RESUMO
Obesity is one of the greatest public health challenges of modern times and its prevalence is increasing worldwide. With food so abundant in developed countries, many people face a conflict between desires for short-term taste and the goal of long-term health, multiple times a day. Recent research suggests that consumers often resolve these conflicts based on their lay beliefs about the healthiness and tastiness of food. Consequently, such lay beliefs can play critical roles not just in food choice but also weight gain. In this research, we show, across six countries and through mediation analysis, that adults who believe that tasty food is unhealthy (the Unhealthy = Tasty Intuition, or "UTI"; Raghunathan, Naylor, & Hoyer 2006) are less likely to consume healthy food, and thereby have a higher body mass index (BMI). In Study 1, we conducted a cross-sectional survey in five countries (Australia, Germany, Hong Kong, India, and the UK), and found that greater strength of belief in UTI was associated with higher BMI, and this relationship was mediated by lower consumption of fruits and vegetables. The observed patterns largely converged across the sampled Western and Asian-Pacific countries. In Study 2, we teased apart the mediating role of vegetable versus fruit consumption and also addressed the issue of reversed causality by predicting BMI with a measure of UTI belief taken 30 months previously. We found that vegetable consumption, but not fruit consumption, mediated the association between UTI belief and BMI. Our findings contribute to the literature by showing how lay beliefs about food can have pervasive and long-lasting effects on dietary practices and health worldwide. Implications for public policy and health practitioners are discussed.
Assuntos
Índice de Massa Corporal , Dieta Saudável/psicologia , Ingestão de Alimentos/psicologia , Preferências Alimentares/psicologia , Paladar , Adulto , Austrália , Comparação Transcultural , Estudos Transversais , Cultura , Dieta Saudável/métodos , Feminino , Frutas , Alemanha , Hong Kong , Humanos , Índia , Masculino , Análise de Mediação , Pessoa de Meia-Idade , Obesidade/etiologia , Obesidade/psicologia , Inquéritos e Questionários , Reino Unido , VerdurasRESUMO
AIMS: To elucidate different patterns of progression of midbrain atrophy in patients with Richardson's syndrome (RS), progressive supranuclear palsy-parkinsonism (PSP-P), and Parkinson's disease (PD) using magnetic resonance imaging (MRI)-based visual rating indexes. METHODS: We recruited 12 patients with PSP-RS, 12 with PSP-P, and 23 with PD for whom MRIs had been followed up for at least 2 years (mean ± SD, 4.9 ± 1.6 years) after the initial MRI. MRI-based visual rating indexes were used to estimate midbrain atrophy, including the ratio of the pontine to midbrain tegmental areas (P/M ratio) on a midsagittal image, the length between the interpeduncular fossa and the center of the cerebral aqueduct at the midmammillary-body level (MTEGM) on axial images, and the morning glory sign. RESULTS: Initially, there were no differences in MRI-based visual rating indexes between PSP-P and PD, while PSP-RS showed a higher P/M ratio and lower MTEGM compared with PSP-P and PD. In PD, the P/M ratio and MTEGM remained stable with disease progression. However, the extent of changes between initial and follow-up indexes was similarly greater for both PSP-RS and PSP-P than for PD. Finally, PSP-P showed a higher P/M ratio and lower MTEGM compared with PD in the follow-up, while PSP-RS still exhibited the most profound changes. CONCLUSIONS: Midbrain atrophy progresses differentially in patients with PSP-RS, PSP-P, and PD. Longitudinal measurements of midbrain atrophy using MRI-based visual rating indexes can help distinguish patients with PSP-P from those with PSP-RS and PD.
