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INTRODUCTION: Parkinson's disease represents a burdensome condition with complex manifestations. A licensed, standardized paper-based questionnaire is completed by both patients and physicians to monitor the progression and state of the disease. However, integrating the obtained scores into digital systems still poses a challenge. METHODS: Paper-based handwriting is intuitive and an efficient mode of human-computer interaction. Accordingly, we transformed a consumer-grade tablet into a device where an exact digital copy of the disease-specific questionnaire can be filled with the supplied pen. Utilizing a small convolutional neural network directly on the device and trained on MNIST data, we translated the handwritten digits to appropriate LOINC codes and made them accessible through a FHIR-compatible HTTP interface. RESULTS: When evaluating the usability from a patient-centric point of view, the System Usability Score revealed an excellent rating (SUS = 83.01) from the participants. However, we identified some challenges associated with the magnetic pen and the flat design of the device. CONCLUSION: In setups where certified medical devices are not required, consumer hardware can be used to map handwritten digits of patients to appropriate medical standards without manual intervention through healthcare professionals.

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Patients with advanced Parkinson's disease often suffer from severe gait and balance problems, impacting quality of live and persisting despite optimization of standard therapies. The aim of this review was to systematically review the efficacy of STN-DBS programming techniques in alleviating gait disturbances in patients with advanced PD. Searches were conducted in PubMed, Embase, and Lilacs databases, covering studies published until May 2024. The review identified 36 articles that explored five distinct STN-DBS techniques aimed at addressing gait and postural instability in Parkinson's patients: low-frequency stimulation, ventral STN stimulation for simultaneous substantia nigra activation, interleaving, asymmetric stimulation and a short pulse width study. Among these, 21 articles were included in the meta-analysis, which revealed significant heterogeneity among studies. Notably, low-frequency STN-DBS demonstrated positive outcomes in total UPDRS-III score and FOG-Q, especially when combined with dopaminergic therapy. The most favorable results were found for low-frequency STN stimulation. The descriptive analysis suggests that unconventional stimulation approaches may be viable for gait problems in patients who do not respond to standard therapies.

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Coronavirus disease 2019 (COVID-19) has been associated with a variety of neurological manifestations (i.e., anosmia, ageusia, myalgia, headache) and neurological syndromes (i.e., encephalopathy, ischemic and hemorrhagic stroke, myelitis, encephalitis) underlying different pathogenetic mechanisms. COVID-19 has also been associated with various movement disorders including acute or subacute parkinsonism. However, to date, only few cases of parkinsonism linked to COVID-19 have been reported, nevertheless raising the possibility of a post-viral parkinsonian syndrome. Furthermore, various studies in vitro and in animal models have highlighted a close relationship between SARS-CoV-2 virus and α-synuclein, leading to the hypothesis that COVID-19 could represent a factor favoring the long-term development of α-synucleopathies. In this chapter, we will discuss the pathophysiological mechanisms related to movement disorders' manifestations of COVID-19 focusing on the possible overlap between pathogenetic mechanisms of Parkinson's Disease and COVID-19.

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MR-guided focused ultrasound (MRgFUS) has proven its efficacy and safety for the treatment of essential tremor (ET) and/or Parkinson's disease (PD). However, having a cardiac pacemaker has been considered an exclusion criterion for the use of MRgFUS. Only 2 patients with a cardiac pacemaker treated with MRgFUS have been previously reported, both treated using 1.5-T MRI. In this paper, the authors present their experience performing 3-T MRgFUS thalamotomy in 4 patients with an implanted cardiac pacemaker. Treatments were uneventful regarding complications or severe side effects. MRgFUS using 3-T MRI was found to be an efficient and safe treatment for ET and/or PD in patients with an MRI-compatible pacemaker.

