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1.
Hum Brain Mapp ; 45(4): e26618, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38414286

RESUMO

BACKGROUND: Age-related cognitive decline is linked to changes in the brain, particularly the deterioration of white matter (WM) microstructure that accelerates after the age of 60. WM deterioration is associated with mild cognitive impairment and dementia, but the origin and role of white matter signal abnormalities (WMSA) seen in standard MRI remain debated due to their heterogeneity. This study explores the potential of single-shell 3-tissue constrained spherical deconvolution (SS3T-CSD), a novel technique that models diffusion data in terms of gray matter (TG ), white matter (Tw ), and cerebrospinal fluid (TC ), to differentiate WMSA from normal-appearing white matter and better understand the interplay between changes in WM microstructure and decline in cognition. METHODS: A total of 189 individuals from the GENIC cohort were included. MRI data, including T1-weighted and diffusion images, were obtained. Preprocessing steps were performed on the diffusion MRI data, followed by the SS3T-CSD. WMSA were segmented using FreeSurfer. Statistical analyses were conducted to assess the association between age, WMSA volume, 3-tissue signal fractions (Tw , TG , and TC ), and neuropsychological variables. RESULTS: Participants above 60 years old showed worse cognitive performance and processing speed compared to those below 60 (p < .001). Age was negatively associated with Tw in normal-appearing white matter (p < .001) and positively associated with TG in both WMSA (p < .01) and normal-appearing white matter (p < .001). Age was also significantly associated with WMSA volume (p < .001). Higher processing speed was associated with lower Tw and higher TG , in normal-appearing white matter (p < .01 and p < .001, respectively), as well as increased WMSA volume (p < .001). Similarly, lower MMSE scores correlated with lower Tw and higher TG in normal-appearing white matter (p < .05). High cholesterol and hypertension were associated with higher WMSA volume (p < .05). CONCLUSION: The microstructural heterogeneity within normal-appearing white matter and WMSA is associated with increasing age and cognitive variation, in cognitively unimpaired individuals. Furthermore, the 3-tissue signal fractions are more specific to potential white matter alterations than conventional MRI measures such as WMSA volume. These findings also support the view that the WMSA volumes may be more influenced by vascular risk factors than the 3-tissue metrics. Finally, the 3-tissue metrics were able to capture associations with cognitive tests and therefore capable of capturing subtle pathological changes in the brain in individuals who are still within the normal range of cognitive performance.


Assuntos
Substância Branca , Humanos , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imagem de Difusão por Ressonância Magnética , Envelhecimento/patologia , Cognição , Imageamento por Ressonância Magnética
2.
Brain ; 146(5): 2075-2088, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36288546