Assuntos
Mesencéfalo/diagnóstico por imagem , Transtornos Parkinsonianos/diagnóstico por imagem , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Idoso , Atrofia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
When people cannot get what they want, they often satisfy their desire by consuming a substitute. Substitutes can originate from within the taxonomic category of the desired stimulus (i.e., within-category substitutes) or from a different taxonomic category that serves the same basic goal (i.e., cross-category substitutes). Both a store-brand chocolate (within-category substitute) and a granola bar (cross-category substitute), for example, can serve as substitutes for gourmet chocolate. Here, we found that people believe that within-category substitutes, which are more similar to desired stimuli, will more effectively satisfy their cravings than will cross-category substitutes (Experiments 1, 2a, and 2b). However, because within-category substitutes are more similar than cross-category substitutes to desired stimuli, they are more likely to evoke an unanticipated negative contrast effect. As a result, unless substitutes are equivalent in quality to the desired stimulus, cross-category substitutes more effectively satisfy cravings for the desired stimulus (Experiments 3 and 4).
Assuntos
Comportamento de Escolha/fisiologia , Preferências Alimentares , Adulto , Feminino , Humanos , MasculinoRESUMO
Postmortem studies of essential tremor (ET) have demonstrated the presence of degenerative changes in the cerebellum, and imaging studies have examined related structural changes in the brain. However, their results have not been completely consistent and the number of imaging studies has been limited. We aimed to study cerebellar involvement in ET using MRI segmental volumetric analysis. In addition, a unique feature of this study was that we stratified ET patients into subtypes based on the clinical presence of cerebellar signs and compared their MRI findings. Thirty-nine ET patients and 36 normal healthy controls, matched for age and sex, were enrolled. Cerebellar signs in ET patients were assessed using the clinical tremor rating scale and International Cooperative Ataxia Rating Scale. ET patients were divided into two groups: patients with cerebellar signs (cerebellar-ET) and those without (classic-ET). MRI volumetry was performed using CIVET pipeline software. Data on whole and segmented cerebellar volumes were analyzed using SPSS. While there was a trend for whole cerebellar volume to decrease from controls to classic-ET to cerebellar-ET, this trend was not significant. The volume of several contiguous segments of the cerebellar vermis was reduced in ET patients versus controls. Furthermore, these vermis volumes were reduced in the cerebellar-ET group versus the classic-ET group. The volume of several adjacent segments of the cerebellar vermis was reduced in ET. This effect was more evident in ET patients with clinical signs of cerebellar dysfunction. The presence of tissue atrophy suggests that ET might be a neurodegenerative disease.
Assuntos
Vermis Cerebelar/fisiopatologia , Tremor Essencial/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia/metabolismo , Ataxia Cerebelar/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
In spinocerebellar ataxia type 6 (SCA6), the vestibular dysfunction and its correlation with other clinical parameters require further exploration. We determined vestibular responses over a broad range of stimulus acceleration in 11 patients with SCA6 (six men, age range=33-72 years, mean age±SD=59±12 years) using bithermal caloric irrigations, rotary chair, and head impulse tests. Correlations were also pursued among disability scores, as measured using the International Cooperative Ataxia Rating Scale, disease duration, age at onset, cytosine-adenine-guanine (CAG) repeat length, and the gain of the vestibulo-ocular reflex (VOR). In response to relatively low-acceleration, low-frequency rotational and bithermal caloric stimuli, the VOR gains were normal or increased regardless of the severity of disease. On the other hand, with relatively high-acceleration, high-frequency head impulses, there was a relative increase in gain in the mildly affected patients and a decrease in gain in the more severely affected patients and gains were negatively correlated with the severity of disease (Spearman correlation, R=-0.927, p<0.001). Selective decrease of the vestibular responses during high-acceleration, high-frequency stimuli may be ascribed to degeneration of either the flocculus or vestibular nuclei. The performance of the VOR during high-acceleration, high-frequency head impulses may be a quantitative indicator of clinical decline in SCA6.
