MARCOS VASCONCELOS PAIS
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- 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.
- 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.
- 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.
- 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.
- Neuropsychiatric symptoms and cerebrovascular risk in non-demented elders: cross-sectional study using the mild behavioural impairment checklist (MBI-C)(2022) STELLA, Florindo; V, Marcos Pais; LOUREIRO, Julia C.; RADANOVIC, Marcia; FORLENZA, Orestes V.Background Neuropsychiatric symptoms (NPS) may represent early clinical manifestations of evolving brain diseases. Studies underpin the occurrence of NPS in the context of mild cognitive impairment (MCI) and prodromal Alzheimer's disease, where symptoms referred to as 'mild behavioural impairment' (MBI) have been shown to predict conversion to dementia and to hasten cognitive/functional decline. However, the association between NPS and cerebrovascular risk factors has been poorly investigated, despite the high prevalence of the latter among individuals with MCI. The aim of the present study was to investigate the association between MBI and cerebrovascular risk in a clinical sample of non-demented elders. Methods Sixty-five MCI and 15 cognitively unimpaired older adults were cross-sectionally assessed with the Mild Behavioural Impairment Checklist (MBI-C), using the cut-off score > 6.5 to define positive screening. Participants were submitted to the Hachinski Ischaemic Score (HIS) to account for cerebrovascular symptoms, vascular risk, and related comorbidities. Neuroimaging scans (magnetic resonance imaging and/or 18F-fluorodeoxyglucose-positron emission tomography) and apolipoprotein E genotype were obtained. Results Positive associations were found between total MBI-C scores and increasing number of comorbidities present (0-2 comorbidities), but not with three comorbidities. Two domains of the MBI-C-impulse dyscontrol and social inappropriateness-followed the same trend of the MBI-C total score, with higher scores with the increasing numbers of comorbidities. No significant associations were found between MBI symptoms and HIS or cerebrovascular burden in neuroimaging assessment. Conclusion We found weak associations between MBI-C total score and the presence of comorbidities with cerebrovascular risk, but not with structural or functional neuroimaging abnormalities or HIS. This finding may represent that the presence of comorbidities adds limited risk to the occurrence of MBI in this sample of non-demented elders.
- Mental Health Status of Psychogeriatric Patients During the 2019 New Coronavirus Disease (COVID-19) Pandemic and Effects on Caregiver Burden(2020) PENTEADO, Camila T.; LOUREIRO, Julia C.; PAIS, Marcos V.; CARVALHO, Claudia L.; SANT'ANA, Livea F. G.; VALIENGO, Leandro C. L.; STELLA, Florindo; FORLENZA, Orestes V.Introduction: There is a growing awareness about the noxious effects of the 2019 Coronavirus Disease (COVID-19) pandemic on the mental health of the elderly. However, there is limited information from clinically driven research. The objectives of the present study were to examine the magnitude of psychiatric symptoms and to determine their association with caregiver distress, in a cross-section of community-dwelling older adults and a subsample of aging adults with Down syndrome (DS) attending a psychogeriatric service in Sao Paulo, Brazil. Method: Telephone-based interviews and electronically filled self-assessment questionnaires were used to collect information from patients and caregivers, addressing their impressions and concerns about the pandemic and related effects on the patient's emotional state and behavior. Clinical information was obtained from hospital charts, medical records, and psychometric tests administered through telephone interviews [Hospital Anxiety and Depression Scale (HADS) and Neuropsychiatric Inventory Questionnaire (NPI-Q)]. Results: We included 100 consecutive participants, comprising 71 older adults with psychogeriatric/neurocognitive disorders and 29 aging adults with DS. Higher HADS and NPI-Q scores were significantly associated with caregiver distress (p < 0.05) in both groups. Correlation analyses indicated strong, positive associations between caregiver burden and scores in HADS anxiety (HADS-A) and HADS depression (HADS-D) scales in the subsamples of euploid and DS subjects. Higher NPI-Q scores in the former group were also correlated with caregiver distress, with stronger associations for neuropsychiatric symptoms. Similar findings were observed among DS subjects. ANOVA tests indicated significant associations between NPI-Q scores and caregiver distress among dementia patients, as well as with HADS scores. Similar results were found after multiple linear regressions; as such, among the elderly subsample, higher scores in HADS-A (p = 0.002) and HADS-D (p = 0.001) predict a significant impact on caregiver burden (p < 0.00001, R-2 0.46); taking into consideration caregiver burden as a dependent variable and NPI-Q total score as an independent variable, we obtained significant strong prediction values for either DS (p < 0.00001, R-2 0.95) or elderly adults (p < 0.00001, R-2 0.88). Conclusion: During the COVID-19 pandemic, patients with neurocognitive disorders present with clinically relevant neuropsychiatric symptoms, with significant impact on caregiver distress. Apathy, aberrant motor behavior, sleep disorders, and psychoses were the main psychopathological domains, which had determined caregiver burden worsening.
bookPart Tratamento dos transtornos neurocognitivos e outros sintomas associados às demências: demência na doença de Parkinson, demência com corpos de Lewy, degeneração lobar frontotemporal e demência vascular(2021) SILVA, Luiz Fernando de Almeida Lima e; RADANOVIC, Márcia; LOUREIRO, Júlia Cunha; PAIS, Marcos Vasconcelos; STELLA, Florindo; FORLENZA, Orestes Vicente- Cognitive impairment in remitted late -life depression is not associated with Alzheimer's disease -related CSF biomarkers(2020) LOUREIRO, Julia C.; STELLA, Florindo; PAIS, Marcos V.; RADANOVIC, Marcia; CANINEU, Paulo R.; JOAQUIM, Helena P. G.; TALIB, Leda L.; FORLENZA, Orestes V.
- Early diagnosis and treatment of Alzheimer's disease: new definitions and challenges(2020) PAIS, Marcos; MARTINEZ, Luana; RIBEIRO, Octavio; LOUREIRO, Julia; FERNANDEZ, Romel; VALIENGO, Leandro; CANINEU, Paulo; STELLA, Florindo; TALIB, Leda; RADANOVIC, Marcia; FORLENZA, Orestes V.The prevalence of Alzheimer's disease (AD), a progressive neurodegenerative disorder, is expected to more than double by 2050. Studies on the pathophysiology of AD have been changing our understanding of this disorder and setting a new scenario for drug development and other therapies. Concepts like the ""amyloid cascade"" and the ""continuum of AD,"" discussed in this article, are now well established. From updated classifications and recommendations to advances in biomarkers of AD, we aim to critically assess the literature on AD, addressing new definitions and challenges that emerged from recent studies on the subject. Updates on the status of major clinical trials are also given, and future perspectives are discussed.
bookPart Tratamento dos transtornos neurocognitivos: comprometimento cognitivo leve e doença de Alzheimer(2021) PAIS, Marcos Vasconcelos; LOUREIRO, Júlia Cunha; SILVA, Luiz Fernando de Almeida Lima e; RADANOVIC, Márcia; STELLA, Florindo; FORLENZA, Orestes Vicente