ORESTES VICENTE FORLENZA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Psiquiatria, Faculdade de Medicina - Docente
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
14 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 14
- Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters (vol 45, pg 616, 2020)(2020) COUTINHO, Artur Martins; BUSATTO, Geraldo F.; PORTO, Fabio Henrique de Gobbi; FARIA, Daniele de Paula; ONO, Carla Rachel; GARCEZ, Alexandre Teles; SQUARZONI, Paula; DURAN, Fabio Luiz de Souza; OLIVEIRA, Maira Okada de; TRES, Eduardo Sturzeneker; BRUCKI, Sonia Maria Dozzi; FORLENZA, Orestes Vicente; NITRINI, Ricardo; BUCHPIGUEL, Carlos Alberto
- Three plasma metabolites in elderly patients differentiate mild cognitive impairment and Alzheimer's disease: a pilot study(2020) COSTA, Alana C.; JOAQUIM, Helena P. G.; FORLENZA, Orestes V.; GATTAZ, Wagner F.; TALIB, Leda L.The metabolomic profile of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) may suggest potential diagnostic biomarkers and provide information on the pathophysiology of dementia. Our aim was to quantify plasmatic metabolites of AD patients, MCI and controls. We investigated the metabolomic profile-using the AbsoluteIDQ (R) p180 assay-of 79 older adults with primary cognitive impairment (34 AD and 20 MCI) and 25 healthy elders (controls). A cluster analysis revealed that a combination C12-DC, C12 and PCaaC26:0 could differentiate the patients according to diagnostic. Future studies should combine metabolomic profiles with other biomarkers to identify diagnostic groups.
- 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.
- Neuronal-Glial Interaction in a Triple-Transgenic Mouse Model of Alzheimer's Disease: Gene Ontology and Lithium Pathways(2020) ROCHA, Nicole Kemberly R.; THEMOTEO, Rafael; BRENTANI, Helena; FORLENZA, Orestes V.; PAULA, Vanessa De Jesus Rodrigues DeNeuronal-glial interactions are critical for brain homeostasis, and disruption of this process may lead to excessive glial activation and inadequate pro-inflammatory responses. Abnormalities in neuronal-glial interactions have been reported in the pathophysiology of Alzheimer's disease (AD), where lithium has been shown to exert neuroprotective effects, including the up-regulation of cytoprotective proteins. In the present study, we characterize by Gene Ontology (GO) the signaling pathways related to neuronal-glial interactions in response to lithium in a triple-transgenic mouse model of AD (3x-TgAD). Mice were treated for 8 months with lithium carbonate (Li) supplemented to chow, using two dose ranges to yield subtherapeutic working concentrations (Li1, 1.0 g/kg; and Li2, 2.0 g/kg of chow), or with standard chow (Li0). The hippocampi were removed and analyzed by proteomics. A neuronal-glial interaction network was created by a systematic literature search, and the selected genes were submitted to STRING, a functional network to analyze protein interactions. Proteomics data and neuronal-glial interactomes were compared by GO using ClueGo (Cytoscape plugin) with p <= 0.05. The proportional effects of neuron-glia interactions were determined on three GO domains: (i) biological process; (ii) cellular component; and (iii) molecular function. The gene ontology of this enriched network of genes was further stratified according to lithium treatments, with statistically significant effects observed in the Li2 group (as compared to controls) for the GO domains biological process and cellular component. In the former, there was an even distribution of the interactions occurring at the following functions: ""positive regulation of protein localization to membrane,"" ""regulation of protein localization to cell periphery,"" ""oligodendrocyte differentiation,"" and ""regulation of protein localization to plasma membrane."" In cellular component, interactions were also balanced for ""myelin sheath"" and ""rough endoplasmic reticulum."" We conclude that neuronal-glial interactions are implicated in the neuroprotective response mediated by lithium in the hippocampus of AD-transgenic mice. The effect of lithium on homeostatic pathways mediated by the interaction between neurons and glial cells are implicated in membrane permeability, protein synthesis and DNA repair, which may be relevant for the survival of nerve cells amidst AD pathology.
- 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.