Assuntos
Aceleração , Reflexo Vestíbulo-Ocular , Ataxias Espinocerebelares/fisiopatologia , Adulto , Idoso , Feminino , Teste do Impulso da Cabeça/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Rotação , Índice de Gravidade de Doença , Testes de Função Vestibular/métodos , Núcleos Vestibulares/fisiopatologiaRESUMO
A 43-year-old man with a high-grade glioma involving the cerebellar nodulus showed a near-complete suppression of periodic alternating nystagmus (PAN) in the lateral decubitus position to either side. This positional modulation of PAN is consistent with suppression of the velocity storage mechanism by head position changes (tilt dumping) and is supportive of the role of the velocity storage mechanism in generating PAN.
Assuntos
Neoplasias Encefálicas/complicações , Glioma/complicações , Nistagmo Patológico/etiologia , Adulto , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia por Emissão de PósitronsRESUMO
Urban safety plays an essential role in the quality of citizens' lives and in the sustainable development of cities. In recent years, researchers have attempted to apply machine learning techniques to identify the role of location-specific attributes in the development of urban safety. However, existing studies have mainly relied on limited images (e.g., map images, single- or four-directional images) of areas based on a relatively large geographical unit and have narrowly focused on severe crime rates, which limits their predictive performance and implications for urban safety. In this work, we propose a novel method that predicts "deviance," which includes formal deviant crimes (e.g., murders) and informal deviant behaviors (e.g., loud parties at night). To do this, we first collect a large-scale geo-tagged dataset consisting of incident report data for seven metropolitan cities, along with corresponding sequential images around incident sites obtained from Google Street View. We then design a convolutional neural network that learns spatio-temporal visual attributes of deviant streets. Experimental results show that our framework is able to reliably recognize real-world deviance in various cities. Furthermore, we analyze which visual attribute is important for deviance identification and severity estimation with respect to social science as well as activated feature maps in the neural network. We have released our dataset and source codes on https://github.com/JinhwiPark/DevianceNet/.
RESUMO
OBJECTIVE: To determine the patterns and diagnostic value of head-shaking nystagmus (HSN) in patients with acute audiovestibular loss. METHOD: Eighteen patients underwent evaluation of spontaneous nystagmus, gaze-evoked nystagmus, HSN, head impulse test, ocular tilt reaction, subjective visual vertical, bithermal caloric tests, and pure-tone audiogram. The findings were compared with those of 21 patients with labyrinthitis. RESULTS: Fifteen patients (83%) exhibited HSN, and the horizontal HSN usually beat contralesionally (10/14, 71%). However, 9 (50%) patients also showed patterns of central HSN that included perverted HSN (n=7), HSN in the opposite direction of spontaneous nystagmus (n=4), and HSN beating towards unilateral canal paresis or abnormal head impulse testing (n=3). Overall, central HSN, gaze-evoked nystagmus, and normal head impulse testing were specific for anterior inferior cerebellar artery (AICA) infarction. Moreover, central HSN was the only sign that indicated stroke in 1 of our patients with isolated audiovestibular syndrome. Lesion subtraction analyses revealed that damage to the flocculus was relatively frequent in patients with perverted HSN. CONCLUSIONS: In AICA infarction, HSN was common with both peripheral and central patterns. Careful evaluation of HSN may provide clues for AICA infarction in patients with acute audiovestibular loss.