RESUMO

Previous studies have shown that the cholinergic nucleus basalis of Meynert and its white matter projections are affected in Alzheimer's disease dementia and mild cognitive impairment. However, it is still unknown whether these alterations can be found in individuals with subjective cognitive decline, and whether they are more pronounced than changes found in conventional brain volumetric measurements. To address these questions, we investigated microstructural alterations of two major cholinergic pathways in individuals along the Alzheimer's disease continuum using an in vivo model of the human cholinergic system based on neuroimaging. We included 402 participants (52 Alzheimer's disease, 66 mild cognitive impairment, 172 subjective cognitive decline and 112 healthy controls) from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study. We modelled the cholinergic white matter pathways with an enhanced diffusion neuroimaging pipeline that included probabilistic fibre-tracking methods and prior anatomical knowledge. The integrity of the cholinergic white matter pathways was compared between stages of the Alzheimer's disease continuum, in the whole cohort and in a CSF amyloid-beta stratified subsample. The discriminative power of the integrity of the pathways was compared to the conventional volumetric measures of hippocampus and nucleus basalis of Meynert, using a receiver operating characteristics analysis. A multivariate model was used to investigate the role of these pathways in relation to cognitive performance. We found that the integrity of the cholinergic white matter pathways was significantly reduced in all stages of the Alzheimer's disease continuum, including individuals with subjective cognitive decline. The differences involved posterior cholinergic white matter in the subjective cognitive decline stage and extended to anterior frontal white matter in mild cognitive impairment and Alzheimer's disease dementia stages. Both cholinergic pathways and conventional volumetric measures showed higher predictive power in the more advanced stages of the disease, i.e. mild cognitive impairment and Alzheimer's disease dementia. In contrast, the integrity of cholinergic pathways was more informative in distinguishing subjective cognitive decline from healthy controls, as compared with the volumetric measures. The multivariate model revealed a moderate contribution of the cholinergic white matter pathways but not of volumetric measures towards memory tests in the subjective cognitive decline and mild cognitive impairment stages. In conclusion, we demonstrated that cholinergic white matter pathways are altered already in subjective cognitive decline individuals, preceding the more widespread alterations found in mild cognitive impairment and Alzheimer's disease. The integrity of the cholinergic pathways identified the early stages of Alzheimer's disease better than conventional volumetric measures such as hippocampal volume or volume of cholinergic nucleus basalis of Meynert.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Substância Branca , Humanos , Doença de Alzheimer/psicologia , Encéfalo , Disfunção Cognitiva/psicologia , Colinérgicos
3.
Alzheimers Dement ; 20(3): 1815-1826, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38131463

RESUMO

INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. HIGHLIGHTS: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.


Assuntos
Doença de Alzheimer , Doença por Corpos de Lewy , Humanos , Masculino , Feminino , Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/patologia , Doença de Alzheimer/patologia , Caracteres Sexuais , Córtex Cerebral/patologia , Atrofia/patologia , Imageamento por Ressonância Magnética
4.
Hum Brain Mapp ; 44(4): 1289-1308, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36468536

RESUMO

Predicting brain aging can help in the early detection and prognosis of neurodegenerative diseases. Longitudinal cohorts of healthy subjects scanned through magnetic resonance imaging (MRI) have been essential to understand the structural brain changes due to aging. However, these cohorts suffer from missing data due to logistic issues in the recruitment of subjects. This paper proposes a methodology for filling up missing data in longitudinal cohorts with anatomically plausible images that capture the subject-specific aging process. The proposed methodology is developed within the framework of diffeomorphic registration. First, two novel modules are introduced within Synthmorph, a fast, state-of-the-art deep learning-based diffeomorphic registration method, to simulate the aging process between the first and last available MRI scan for each subject in three-dimensional (3D). The use of image registration also makes the generated images plausible by construction. Second, we used six image similarity measurements to rearrange the generated images to the specific age range. Finally, we estimated the age of every generated image by using the assumption of linear brain decay in healthy subjects. The methodology was evaluated on 2662 T1-weighted MRI scans from 796 healthy participants from 3 different longitudinal cohorts: Alzheimer's Disease Neuroimaging Initiative, Open Access Series of Imaging Studies-3, and Group of Neuropsychological Studies of the Canary Islands (GENIC). In total, we generated 7548 images to simulate the access of a scan per subject every 6 months in these cohorts. We evaluated the quality of the synthetic images using six quantitative measurements and a qualitative assessment by an experienced neuroradiologist with state-of-the-art results. The assumption of linear brain decay was accurate in these cohorts (R2  ∈ [.924, .940]). The experimental results show that the proposed methodology can produce anatomically plausible aging predictions that can be used to enhance longitudinal datasets. Compared to deep learning-based generative methods, diffeomorphic registration is more likely to preserve the anatomy of the different structures of the brain, which makes it more appropriate for its use in clinical applications. The proposed methodology is able to efficiently simulate anatomically plausible 3D MRI scans of brain aging of healthy subjects from two images scanned at two different time points.