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We have read with a great deal of interest the article by Hwang et al. (1) and appreciate the authors'' commendable efforts. The article was intelligently written and provides a significant insight into the study carried out by the authors. We greatly acknowledge the brief concepts the authors have shared regarding Parkinson's disease and epilepsy, which are without doubt an asset to the field of neurology. The study has laid a good foundation for future related studies. The article mentions epilepsy as an uncommon comorbidity of Parkinson's disease and the transition of a non-epilepsy brain to an epilepsy brain. It is also mentioned that PD is a progressive neurodegenerative disorder of dopaminergic neurons in the substantia nigra, and the incidence of the two diseases. However, as we assess the article in depth, we have found some shortcomings that would have enhanced the sense and purpose of the study.

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INTRODUCTION: Parkinson's disease (PD) is a progressive neurological condition resulting from the degeneration of dopaminergic neurons in the substantia nigra. Impaired manual dexterity and cognitive impairment are common symptoms and are often associated with recurrent adverse events in this population. OBJECTIVE: To verify the association between cognitive performance and manual dexterity in people with PD. METHODS: This is a cross-sectional observational study, with 29 participants, who underwent cognitive and manual dexterity assessments, and the following tools were used: Trail Making Test, box and block test (BBT), Learning Test of Rey and Nine Hole Peg Test. Descriptive statistics for clinical and demographic data were performed using mean and standard deviation, and data normality was assessed using the Shapiro-Wilk test. Spearman's nonparametric test was used to determine the correlation between variables. RESULTS: Our findings revealed significant associations between cognitive performance and manual dexterity. The nine-hole peg test positively correlated with TMT-Part A and Part B, establishing a relationship between manual dexterity and cognitive functions such as attention and mental flexibility. On the other hand, BBT showed an inverse relationship with TMT-Part B, indicating that longer time on this task was associated with lower manual dexterity. CONCLUSION: Fine manual dexterity had a significant correlation with visual search skills and motor speed, while gross motor dexterity had a negative correlation with cognitive skills. No significant results were demonstrated regarding the interaction between manual dexterity and memory.

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BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by dopaminergic neuron degeneration and diverse motor and nonmotor symptoms. Early diagnosis and intervention are crucial but challenging due to reliance on clinical presentation. Recent research suggests potential biomarkers for early detection, including plasma netrin-1 (NTN-1), a protein implicated in neuronal survival. METHODS: This cross-sectional study recruited 105 PD patients and 65 healthy controls, assessing plasma NTN-1 levels and correlating them with clinical characteristics. Statistical analyses explored associations between NTN-1 levels and PD symptoms, considering demographic factors. RESULTS: PD patients exhibited significantly lower plasma NTN-1 levels compared to controls. NTN-1 demonstrated moderate potential as a PD biomarker. Positive correlations were found between NTN-1 levels and motor, depression, and cognitive symptoms. Multiple regression analysis revealed disease duration and NTN-1 levels as key factors influencing symptom severity. Gender also impacted symptom scores. CONCLUSION: Reduced plasma NTN-1 levels correlate with PD severity, suggesting its potential as a biomarker. However, further research is needed to elucidate the roles of NTN-1 in PD pathophysiology and validate its diagnostic and therapeutic implications. Understanding the involvement of NTN-1 may lead to personalized management strategies for PD.

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Orthostatic hypotension (OH) is the most common manifestation of cardiovascular autonomic dysfunction in Parkinson's disease. In this viewpoint, we discuss five practical questions regarding OH in Parkinson's disease: 1) How common is the problem? 2) Why should people with Parkinson's disease and providers care about OH? 3) What are the symptoms of OH? 4) How to confirm a diagnosis of OH? And 5) How to treat OH? OH is an important non-motor symptom of Parkinson's disease for which we have available treatments to significantly mitigate morbidity and possibly positively impact the disease course.