Assuntos
Técnicas de Diagnóstico Neurológico , Movimentos da Cabeça/fisiologia , Infarto da Artéria Cerebral Posterior/diagnóstico , Nistagmo Patológico/diagnóstico , Vertigem/diagnóstico , Doenças Vestibulares/diagnóstico , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Cerebelo/irrigação sanguínea , Estudos Transversais , Movimentos Oculares/fisiologia , Feminino , Humanos , Infarto da Artéria Cerebral Posterior/fisiopatologia , Labirintite/diagnóstico , Labirintite/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Nistagmo Patológico/fisiopatologia , Membrana dos Otólitos/fisiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Vertigem/fisiopatologia , Doenças Vestibulares/fisiopatologiaRESUMO
OBJECTIVE: We identify individuals who set daily intake budgets and examine if an intervention making people estimate their calorie intake up to a certain point in the day helps those setting daily budgets to regulate their calorie intake for the remainder of the day, after high prior consumption. DESIGN: We conducted an online experiment in five countries: Australia, China, Germany, India, and the UK (n = 3,032) using a 2 (setting calorie budget: yes vs. no, measured) x 2 (intervention: intake reminder vs. control, manipulated) between-subjects design, with the amount of prior consumption measured. Participants were contacted in the afternoon. Those in the intervention condition were asked to estimate their prior calorie intake on that day. MAIN OUTCOME MEASURES: We measured the individual characteristics of those who set daily calorie budgets and the intended calorie intake for the remainder of the day. RESULTS: Among people who set daily calorie budgets, the intervention reduced intended calorie intake for the remainder of the day by 176 calories if they had already consumed a high amount of calories that day. CONCLUSION: A timely intervention to estimate one's calorie intake can lower additional intended calorie intake among those who set daily calorie budget.
Assuntos
Ingestão de Energia , Humanos , Ingestão de Energia/fisiologia , Austrália , China , Alemanha , ÍndiaRESUMO
Glucosylceramidase beta 1 (GBA1) variants have attracted enormous attention as the most promising and important genetic candidates for precision medicine in Parkinson's disease (PD). A substantial correlation between GBA1 genotypes and PD phenotypes could inform the prediction of disease progression and promote the development of a preventive intervention for individuals at a higher risk of a worse disease prognosis. Moreover, the GBA1-regulated pathway provides new perspectives on the pathogenesis of PD, such as dysregulated sphingolipid metabolism, impaired protein quality control, and disrupted endoplasmic reticulum-Golgi trafficking. These perspectives have led to the development of novel disease-modifying therapies for PD targeting the GBA1-regulated pathway by repositioning treatment strategies for Gaucher's disease. This review summarizes the current hypotheses on a mechanistic link between GBA1 variants and PD and possible therapeutic options for modulating GBA1-regulated pathways in PD patients.
RESUMO
Horizontal head-shaking may induce nystagmus in peripheral as well as central vestibular lesions. While the patterns and mechanism of head-shaking nystagmus are well established in peripheral vestibulopathy, they require further exploration in central vestibular disorders. To define the characteristics and mechanism of head-shaking nystagmus in central vestibulopathies, we investigated spontaneous nystagmus and head-shaking nystagmus in 72 patients with isolated cerebellar infarction. Spontaneous nystagmus was observed in 28 (39%) patients, and was mostly ipsilesional when observed in unilateral infarction (15/18, 83%). Head-shaking nystagmus developed in 37 (51%) patients, and the horizontal component of head-shaking nystagmus was uniformly ipsilesional when induced in patients with unilateral infarction. Perverted head-shaking nystagmus occurred in 23 (23/37, 62%) patients and was mostly downbeat (22/23, 96%). Lesion subtraction analyses revealed that damage to the uvula, nodulus and inferior tonsil was mostly responsible for generation of head-shaking nystagmus in patients with unilateral posterior inferior cerebellar artery infarction. Ipsilesional head-shaking nystagmus in patients with unilateral cerebellar infarction may be explained by unilateral disruption of uvulonodular inhibition over the velocity storage. Perverted (downbeat) head-shaking nystagmus may be ascribed to impaired control over the spatial orientation of the angular vestibulo-ocular reflex due to uvulonodular lesions or a build-up of vertical vestibular asymmetry favouring upward bias due to lesions involving the inferior tonsil.
