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Background: A possible genetic contribution of dopamine D3 receptor (DRD3) to cognitive impairment in Parkinson's disease (PD) has yet to be investigated. Objective: To explore the effects of rs6280 (Ser9Gly) genotype on PD patients' cognitive performance and to clarify possible interactions with psychopathology. Methods: Two hundred and fifty-three consecutive PD patients underwent neurological and neuropsychological evaluations, which included: Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr scale (H&Y), Dementia Rating Scale-2 (DRS-2), and Hospital Anxiety and Depression Scale (HADS). rs6280 polymorphism was genotyped for all PD patients and for 270 ethnically matched healthy volunteers (HC). Non-parametric group comparisons and logistic regressions were used for data analyses. Results: rs6280 genotype did not differ between PD and HC groups. PD patients with rs6280 CC genotype had more impaired cognitive performance (i.e., <1st percentile of demographically adjusted norms) on DRS-2 subscales Initiation/Perseveration and Construction than those with TT genotype. These associations remained statistically significant when other covariates (e.g., demographic features, disease duration, severity of motor symptoms in OFF and ON states, anti-parkinsonian medication, and psychopathology symptoms) were taken into consideration. PD patients with rs6280 TC had less anxiety (i.e., HADS Anxiety≥11) than those with TT (pâ=â0.012). This association was also independent of other covariates. Conclusions: Study findings suggest that rs6280 CC genotype predisposes to executive dysfunction and visuoconstructional deficits, whereas the heterozygous genotype protects from anxiety in PD. These effects do not appear to be dependent of one another. rs6280 is not a genotypic susceptibility factor for PD.
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Disfunção Cognitiva , Doença de Parkinson , Humanos , Receptores de Dopamina D3/genética , Doença de Parkinson/complicações , Doença de Parkinson/genética , Doença de Parkinson/tratamento farmacológico , Disfunção Cognitiva/genética , Disfunção Cognitiva/complicações , Polimorfismo Genético , Ansiedade/genéticaRESUMO
Brain manganese (Mn) accumulation is a key feature in patients with acquired hepatocerebral degeneration (AHD). The role of trace elements other than Mn in AHD needs to be clarified. In this study, using inductively coupled plasma mass spectrometry, we aimed to evaluate blood levels of trace elements in patients with AHD before and after liver transplantation (LT). Trace element levels in the AHD group were also compared with those of healthy controls (blood donors, n = 51). Fifty-one AHD patients were included in the study (mean age: 59.2 ± 10.6 years; men: 72.5%). AHD patients had higher levels of Mn, Li, B, Ni, As, Sr, Mo, Cd, Sb, Tl and Pb and a higher Cu/Se ratio, and lower levels of Se and Rb. Six patients (two women; mean age 55 ± 8.7 years) underwent LT, and there was an improvement in neurological symptoms, a significant increase in the Zn, Se and Sr levels, and a decrease in the Cu/Zn and Cu/Se ratios. In summary, several trace element imbalances were identified in AHD patients. Liver transplantation resulted in the improvement of neurological manifestations and the oxidant/inflammatory status. It is possible that observed changes in trace element levels may play a role in the pathophysiology and symptomatology of AHD.