Assuntos
Encéfalo , Imageamento Tridimensional , Humanos , Imageamento Tridimensional/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Envelhecimento , Processamento de Imagem Assistida por Computador/métodos , Algoritmos
5.
Mov Disord ; 38(1): 4-15, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36253921

RESUMO

Studies on dementia with Lewy bodies (DLB) have mainly focused on the degeneration of distinct cortical and subcortical regions related to the deposition of Lewy bodies. In view of the proposed trans-synaptic spread of the α-synuclein pathology, investigating the disease only in this segregated fashion would be detrimental to our understanding of its progression. In this systematic review, we summarize findings on structural and functional brain connectivity in DLB, as connectivity measures may offer better insights on how the brain is affected by the spread of the pathology. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched Web of Science, PubMed, and SCOPUS for relevant articles published up to November 1, 2021. Of 1215 identified records, we selected and systematically reviewed 53 articles that compared connectivity features between patients with DLB and healthy controls. Structural and functional magnetic resonance imaging, positron emission tomography, single-positron emission computer tomography, and electroencephalography assessments of patients revealed widespread abnormalities within and across brain networks in DLB. Frontoparietal, default mode, and visual networks and their connections to other brain regions featured the most consistent disruptions, which were also associated with core clinical features and cognitive impairments. Furthermore, graph theoretical measures revealed disease-related decreases in local and global network efficiency. This systematic review shows that structural and functional connectivity characteristics in DLB may be particularly valuable at early stages, before overt brain atrophy can be observed. This knowledge may help improve the diagnosis and prognosis in DLB as well as pinpoint targets for future disease-modifying treatments. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Doença de Alzheimer , Doença por Corpos de Lewy , Humanos , Doença por Corpos de Lewy/patologia , Corpos de Lewy/patologia , Encéfalo/patologia , Eletroencefalografia , Tomografia por Emissão de Pósitrons , Doença de Alzheimer/patologia
6.
BMC Geriatr ; 23(1): 853, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38097933

RESUMO

BACKGROUND: The benefits of physical activity (PA) and adequate sleep are well documented, and their importance strengthens with the increasing prevalence of chronic diseases and multimorbidity (MM). Interventions to promote physical activity and sleep that use commercial activity trackers may be useful non-pharmacological approaches to managing individual health; however, limited evidence exists on their use to improve physical activity in older adult patients with MM. METHODS: This study aims to measure the effects of behavioral change techniques (BCTs) delivered by a wearable device on physical activity and quality of sleep (QS) in older adult patients with MM. We designed an open-label randomized controlled trial with participants recruited through primary care and a specialist outpatient clinic. Participants must be more than 65 years old, have MM, and have access to smartphones. All eligible participants will receive PA promotion content and will be randomly assigned to wear a smartwatch. The primary outcome will be the participants' PA measurement at baseline and at six months using the International Physical Activity Questionnaire - Short Form (IPAQ-SF). Secondary outcomes will include changes in the participants' frailty status, biometric measurements, quality of life, and biopsychosocial assessments. A sample size of 40 participants per arm was calculated to detect group differences, with 50 participants planned to recruit and randomize into each arm. DISCUSSION: This study aims to contribute to a better understanding of PA patterns and the impact of wearable-based PA interventions in patients with MM. In addition, we aim to contribute to more knowledge about the relationship between PA patterns, Patient Reported Outcomes Measures (PROMs), and healthcare resource utilization in patients with MM. To achieve this, the study will leverage a locally developed PROMs registry and assess data from participants' medical records, in order to understand the added impact of wearable data and medical information data on predicting PROMs and unplanned hospital admissions. TRIAL REGISTRATION: NCT05777291.