Assuntos
Cerebelo/irrigação sanguínea , Cerebelo/patologia , Infarto/patologia , Nistagmo Patológico/patologia , Reflexo Vestíbulo-Ocular/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes Calóricos , Cerebelo/fisiopatologia , Feminino , Humanos , Infarto/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nistagmo Patológico/fisiopatologiaRESUMO
Trehalose has been recently revealed as an attractive candidate to prevent and modify Parkinson's disease (PD) progression by regulating autophagy; however, studies have only focused on the reduction of motor symptoms rather than the modulation of disease course from prodromal stage. This study aimed to evaluate whether trehalose has a disease-modifying effect at the prodromal stage before the onset of a motor deficit in 8-week-old male C57BL/6 mice exposed to rotenone. We found significant decrease in tyrosine hydroxylase immunoreactivity in the substantia nigra and motor dysfunction after 2 weeks rotenone treatment. Mice exposed to rotenone for a week showed an accumulation of protein aggregates in the brain and prodromal non-motor deficits, such as depression and olfactory dysfunction, prior to motor deficits. Trehalose significantly improved olfactory dysfunction and depressive-like behaviors and markedly reduced α-synuclein and p62 deposition in the brain. Trehalose further ameliorated motor impairment and loss of nigral tyrosine hydroxylase-positive cells in rotenone-treated mice. We demonstrated that prodromal non-motor signs in a rotenone-induced PD mouse model are associated with protein aggregate accumulation in the brain and that an autophagy inducer could be valuable to prevent PD progression from prodromal stage by regulating abnormal protein accumulation.
Assuntos
Transtornos do Olfato , Doença de Parkinson , Trealose , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doença de Parkinson/tratamento farmacológico , Sintomas Prodrômicos , Rotenona/toxicidade , Trealose/farmacologia , Trealose/uso terapêutico , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
OBJECTIVE: Nutrition and menu labelling have been increasingly implemented worldwide. This research examines the effect of nutrition information provision on the immediate and subsequent consumption decisions of restrained and unrestrained eaters. DESIGN: We conducted three scenario-based experiments. In Study 1 (N = 478) and Study 2 (N = 199), we manipulated the availability of nutrition information and measured dietary restraint. Study 3 (N = 275) extended Study 2 by adding a condition where we provided reference information about recommended daily calories. MAIN OUTCOME MEASURES: We measured choices between relatively low-calorie and high-calorie alternatives (Studies 1-3) and measured a subsequent decision to consume indulgent food (Studies 2 and 3). RESULTS: Nutrition information did not generally affect choices between low-calorie and high-calorie options, irrespective of dietary restraint. However, restrained eaters who chose a high-calorie option in the presence of nutrition information indicated they would reduce subsequent intake. CONCLUSION: Nutrition information does not necessarily reduce the choice of relatively high-calorie food, but it can help restrained eaters reduce subsequent intake after a high-calorie choice. These results suggest that despite not having an immediate effect on choices, nutrition and menu labelling may benefit restrained eaters at a later time.
Assuntos
Dieta , Preferências Alimentares , Ingestão de Energia , Alimentos , Rotulagem de Alimentos/métodos , HumanosRESUMO
Background: Exercise is an important treatment for Parkinson's disease (PD). Therefore, recognizing determinants of exercise behavior for PD based on disease stage is essential. We sought to find whether the determinants differ based on presence of postural instability (PI), which is indicative of disease stage in PD. Methods: We enrolled patients at Samsung Medical Center from September 2019 to November 2020, who had the ability to perform exercise [modified Hoehn and Yahr (HY) stage ≤ 3]. All the motor and non-motor symptoms were investigated. The exercise of the PD patients was evaluated using the Physical Activity Scale of the Elderly (PASE)-leisure score. We classified patients into PD without PI (HY stage 1 - 2) and PD with PI (HY stage 2.5 - 3) groups. Multivariate linear regression was performed using backward elimination in each group to determine factors associated with PASE-leisure score. Results: A total of 233 patients were enrolled. In the PD without PI group (n = 177), the positive determinant of exercise was Activities-Specific Balance Confidence (ABC) score (ß = 0.142, p = 0.032), and the negative determinants were fatigue score (ß = -0.228, p = 0.018), female (ß = -6.900, p = 0.016) and currently employed status (ß = -6.072, p = 0.046). In the PD with PI group (n = 56), the positive determinant was non-motor symptom scale (NMSS) score (ß = 0.221, p = 0.017) and disease duration (ß = 1.001, p = 0.036), while the negative determinants were UPDRS part 3 score (ß = -0.974, p < 0.001), UPDRS part 4 score (ß = -2.192, p = 0.002), and age (ß = -1.052, p < 0.001). Conclusion: Different motor and non-motor symptoms were associated with the exercise in PD patients with and without PI. When encouraging PD patients to exercise, personalized and different strategies should be applied based on the presence of PI.
