RESUMO
The retina may serve as putative window into neuropathology of synaptic loss in Alzheimer's disease (AD). Here, we investigated synapse-rich layers versus layers composed by nuclei/cell bodies in an early stage of AD. In addition, we examined the associations between retinal changes and molecular and structural markers of cortical damage. We recruited 20 AD patients and 17 healthy controls (HC). Combining optical coherence tomography (OCT), magnetic resonance (MR), and positron emission tomography (PET) imaging, we measured retinal and primary visual cortex (V1) thicknesses, along with V1 amyloid ß (Aß) retention ([11C]-PiB PET tracer) and neuroinflammation ([11C]-PK11195 PET tracer). We found that V1 showed increased amyloid-binding potential, in the absence of neuroinflammation. Although thickness changes were still absent, we identified a positive association between the synapse-rich inner plexiform layer (IPL) and V1 in AD. This retinocortical interplay might reflect changes in synaptic function resulting from Aß deposition, contributing to early visual loss.
Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Substância Cinzenta/patologia , Retina/patologia , Sinapses/patologia , Córtex Visual/patologia , Idoso , Feminino , Substância Cinzenta/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Retina/metabolismo , Sinapses/metabolismo , Córtex Visual/metabolismoRESUMO
INTRODUCTION: Neurofibrillary tangles and tau protein, the neuropathological hallmarks of Alzheimer's disease (AD), have been identified in patients with epilepsy. Tau protein was also associated with the modulation of neuronal excitability in animal models of AD. MATERIALS AND METHODS: We evaluated in 292 patients with AD the association between the risk of seizure development and AD cerebrospinal fluid (CSF) biomarkers, demographic characteristics, baseline Mini-Mental State Examination (MMSE) score, comorbidities, and apolipoprotein E status. RESULTS: The development of seizures was associated with younger age at dementia's onset, lower baseline MMSE, and higher CSF total tau protein levels, but only MMSE (hazard ratio [HR]â¯=â¯0.935; 95% confidence interval [CI]â¯=â¯[0.903, 0.968]; pâ¯<â¯0.001) and CSF tau (HRâ¯=â¯1.001; 95%CIâ¯=â¯[1.001, 1.002]; pâ¯=â¯0.001) were independent predictors on multivariate analysis. DISCUSSION: While CSF tau and lower baseline MMSE association with seizure development could in part be explained by a greater degree of cortical damage, the role of tau in the modulation of neuronal excitability may also play a role and should be further investigated.
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Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Convulsões/líquido cefalorraquidiano , Convulsões/diagnóstico , Proteínas tau/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/epidemiologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Convulsões/epidemiologiaRESUMO
BACKGROUND/AIMS: The head turning sign (HTS) is frequently noticed in clinical practice, but few studies have investigated its etiological and neuropsychological correlates. METHODS: The presence and frequency of the HTS was operationalized and prospectively evaluated in patients with Alzheimer's disease (AD), amnestic mild cognitive impairment (MCI), and behavioral-variant frontotemporal dementia (bvFTD). Cerebrospinal fluid (CSF) samples for AD biomarkers were collected. Mini-Mental State Examination, Montreal Cognitive Assessment, Geriatric Depression Scale (GDS), and insight scale scores were ascertained. RESULTS: A total of 84 patients were included. The HTS was more prevalent in AD than in MCI or bvFTD. It correlated negatively with cognitive measures and depression. It also had a positive correlation with CSF total tau and hyperphosphorylated tau proteins. Total tau protein and GDS score were the only variables independently associated with the HTS. CONCLUSIONS: The presence of the HTS in a cognitively impaired individual suggests a diagnosis of AD. A higher HTS frequency correlates with higher CSF total tau levels, a smaller GDS score, and worse cognitive measures. In the MCI subgroup, the HTS may suggest a higher risk of progression.