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Introduction Neurological manifestations are frequent after acquiring COVID-19 and may persist long-term as part of post-COVID-19 syndrome. Cognitive impairment, chronic fatigue, sleep disturbances, and headache complaints are the most reported neurological features. During the COVID-19 pandemic, health care workers were particularly vulnerable due to the high workload and levels of stress associated with this period, but acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may also contribute. The authors aimed to evaluate the neurological involvement of acquiring SARS-CoV-2 in a population of hospital health care workers and its impact on their personal and professional lives. Methods A sample of health care workers who did and did not acquire SARS-CoV-2 matched by age and sociodemographic variables was studied. Through an online questionnaire, data were collected regarding the symptoms in the acute phase of the disease (for those who acquired it) and for all in the last 6 months of the study period. Proportion of neurological complaints were compared between groups, adjusting for age, sex, and professional class (using a rate ratio (RR)). Results This study included 326 participants (174 cases and 152 controls). The mean age (standard deviation) was 39.7 (10.2) years, and the female:male ratio was 3:1. Headache and cognitive complaints were the most prevalent neurological complaints in the last 6 months of the study period. The health care workers who acquired SARS-CoV-2 were more likely to report headache and cognitive complaints than the control group (RR = 1.51, 95% confidence interval = 1.17-1.9 and RR = 2.02, 95% confidence interval = 1.53-2.65, respectively). Conclusion In a population of health care workers, those who acquired SARS-CoV-2 were more likely to have long-term cognitive complaints and persistent headaches.
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COVID-19 , SARS-CoV-2 , Masculino , Feminino , Humanos , Adulto , COVID-19/epidemiologia , Pandemias , Síndrome de COVID-19 Pós-Aguda , Pessoal de Saúde/psicologia , Cefaleia/epidemiologia , Cefaleia/etiologia , CogniçãoRESUMO
OBJECTIVES: (a) To characterize the frequency of objective cognitive deficits and self-perceived cognitive difficulties and (b) to explore demographic and clinical predictors of cognitive dysfunction and cognitive complaints. METHOD: One hundred and ten adults diagnosed with COVID-19 between March and November 2020, aged ≤ 74 years underwent a brief neuropsychological evaluation 12 months after infection, which included: Brief Visuospatial Memory Test-Revised, California Verbal Learning Test, and Symbol Digit Modalities Test. T scores < 38 were considered abnormal performance; cognitive dysfunction was defined as ≥ 2 abnormal tests. Participants also completed Broadbent's Cognitive Failure Questionnaires (CFQ), Hospital Anxiety and Depression Scale, Modified Fatigue Impact Scale, and Short-Form Health Survey. CFQ ≥ 43 was considered indicative of cognitive complaints. RESULTS: Twenty participants (18.2%) had cognitive dysfunction and 36 (33.3%) had cognitive complaints. Cognitive dysfunction was related to lower education, preinfection history of headache/migraine, and acute COVID-19 symptoms of headache and sleep disturbance. Cognitive complaints were more likely to occur in women, those with fewer years of education, and acute COVID-19 symptoms of headache and sleep disturbance. Cognitive complaints were also significantly related to symptoms of anxiety, depression, and fatigue. Sex and psychopathology were not significant predictors of cognitive dysfunction. Modest associations were found between CFQ total score and cognitive test performance. DISCUSSION: A subset of individuals develops cognitive difficulties in the context of post-COVID syndrome. Results may support the protective effect of education, a known proxy of cognitive reserve. COVID-19 infection symptoms of headache and sleep disturbance appear to be risk factors for long-term cognitive difficulties. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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COVID-19 , Transtornos Cognitivos , Disfunção Cognitiva , Adulto , Humanos , Feminino , COVID-19/complicações , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Transtornos Cognitivos/psicologia , Fadiga/diagnóstico , Fadiga/epidemiologia , Fadiga/etiologia , Testes Neuropsicológicos , Cefaleia/complicaçõesRESUMO
BACKGROUND: Cognitive dysfunction is part of the broad spectrum of clinical manifestations in older untreated hereditary transthyretin amyloidosis patients with peripheral polyneuropathy. OBJECTIVE: The objective of this study is to systematically explore cognitive dysfunction in ATTRV30M amyloidosis patients whose disease course was modified by liver transplant (LT). METHODS: A series of 269 carriers of TTRVal30Met mutation treated with LT underwent a neuropsychological assessment. Clinical charts were reviewed to identify focal neurological episodes (FNEs), cognitive complaints and laboratory results. Chi-square and Mann-Whitney tests explored potential predictors of cognitive dysfunction. RESULTS: Cognitive dysfunction was identified in 35 patients (13%)-14 (5%) had mild and 21 (8%) had moderate dysfunction. In comparison to normal cognition, both mild and moderate cognitive dysfunction patients had older age, higher mPND score and elevated NT-proBNP and Cystatin C values. Mild cognitive dysfunction was associated with longer disease duration and history of FNEs, whereas moderate dysfunction was related to older age at disease onset and more cognitive complaints and depression symptoms. CONCLUSIONS: Consistent with the natural history of the disease, older age and higher severity of the disease are significantly associated and potentially predictors of cognitive dysfunction in ATTRV30M patients treated with LT. The level of cognitive dysfunction may depend on some clinical variables.
