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
50 resultados
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- Cognitive Reserve Relates to Functional Network Efficiency in Alzheimer's Disease(2018) WEILER, Marina; CASSEB, Raphael Fernandes; CAMPOS, Brunno Machado de; TEIXEIRA, Camila Vieira de Ligo; CARLETTI-CASSANI, Ana Flavia Mac Knight; VICENTINI, Jessica Elias; MAGALHAES, Thamires Naela Cardoso; ALMEIRA, Debora Queiroz de; TALIB, Leda Leme; FORLENZA, Orestes Vicente; BALTHAZAR, Marcio Luiz Figueredo; CASTELLANO, GabrielaAlzheimer's disease (AD) is the most common form of dementia, with no means of cure or prevention. The presence of abnormal disease-related proteins in the population is, in turn, much more common than the incidence of dementia. In this context, the cognitive reserve (CR) hypothesis has been proposed to explain the discontinuity between pathophysiological and clinical expression of AD, suggesting that CR mitigates the effects of pathology on clinical expression and cognition. fMRI studies of the human connectome have recently reported that AD patients present diminished functional efficiency in resting-state networks, leading to a loss in information flow and cognitive processing. No study has investigated, however, whether CR modifies the effects of the pathology in functional network efficiency in AD patients. We analyzed the relationship between CR, pathophysiology and network efficiency, and whether CR modifies the relationship between them. Fourteen mild AD, 28 amnestic mild cognitive impairment (aMCI) due to AD, and 28 controls were enrolled. We used education to measure CR, cerebrospinal fluid (CSF) biomarkers to evaluate pathophysiology, and graph metrics to measure network efficiency. We found no relationship between CR and CSF biomarkers; CR was related to higher network efficiency in all groups; and abnormal levels of CSF protein biomarkers were related to more efficient networks in the AD group. Education modified the effects of tau-related pathology in the aMCI and mild AD groups. Although higher CR might not protect individuals from developing AD pathophysiology, AD patients with higher CR are better able to cope with the effects of pathology-presenting more efficient networks despite pathology burden. The present study highlights that interventions focusing on cognitive stimulation might be useful to slow age-related cognitive decline or dementia and lengthen healthy aging.
conferenceObject COGNITIVE PROFILE OF ADULTS AND SENIORS WITH DOWN'S SYNDROME: DATA FROM THE CAMBRIDGE EXAMINATION FOR MENTAL DISORDERS OF OLDER PEOPLE WITH DOWN SYNDROME BRAZILIAN VERSION - CAMDEX-DS ADAPTED AND VALIDATED FOR THE BRAZILIAN POPULATION(2019) CARVALHO, C. L.; ARAUJO, M. C. Cristianini; NOGUEIRA, C.; GONCALVES, A.; BELAN, A.; BRAM, J.; SANTANA, L.; BECKER, A.; RADANOVIC, M.; FORLENZA, O.conferenceObject Demographic and Clinical Characteristics of Antipsychotic Drug- Treated Older Adults With Bipolar Disorder From the Global Aging and Geriatric Experiments in Bipolar Disorder Database (GAGE -BD) Project(2021) SAJATOVIC, Martha; CHEN, Peijun; GILDENGERS, Ariel; DOLS, Annemiek; REJ, Soham; ALMEIDA, Osvaldo; BEUNDERS, Alexandra; BLUMBERG, Hilary; BRIGGS, Farren; FORESTER, Brent; PATRICK, Regan; FORLENZA, Orestes; JIMENEZ, Esther; MULSANT, Benoit; SCHOUWS, Sigfried; PAANS, Nadine; SARNA, Kaylee; SUTHERLAND, Ashley; VIETA, Eduard; TSAI, Shangying; YALA, Joy; EYLER, Lisa- Sentence processing in mild cognitive impairment(2022) PEREIRA, Diana Nakamura; SOUZA, Wellington da Cruz; BELAN, Ariella Fornachari Ribeiro; CAMARGO, Marina von Zuben de Arruda; FORLENZA, Orestes Vicente; RADANOVIC, MarciaDifficulties in sentence processing have been reported in patients with Mild Cognitive Impairment (MCI), which may be due to impairment in primary syntactic abilities or short-term memory. In the present study, we investigated the relationship between overt sentence production (SP) and comprehension (SC) with short-term memory performance in MCI. Cognitively healthy elderly (n = 34), amnestic MCI (aMCI,n = 22), non-amnestic MCI (naMCI,n = 45), and Alzheimer's disease (AD,n = 18) patients were asked to complete tests of constrained SP and oral SC. We tested the association between performance in SP and SC with memory tasks and performed a qualitative analysis of the frequency and type of errors in SC. Our results showed that there were no intergroup differences in SC and SP performances. SC scores were associated with delayed recall for words in the naMCI group (p = 0.003), and immediate (p = 0.001) and delayed recall for shapes (p = 0.031) in AD. There were no predictors for NAT scores in any group. In conclusion, the three groups performed similarly in SC and SP tasks. Short-term memory was not associated with performance in the SP task. There was an association between performance in the SC task and verbal memory in naMCI and non-verbal memory in AD; the latter may reflect visuospatial processing demands embedded in the SC task.