Assuntos
Doença de Alzheimer/diagnóstico , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Demência Frontotemporal/diagnóstico , Movimentos da Cabeça , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Progressão da Doença , Feminino , Demência Frontotemporal/líquido cefalorraquidiano , Movimentos da Cabeça/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Fatores de Risco , Estatística como Assunto , Proteínas tau/líquido cefalorraquidianoRESUMO
The Clock Drawing Test (CDT) has a known potential for the detection of cognitive impairment in populations with dementia, especially Alzheimer disease (AD). Our aim was to compare the clinical utility of 3 CDT scoring systems (Rouleau, Cahn, and Babins) in several pathologies with cognitive compromise from a tertiary center memory clinic. We selected patients with a clinical diagnosis of mild stage AD, behavioral variant frontotemporal dementia (FTD), vascular dementia (VaD), dementia with Lewy bodies (DLB), and Parkinson disease with dementia (PDD). The results showed significant differences between the several diagnoses with the following pattern of results: AD, DLB < FTD, VaD, PDD. Qualitative analysis of clock drawing errors confirmed the stimulus-bound response as a hallmark of AD, while conceptual deficit was significantly more prevalent in patients with AD and DLB. Our results supported the CDT potential as a cognitive screening measure for mild dementia, particularly sensitive to AD and DLB, especially when we used the Cahn scoring system and its analysis of qualitative errors.
Assuntos
Doença de Alzheimer/diagnóstico , Demência Vascular/diagnóstico , Demência/diagnóstico , Doença por Corpos de Lewy/diagnóstico , Testes Neuropsicológicos , Psicometria/métodos , Idoso , Doença de Alzheimer/psicologia , Disfunção Cognitiva , Demência Vascular/psicologia , Feminino , Demência Frontotemporal/diagnóstico , Humanos , Doença por Corpos de Lewy/psicologia , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
We describe a patient with downbeat nystagmus (DBN) evoked only by eye closure. Brain and spinal cord magnetic resonance imaging revealed a T2 paramedian lesion in the left lower basis pontis and other white matter lesions consistent with multiple sclerosis. One potential mechanism for DBN in this case involves transverse ephaptic spread of excitation from areas that subserve coordinated lid closure to the decussating ventral tegmental tract.
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Movimentos Oculares , Nistagmo Patológico/etiologia , Nistagmo Patológico/patologia , Área Tegmentar Ventral/patologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Gravação em Vídeo , Acuidade Visual/fisiologiaRESUMO
BACKGROUND: Progranulin (PGRN) mutations are associated with different clinical phenotypes, including frontotemporal lobar degeneration (FTLD), corticobasal syndrome (CBS) and Alzheimer's disease (AD). As all pathogenic PGRN mutations identified so far cause disease through haploinsufficiency, determination of PGRN levels has been proposed as a reliable method to identify mutation carriers. OBJECTIVE: To evaluate the accuracy of peripheral PGRN levels in the identification of the PGRN mutation carriers detected thus far in our Portuguese cohort. METHODS: Serum PGRN levels were measured in 244 subjects (124 patients in the spectrum of FTLD, 2 asymptomatic descendants of a FTLD patient, 56 AD patients and 64 controls) by a novel commercial ELISA kit. RESULTS: Low PGRN levels were detected in 7 individuals (5 behavioral variant frontotemporal dementia, 1 CBS, and 1 still clinically unaffected) that constituted the group of the null PGRN mutation carriers previously identified in our molecular diagnostic laboratory. The pathogenic mutations found consisted of 4 insertion-deletions, causing frameshifts resulting in premature stop codons, 3 of which were novel. In addition, a normal PGRN level was found in a patient harboring a novel missense variant. For this novel ELISA kit, we established a PGRN cut-off level that identified with 100% accuracy the pathogenic mutation carriers. CONCLUSION: This study supports the use of a novel assay for the determination of PGRN levels as a screening procedure to identify patients harboring null PGRN mutations. This approach would significantly decrease the required PGRN mutation analysis workload and should be extended to other clinical phenotypes than behavioral variant frontotemporal dementia and to apparently sporadic cases.