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Neuropatias Amiloides Familiares , Disfunção Cognitiva , Transplante de Fígado , Humanos , Idoso , Transplante de Fígado/efeitos adversos , Pré-Albumina/genética , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/genética , Neuropatias Amiloides Familiares/cirurgia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/genéticaRESUMO
The ability of the Auditory Verbal Learning Test (AVLT) to lateralize hippocampal sclerosis (HS) in mesial temporal lobe epilepsy (MTLE) was explored in a sample of 50 patients with MTLE-HS (23 right and 27 left). Patients' AVLT scores were adjusted to the demographic characteristics of each individual in accordance with the Portuguese normative data. The laterality of the HS was determined by consensus by two neuroradiologists. ROC curves were used to identify the best AVLT cutoff scores to differentiate right vs. left HS. Diagnostic statistics were applied to different AVLT measures. The study results revealed that four AVLT scores can correctly classify the laterality of HS in the total sample and a sub-group of 39 right-handed patients (Edinburgh Laterality Inventory +100): delayed recall trial (76 and 80%, respectively), delayed recognition trial (64 and 67%, respectively), learning over trials index (64 and 74%, respectively), and long-term percent retention index (68 and 72%, respectively). In right-handed patients, the diagnostic capability of the delayed recall trial was improved by pairing it with the learning over trials index (accuracy of 85%). In sum, AVLT measures of verbal memory differentiate left from right HS in MTLE. The delayed recall trial demonstrated good diagnostic capacity.
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BACKGROUND: Cognitive dysfunction as a predictor of clinical progression and mortality in multiple sclerosis (MS) is still a matter of debate. OBJECTIVE: The aim of this study was to explore the long-term outcome associated with neuropsychological performance in a cohort of patients with MS. METHODS: A series of 408 MS patients had previously undergone a comprehensive neuropsychological assessment and a contemporaneous neurological evaluation (T1). A retrospective review of the clinical records was conducted 102-192 months after T1. Demographic and clinical data regarding the last clinical appointment with EDSS measurement (T2) were collected and the date of the last clinical contact or death (TS) was recorded. RESULTS: This review revealed that cognitive dysfunction (T1) was associated with higher odds of transitioning from relapsing-remitting course to a progressive disease course (adjusted odds ratio (OR) = 2.29, p = 0.043) and higher hazard of death in the total sample (adjusted hazard ratio (HR) = 3.07, p = 0.006) and the progressive disease course subgroup (adjusted HR = 3.68, p = 0.007), even when adjusting for other covariates. DISCUSSION: The study results demonstrate that cognitive dysfunction in MS is predictive of poorer prognosis and mortality.