Assuntos
Multimorbidade , Dispositivos Eletrônicos Vestíveis , Humanos , Idoso , Qualidade de Vida/psicologia , Exercício Físico/psicologia , Sono , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Alzheimers Dement ; 19(7): 3186-3202, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37096339

RESUMO

INTRODUCTION: Operationalized research criteria for mild cognitive impairment with Lewy bodies (MCI-LB) were published in 2020. The aim of this systematic review and meta-analysis was to review the evidence for the diagnostic clinical features and biomarkers in MCI-LB set out in the criteria. METHODS: MEDLINE, PubMed, and Embase were searched on 9/28/22 for relevant articles. Articles were included if they presented original data reporting the rates of diagnostic features in MCI-LB. RESULTS: Fifty-seven articles were included. The meta-analysis supported the inclusion of the current clinical features in the diagnostic criteria. Evidence for striatal dopaminergic imaging and meta-iodobenzylguanidine cardiac scintigraphy, though limited, supports their inclusion. Quantitative electroencephalogram (EEG) and fluorodeoxyglucose positron emission tomography (PET) show promise as diagnostic biomarkers. DISCUSSION: The available evidence largely supports the current diagnostic criteria for MCI-LB. Further evidence will help refine the diagnostic criteria and understand how best to apply them in clinical practice and research. HIGHLIGHTS: A meta-analysis of the diagnostic features of MCI-LB was carried out. The four core clinical features were more common in MCI-LB than MCI-AD/stable MCI. Neuropsychiatric and autonomic features were also more common in MCI-LB. More evidence is needed for the proposed biomarkers. FDG-PET and quantitative EEG show promise as diagnostic biomarkers in MCI-LB.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença por Corpos de Lewy , Humanos , Doença de Alzheimer/diagnóstico , Corpos de Lewy , Sensibilidade e Especificidade , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Biomarcadores , Doença por Corpos de Lewy/diagnóstico por imagem
8.
Alzheimers Dement ; 19(1): 318-332, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36239924

RESUMO

Dementia with Lewy bodies (DLB) is clinically defined by the presence of visual hallucinations, fluctuations, rapid eye movement (REM) sleep behavioral disorder, and parkinsonism. Neuropathologically, it is characterized by the presence of Lewy pathology. However, neuropathological studies have demonstrated the high prevalence of coexistent Alzheimer's disease, TAR DNA-binding protein 43 (TDP-43), and cerebrovascular pathologic cases. Due to their high prevalence and clinical impact on DLB individuals, clinical trials should account for these co-pathologies in their design and selection and the interpretation of biomarkers values and outcomes. Here we discuss the frequency of the different co-pathologies in DLB and their cross-sectional and longitudinal clinical impact. We then evaluate the utility and possible applications of disease-specific and disease-nonspecific biomarkers and how co-pathologies can impact these biomarkers. We propose a framework for integrating multi-modal biomarker fingerprints and step-wise selection and assessment of DLB individuals for clinical trials, monitoring target engagement, and interpreting outcomes in the setting of co-pathologies.


Assuntos
Doença por Corpos de Lewy , Humanos , Doença de Alzheimer/patologia , Biomarcadores , Ensaios Clínicos como Assunto , Estudos Transversais , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/patologia , Transtornos Parkinsonianos/etiologia , Transtorno do Comportamento do Sono REM/etiologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo
9.
J Urol ; 207(3): 647-656, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34694154

RESUMO

PURPOSE: High-quality evidence comparing supine to prone percutaneous nephrolithotomy (PCNL) for the treatment of complex stones is lacking. This study aimed to compare the outcomes of supine position (SUP) and prone position (PRO) PCNL. MATERIALS AND METHODS: A noninferior randomized controlled trial was performed according to the CONSORT (Consolidated Standards for Reporting Trials) criteria. The inclusion criteria were patients over 18 years of age with complex stones. SUP was performed in the Barts flank-free modified position. Except for positioning, all the surgical parameters were identical. The primary outcome was the difference in the success rate on the first postoperative day (POD1) between groups. The secondary outcome was the difference in the stone-free rate (SFR) on the 90th postoperative day (final SFR). A noninferiority margin of 15% was used. Demographic, operative, and safety variables were compared between the groups. Statistical significance was set at p <0.05. RESULTS: Overall, 112 patients were randomized and their demographic characteristics were comparable. The success rates on POD1 were similar (SUP: 62.5% vs PRO: 57.1%, p=0.563). The difference observed (-5.4%) was lower than the predefined limit. The final SFRs were also similar (SUP: 55.4% vs PRO: 50.0%, p=0.571). SUP had a shorter operative time (mean±SD 117.9±39.1 minutes vs 147.6±38.8 minutes, p <0.001) and PRO had a higher rate of Clavien ≥3 complications (14.3% vs 3.6%, p=0.045). CONCLUSIONS: Positioning during PCNL for complex kidney stones did not impact the success rates; consequently, both positions may be suitable. However, SUP might be associated with a lower high-grade complication rate.


