MARCOS VASCONCELOS PAIS
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bookPart Depressão geriátrica(2023) SILVA, Jéssica Formiga e; LOUREIRO, Júlia Cunha; PAIS, Marcos Vasconcelos- Heterogeneity of Cerebrospinal Fluid Biomarkers Profiles in Individuals with Distinct Levels of Cognitive Decline: A Cross-Sectional Study(2021) PAIS, Marcos; LOUREIRO, Julia; VALE, Vagner do; RADANOVIC, Marcia; TALIB, Leda; STELLA, Florindo; FORLENZA, OrestesBackground: Decreased cerebrospinal fluid (CSF) concentrations of the amyloid-beta (A beta), along with increased total (T-tau) and phosphorylated tau protein (P-tau), are widely accepted as core biomarkers of Alzheimer's disease (AD) pathology. Nonetheless, there are a few remaining caveats that still preclude the full incorporation of AD biomarkers into clinical practice. Objective: To determine the frequency of clinical-biological mismatches in a clinical sample of older adults with varying degrees of cognitive impairment. Methods: 204 participants were enrolled for a cross-sectional assessment and allocated into diagnostic groups: probable AD (n = 60, 29.4%); MCI (n = 84, 41.2%); or normal cognition (NC, n = 60, 29.4%). CSF concentrations of A beta(42), T-tau, and (181)Thr-P-tau were determined, and A beta(42)/P-tau ratio below 9.53 was used as a proxy of AD pathology. The AT(N) classification was further used as a framework to ascertain the biological evidence of AD. Results: The majority (73.7%) of patients in the AD group had the A beta(42)/P-tau ratio below the cut-off score for AD, as opposed to a smaller proportion in the MCI (42.9%) and NC (23.3%) groups. In the latter, 21 subjects (35%) were classified as A+, 28 (46.7%) as T+, and 23 (38.3%) as N+. In the AD group, 66.7% of the cases were classified as A+, 78.3% as T+, and 80% as N+. Conclusion: Analysis of CSF biomarkers was able to discriminate between AD, MCI, and NC. However, clinical-biological mismatches were observed in a non-negligible proportion of cases.
bookPart Exames laboratoriais, marcadores genéticos e biomarcadores humorais(2021) TALIB, Leda Leme; PAIS, Marcos Vasconcelos; DINIZ, Breno; BRAM, Jessyka Maria de França; JOAQUIM, Helena Passarelli Giroud; COSTA, Alana Caroline; FORLENZA, Orestes Vicente- Decision tree-based classification as a support to diagnosis in the Alzheimer's disease continuum using cerebrospinal fluid biomarkers: insights from automated analysis(2022) COSTA, Alana; PAIS, Marcos; LOUREIRO, Julia; STELLA, Florindo; RADANOVIC, Marcia; GATTAZ, Wagner; FORLENZA, Orestes; TALIB, LedaObjective: Cerebrospinal fluid (CSF) biomarkers add accuracy to the diagnostic workup of cognitive impairment by illustrating Alzheimer's disease (AD) pathology. However, there are no universally accepted cutoff values for the interpretation of AD biomarkers. The aim of this study is to determine the viability of a decision-tree method to analyse CSF biomarkers of AD as a support for clinical diagnosis. Methods: A decision-tree method (automated classification analysis) was applied to concentrations of AD biomarkers in CSF as a support for clinical diagnosis in older adults with or without cognitive impairment in a Brazilian cohort. In brief, 272 older adults (68 with AD, 122 with mild cognitive impairment [MCI], and 82 healthy controls) were assessed for CSF concentrations of A beta(1-42), total-tau, and phosphorylated-tau using multiplexed Luminex assays; biomarker values were used to generate decision-tree algorithms (classification and regression tree) in the R statistical software environment. Results: The best decision tree model had an accuracy of 74.65% to differentiate the three groups. Cluster analysis supported the combination of CSF biomarkers to differentiate AD and MCI vs. controls, suggesting the best cutoff values for each clinical condition. Conclusion: Automated analyses of AD biomarkers provide valuable information to support the clinical diagnosis of MCI and AD in research settings.