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Disfunção Cognitiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Disfunção Cognitiva/etiologia , Progressão da Doença , Humanos , Esclerose Múltipla/complicações , Testes Neuropsicológicos , Estudos RetrospectivosRESUMO
Hereditary cerebellar ataxias comprise a heterogeneous group of neurodegenerative disorders affecting the cerebellum and/or cerebellar pathways. Next-generation sequencing techniques have contributed substantially to the expansion of ataxia-causing genes, including genes classically described in alternative phenotypes. Herein, we describe a patient with adult-onset cerebellar ataxia, minor dystonia, neuropathy, seizure and ophthalmological pathology, who bears a novel variant in KMT2B (NM_014727.2:c.3334 + 1G > A). Bioinformatic analysis suggested this variant completely abolished the splice-site at exon 8/intron 8, which was confirmed through analysis of mRNA extracted from fibroblasts. Exon 8 skipping would ultimately translate as an in-frame deletion at the protein level, corresponding to the loss of 91 aminoacids [p.(Gly1020_Asn1111del)]. So far, KMT2B disease causing variants have been described in patients with dystonia or neurodevelopmental delay, with no reports of a cerebellar predominant phenotype. Our findings highlight the possible role of KMT2B as a gene involved in hereditary cerebellar ataxias.
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Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Histona-Lisina N-Metiltransferase/genética , Mutação , Fenótipo , Alelos , Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Criança , Eletroencefalografia , Feminino , Perfilação da Expressão Gênica , Estudos de Associação Genética/métodos , Genótipo , Humanos , Imageamento por Ressonância Magnética , Sequenciamento do ExomaRESUMO
BACKGROUND: Mood disorders, as depression and anxiety, are frequent in Multiple Sclerosis (MS) patients. High pro-inflammatory cytokine levels (e.g. IL-1ß) have been reported in depressed individuals. OBJECTIVE: We aimed to investigate the role of the rs16944 (IL-1ß-511 C>T) polymorphism in the development of anxiety and depression symptoms in a Portuguese cohort of MS patients. METHODS: 393 MS patients answered the Hospital Anxiety and Depression Scale (HADS) at T1. This questionnaire was reapplied to a subgroup of 175 MS patients approximately three years later (T2). HADS cut-off scores for anxiety and depression were respectively ≥11 and ≥8. RESULTS: At T1, anxiety was found in 106 MS patients (27.0%) and 11 controls (16.7%); whereas depression was identified in 116 (29.5%) MS patients and 9 controls (13.6%). Persistent anxiety and depression were respectively recorded in 12% and 20% of MS patients. The rs16944TT genotype was found to be a susceptibility factor for the occurrence of depression at T1 (OR = 3.16, p=0.002) and the development of persistent depression (OR = 5.63, p=0.003) in MS. CONCLUSION: Study results support the hypothesis that inflammation is a significant factor in psychopathology development.
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Esclerose Múltipla , Ansiedade , Transtornos de Ansiedade , Depressão , Humanos , Interleucina-1betaRESUMO
Congenital ataxias are a heterogeneous group of disorders characterized by congenital or early-onset ataxia. Here, we describe two siblings with congenital ataxia, who acquired independent gait by age 4 years. After 16 years of follow-up they presented near normal cognition, cerebellar ataxia, mild pyramidal signs, and dystonia. On exome sequencing, a novel homozygous variant (c.1580-18C > G - intron 17) in ATP8A2 was identified. A new acceptor splice site was predicted by bioinformatics tools, and functionally characterized through a minigene assay. Minigene constructs were generated by PCR-amplification of genomic sequences surrounding the variant of interest and cloning into the pCMVdi vector. Altered splicing was evaluated by expressing these constructs in HEK293T cells. The construct with the c.1580-18C > G homozygous variant produced an aberrant transcript, leading to retention of 17 bp of intron 17, by the use of an alternative acceptor splice site, resulting in a premature stop codon by insertion of four amino acids. These results allowed us to establish this as a disease-causing variant and expand ATP8A2-related disorders to include less severe forms of congenital ataxia.
