein/cerebrospinal fluidABSTRACT
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. In this study, the tear proteome profile of patients with idiopathic PD (iPD, n = 24), carriers of the E46K-SNCA mutation (n = 3) and healthy control (CT, n = 27) subjects was analyzed to identify candidate biomarkers for the diagnosis of PD. An observational, prospective and case-control pilot study was carried out, analyzing the participants tear samples by nano-liquid chromatography-mass spectrometry (nLC-MS/MS) and assessing their neurological impairment. The proteomic data obtained are available at ProteomeXchange with identifier 10.6019/PXD028811. These analyses led to the identification of 560 tear proteins, some of which were deregulated in PD patients and that have been implicated in immune responses, inflammation, apoptosis, collagen degradation, protein synthesis, defense, lipid transport and altered lysosomal function. Of these proteins, six were related to neurodegenerative processes and showed a good capacity to classify patients and controls. These findings revealed that certain proteins were upregulated in the tears of PD patients, mainly proteins involved in lysosomal function. Thus, in this study, tear proteins were identified that are implicated in neurodegeneration and that may be related to an aggressive disease phenotype in PD patients.