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Background: Measurement of freezing of gait (FOG) relies on the sensitivity and reliability of tasks to provoke FOG. It is currently unclear which tasks provide the best outcomes and how medication state plays into this. Objective: To establish the sensitivity and test-retest reliability of various FOG-provoking tasks for presence and severity of FOG, with (ON) and without (OFF) dopaminergic medication. Methods: FOG-presence and percentage time frozen (% TF) were derived from video annotations of a home-based FOG-provoking protocol performed in OFF and ON. This included: the four meter walk (4MW), Timed Up and Go (TUG) single (ST) and dual task (DT), 360° turns in ST and DT, a doorway condition, and a personalized condition. Sensitivity was tested at baseline in 63 definite freezers. Test-retest reliability was evaluated over 5 weeks in 26 freezers. Results: Sensitivity and test-retest reliability were highest for 360° turns and higher in OFF than ON. Test-retest intra-class correlation coefficients of % TF varied between 0.63-0.90 in OFF and 0.18-0.87 in ON, and minimal detectable changes (MDCs) were high. The optimal protocol included TUG ST, 360° turns ST, 360° turns DT and a doorway condition, provoking FOG in all freezers in OFF and 91.9% in ON and this could be done reliably in 95.8% (OFF) and 84.0% (ON) of the sample. Combining OFF and ON further improved outcomes. Conclusions: The highest sensitivity and reliability was achieved with a multi-trigger protocol performed in OFF + ON. However, the high MDCs for % TF underscore the need for further optimization of FOG measurement.

Freezing of gait is a very burdensome and episodic symptom in Parkinson's disease that is difficult to measure. Measurement of freezing is needed to determine whether someone has freezing and how severe this is, and relies on observation during a freezing-triggering protocol. However, it is unclear what protocol is sufficiently sensitive to trigger freezing in many freezers, and whether freezing can be triggered reliably at different timepoints. Here, we investigated 1) which tasks can trigger freezing-presence and freezing-severity sensitively and reliably, 2) how medication state influences this, and 3) what task combination was most reliable. Sixty-three patients with daily freezing performed several freezing-triggering tasks in their homes, both with (ON) and without (OFF) anti-Parkinsonian medication. In twenty-six patients, the measurement was repeated 5 weeks later to determine test-retest reliability. First, we found that performing 360° turns in place with a cognitive dual task was the most sensitive and reliable task to trigger FOG. Second, sensitivity and reliability were better in OFF than in ON. Third, the most reliable protocol included: the Timed-Up and Go, 360° turns in place with and without the dual task, and a doorway condition. This protocol triggered freezing in all patients in OFF and 91.9% in ON and did so reliably in 95.8% (OFF) and 84.0% (ON) of the sample. We recommend to measure freezing with this protocol in OFF + ON, which further improved reliability. However, the measurement error for freezing-severity was high, even for this optimal protocol, underscoring the need for further optimization of freezing measurement.

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INTRODUCTION: Dysgraphia, a recognized PD motor symptom, lacks effective clinical assessment. Current evaluation relies on motor assessment scales. Computational methods introduced over the past decade offer an objective dysgraphia assessment, considering size, duration, speed, and handwriting fluency. Objective evaluation of dysgraphia may be of help for early diagnosis of PD. OBJECTIVE: Computerized assessment of dysgraphia in de novo PD patients and its correlation with clinical scales. METHODS: We evaluated 38 recently diagnosed, premedication PD patients and age-matched controls without neurological disorders. Participants wrote "La casa de Pamplona es bonita" three times on paper and once on a Wacom tablet under the paper, totaling four phrases. Writing segments of 5-10 s were analyzed. The Wacom tablet captured kinematic data, including mean velocity, mean acceleration, and pen pressure. Data were saved in.svc format and analyzed using specialized software developed by Tecnocampus Mataró. Standard clinical practice data, Hoehn & Yahr staging, and UPDRS scales were used for evaluation. RESULTS: Significant kinematic differences existed; patients had lower mean speed (27 ± 12 vs. 48 ± 18, p < 0.0001) and mean acceleration (7.2 ± 3.9 vs. 15.01 ± 7, p < 0.0001) than controls. Mean speed and mean acceleration correlated significantly with UPDRS III scores (speed: r = -0.52, p < 0.0007; acceleration: r = 0.60, p < 0.0001), indicating kinematic parameters' potential in PD evaluation. CONCLUSIONS: Dysgraphia is identifiable in PD patients, even de novo, indicating an early symptom and correlates with clinical scales, offering potential for objective PD patient evaluation.