Assuntos
Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/métodos , Posicionamento do Paciente , Cistoscopia , Feminino , Fluoroscopia , Humanos , Cálculos Renais/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Decúbito Ventral , Decúbito Dorsal , Tomografia Computadorizada por Raios X
10.
Dement Geriatr Cogn Disord ; 51(1): 63-72, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35339996

RESUMO

INTRODUCTION: Early markers of neurodegeneration provide an opportunity to detect, monitor, and initiate interventions in individuals who have an increased risk of developing dementia. Here, we investigated whether the Timed Up and Go (TUG) test is associated with early brain neurodegeneration and whether the TUG test could be a marker of cognitive decline in people with subjective cognitive decline (SCD). METHODS: This is a longitudinal analysis of the Dementia Disease Initiation Study, a prospective, community-based, cohort study from Norway, designed to investigate early markers of cognitive impairment and dementia. Participants were classified as SCD and healthy controls (HC). The main studied variables were the TUG test and cognition as measured by the Mini-Mental State Examination and the Consortium to Establish a Registry for Alzheimer's Disease memory composite score. Additionally, we investigated the cross-sectional association of brain morphology with the TUG using 1.5T-MRI. RESULTS: The sample included 45 participants (SCD = 21, HC = 24) followed during a mean time of 1.50 ± 0.70 years. At baseline, the cognitive performance did not differ between the groups, but TUG was longer in SCD. Slower baseline TUG was associated with a faster cognitive decline in both groups and it was also associated with reduced cortical thickness especially in motor, executive, associative, and somatosensory cortical regions in people with SCD. DISCUSSION/CONCLUSION: TUG predicted cognitive change in individuals with SCD, and there was a negative association between TUG and cortical thickness. TUG is a promising cheap and noninvasive marker of early cognitive decline and may help initiate interventions in individuals who have an increased risk of dementia.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Cognição , Disfunção Cognitiva/psicologia , Estudos de Coortes , Estudos Transversais , Humanos , Estudos Prospectivos
11.
Cereb Cortex ; 31(8): 3832-3845, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33866353

RESUMO

Elucidating compensatory mechanisms underpinning phonemic fluency (PF) may help to minimize its decline due to normal aging or neurodegenerative diseases. We investigated cortical brain networks potentially underpinning compensation of age-related differences in PF. Using graph theory, we constructed networks from measures of thickness for PF, semantic, and executive-visuospatial cortical networks. A total of 267 cognitively healthy individuals were divided into younger age (YA, 38-58 years) and older age (OA, 59-79 years) groups with low performance (LP) and high performance (HP) in PF: YA-LP, YA-HP, OA-LP, OA-HP. We found that the same pattern of reduced efficiency and increased transitivity was associated with both HP (compensation) and OA (aberrant network organization) in the PF and semantic cortical networks. When compared with the OA-LP group, the higher PF performance in the OA-HP group was associated with more segregated PF and semantic cortical networks, greater participation of frontal nodes, and stronger correlations within the PF cortical network. We conclude that more segregated cortical networks with strong involvement of frontal nodes seemed to allow older adults to maintain their high PF performance. Nodal analyses and measures of strength were helpful to disentangle compensation from the aberrant network organization associated with OA.