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Doença de Alzheimer/diagnóstico , Demência Frontotemporal/diagnóstico , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Peptídeos e Proteínas de Sinalização Intercelular/genética , Mutação , Idoso , Doença de Alzheimer/sangue , Doença de Alzheimer/genética , Estudos de Coortes , Feminino , Demência Frontotemporal/sangue , Demência Frontotemporal/genética , Humanos , Masculino , Pessoa de Meia-Idade , Portugal/epidemiologia , ProgranulinasRESUMO
We assessed the geographical distribution of C9orf72 G(4) C(2) expansions in a pan-European frontotemporal lobar degeneration (FTLD) cohort (n = 1,205), ascertained by the European Early-Onset Dementia (EOD) consortium. Next, we performed a meta-analysis of our data and that of other European studies, together 2,668 patients from 15 Western European countries. The frequency of the C9orf72 expansions in Western Europe was 9.98% in overall FTLD, with 18.52% in familial, and 6.26% in sporadic FTLD patients. Outliers were Finland and Sweden with overall frequencies of respectively 29.33% and 20.73%, but also Spain with 25.49%. In contrast, prevalence in Germany was limited to 4.82%. In addition, we studied the role of intermediate repeats (7-24 repeat units), which are strongly correlated with the risk haplotype, on disease and C9orf72 expression. In vitro reporter gene expression studies demonstrated significantly decreased transcriptional activity of C9orf72 with increasing number of normal repeat units, indicating that intermediate repeats might act as predisposing alleles and in favor of the loss-of-function disease mechanism. Further, we observed a significantly increased frequency of short indels in the GC-rich low complexity sequence adjacent to the G(4) C(2) repeat in C9orf72 expansion carriers (P < 0.001) with the most common indel creating one long contiguous imperfect G(4) C(2) repeat, which is likely more prone to replication slippage and pathological expansion.
Assuntos
Degeneração Lobar Frontotemporal/epidemiologia , Degeneração Lobar Frontotemporal/genética , Instabilidade Genômica , Proteínas/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/genética , Sequência de Bases , Proteína C9orf72 , Cromossomos Humanos Par 9/genética , Estudos de Coortes , Expansão das Repetições de DNA , Europa (Continente)/epidemiologia , Finlândia/epidemiologia , Estudo de Associação Genômica Ampla/métodos , Alemanha/epidemiologia , Haplótipos , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Prevalência , Espanha/epidemiologia , Suécia/epidemiologiaRESUMO
OBJECTIVE: Maternal lateral postures provide advantages during childbirth. This study aims to investigate the feasibility of assisting vacuum births in maternal lateral postures in a simulation model. STUDY DESIGN: In a simulation model, four obstetricians and four medical students were randomly allocated to perform vacuum-assisted births first in maternal lateral posture or lithotomy. A modification of Aldo Vacca's 5-step technique was developed to assist vacuum-assisted births in lateral posture. The lateral distance, vertical distance, and distance from the cup center to the flexion point were measured for every placement of the cup. RESULTS AND CONCLUSIONS: A total of 128 vacuum-assisted births were performed. The mean distance to the flexion point was 1.15 ± 0.71 cm for the lithotomy posture and 1.31 ± 0.82 cm for the lateral posture (P = 0.127). There were no statistically significant differences in vacuum extractor cup placement accuracy based on maternal posture. Performing vacuum-assisted births in maternal lateral posture is feasible in a simulation model. The technique is easy to learn, and the differences in cup placement between the lateral and lithotomy postures are small.
Assuntos
Parto Obstétrico , Postura , Feminino , Humanos , Gravidez , Simulação por Computador , Parto Obstétrico/métodos , Vácuo-ExtraçãoRESUMO
Banana wastes can be valorised in bioethanol due to its high content in cellulose (more than 30% of total on a dry basis) and hemicelluloses (25% of total). Large amount of these wastes is generated during the banana cultivation and harvesting stage. This study proposes the use of, beside conventional acid sulphuric, different organic acids (tartaric, oxalic and citric) during acid pretreatment step, to suppress the unwanted compounds formation and improve bioethanol production. Instead, bioethanol production generates a solid waste flow that is managed in an anaerobic digestion plant, obtaining biogas, to be converted into energy, and digestate, considered as a potential biofertiliser. Life cycle assessment methodology is used to analyse the environmental profiles of four valorisation scenarios to produce bioethanol from banana peel waste. According to the results, reported per kilogram of bioethanol, the citric acid-based scenario has the worst environmental profile due to the background processes involved in the acid production (around 55% for most impact categories). Conversely, the oxalic acid-based scenario has the best environmental profile, with a decrease of around 20% and 35%, depending on the impact category, compared to the citric acid scenario. The energy requirements production (mostly thermal energy) is the main hotspot in numerous subsystems regardless of the scenario (ranging from 30% to 50% depending on the impact category). Therefore, the use of renewable energy sources to satisfy energy requirements combined with an energy optimisation of the valorisation strategies through the reuse of some internal steams, is proposed as improvement activities.