- Impact of SARS-CoV-2 pandemic on mental health in the elderly: perspective from a psychogeriatric clinic at a tertiary hospital in Sao Paulo, Brazil(2020) FORLENZA, Orestes V.; STELLA, Florindo
- Visual Search Efficiency in Mild Cognitive Impairment and Alzheimer's Disease: An Eye Movement Study(2020) PEREIRA, Marta Luisa Goncalves de Freitas; CAMARGO, Marina von Zuben de Arruda; BELLAN, Ariella Fornachari Ribeiro; TAHIRA, Ana Carolina; SANTOS, Bernardo dos; SANTOS, Jessica dos; MACHADO-LIMA, Ariane; NUNES, Fatima L. S.; FORLENZA, Orestes VicenteBackground: Visual search abilities are essential to everyday life activities and are known to be affected in Alzheimer's disease (AD). However, little is known about visual search efficiency in mild cognitive impairment (MCI), a transitive state between normal aging and dementia. Eye movement studies and machine learning methods have been recently used to detect oculomotor impairments in individuals with dementia. Objective: The aim of the present study is to investigate the association between eye movement metrics and visual search impairment in MCI and AD. Methods: 127 participants were tested: 43 healthy controls, 51 with MCI, and 33 with AD. They completed an eyetracking visual search task where they had to find a previously seen target stimulus among distractors. Results: Both patient groups made more fixations on the screen when searching for a target, with longer duration than controls. MCI and AD fixated the distractors more often and for a longer period of time than the target. Healthy controls were quicker and made less fixations when scanning the stimuli for the first time. Machine-learning methods were able to distinguish between controls and AD subjects and to identify MCI subjects with a similar oculomotor profile to AD with a good accuracy. Conclusion: Results showed that eye movement metrics are useful for identifying visual search impairments in MCI and AD, with possible implications in the early identification of individuals with high-risk of developing AD.
- In vivo imaging evidence of poor cognitive resilience to Alzheimer's disease pathology in subjects with very low cognitive reserve from a low-middle income environment(2020) BUSATTO, Geraldo F.; PORTO, Fabio Henrique de Gobbi; FARIA, Daniele de Paula; SQUARZONI, Paula; COUTINHO, Artur Martins; GARCEZ, Alexandre Teles; ROSA, Pedro Gomes Penteado; COSTA, Naomi Antunes da; CARVALHO, Cleudiana Lima; TORRALBO, Leticia; HERNANDES, Jullie Rosana de Almeida; ONO, Carla Rachel; BRUCKI, Sonia Maria Dozzi; NITRINI, Ricardo; BUCHPIGUEL, Carlos Alberto; DURAN, Fabio Luis Souza; FORLENZA, Orestes VicenteINTRODUCTION: Reduced cognitive reserve (CR) due to very low educational (VLE) levels may influence high dementia rates in low-middle income environments, leading to decreased cognitive resilience (RES) to Alzheimers disease (AD) pathology. However, in vivo findings in VLE groups confirming this prediction are lacking. METHODS: Cognitively impaired patients (with clinically defined AD dementia or amnestic mild cognitive impairment) and cognitively unimpaired older adults (n = 126) were recruited for a positron emission tomography (PET) and magnetic resonance imaging (MRI) investigation in Brazil, including 37 VLE individuals (<= 5 years of education). A CR score was generated combining educational attainment and vocabulary knowledge. RES indices to AD pathology were calculated using standardized residuals from linear regression models relating current cognitive performance (episodic memory or overall cognition) to amyloid beta (A beta) burden Pittsburgh compound-B ([11C]PiB-PET). RESULTS: A beta burden was lower in VLE relative to highly-educated subjects (controlling for age, sex, and Mini-Mental Status Exam [MMSE] scores) in the overall cognitively impaired sample, and in dementia subjects when the three clinically defined groups were evaluated separately. In bivariate regression analyses for the overall sample, the RES index based on a composite cognitive score was predicted by CR, socioeconomic status, and hippocampal volume (but not white matter hyperintensities or intracranial volume [ICV]); in the multivariate model, only CR retained significance (and similar results were obtained in the A beta-positive subsample). In the multivariate model for the overall sample using the RES index based on memory performance, CR, hippocampal volume, and ICV were significant predictors, whereas only CR retained significance in A beta-positive subjects. DISCUSSION: Lower CR consistently predicted less resilience to AD pathology in older adults from a low-middle income environment.
- 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.