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Adenosina Trifosfatases/genética , Ataxia Cerebelar/genética , Variação Genética/genética , Proteínas de Transferência de Fosfolipídeos/genética , Adulto , Linhagem Celular , Códon sem Sentido/genética , Feminino , Células HEK293 , Homozigoto , Humanos , Íntrons/genética , Masculino , Linhagem , Sítios de Splice de RNA/genética , Splicing de RNA/genéticaRESUMO
INTRODUCTION: The vermiform appendix is a potential site of initiation of Parkinson's disease (PD) pathology. We hypothesized that the appendectomy earlier in life may alter the clinical expression of PD. OBJECTIVE: To explore the effects of appendectomy prior to onset of PD motor symptoms on patients' symptoms, in particular on cognitive dysfunction. METHODS: Two hundred and sixty-two consecutive PD patients were asked about past history of appendectomy and underwent an evaluation, which included the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr scale (H&Y), Schwab & England Independence Scale (S&E), Dementia Rating Scale-2 (DRS-2), Apathy Evaluation Scale, Hospital Anxiety and Depression Scale, and Brief Smell Identification Test. Motor symptoms were evaluated in OFF and ON states. Non-parametric group comparisons and logistic regressions were used for data analyses. RESULTS: Thirty-one patients (11.8%) had history of appendectomy prior to PD onset. These patients had more severe motor symptoms (UPDRS-III and H&Y) and lower functional independence (S&E) in ON and had higher frequency of cognitive dysfunction (DRS-2 Initiation/Perseveration, Conceptualization, and Memory subscales) (p < 0.05). The association between history of appendectomy and cognitive dysfunction was evident only in patients with late onset PD (≥ 55 years) and with disease duration ≤ 5 years. History of appendectomy remained statistically associated with impairment on DRS-2 Conceptualization and Memory subscales, when demographic and clinical variables were considered. CONCLUSION: History of appendectomy appears to alter the clinical expression of late onset PD, with early cognitive impairment, more severe motor symptoms in ON, and poorer functional independence under anti-parkinsonian medication.
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Apatia , Disfunção Cognitiva , Doença de Parkinson , Apendicectomia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Inglaterra , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologiaRESUMO
BACKGROUND: Pain in Parkinson's disease (PD) is a common and heterogeneous non-motor symptom. Although the characteristics and predictors of pain in general and of central pain in particular are still largely unknown. METHODS: A semi-structured interview, the Brief Pain Inventory and the Pain Disability Index were used to identify and characterize pain in a consecutive series of 292 PD patients. Unified PD Rating Scale-III, Hoehn & Yahr, Schwab and England Independence Scale and Freezing of Gait Questionnaire were applied to assess motor symptoms and functional independence in off and on conditions. Hospital Anxiety and Depression Scale and Questionnaire of Impulsive-Compulsive Control Disorders were used to screen for anxiety, depression and impulse control disorders. RESULTS: Two hundred and twelve patients (73%) reported pain, which was classified as: musculoskeletal (63%), dystonia-related (27%), central parkinsonian (22%) and/or radicular or neuropathic (9%). Patients with pain had more comorbidities and more severe motor symptoms. Patients with central parkinsonian pain were significantly younger, had earlier disease onset, fewer comorbidities, greater non-axial motor symptom severity in on, more pain-related disability and more relief of pain with antiparkinsonian medication than patients with non-central parkinsonian pain. CONCLUSIONS: PD patients with central parkinsonian pain have some distinctive demographic and clinical features, including lower levodopa responsiveness of motor appendicular/limb symptoms to levodopa, associated with greater responsiveness of pain symptoms to these same medications. These findings suggest the need for a more integrated approach to motor and non-motor symptoms in these patients' clinical care. SIGNIFICANCE: In a consecutive series of 292 patients with PD, almost three quarters of patients with PD reported pain. The study results revealed that pain was related to more severe motor symptoms, anxiety symptoms and comorbidities. Among patients with pain, those with central parkinsonian subtype had distinct demographic and clinical features, including lower levodopa responsiveness for non-axial motor symptoms and greater responsiveness of pain to antiparkinsonian treatment.