Assuntos
Musa , Biocombustíveis , Resíduos SólidosRESUMO
BACKGROUND: The ATN scheme was proposed as an unbiased biological characterization of the Alzheimer's disease (AD) spectrum, grouping biomarkers into three categories: brain Amyloidosis-A, Tauopathy-T, Neurodegeneration-N. Although this scheme was mainly recommended for research, it is relevant for diagnosis. OBJECTIVE: To evaluate the ATN scheme performance in real-life cohorts reflecting the inflow of patients with cognitive complaints and different underlying disorders in general neurological centers. METHODS: We included patients (nâ=â1,128) from six centers with their core cerebrospinal fluid-AD biomarkers analyzed centrally. A was assessed through Aß42/Aß40, T through pTau-181, and N through tTau. Association between demographic features, clinical diagnosis at baseline/follow-up and ATN profiles was assessed. RESULTS: The prevalence of ATN categories was: A-T-N-: 28.3%; AD continuum (Aâ+âT-/+N-/+): 47.8%; non-AD (A- plus T or/and N+): 23.9%. ATN profiles prevalence was strongly influenced by age, showing differences according to gender, APOE genotype, and cognitive status. At baseline, 74.6% of patients classified as AD fell in the AD continuum, decreasing to 47.4% in mild cognitive impairment and 42.3% in other neurodegenerative conditions. At follow-up, 41% of patients changed diagnosis, and 92% of patients that changed to AD were classified within the AD continuum. Aâ+âwas the best individual marker for predicting a final AD diagnosis, and the combinations Aâ+âT+ (irrespective of N) and Aâ+âT+N+ had the highest overall accuracy (83%). CONCLUSION: The ATN scheme is useful to guide AD diagnosis in real-life neurological centers settings. However, it shows a lack of accuracy for patients with other types of dementia. In such cases, the inclusion of other markers specific for non-AD proteinopathies could be an important aid to the differential diagnosis.
Assuntos
Doença de Alzheimer , Amiloidose , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides , Proteínas tau , Disfunção Cognitiva/diagnóstico , Biomarcadores , Proteínas Amiloidogênicas , Fragmentos de PeptídeosRESUMO
BACKGROUND AND AIMS: Increasing evidence suggests that inflammation plays an important role in brain aging and neurodegeneration. Pathological studies demonstrate the presence of C-reactive protein (CRP) in the senile plaques and neurofibrillary tangles in Alzheimer's disease (AD) brain tissue suggesting that CRP may play a role in its neuropathological processes. Some findings suggest that midlife elevations of serum CRP are a risk factor for AD. However, others found lower CRP levels in mild or moderate AD than in controls, suggesting that CRP levels could be different in different stages of disease. We aimed to assess the role of CRP as a predictor of Mild cognitive impairment (MCI) conversion into AD dementia. METHODS: We retrospectively reviewed the cohort of MCI patients followed at the Dementia Clinic, Neurology Department of University Hospital of Coimbra. We collected demographical, neuropsychological, genetic and laboratorial variables (including serum CRP measurements at the time of baseline laboratory tests). A Cox regression model was performed adjusted for the collected variables preconsidered to be predictors of dementia and the variable being studied (CRP) to assess for independent predictors of conversion. RESULTS: We included 130 patients, 58.5% female, with a mean age of onset of 65.5 ± 9.1 years and age at first assessment of 69.3 ± 8.5 years. The mean CRP was 0.33 ± 0.58 mg/dl. At follow-up (mean, 36.9 ± 27.0 months) 42.3% of MCI patients converted to dementia. Lower CSF Aß42 (HR = 0.999, 95%CI = [0.997, 1.000], p = 0.015), lower MMSE score (HR = 0.864, 95%CI = [0.510, 1.595], p = 0.008) and lower CRP quartile (HR = 0.597, 95%CI = [0.435, 0.819], p = 0.001) were independent predictors of conversion. CONCLUSION: CRP may add information of risk of conversion in MCI patients. Patients with lower CRP levels appear to have a more rapid conversion to AD dementia.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Idoso , Doença de Alzheimer/diagnóstico , Proteína C-Reativa , Disfunção Cognitiva/diagnóstico , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos RetrospectivosRESUMO
Objectives: The aim of this study was to analyze the psychometric and diagnostic properties of the Clock Drawing Test (CDT), scored according to the Babins, Rouleau, and Cahn scoring systems, for Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD) screening, and develop corresponding cutoff scores. Additionally, we assessed the construct validity of the CDT through exploratory and confirmatory factor analysis. Methods: We developed a cross-sectional study of ambulatory MCI and AD patients, divided in two clinical groups (450 MCI and 250 mild AD patients) and a normal control group (N = 400). All participants were assessed with the CDT, Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) for convergent validity. Results: The selected scoring systems presented adequate validity and reliability values. The proposed cutoff scores showed 60 to 65% sensitivity and 58 to 62% specificity to identify MCI patients. The corresponding values for AD were 84 to 90% sensitivity and 76 to 78% specificity. Exploratory and confirmatory factor analysis revealed that the Babins scoring system had good construct validity and allowed us to propose a three-factor model for this system. Conclusions: Our results confirmed the complexity of the CDT and support it as a cognitive screening instrument particularly sensitive to AD. The use of the CDT with MCI patients should be interpreted with more caution due to the lower sensitivity and specificity for milder forms of cognitive impairment.
Assuntos
Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Testes Neuropsicológicos/normas , Psicometria/métodos , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: This study aimed to understand the relationship between the Clock Drawing Test (CDT) and decreased blood flow in mild cognitive impairment (MCI) patients, using single-photon emission computed tomography. METHOD: We characterized regional cerebral blood flow (rCBF) and the correlation with clinical variables and future conversion to dementia in 94 amnestic MCI patients. Blood perfusion data was correlated with the CDT (quantitative and qualitative scores) in order to evaluate their relationship and usefulness in predicting conversion to dementia. RESULTS: MCI patients displayed reduced rCBF in brain areas including the caudate nucleus; the frontal, parietal, and temporal lobes; as well as the cerebral cortex and cerebellum. The decrease in rCBF was higher for patients who later developed dementia. At baseline, CDT scores of these patients correlated with hypoperfusion in cortical and subcortical areas typically affected in Alzheimer's disease (AD) median 3 years before developing dementia. CDT total score was significantly correlated with rCBF in the left temporal lobe and the putamen; the analysis of rCBF in Brodmann areas showed significant correlations between the several clock elements (face, numbers, and hands), underlying qualitative errors (stimulus-bound response and conceptual deficit), and rCBF, most significantly in the left inferior temporal gyrus, posterior entorhinal cortex, posterior cingulate cortex, left parahippocampal cortex, and left inferior prefrontal gyrus. CONCLUSIONS: This study showed that a quantitative score and a qualitative assessment of clock drawing (error analysis) corresponded to dysfunction in AD key areas at an early stage, supporting the CDT utility in the detection of prodromal AD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Assuntos
Encéfalo/fisiopatologia , Circulação Cerebrovascular/fisiologia , Disfunção Cognitiva/fisiopatologia , Demência/fisiopatologia , Progressão da Doença , Desempenho Psicomotor/fisiologia , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Demência/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