Assuntos
Envelhecimento/fisiologia , Córtex Cerebral/fisiologia , Rede Nervosa/fisiologia , Comportamento Verbal/fisiologia , Adulto , Idoso , Mapeamento Encefálico , Função Executiva , Feminino , Lobo Frontal/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Desempenho Psicomotor/fisiologia
12.
An Acad Bras Cienc ; 94(4): e20190944, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36449886

RESUMO

The water retention curve is widely used in studies involving soil. The management systems directly influence soil structure by altering water retention dynamics. Several equations are used to adjust the retention of water in the soil, but most of the time, the choice of these models occurs in an arbitrary way. From this problem, it was proposed with the present study to relate the best mathematical model to water retention, taking into account the different management systems adopted, based on previously established adjustment criteria. For the accomplishment the study, a soil of caulinitic mineralogy and average texture was utilized. The treatments were area under native Cerrado (Savanna), eucalyptus plantation with six and twelve years of cultivation, pasture with two and six years of cultivation, conventional plantation with two and eight years of cultivation, no-till with three and six years of cultivation. From the adjustment criteria for non-linear models, it was found that the management influences the choice of the water retention model. It is possible to observe that the greatest divergences between the models occurred close to the soil saturation zone, and that the Fredlung-Xing model is more efficient in adjusting the water retention curve under conservationist management systems.


Assuntos
Eucalyptus , Solo , Água
13.
Alzheimers Dement ; 18(7): 1383-1395, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34877786

RESUMO

INTRODUCTION: Harboring two copies of the apolipoprotein E (APOE) ε2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. METHODS: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired ε2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of ε2 genotypic groups were compared to each other and to the reference group (APOE ε3/ε3). RESULTS: Carrying at least one ε2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE ε2 homozygotes, but not APOE ε2 heterozygotes, showed larger GM volumes in areas related to successful aging. DISCUSSION: In addition to the known resistance against amyloid-ß deposition, the larger GM volumes in key brain regions may confer APOE ε2 homozygotes additional protection against AD-related cognitive decline.


Assuntos
Doença de Alzheimer , Apolipoproteína E2 , Disfunção Cognitiva , Dosagem de Genes , Alelos , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Apolipoproteína E2/genética , Disfunção Cognitiva/genética , Genótipo , Substância Cinzenta/patologia , Humanos
14.
Alzheimers Dement ; 18(1): 29-42, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33984176

RESUMO

INTRODUCTION: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts. METHODS: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives. RESULTS: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes. DISCUSSION: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.


Assuntos
Disfunção Cognitiva , Conferências de Consenso como Assunto , Conjuntos de Dados como Assunto/normas , Testes Neuropsicológicos/normas , Fatores Etários , Cognição , Disfunção Cognitiva/classificação , Disfunção Cognitiva/diagnóstico , Escolaridade , Europa (Continente) , Prova Pericial , Humanos , Idioma , Fatores Sexuais
15.
J Stroke Cerebrovasc Dis ; 31(4): 106313, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35093627

RESUMO

BACKGROUND AND PURPOSE: Contrary to anterior circulation, the legitimacy of endovascular treatment in posterior circulation stroke is still being questioned. Finding reliable prognostic factors and determining how patient selection should be done has become top priority. METHODS: Observational and retrospective study from two Portuguese hospitals, including all consecutive patients with posterior circulation occlusions who underwent thrombectomy between January 1st 2015 and December 31st 2019. RESULTS: Out of a total of 126 patients, the median age was 74 (IQR 61-80) and 39.7% were female. A good clinical outcome (mRS ≤2) was associated with a lower incidence of coma (24,2% vs 66,7%, p < 0,001) and of sudden onset coma (3% vs 18%,=0,04), a lower NIHSS at admission (14 vs 19, p < 0,001), a higher pc-ASPECTS at admission (10 vs 9, p < 0,001) and at 24 h (8 vs 6, p < 0,001) and a higher BATMAN score (7 vs 6, p = 0,017). Differences in the times of symptom-onset-to-recanalization (496 vs 536, p = 0,19) and symptom-onset-to-coma (130 vs 195, p = 0,52) were not remarkable. When excluding NIHSS and pc-ASPECTS at 24 h, coma (p = 0,003; OR=0,22; 95% CI: 0,08-0,59) and the pc-ASPECTS at admission (p = 0,037; OR=1,63; 95% CI: 1,03-2,57) become independent predictors of good outcome. CONCLUSIONS: In strokes from the posterior circulation, coma, more than time, appears to be an important prognostic factor. The BATMAN and the pc-ASPECTS scores were also associated with clinical outcome and coma.