RESUMO
Objective: Pisa syndrome (PS) is a disabling postural deformity in Parkinson's disease (PD). We aimed to elucidate clinical factors determining the severity and laterality of PS in PD. Methods: In 54 PD patients with PS, we measured the clinical factors that are previously known to contribute to the occurrence of PS as follows: asymmetry of motor symptoms for the evaluation of asymmetric basal ganglia dysfunction, the degree and direction of subjective visual vertical (SVV) tilt for the misperception of body verticality, the canal paresis for unilateral peripheral vestibulopathy, and the tonic electromyographic (EMG) hyperactivity of paraspinal muscles for dystonia. Multivariable linear and logistic regression analyses were conducted to identify the clinical factors associated with the degree of truncal tilt, for the quantification of the severity of PS, and PS tilting to the less affected side, respectively. Results: The multivariable linear regression analyses revealed that the larger degree of SVV tilt (ß = 0.29, SE = 0.10, p = 0.005), right-sided SVV tilt (ß = 2.32, SE = 0.82, p = 0.007), and higher Hoehn and Yahr (HY) stage (ß = 4.01, SE = 1.29, p = 0.003) significantly increased the severity of PS. In the multivariable logistic regression analyses, greater asymmetry of motor symptoms [odds ratio (OR) = 2.01, 95% CI = 1.34-3.49] was significantly associated with PS tilting to the less affected side, while right-sided SVV tilt (OR = 0.02, 95% CI = 0.001-0.21), unilateral canal paresis (OR = 0.06, 95% CI = 0.003-0.79), and higher HY stage (OR = 0.04, 95% CI = 0.002-0.46) were associated with PS tilting to the more affected side. Conclusion: Misperception of verticality, asymmetric basal ganglia dysfunction, unilateral peripheral vestibulopathy, and motor disability are the clinical factors associated with the severity and laterality of PS in patients with PD.
RESUMO
Protein-coding variants in the GBA gene modulate susceptibility and progression in ~10% of patients with Parkinson's disease (PD). GBA encodes the ß-glucocerebrosidase enzyme that hydrolyzes glucosylceramide. We hypothesized that GBA mutations will lead to glucosylceramide accumulation in cerebrospinal fluid (CSF). Glucosylceramide, ceramide, sphingomyelin, and lactosylceramide levels were measured by liquid chromatography-tandem mass spectrometry in CSF of 411 participants from the Parkinson's Progression Markers Initiative (PPMI) cohort, including early stage, de novo PD patients with abnormal dopamine transporter neuroimaging and healthy controls. Forty-four PD patients carried protein-coding GBA variants (GBA-PD) and 227 carried wild-type alleles (idiopathic PD). The glucosylceramide fraction was increased (P = 0.0001), and the sphingomyelin fraction (a downstream metabolite) was reduced (P = 0.0001) in CSF of GBA-PD patients compared to healthy controls. The ceramide fraction was unchanged, and lactosylceramide was below detection limits. We then used the ratio of glucosylceramide to sphingomyelin (the GlcCer/SM ratio) to explore whether these two sphingolipid fractions altered in GBA-PD were useful for stratifying idiopathic PD patients. Idiopathic PD patients in the top quartile of GlcCer/SM ratios at baseline showed a more rapid decline in Montreal Cognitive Assessment scores during longitudinal follow-up compared to those in the lowest quartile with a P-value of 0.036. The GlcCer/SM ratio was negatively associated with α-synuclein levels in CSF of PD patients. This study highlights glucosylceramide as a pathway biomarker for GBA-PD patients and the GlcCer/SM ratio as a potential stratification tool for clinical trials of idiopathic PD patients. Our sphingolipids data together with the clinical, imaging, omics, and genetic characterization of PPMI will contribute a useful resource for multi-modal biomarkers development.