This study aims to investigate the relationship between structural changes in the retina and white matter in the brain, in early Alzheimer's disease (AD). Twenty-three healthy controls (mean ageâ=â63.4±7.5 years) and seventeen AD patients (mean ageâ=â66.5±6.6 years) were recruited for this study. By combining two imaging techniques-optical coherence tomography and diffusion tensor imaging (DTI)-the association between changes in the thickness of individual retinal layers and white matter dysfunction in early AD was assessed. Retinal layers were segmented, and thickness measurements were obtained for each layer. DTI images were analyzed with a quantitative data-driven approach to evaluating whole-brain diffusion metrics, using tract-based spatial statistics. Diffusion metrics, such as fractional anisotropy, are markers for white matter integrity. Multivariate and partial correlation analyses evaluating the association between individual retinal layers thickness and diffusion metrics were performed. We found that axial diffusivity, indexing axonal integrity, was significantly reduced in AD (pâ=â0.016, Cohen's dâ=â1.004) while in the retina, only a marginal trend for significance was found for the outer plexiform layer (pâ=â0.084, Cohen's dâ=â0.688). Furthermore, a positive association was found in the AD group between fractional anisotropy and the inner nuclear layer thickness (pâ<â0.05, râ=â0.419, corrected for multiple comparisons by controlling family-wise error rate). Our findings suggest that axonal damage in the brain dominates early on in this condition and shows an association with retinal structural integrity already at initial stages of AD. These findings are consistent with an early axonal degeneration mechanism in AD.
Assuntos
Doença de Alzheimer , Retina , Substância Branca , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Axônios/patologia , Disfunção Cognitiva/diagnóstico , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retina/diagnóstico por imagem , Retina/patologia , Tomografia de Coerência Óptica/métodos , Substância Branca/diagnóstico por imagem , Substância Branca/patologiaRESUMO
Frontotemporal lobar degeneration, the neuropathological substrate of frontotemporal dementia (FTD), is characterized by the deposition of protein aggregates, including tau. Evidence has shown concomitant amyloid pathology in some of these patients, which seems to contribute to a more aggressive disease. Our aim was to evaluate cerebrospinal fluid (CSF) amyloid-beta as a predictor of the mortality of FTD patients. We included 99 patients diagnosed with FTD-both behavioral and language variants-with no associated motor neuron disease, from whom a CSF sample was collected. These patients were followed prospectively in our center, and demographic and clinical data were obtained. The survival analysis was carried through a Cox regression model. Patients who died during follow up had a significantly lower CSF amyloid-beta1-42 than those who did not. The survival analysis demonstrated that an increased death rate was associated with a lower CSF amyloid-beta1-42 (HR = 0.999, 95% CI = [0.997, 1.000], p = 0.049). Neither demographic nor clinical variables, nor CSF total tau or p-tau were significantly associated with this endpoint. These results suggest that amyloid deposition in FTD patients may be associated with a higher mortality.
RESUMO
Mutations in the progranulin (PGRN) gene were recently described as the cause of ubiquitin positive frontotemporal dementia (FTD) in many families. Different frequencies of these genetic changes have been reported in diverse populations leading us to determine if these mutations were a major cause of FTD in the Portuguese population. The entire coding sequence plus exon 0 of PGRN were sequenced in a consecutive series of 46 FTD/CBS Portuguese patients. Two mutations were found: a novel pathogenic insertion (p.Gln300GlnfsX61) and a previously described point variant (p.T182M) of unclear pathogenicity. Pathogenic mutations in the PGRN gene were found in one of the 36 probands studied (3% of the probands in our series) who had a corticobasal syndrome presentation, indicating that in the Portuguese population, mutations in this gene are not a major cause of FTD.