Assuntos
Procedimentos Endovasculares , Acidente Vascular Cerebral , Idoso , Encéfalo , Coma/diagnóstico , Coma/terapia , Feminino , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Trombectomia , Resultado do Tratamento
16.
Pharmacol Res ; 164: 105309, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33212291

RESUMO

In the last decade, immunotherapy led to a paradigm shift in the treatment of numerous malignancies. Alongside with monoclonal antibodies blocking programmed cell death receptor-1 (PD-1)/PD-L1 and cytotoxic T- lymphocyte antigen 4 (CTLA-4) immune checkpoints, cell-based approaches such as CAR-T cells and dendritic cell (DC) vaccines have strongly contributed to pushing forward this thrilling field. While initial strategies were mainly focused on monotherapeutic regimens, it is now consensual that the combination of immunotherapies tackling multiple cancer hallmarks can result in superior clinical outcomes. Here, we review in depth the pharmacological combination of DC-based vaccines that boost tumour elimination by eliciting and expanding effector immune cells, with the PD-1 inhibitor Nivolumab that allows blocking key tumour immune escape mechanisms. This combination represents an important step in cancer therapy, with a significant enhancement in patient survival in several types of tumours, paving an important way in establishing combinatorial immunotherapeutic strategies as first-line treatments.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Células Dendríticas/imunologia , Inibidores de Checkpoint Imunológico/administração & dosagem , Imunoterapia , Neoplasias/terapia , Nivolumabe/administração & dosagem , Animais , Terapia Combinada , Humanos , Receptor de Morte Celular Programada 1/antagonistas & inibidores
17.
Acta Neurol Scand ; 144(2): 221-225, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33835482

RESUMO

BACKGROUND: The COVID-19 pandemic forced the implementation of social distancing and circulation restrictions. This affected all aspects of society including health care. In the field of chronic neurological disorders such as Parkinson's disease (PD), teleneurology is employed in scenarios where face-to-face interactions are not possible. A growing number of clinicians and institutions are turning to teleneurology in order to providing medical care. AIMS OF THE ARTICLE: In this manuscript, we present a practical, 'how we do it in real life', example of a teleneurology appointment with a person with PD (PwP). METHODS: We elaborated a step-by-step approach of the main aspects of a consultation with a PwP and provide video illustration. RESULTS: The key aspects of a teleneurology appointment were separated into: (1) In the office, before the appointment; (2) History taking; (3) Examination; and (4) Finishing up. CONCLUSIONS: We discuss the strengths and weaknesses of this approach and provide our experience in overcoming commonly encountered difficulties.


Assuntos
COVID-19 , Neurologia , Doença de Parkinson , Telemedicina , Comunicação por Videoconferência , COVID-19/prevenção & controle , Humanos , Guias de Prática Clínica como Assunto
18.
J Mater Sci Mater Med ; 32(4): 39, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792773