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Transtornos Neurológicos da Marcha/epidemiologia , Neuralgia/epidemiologia , Doença de Parkinson/epidemiologia , Idoso , Antiparkinsonianos/uso terapêutico , Ansiedade/diagnóstico , Depressão/diagnóstico , Pessoas com Deficiência , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Cumulative data suggest that neuroinflammation plays a prominent role in Alzheimer's disease (AD) pathogenesis. The purpose of this work was to assess if patients with AD present a specific cerebrospinal fluid (CSF) cytokine profile and if it correlates to disease progression. We determined the levels of 27 cytokines in CSF of patients with AD and compared them with patients with frontotemporal dementia and nondemented controls. In addition, we correlated the cytokine levels with cognitive status and disease progression after 12 months. Patients with AD had higher levels of proinflammatory and anti-inflammatory cytokines (eotaxin, interleukin [IL]-1ra, IL-4, IL-7, IL-8, IL-9, IL-10, IL-15, granulocyte colony-stimulating factor, monocyte chemotactic protein 1, platelet-derived growth factor, tumor necrosis factor alfa) compared to nondemented controls. There was a negative correlation between the disease progression and the levels of several cytokines (IL-1ß, IL-4, IL-6, IL-9, IL-17A, basic fibroblast growth factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon gamma, macrophage inflammatory proteins-1ß). To the best of our knowledge, this is the first study reporting a "protective" role of the upregulation of specific intrathecal cytokine levels in AD. This finding supports that a fine "rebalancing" of the immune system represents a new target in AD therapeutic approach.
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Doença de Alzheimer/diagnóstico , Doença de Alzheimer/imunologia , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/imunologia , Citocinas/líquido cefalorraquidiano , Mediadores da Inflamação/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/psicologia , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/psicologia , Progressão da Doença , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Regulação para CimaRESUMO
OBJECTIVE: To investigate the longterm psychological outcome in survivors of critical illness after intensive care unit discharge. METHODS: A prospective cohort of survivors admitted to a mixed intensive care unit between January and September 2010 was evaluated six months and five years after hospital discharge. The Dementia Rating Scale-2, the Hospital Anxiety and Depression Scale, the Posttraumatic stress syndrome 14-questions inventory, the Euro Quality of Life 5 Dimensions (EQ-5-D), and the Visual Analogue Scale (EQ VAS) were assessed at both follow-up periods. RESULTS: Of 267 patients, 25 patients were evaluated at 6 months after discharge (62 ± 16 years); 12 (48%) presented cognitive impairment, 6 (24%) anxiety, 4 (16%) depression, and 4 (16%) post-traumatic stress disorder. Among those re-evaluated five years after discharge (n = 17; 65 ± 15 years), the frequency of cognitive impairment dropped from 8 (47%) to 3 (18%) (p = 0.063), due to improvement in these patients over time, and other patients did not acquire any dysfunction after discharge. At five years after discharge, only two patients (12%) reported anxiety, and none had depression or post-traumatic stress disorder. No differences were found between the six-month and five-year follow-ups regarding EQ-5-D and EQ VAS. CONCLUSION: Survivors do not show a progressive decline in cognitive function or quality of life within five years after intensive care unit discharge. Psychopathological symptoms tend to decrease with time.