Assuntos
Demência/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Mutação/genética , Análise Mutacional de DNA , Proteínas de Ligação a DNA/metabolismo , Demência/metabolismo , Saúde da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Portugal/epidemiologia , ProgranulinasRESUMO
The amyloid cascade hypothesis proposes amyloid-ß (Aß) as the earliest and key pathological hallmark of Alzheimer's disease (AD), but this mandatory "amyloid-first pathway" has been contested. Longitudinal studies of mild cognitive impairment (MCI) patients represent an opportunity to investigate the intensity of underlying biological processes (amyloidosis versus neurodegeneration) and their relevance for progression to AD. We re-examined our cohort of amnestic MCI, grouped according to cerebrospinal fluid (CSF) biomarkers, aiming at establishing their prognostic value for Alzheimer-type dementia and testing the hypothetical model of biomarkers sequence, based on the amyloid cascade. Our baseline population consisted of 217 MCI patients, 63% with neurodegeneration markers and 47% with amyloidosis. Within the longitudinal study-group (nâ=â165), 85 progressed to AD and 80 remained cognitively stable. Age, CSF Aß42, and t-Tau were identified as the best single predictors of conversion to AD. Regarding MCI classification according to the NIA-AA criteria, the high-AD-likelihood group (HL-both amyloid and neurodegeneration markers) was the most frequent (42%); followed by the Suspected Non-Alzheimer Pathophysiology group (SNAP-26%), the low-AD-likelihood group (LL-negative biomarkers-22%), and the Isolated Amyloid Pathology group (IAP-10%). Risk of progression to AD was higher in HL in relation to the LL group (HRâ=â6.1, 95% CIâ=â2.1-18.0, pâ=â0.001). SNAP and IAP groups were equivalent in terms of risk of progression to AD (IAP: HRâ=â2.6, 95% CIâ=â0.7-9.3, pâ=â0.141; SNAP: HRâ=â3.1, 95% CIâ=â1.1-9.6; pâ=â0.046), but only SNAP was significantly different from the LL group. These results support different neurobiological pathways to AD beyond the amyloid hypothesis, highlighting the alternative "neurodegeneration-first pathway" for further investigation.
Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Amiloidose/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Amnésia/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Progressão da Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Testes Neuropsicológicos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidianoRESUMO
RESUMO Objetivo: O objetivo deste estudo foi analisar o comportamento alimentar de crianças e adolescentes com transtorno do espectro autista. Métodos: Participaram deste estudo 21 crianças e adolescentes com TEA, na faixa etária de 2 a 14 anos de idade, de ambos os sexos. Foi aplicado um questionário sobre o comportamento alimentar com os 21 pais e/ou responsáveis das crianças. Esse instrumento é composto por 53 questões, distribuídas nas seguintes categorias: Motricidade na mastigação; Seletividade alimentar; Aspectos comportamentais; Sintomas gastrointestinais; Sensibilidade sensorial e Habilidades nas refeições. Resultados: A análise dos dados obtidos revela que as crianças com TEA apresentaram maiores alterações no comportamento alimentar nas categorias Seletividade alimentar (34,4%), Aspectos comportamentais (27,1%) e Motricidade na mastigação (21,9%). E houve correlação entre a categoria Motricidade na mastigação com todas as outras categorias. Houve também correlação entre seletividade alimentar com aspectos comportamentais e aspectos comportamentais com sensibilidade sensorial e habilidades nas refeições. Conclusão: Portanto, é possível observar que, no comportamento alimentar de crianças e adolescentes com TEA, há uma tendência a seletividade alimentar, comportamentos habituais durante as refeições e dificuldades motoras no que se refere à mastigação e à ingestão dos alimentos.
ABSTRACT Objective: The objective of this study was to analyze feeding behavior in children with autism spectrum disorder. Methods: Twenty-one children with autism spectrum disorder (ASD) participated in this study, aged 2 to 14 years old, of both sexes. A questionnaire on feeding behavior was applied to the 21 parents and/or responsible of the children. This instrument consists of 53 questions, distributed in the following categories: Motricity in chewing; Food selectivity; Behavioral aspects; Gastrointestinal symptoms; Sensory sensitivity and Skills in meals. Results: The analysis of the data obtained reveals that children with ASD showed greater changes in eating behavior in the categories Food selectivity (34.4%), Behavioral aspects (27.1%) and Motricity in mastication (21.9%). And there was a correlation between the chewing motricity category with all other categories. There was also a correlation between food selectivity with behavioral aspects and behavioral aspects with sensory sensitivity and mealtime skills. Conclusion: Therefore, it is possible to observe that in the eating behavior of children with autism spectrum disorder there is a tendency towards food selectivity, habitual behaviors during meals and motor difficulties with regard to chewing and food intake.
