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BACKGROUND: Progressive supranuclear palsy (PSP) is a rare 4R-tauopathy. Transcranial direct current stimulation (tDCS) may improve specific symptoms. OBJECTIVES: This randomized, double-blinded, sham-controlled trial aimed at verifying the short-, mid-, and long-term effect of multiple sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) cortex in PSP. METHODS: Twenty-five patients were randomly assigned to active or sham stimulation (2 mA for 20 minute) for 5 days/week for 2 weeks. Participants underwent assessments at baseline, after the 2-week stimulation protocol, then after 45 days and 3 months from baseline. Primary outcomes were verbal and semantic fluency. The efficacy was verified with analysis of covariance. RESULTS: We failed to detect a significant effect of active stimulation on primary outcomes. Stimulation was associated to worsening of specific behavioral complaints. CONCLUSIONS: A 2-week protocol of anodal left DLPFC tDCS is not effective in PSP. Specific challenges in running symptomatic clinical trials with classic design are highlighted. © 2024 International Parkinson and Movement Disorder Society.
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Córtex Pré-Frontal , Paralisia Supranuclear Progressiva , Estimulação Transcraniana por Corrente Contínua , Humanos , Paralisia Supranuclear Progressiva/terapia , Paralisia Supranuclear Progressiva/fisiopatologia , Masculino , Feminino , Estimulação Transcraniana por Corrente Contínua/métodos , Idoso , Pessoa de Meia-Idade , Método Duplo-Cego , Córtex Pré-Frontal/fisiopatologia , Resultado do Tratamento , Córtex Pré-Frontal Dorsolateral/fisiologiaRESUMO
OBJECTIVES: The Caregiver's Inventory Neuropsychological Diagnosis Dementia (CINDD) is an easy tool designed to quantify cognitive, behavioural and functional deficits of patients with cognitive impairment. Aim of the present study was to analyse the psychometric properties of the CINDD in Mild Cognitive Impairment (MCI) and Dementia (D). DESIGN, SETTING AND PARTICIPANTS: The CINDD, composed by 9 sub-domains, was administered to fifty-six caregivers of patients with different types of dementia (D) and 44 caregivers of patients with MCI. All patients underwent an extensive neuropsychological assessment, the Neuropsychiatric Inventory (NPI) and functional autonomy scales. The reliability, convergent construct validity and possible cut-off of CINND were measured by Cronbach's alpha (α), Pearson's correlation and ROC analysis, respectively. RESULTS: The D and MCI patients differed only for age (p=0.006). The internal consistency of CINDD was high (α= 0.969). The α-value for each CINDD domain was considered acceptable, except the mood domain (α=0.209). The CINDD total score correlated with cognitive screening tests; each domain of the CINDD correlated with the corresponding score from either tests or NPI (p<0.05), except for visuo-spatial perception skills and apathy. A screening cut-off equal to 59, can be used discriminate D from MCI (Sensitivity=0.70, Specificity=0.57). CONCLUSION: The CINDD is a feasible, accurate and reliable tool for the assessment of cognitive and behavioural difficulties in patients with different degree of cognitive impairment. It may be used to quantify and monitor caregiver-reported ecological data in both clinical and research settings.
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Disfunção Cognitiva , Demência , Humanos , Cuidadores/psicologia , Psicometria , Reprodutibilidade dos Testes , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Testes NeuropsicológicosRESUMO
INTRODUCTION: Alterations in metabolic status, body composition, and food intake are present in all neurodegenerative diseases. Aim of this study was to detect the progression of these changes in Progressive Supranuclear Palsy (PSP). METHODS: We conducted a longitudinal study of 15 patients with PSP. The assessments were performed at baseline (T0) and after 7(IQR = 5) months of follow-up (T1). We collected anthropometric measures including body weight, height, body mass index and waist circumference, metabolic parameters through indirect calorimeters, body composition using bioimpedance analysis, and dietary habits with a validated questionnaire. PSP-rating scale (PSP-rs) was used to evaluate disease severity and dysphagia. RESULTS: The majority of patients (66.66%) presented PSP-Richardson Syndrome and 33.33% the other variant syndromes of the disease. At T1 there was a decrease in intake of total daily calories (p < 0.001), proteins (p < 0.001), fibers (p = 0.001), calcium (p = 0.008), iron (p < 0.001), zinc (0.034), vitamin E (p = 0.006) and folates (p = 0.038) compared to T0. No other changes were found. As for T1 data, no significant differences were shown according to disease phenotypes or the presence of clinically significant dysphagia for solids. CONCLUSIONS: Within a mid-term follow up, PSP patients presented reduced caloric and proteins intake regardless the presence of dysphagia. The PSP-rs is likely not adequate to assess dysphagia, which should be investigated by specific clinical scales or instrumental examinations. With the goal of maintaining adequate nutritional status, the administration of protein and vitamin supplements should be considered even in the absence of dysphagia evidenced by the rating scales.