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Ansiedade/epidemiologia , Cuidados Críticos/psicologia , Estado Terminal/psicologia , Sobreviventes/psicologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Fatores de TempoRESUMO
RESUMO Objetivo: Investigar o desfecho psicológico em longo prazo em sobreviventes de doenças críticas, após alta da unidade de terapia intensiva. Métodos: Avaliou-se coorte prospectiva de pacientes sobreviventes após admissão a uma unidade de terapia intensiva mista entre janeiro e setembro de 2010, 6 meses e 5 anos após a alta hospitalar. Aplicaram-se em todos os momentos as seguintes escalas: Dementia Rating Scale-2, Hospital Anxiety and Depression Scale, Post-Traumatic Stress Syndrome 14-Questions Inventory, Euro Quality of Life 5 Dimensions (EQ-5-D) e Visual Analogue Scale (EQ VAS). Resultados: Dentre 267 pacientes, 25 foram avaliados após 6 meses (idade: 62 ± 16 anos). Aos 6 meses, 48% apresentavam comprometimento cognitivo; 24% ansiedade, 16% depressão e 16% transtorno de estresse pós-traumático. Foram reavaliados 5 anos após a alta 17 pacientes, com idade: 65 ± 15 anos. Dentre eles, a frequência de comprometimento cognitivo caiu de 47% para 18% (p = 0,063), em razão da melhora destes pacientes ao longo do tempo e do não surgimento desta condição em outros pacientes após a alta. Ainda após 5 anos, apenas 12% da amostra relatou ansiedade, e nenhum tinha depressão ou transtorno de estresse pós-traumático. Não se encontraram diferenças em termos das escalas EQ-5-D e EQ VAS entre as avaliações após 6 meses e 5 anos. Conclusão: Os sobreviventes não apresentaram declínio progressivo da função cognitiva ou da qualidade de vida dentro de 5 anos após a alta da unidade de terapia intensiva. Os sintomas psicopatológicos tenderam a diminuir com o tempo.
ABSTRACT Objective: To investigate the longterm psychological outcome in survivors of critical illness after intensive care unit discharge. Methods: A prospective cohort of survivors admitted to a mixed intensive care unit between January and September 2010 was evaluated six months and five years after hospital discharge. The Dementia Rating Scale-2, the Hospital Anxiety and Depression Scale, the Posttraumatic stress syndrome 14-questions inventory, the Euro Quality of Life 5 Dimensions (EQ-5-D), and the Visual Analogue Scale (EQ VAS) were assessed at both follow-up periods. Results: Of 267 patients, 25 patients were evaluated at 6 months after discharge (62 ± 16 years); 12 (48%) presented cognitive impairment, 6 (24%) anxiety, 4 (16%) depression, and 4 (16%) post-traumatic stress disorder. Among those re-evaluated five years after discharge (n = 17; 65 ± 15 years), the frequency of cognitive impairment dropped from 8 (47%) to 3 (18%) (p = 0.063), due to improvement in these patients over time, and other patients did not acquire any dysfunction after discharge. At five years after discharge, only two patients (12%) reported anxiety, and none had depression or post-traumatic stress disorder. No differences were found between the six-month and five-year follow-ups regarding EQ-5-D and EQ VAS. Conclusion: Survivors do not show a progressive decline in cognitive function or quality of life within five years after intensive care unit discharge. Psychopathological symptoms tend to decrease with time.
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Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Ansiedade/epidemiologia , Estado Terminal/psicologia , Sobreviventes/psicologia , Cuidados Críticos/psicologia , Alta do Paciente , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Fatores de Tempo , Estudos Prospectivos , Estudos de Coortes , Seguimentos , Unidades de Terapia Intensiva , Pessoa de Meia-IdadeRESUMO
The expansion in the C9orf72 gene has been recently reported as a genetic cause of Huntington's disease (HD) phenocopies. We aim to assess the frequency of the C9orf72 gene expansion in a Portuguese HD phenocopies cohort. Twenty HD phenotype-like patients without diagnosis were identified in our institutional database. C9orf72 gene expansion was detected using repeat-primed PCR. Clinical files were reviewed to characterize the phenotype of expansion-positive cases. One patient (5%) was positive for the C9orf72 expansion. A second patient presented 27 repeats-within the intermediate size interval. Both had familial neuropsychiatric disease characterized by diverse movement disorders, dementia, and psychiatric dysfunction that was distinct in severity and clinical expression. C9orf72 disease is clinically heterogeneous and without evident imaging markers. The definition of the role of intermediate alleles and of the pathological threshold for C9orf72 repeat expansions may have diagnostic implications.