RESUMO
Amnestic mild cognitive impairment (aMCI) patients carry a greater risk of conversion to Alzheimer's disease (AD). Therefore, the International Working Group (IWG) on AD aims to consider some cases of aMCI as symptomatic prodromal AD. The core diagnostic marker of AD is a significant and progressive memory deficit, and the Free and Cued Selective Reminding Test (FCSRT) was recommended by the IWG to test memory in cases of possible prodromal AD. This study aims to investigate whether the performance on the FCSRT would enhance the ability to predict conversion to AD in an aMCI group. A longitudinal study was conducted on 88 aMCI patients, and neuropsychological tests were analysed on the relative risk of conversion to AD. During follow-up (23.82 months), 33% of the aMCI population converted to AD. An impaired FCSRT TR was significantly associated with the risk of conversion to dementia, with a mean time to conversion of 25 months. The FCSRT demonstrates utility for detecting AD at its prodromal stage, thus supporting its use as a valid clinical marker.
Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/etiologia , Disfunção Cognitiva/fisiopatologia , Idoso , Apolipoproteínas E/genética , Disfunção Cognitiva/genética , Sinais (Psicologia) , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Valor Preditivo dos Testes , Estudos Retrospectivos , Estatísticas não ParamétricasRESUMO
Objetivo: identificar a percepção dos discentes de cursos técnicos e de graduação da área da saúde sobre o atendimento às pessoas com deficiência auditiva nos serviços de saúde e sua capacitação para realizar esse atendimento. Método: Foi realizada uma pesquisa quantitativa, exploratória e descritiva, entre novembro e dezembro de 2021, por meio de questionário online. Resultados: Participaram 198 discentes de uma instituição de ensino de São Paulo.67,68% dos discentes declararam não ter conhecimento em Libras;74,24% discordaram de que foram preparados, durante a formação, para assistir integralmente o paciente com deficiência auditiva. Para 87,88%Libras deveria ser uma matéria obrigatória nos cursos da área da saúde e 80,30% não consideram suficiente o conteúdo que foi abordado sobre o atendimento aos deficientes auditivo. Conclusão:Evidenciou-se a necessidade de capacitação dos discentes da área de saúdepara que o atendimento às pessoas com deficiência auditiva possa ser realizado de maneira qualificada.(AU)
Objective: to identify the perception of students of technical and undergraduate courses in the health area about the care for people with hearing impairment in health services and their training to perform this care. Method: A quantitative, exploratory and descriptive research was carried out between November and December 2021, using an online questionnaire. Results: 198 students from an educational institution in São Paulo participated. 67.68% of the students declared not having knowledge in Libras; 74.24% disagreed that they were prepared, during training, to fully assist the patient with hearing impairment. For 87.88% Libras should be a mandatory subject in courses in the health area and 80.30% do not consider the content that was addressed on the care of the hearing impaired to be sufficient. Conclusion: There is a need to train students in the health area so that the care for people with hearing impairment can be carried out in a qualified manner.(AU)
Objetivo: identificar la percepción de estudiantes de carreras técnicas y de pregrado en el área de la salud sobre la atención a las personas con deficiencia auditiva en los servicios de salud y su formación para realizar esa atención. Método: Se realizó una investigación cuantitativa, exploratoria y descriptiva entre noviembre y diciembre de 2021, mediante un cuestionario en línea. Resultados: Participaron 198 estudiantes de una institución educativa de São Paulo, el 67,68% de los estudiantes declararon no tener conocimiento en Libras, el 74,24% no estuvo de acuerdo con que estuvieran preparados, durante la formación, para asistir integralmente al paciente con deficiencia auditiva. Para el 87,88% Libras debería ser materia obligatoria en los cursos del área de la salud y el 80,30% no considera suficiente el contenido que se abordó sobre la atención al sordo. Conclusión: Existe la necesidad de formar a los estudiantes del área de la salud para que la atención a las personas con deficiencia auditiva pueda ser realizada de forma calificada.(AU)