RESUMO

Biomaterials used in tissue regeneration processes represent a promising option for the versatility of its physical and chemical characteristics, allowing for assisting or speeding up the repair process stages. This research has characterized a polyurethane produced from castor oil monoacylglyceride (Ricinus communis L) and tested its effect on reconstructing bone defects in rat calvaria, comparing it with commercial castor oil polyurethane. The characterizations of the synthesized polyurethane have been performed by spectroscopy in the infrared region with Fourier transform (FTIR); thermogravimetric analysis (TG/DTG); X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM). For the in vivo test, 24 animals have been used, divided into 3 groups: untreated group (UG); control group treated with Poliquil® castor polyurethane (PCP) and another group treated with castor polyurethane from the Federal University of Piauí - UFPI (CPU). Sixteen weeks after surgery, samples of the defects were collected for histological and histomorphometric analysis. FTIR analysis has shown the formation of monoacylglyceride and polyurethane. TG and DTG have indicated thermal stability of around 125 °C. XRD has determined the semi-crystallinity of the material. The polyurethane SEM has shown a smooth morphology with areas of recesses. Histological and histomorphometric analyzes have indicated that neither CPU nor PCP induced a significant inflammatory process, and CPU has shown, statistically, better performance in bone formation. The data obtained shows that CPU can be used in the future for bone reconstruction in the medical field.


Assuntos
Fraturas Ósseas/cirurgia , Monoglicerídeos/química , Poliuretanos/química , Ricinus/química , Animais , Materiais Biocompatíveis/química , Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/farmacologia , Osso e Ossos/metabolismo , Óleo de Rícino/química , Consolidação da Fratura , Inflamação , Masculino , Teste de Materiais , Microscopia Eletrônica de Varredura , Osteogênese/efeitos dos fármacos , Ratos , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Difração de Raios X
19.
An Acad Bras Cienc ; 93(3): e20190731, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33950135

RESUMO

The objective of this study was to evaluate high-concentrate diets and two energy sources on intake, performance and meat quality parameters of feedlot Nellore heifers. Twenty-eight heifers (200 ± 22.5 kg BW) were randomly assigned to four treatments in a 2×2 factorial arrangement: two concentrate levels (70 and 80%) and two energy sources (corn and corn germ meal). At the end of day 112, heifers were slaughtered. There was no interaction (P>0.05) of concentrate levels and energy sources for dry matter intake, unlike crude protein (CP) and neutral detergent fiber (NDF) intakes. The concentrate level of 80% and corn, allowed the highest CP (1.17 kg/day) and NDF (4.05 kg/day) intakes. Final BW (P<0.05) and daily gain (P<0.01) were influenced just by energy source. The carcass composition represented by muscle and fat was affected by concentrate level (P<0.05). Treatments affected (P<0.01) carcass fat deposition, global preference and texture of Longissimus muscle (P<0.05). It was concluded that high proportions of concentrate containing corn as energy source provided the best performance in heifers, and that the total replacement of corn with corn germ meal in high-concentrate diets is not recommended for performance Nellore heifers, but provided good sensory quality to the meat.


Assuntos
Ração Animal , Dieta , Ração Animal/análise , Animais , Bovinos , Dieta/veterinária , Feminino , Carne , Zea mays
20.
Int J Sports Med ; 42(9): 853-858, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33440443

RESUMO

The validation of a 4-domain PROM tailored to orthopedic sports medicine was performed through item generation, item scaling, validity and reliability testing, statistical analysis, as well as item reduction. Conbrach's alpha was used to verify item homogeneity, i. e. their accuracy or consistency. This PROM showed acceptable statistical accuracy and clinical applicability for a variety of surgical treatments, regardless of the anatomical injury sites. Moreover, this PROM considers the athletes' primary physical demands in an non-injured baseline condition, their motivation to continue sports practice and participation, and the influence of sports practice on their quality of life. This 4-domain PROM tailored for orthopedic sports medicine appears to be a valid tool to assess athletes and high-performing practitioners with sports injuries, recording their perception of injury, expectations of treatment; evaluation of postoperative care and treatment received, and perceived outcomes compared to their pre-injury status of physical demands in sports activity. The tool is unique, allowing direct comparisons between athletes' perception of pre-injury baseline, injury, treatment, and outcome. It will be a welcome adjunct to the sports medicine professional's tool box when assessing athlete's status and outcome after injury and intervention.


Assuntos
Traumatismos em Atletas/terapia , Ortopedia/normas , Medidas de Resultados Relatados pelo Paciente , Medicina Esportiva/normas , Adolescente , Adulto , Idoso , Atletas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Adulto Jovem
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