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Proteína C9orf72/genética , Doença de Huntington/genética , Idoso , Alelos , Esclerose Lateral Amiotrófica/genética , Estudos de Coortes , Expansão das Repetições de DNA/genética , Feminino , Humanos , Masculino , FenótipoRESUMO
Central nervous system (CNS) involvement in hereditary transthyretin (TTR) amyloidosis has been described in patients whose disease course was modified by liver transplant. However, cognitive dysfunction has yet to be investigated in those patients. Moreover, CNS involvement in untreated patients or asymptomatic mutation carriers remains to be studied. A series of 340 carriers of the TTRVal30Met mutation (180 symptomatic and 160 asymptomatic) underwent a neuropsychological assessment, which included the Dementia Rating Scale-2 (DRS-2), auditory verbal learning test, semantic fluency, phonemic fluency, and trail making test. Cognitive deficits were identified at the individual level, after adjusting the neuropsychological test scores for demographic characteristics (sex, age, and education), based on large national normative data. The presence of cognitive dysfunction was determined by deficit in DRS-2 and/or multiple cognitive domains. Participants were also screened for depression based on a self-report questionnaire. The frequency of cognitive dysfunction was higher (p = 0.003) in symptomatic (9%) than in asymptomatic (2%) carriers. Among older carriers (≥ 50 years), the frequency of cognitive dysfunction was higher (p < 0.001) in symptomatic (36%) than asymptomatic (4%) individuals. Among younger participants (< 50 years), the frequency of cognitive dysfunction was not different (p = 0.631) between symptomatic patients (2%) and asymptomatic (1%) carriers. This cross-sectional study shows that cognitive dysfunction is part of the broad spectrum of clinical manifestations in older hereditary TTR amyloidosis patients with peripheral polyneuropathy, even in the early stages of the disease.
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Envelhecimento , Neuropatias Amiloides Familiares/complicações , Transtornos Cognitivos/etiologia , Adulto , Idade de Início , Neuropatias Amiloides Familiares/genética , Ansiedade/diagnóstico , Ansiedade/etiologia , Distribuição de Qui-Quadrado , Depressão/diagnóstico , Depressão/etiologia , Feminino , Humanos , Masculino , Metionina/genética , Pessoa de Meia-Idade , Mutação/genética , Exame Neurológico , Testes Neuropsicológicos , Pré-Albumina/genética , Estatísticas não Paramétricas , Valina/genéticaRESUMO
BACKGROUND: The rate of Parkinson's disease (PD) progression varies widely between patients. Current knowledge does not allow to accurately predict the evolution of symptoms in a given individual over time. OBJECTIVES: To develop regression-based models of PD progression and to explore its predictive value in a three-year follow-up. METHODS: At baseline, 300 consecutive PD patients were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) - subscales II and III, Hoehn & Yahr (H&Y) and Schwab and England Independence Scale (S&E); and the Freezing of Gait Questionnaire (FOG-Q). UPDRS-III and H&Y were applied in OFF and ON medication conditions. An axial index was derived from the UPDRS-III. Based on multiple linear regression coefficients, algorithms were developed to adjust test scores to the characteristics of each individual. Sixty-eight patients were reevaluated three years later. RESULTS: In the construction of the models, disease duration, age ≥70, age at disease onset ≥55, tremor as the first symptom alone, and medication description explained between 35% (UPDRS-III in ON) and 57% (axial index in ON) of the variance of test scores. The predictive r2 of the models in a 10-fold cross-validation ranged between 33% (UPDRS-III in ON) and 55% (axial index in ON and S&E in OFF). All measures, except UPDRS-III OFF, H&Y ON, and S&E ON, had moderate/good absolute agreement (intraclass correlation coefficient between 0.60 and 0.72) between baseline and follow-up. CONCLUSIONS: A cross-sectional assessment of a PD population allowed the development of models of disease progression, whose predictive value was validated on a three-year longitudinal study.