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Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor and non-motor symptoms including cognitive impairment and dementia. The etiopathogenesis of PD, as well as its protective and susceptibility factors, are still elusive. 3-Hydroxy-3-methyglutaryl coenzyme A reductase (HMGCR) is an enzyme regulating cholesterol synthesis. Single-nucleotide polymorphisms (SNPs) in the gene coding HMGCR have recently been correlated with the risk of Alzheimer's disease. Alternative splicing of exon 13 of the HMGCR transcript and its strongly associated HMGCR haplotype 7 (H7: rs17244841, rs3846662, rs17238540) may downregulate protein activity and cholesterol synthesis, with lower low-density lipoprotein cholesterol (LDL) levels associated with PD that may affect cognitive abilities. We genotyped three SNPs in the H7 HMGCR gene in 306 PD patients divided into three groups-without cognitive decline, with mild cognitive impairment (MCI), and with PD dementia-and in 242 healthy participants. A correlation between the rs17238540 genotype and PD susceptibility as well as a minor association between rs3846662 and cognitive status in PD patients was observed; however, the two-sided analysis of these groups did not reveal any significance. We observed a statistically significant elevated high-density lipoprotein cholesterol (HDL) plasma level in the minor allele carriers of rs17238540 and rs17244841 among PD patients. This study should be replicated in a larger population.

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BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

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The ability to use past learned experiences to guide decisions is an important component of adaptive behavior, especially when decision-making is performed under time pressure or when perceptual information is unreliable. Previous studies using visual discrimination tasks have shown that this prior-informed decision-making ability is impaired in Parkinson's disease (PD), but the mechanisms underlying this deficit and the precise impact of dopaminergic denervation within cortico-basal circuits remain unclear. To shed light on this problem, we evaluated prior-informed decision-making under various conditions of perceptual uncertainty in a sample of 13 clinically established early PD patients, and compared behavioral performance with healthy control (HC) subjects matched in age, sex and education. PD patients and HC subjects performed a random dot motion task in which they had to decide the net direction (leftward vs. rightward) of a field of moving dots and communicate their choices through manual button presses. We manipulated prior knowledge by modulating the probability of occurrence of leftward vs. rightward motion stimuli between blocks of trials, and by explicitly giving these probabilities to subjects at the beginning of each block. We further manipulated stimulus discriminability by varying the proportion of dots moving coherently in the signal direction and speed-accuracy instructions. PD patients used choice probabilities to guide perceptual decisions in both speed and accuracy conditions, and their performance did not significantly differ from that of HC subjects. An additional analysis of the data with the diffusion decision model confirmed this conclusion. These results suggest that the impaired use of priors during visual discrimination observed at more advanced stages of PD is independent of dopaminergic denervation, though additional studies with larger sample sizes are needed to more firmly establish this conclusion.

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BACKGROUND: Multimorbidity is common in elderly people, and one of the major consequences of multimorbidity is low health-related quality of life (HRQoL). The aim of this study was to investigate the frequency of comorbid diseases in patients with Parkinson's disease (PD) and to analyze their relative importance in HRQoL. The aim was also to examine agreement between the generic 15D questionnaire and the PD-specific Parkinson's Disease Questionnaire (PDQ-8) to further validate 15D in the evaluation of HRQoL in patients with PD. METHODS: Patients with PD (N = 551) filled a questionnaire on comorbid diseases, and the 15D questionnaire yielding a 15-dimensional health profile and a score representing the overall HRQoL. Self-organizing map was used for an unsupervised pattern recognition of the health profiles. Relative importance analysis was used to evaluate the contribution of 16 comorbid diseases to the 15D score. The agreement between 15D and PDQ-8 questionnaires was studied in a subset of 81 patients that were examined clinically. RESULTS: 533 patients (96.7%) reported comorbid diseases. The most affected dimensions in the 15D questionnaire were secretion, usual activities, discomfort and symptoms, and sexual activity. Self-organizing map identified three patterns of health profiles that included patients with high, low or transition HRQoL. The transition subgroup was similar to low HRQoL subgroup in non-motor dimensions. Sixteen comorbid diseases explained 33.7% of the variance in the 15D score. Memory deficit, depression, heart failure, and atrial fibrillation had the highest relative importance. The intraclass correlation coefficient between the generic 15D and the PD-specific PDQ-8 was 0.642 suggesting moderate reliability. CONCLUSIONS: The most marked differences in HRQoL were in the dimensions of secretion, usual activities, and sexual activity. Pattern detection of 15D health dimensions enabled the detection of a subgroup with disproportionately poor HRQoL in non-motor dimensions. The comorbid diseases affecting most to HRQoL were memory deficit and depression. The generic 15D questionnaire can be used in the evaluation of HRQoL in PD patients.