- Diagnostic Performance of an Eye-Tracking Assisted Visual Inference Language Test in the Assessment of Cognitive Decline due to Alzheimer's Disease(2023) BELAN, Ariella Fornachari Ribeiro; PAIS, Marcos Vasconcelos; CAMARGO, Marina von Zuben de Arruda; ANA, Livea Carla Fidalgo Garcez Sant'; RADANOVIC, Marcia; FORLENZA, Orestes VicenteBackground: The assessment of language changes associated with visual search impairment can be an important diagnostic tool in the Alzheimer's disease (AD) continuum. Objective: Investigate the performance of an eye-tracking assisted visual inference language task in differentiating subjects with mild cognitive impairment (MCI) or AD dementia from cognitively unimpaired older adults (controls). Methods: We assessed a group of 95 older adults (49 MCI, 18 mild dementia due to AD, and 28 controls). The subjects performed the same task under multiple experimental conditions which generate correlated responses that need to be taken into account. Thus, we performed a non-parametric repeated measures ANOVA model for verbal answers, and a linear mixed model (LMM) or its generalized version for the analysis of eye tracking variables. Results: Significant differences were found in verbal answers across all diagnostic groups independently of type of inference, i.e., logic or pragmatic. Also, eye-tracking parameters were able to discriminate AD from MCI and controls. AD patients did more visits to challenge stimulus (Control-AD, -0.622, SE = 0.190, p = 0.004; MCI-AD, -0.514, SE = 0.173, p = 0.011), more visits to the correct response stimulus (Control-AD, -1.363, SE = 0.383, p = 0.002; MCI-AD, -0.946, SE = 0.349, p = 0.022), more fixations on distractors (Control-AD, -4.580, SE = 1.172, p = 0.001; MCI-AD, -2.940, SE = 1.070, p = 0.020), and a longer time to first fixation on the correct response stimulus (Control-AD, -0.622, SE = 0.190, p = 0.004; MCI-AD, -0.514, SE = 0.173, p = 0.011). Conclusion: The analysis of oculomotor behavior along with language assessment protocols may increase the sensitivity for detection of subtle deficits in the MCI-AD continuum, representing an important diagnostic tool.
bookPart Transtornos de ansiedade no idoso(2021) PAIS, Marcos Vasconcelos; SANT'ANA, Livea Carla Fidalogo Garcêz- Recent advances in the management of neuropsychiatric symptoms in dementia(2017) FORLENZA, Orestes V.; LOUREIRO, Julia Cunha; PAIS, Marcos Vasconcelos; STELLA, FlorindoPurpose of review The present article addresses intriguing questions related to the clinical intervention in distinct neuropsychiatric syndromes of patients with dementia. Recent findings We reviewed 154 articles published between 2015 and 2016 targeting psychopharmacological and nonpharmacological interventions, and safety-tolerability concerns. We selected 115 articles addressing the purpose of this study. Of these, 33 were chosen because they were dedicated to subtopics: agitation (42), depression (33), apathy (18), sleep disorders/anxiety (8), and psychosis (4). Clinical studies using both pharmacological (70) and nonpharmacological (37) interventions were considered; others were included for theoretical support. Regarding the methodological design, we found double-blind RCTs (17), single-blinded RCTs (4), open-label studies (18), case reports (5), cross-sectional or cohort studies (25), epidemiological papers (2), and expert reviews (44). This observation raises concerns about the overall methodological adequacy of a substantial proportion of studies in this field, which limits the potential of generalization of the findings. Finally, 18 studies were designed to determine safety-tolerability issues of psychotropic medications (6 were discussed). Summary Effective and well tolerated treatment of neuropsychiatric syndromes in dementia remains a critically unsolved challenge. We understand that this is an extremely important area of research, and critically required to guide clinical decisions in geriatric neuropsychiatry.
bookPart Transtornos de ansiedade no idoso(2023) PAIS, Marcos Vasconcelos; MATTAR, Guilherme Prado- Passive antiamyloid immunotherapy for Alzheimer's disease(2020) LOUREIRO, Julia C.; PAIS, Marcos V.; STELLA, Florindo; RADANOVIC, Marcia; TEIXEIRA, Antonio Lucio; FORLENZA, Orestes V.; SOUZA, Leonardo Cruz dePurpose of review Antiamyloid therapy of Alzheimer's disease tackles the overproduction and clearance of the amyloid-beta peptide (A beta). Immunotherapeutic compounds were tested in large-scale trials. We revisit the recent literature focusing on randomized-controlled trials (RCT) using monoclonal anti-A beta antibodies. Recent findings Forty-three articles on anti-A beta passive immunotherapy for Alzheimer's disease were published between January 2016 and October 2019 regarding 17 RCTs: 13 phase III trials using the monoclonal antibodies bapineuzumab, solanezumab, gantenerumab, crenezumab, and aducanumab; three phase II with crenezumab and aducanumab; and one phase I trial with BAN2401. Studies resulted largely negative considering the effect of the treatment on primary and secondary outcome variables. The incidence of the most important adverse effect, amyloid-related imaging abnormalities (ARIAs) ranged between 0.2 and 22%, in treatment groups. Primary endpoints were not met in eight trials, and five trials were discontinued prior to completion. Passive immunotherapy RCTs failed to show clinically relevant effects in patients with clinically manifest or prodromal dementia. The high incidence of ARIAs indicates that the risk of adverse events may outweigh the benefits of these interventions. Ongoing studies must determine the benefit of such interventions in preclinical Alzheimer's disease, addressing the effect of antiamyloid immunotherapy in samples of asymptomatic carriers of autosomal-dominant mutations related to early-onset Alzheimer's disease.
- Cognitive impairment: an (in)dependent risk factor for mortality in older men?(2020) LOUREIRO, Julia C.; PAIS, Marcos V.; FORLENZA, Orestes V.
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