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Composição Corporal , Metabolismo Energético , Comportamento Alimentar , Paralisia Supranuclear Progressiva , Humanos , Paralisia Supranuclear Progressiva/fisiopatologia , Masculino , Feminino , Idoso , Estudos Longitudinais , Composição Corporal/fisiologia , Comportamento Alimentar/fisiologia , Metabolismo Energético/fisiologia , Pessoa de Meia-Idade , Progressão da Doença , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/etiologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Heterozygous mutations in GBA1 gene are known as most common genetic risk factor for Parkinson's disease (PD). However, role of GBA1 mutations in non-α-synuclein disorders is unclear. CASES: Case index, 76 year-old woman referred to our movement disorders outpatient clinic for 2-year history of gait impairment, falls and motor slowness, with partial response to levodopa. Clinical and instrumental examinations were consistent with Progressive Supranuclear Palsy-Corticobasal Syndrome (PSP-CBS). Case 2 is older sister reporting depressive symptoms; however, she had dementia (MMSE 18/30), gait apraxia and vertical supranuclear gaze palsy (VSNGP). Case 3 is her deceased older sister who had been diagnosed with Corticobasal Syndrome (CBS). Case 4, older brother had been diagnosed with Parkinson's disease-dementia (PDD) with good response to levodopa. Two affected living siblings harboring same genetic variant. CONCLUSIONS: To our knowledge, this is the first family showing such intrafamilial variability ranging from CBS to PDD to dementia.
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Glucosilceramidase , Doenças Neurodegenerativas , Humanos , Glucosilceramidase/genética , Feminino , Idoso , Masculino , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/diagnóstico , Itália , Doença de Parkinson/genética , Doença de Parkinson/complicações , Mutação , Paralisia Supranuclear Progressiva/genéticaRESUMO
Multiple system atrophy (MSA) is an adult-onset, sporadic synucleinopathy characterized by parkinsonism, cerebellar ataxia, and dysautonomia. The genetic architecture of MSA is poorly understood, and treatments are limited to supportive measures. Here, we performed a comprehensive analysis of whole genome sequence data from 888 European-ancestry MSA cases and 7,128 controls to systematically investigate the genetic underpinnings of this understudied neurodegenerative disease. We identified four significantly associated risk loci using a genome-wide association study approach. Transcriptome-wide association analyses prioritized USP38-DT, KCTD7, and lnc-KCTD7-2 as novel susceptibility genes for MSA within these loci, and single-nucleus RNA sequence analysis found that the associated variants acted as cis-expression quantitative trait loci for multiple genes across neuronal and glial cell types. In conclusion, this study highlights the role of genetic determinants in the pathogenesis of MSA, and the publicly available data from this study represent a valuable resource for investigating synucleinopathies.
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Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Atrofia de Múltiplos Sistemas , Atrofia de Múltiplos Sistemas/genética , Humanos , Predisposição Genética para Doença/genética , Feminino , Masculino , Idoso , Locos de Características Quantitativas/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Autosomal-dominant spinocerebellar ataxia (ADCA) due to intronic GAA repeat expansion in FGF14 (SCA27B) is a recent, relatively common form of late-onset ataxia. OBJECTIVE: Here, we aimed to: (1) investigate the relative frequency of SCA27B in different clinically defined disease subgroups with late-onset ataxia collected among 16 tertiary Italian centers; (2) characterize phenotype and diagnostic findings of patients with SCA27B; (3) compare the Italian cohort with other cohorts reported in recent studies. METHODS: We screened 396 clinically diagnosed late-onset cerebellar ataxias of unknown cause, subdivided in sporadic cerebellar ataxia, ADCA, and multisystem atrophy cerebellar type. We identified 72 new genetically defined subjects with SCA27B. Then, we analyzed the clinical, neurophysiological, and imaging features of 64 symptomatic cases. RESULTS: In our cohort, the prevalence of SCA27B was 13.4% (53/396) with as high as 38.5% (22/57) in ADCA. The median age of onset of SCA27B patients was 62 years. All symptomatic individuals showed evidence of impaired balance and gait; cerebellar ocular motor signs were also frequent. Episodic manifestations at onset occurred in 31% of patients. Extrapyramidal features (17%) and cognitive impairment (25%) were also reported. Brain magnetic resonance imaging showed cerebellar atrophy in most cases (78%). Pseudo-longitudinal assessments indicated slow progression of ataxia and minimal functional impairment. CONCLUSION: Patients with SCA27B in Italy present as an adult-onset, slowly progressive cerebellar ataxia with predominant axial involvement and frequent cerebellar ocular motor signs. The high consistency of clinical features in SCA27B cohorts in multiple populations paves the way toward large-scale, multicenter studies.