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BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) and EEG-guided neurofeedback techniques can reduce motor symptoms in Parkinson's disease (PD). However, the effects of their combination are unknown. Our objective was to determine the immediate and short-term effects on motor and non-motor symptoms, and neurophysiological measures, of rTMS and EEG-guided neurofeedback, alone or combined, compared to no intervention, in people with PD. METHODS: A randomized, single-blinded controlled trial with 4 arms was conducted. Group A received eight bilateral, high-frequency (10 Hz) rTMS sessions over the Primary Motor Cortices; Group B received eight 30-minute EEG-guided neurofeedback sessions focused on reducing average bilateral alpha and beta bands; Group C received a combination of A and B; Group D did not receive any therapy. The primary outcome measure was the UPDRS-III at post-intervention and two weeks later. Secondary outcomes were functional mobility, limits of stability, depression, health-related quality-of-life and cortical silent periods. Treatment effects were obtained by longitudinal analysis of covariance mixed-effects models. RESULTS: Forty people with PD participated (27 males, age = 63 ± 8.26 years, baseline UPDRS-III = 15.63 ± 6.99 points, H&Y = 1-3). Group C showed the largest effect on motor symptoms, health-related quality-of-life and cortical silent periods, followed by Group A and Group B. Negligible differences between Groups A-C and Group D for functional mobility or limits of stability were found. CONCLUSIONS: The combination of rTMS and EEG-guided neurofeedback diminished overall motor symptoms and increased quality-of-life, but this was not reflected by changes in functional mobility, postural stability or depression levels. TRIAL REGISTRATION: NCT04017481.

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BACKGROUND: Deficient postural adaptation and freezing lead to gait initiation abnormalities in Parkinson's disease. Gait initiation is characterized by longer motor preparation, which is a marker of increased risk of falling, and by abnormal postural adjustments. Better understanding the nature of these motor preparation disturbances will enable us to adapt rehabilitation and reduce falls. RESEARCH QUESTION: Our objective was to describe the different components (in the motor, cognitive and limbic domains) of gait initiation parameters in Parkinson's disease. METHODS: Forty-four patients with Parkinson's disease performed repeated step initiations under high attentional load with decision-making. The proportions of multiple anticipatory postural adjustments and anticipatory postural adjustment errors, markers of abnormal motor preparation, were measured. A logistic regression analysis studied the relationships between step initiation perturbations and the demographic, motor, cognitive, and neuropsychiatric characteristics of the patients. RESULTS: Multiple anticipatory postural adjustments and anticipatory postural adjustments errors lengthened step execution time. Motor severity explained the multiple anticipatory postural adjustments, suggesting a pathological role. Attentional performance explained anticipatory postural adjustments errors. Demographic and neuropsychiatric characteristics didn't contribute significantly to the abnormal anticipatory postural adjustments. SIGNIFICANCE: Motor disability contributes to the delay in step execution in Parkinson's disease through multiple anticipatory postural adjustments, highlighting the need to target motor preparation improvement in rehabilitation.