RESUMO
This corrects the article on p. 633 in vol. 16, PMID: 33029970.
RESUMO
OBJECTIVE: To test the relationship between clinically relevant types of GBA mutations (none, risk variants, mild mutations, severe mutations) and ß-glucocerebrosidase activity in patients with Parkinson disease (PD) in cross-sectional and longitudinal case-control studies. METHODS: A total of 481 participants from the Harvard Biomarkers Study (HBS) and the NIH Parkinson's Disease Biomarkers Program (PDBP) were analyzed, including 47 patients with PD carrying GBA variants (GBA-PD), 247 without a GBA variant (idiopathic PD), and 187 healthy controls. Longitudinal analysis comprised 195 participants with 548 longitudinal measurements over a median follow-up period of 2.0 years (interquartile range, 1-2 years). RESULTS: ß-Glucocerebrosidase activity was low in blood of patients with GBA-PD compared to healthy controls and patients with idiopathic PD, respectively, in HBS (p < 0.001) and PDBP (p < 0.05) in multivariate analyses adjusting for age, sex, blood storage time, and batch. Enzyme activity in patients with idiopathic PD was unchanged. Innovative enzymatic quantitative trait locus (xQTL) analysis revealed a negative linear association between residual ß-glucocerebrosidase activity and mutation type with p < 0.0001. For each increment in the severity of mutation type, a reduction of mean ß-glucocerebrosidase activity by 0.85 µmol/L/h (95% confidence interval, -1.17, -0.54) was predicted. In a first longitudinal analysis, increasing mutation severity types were prospectively associated with steeper declines in ß-glucocerebrosidase activity during a median 2 years of follow-up (p = 0.02). CONCLUSIONS: Residual activity of the ß-glucocerebrosidase enzyme measured in blood inversely correlates with clinical severity types of GBA mutations in PD. ß-Glucocerebrosidase activity is a quantitative endophenotype that can be monitored noninvasively and targeted therapeutically.
Assuntos
Glucosilceramidase/genética , Mutação , Doença de Parkinson/genética , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/etiologia , Estudos Transversais , Feminino , Seguimentos , Estudos de Associação Genética , Glucosilceramidase/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Doença de Parkinson/enzimologia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Locos de Características Quantitativas , Índice de Gravidade de DoençaRESUMO
BACKGROUND AND PURPOSE: The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is widely used for estimating the symptoms of Parkinson's disease. Translation and validation of the MDS-UPDRS is necessary for non-English speaking countries and regions. The aim of this study was to validate the Korean version of the MDS-UPDRS. METHODS: Altogether, 362 patients in 19 centers were recruited for this study. We translated the MDS-UPDRS to Korean using the translation-back translation method and cognitive pretesting. We performed both confirmatory and exploratory factor analyses to validate the scale. We calculated the comparative fit index (CFI) for confirmatory factor analysis, and used unweighted least squares for exploratory factor analysis. RESULTS: The CFI was higher than 0.90 for all parts of the scale. Exploratory factor analysis also showed that the Korean MDS-UPDRS has the same number of factors in each part as the English version. CONCLUSIONS: The Korean MDS-UPDRS has the same overall structure as the English MDS-UPDRS. Our translated scale can be designated as the official Korean MDS-UPDRS.