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Olfactory dysfunction is a common non-motor symptom of Parkinson's disease(PD) and may hold valuable insights into the disease's underlying pathophysiology. This study aimed to investigate cortical morphometry alterations in PD patients with severe hyposmia(PD-SH) and mild hyposmia(PD-MH) using surface-based morphometry(SBM) methods. Participants included 36 PD-SH patients, 38 PD-MH patients, and 40 healthy controls(HCs). SBM analysis revealed distinct patterns of cortical alterations in PD-SH and PD-MH patients. PD-MH patients exhibited reduced cortical thickness in the right supramarginal gyrus, while PD-SH patients showed widespread cortical thinning in regions including the bilateral pericalcarine cortex, bilateral lingual gyrus, left inferior parietal cortex, left lateral occipital cortex, right pars triangularis, right cuneus, and right superior parietal cortex. Moreover, PD-SH patients displayed reduced cortical thickness in the right precuneus compared to PD-MH patients. Fractal dimension analysis indicated increased cortical complexity in PD-MH patients' right superior temporal cortex and right supramarginal gyrus, as well as decreased complexity in the bilateral postcentral cortex, left superior parietal cortex, and right precentral cortex. Similarly, cortical gyrification index and cortical sulcal depth exhibited heterogeneous patterns of changes in PD-SH and PD-MH patients compared to HCs. These findings underscore the multifaceted nature of olfactory impairment in PD, with distinct patterns of cortical morphometry alterations associated with different degrees of hyposmia. The observed discrepancies in brain regions showing alterations reflect the complexity of PD's pathophysiology. These insights contribute to a deeper understanding of olfactory dysfunction in PD and provide potential avenues for early diagnosis and targeted interventions.

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BACKGROUND: Although pose estimation algorithms have been used to analyze videos of patients with Parkinson's disease (PD) to assess symptoms, their feasibility for differentiating PD from other neurological disorders that cause gait disturbances has not been evaluated yet. We aimed to determine whether it was possible to differentiate between PD and spinocerebellar degeneration (SCD) by analyzing video recordings of patient gait using a pose estimation algorithm. METHODS: We videotaped 82 patients with PD and 61 patients with SCD performing the timed up-and-go test. A pose estimation algorithm was used to extract the coordinates of 25 key points of the participants from these videos. A transformer-based deep neural network (DNN) model was trained to predict PD or SCD using the extracted coordinate data. We employed a leave-one-participant-out cross-validation method to evaluate the predictive performance of the trained model using accuracy, sensitivity, and specificity. As there were significant differences in age, weight, and body mass index between the PD and SCD groups, propensity score matching was used to perform the same experiment in a population that did not differ in these clinical characteristics. RESULTS: The accuracy, sensitivity, and specificity of the trained model were 0.86, 0.94, and 0.75 for all participants and 0.83, 0.88, and 0.78 for the participants extracted by propensity score matching. CONCLUSION: The differentiation of PD and SCD using key point coordinates extracted from gait videos and the DNN model was feasible and could be used as a collaborative tool in clinical practice and telemedicine.

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BACKGROUNDS AND OBJECTIVES: Severe hyposmia (SH) is a prodromal symptom of dementia associated with Parkinson's disease (PD) caused by Lewy bodies deposited in the limbic regions that connect the frontal and temporal lobes. We aimed to clarify the association between hyposmia and frontal lobe dysfunction (FLD) among patients with PD. METHODS: Patients with PD and Hoehn & Yahr stage 1-3 at on-periods without apparent dementia were screened. FLD was defined as a score of ≤14 on the Frontal Assessment Battery (FAB). SH was defined as an average recognition threshold >4 in the T&T Olfactometer. For each subscore, a recognition score of ≥4 was defined as SH. We examined whether SH and its subscores were associated with FLD and evaluated which FAB subscore might be lower in PD patients with SH using Poisson regression analysis with a robust variance estimator. RESULTS: We included 189 patients (median age, 68 years; 107 [57 %] male). FLD was observed in 53 (28 %) patients. Multivariable analysis showed that SH (PR 1.789, 95 % confidence intervals (CI) 1.115-2.872, p = 0.016) was associated with FLD. Regarding odor domains, only SH for fruity smells was associated with FLD (PR 1.970, 95 % CI 1.306-2.972, p = 0.001). Patients with SH had a higher subscore only for FAB-1 (similarity [conceptualization], p = 0.030), indicating linguistically mediated executive dysfunction. CONCLUSION: In patients with PD, SH is associated with FLD, especially with linguistically mediated executive dysfunction. Particularly, SH for fruity smells may be a sensitive indicator of FLD.

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