- Multidisciplinary rehabilitation program: effects of a multimodal intervention for patients with Alzheimer's disease and cognitive impairment without dementia(2015) SANTOS, Glenda Dias; NUNES, Paula Villela; STELLA, Florindo; BRUM, Paula Schimidt; YASSUDA, Monica Sanches; UENO, Linda Massako; GATTAZ, Wagner Farid; FORLENZA, Orestes VicenteBackground: Non-pharmalogical interventions represent an important complement to standard pharmalogical treatment in dementia. Objective: This study aims to evaluate the effects of a multidisciplinary rehabilitation program on cognitive ability, quality of life and depression symptoms in patients with Alzheimer's disease (AD) and cognitive impairment without dementia (CIND). Methods: Ninety-seven older adults were recruited to the present study. Of these, 70 patients had mild AD and were allocated into experimental (n = 54) or control (n = 16) groups. Two additional active comparison groups were constituted with patients with moderate AD (n = 13) or with CIND (n = 14) who also received the intervention. The multidisciplinary rehabilitation program lasted for 12 weeks and was composed by sessions of memory training, recreational activities, verbal expression and writing, physical therapy and physical training, delivered in two weekly 6-hour sessions. Results: As compared to controls, mild AD patients who received the intervention had improvements in cognition (p = 0.021) and quality of life (p = 0.003), along with a reduction in depressive symptoms (p < 0.001). As compared to baseline, CIND patients displayed at the end of the intervention improvements in cognition (p = 0.005) and depressive symptoms (p = 0.011). No such benefits were found among patients with moderate AD. Discussion: This multidisciplinary rehabilitation program was beneficial for patients with mild AD and CIND. However, patients with moderate dementia did not benefit from the intervention.
- Lithium and neuroprotection: translational evidence and implications for the treatment of neuropsychiatric disorders(2013) DINIZ, Breno Satler; MACHADO-VIEIRA, Rodrigo; FORLENZA, Orestes VicenteIn the last two decades, a growing body of evidence has shown that lithium has several neuroprotective effects. Several neurobiological mechanisms have been proposed to underlie these clinical effects. Evidence from preclinical studies suggests that neuroprotection induced by lithium is mainly related to its potent inhibition of the enzyme glycogen synthase kinase-3 beta (GSK-3 beta) and its downstream effects, ie, reduction of both tau protein phosphorylation and amyloid-beta(42) production. Additional neuroprotective effects include increased neurotrophic support, reduced proinflammatory status, and decreased oxidative stress. More recently, neuroimaging studies in humans have demonstrated that chronic use is associated with cortical thickening, higher volume of the hippocampus and amygdala, and neuronal viability in bipolar patients on lithium treatment. In line with this evidence, observational and case registry studies have shown that chronic lithium intake is associated with a reduced risk of Alzheimer's disease in subjects with bipolar disorder. Evidence from recent clinical trials in patients with mild cognitive impairment suggests that chronic lithium treatment at subtherapeutic doses can reduce cerebral spinal fluid phosphorylated tau protein. Overall, convergent lines of evidence point to the potential of lithium as an agent with disease modifying properties in Alzheimer's disease. However, additional long-term studies are necessary to confirm its efficacy and safety for these patients, particularly as chronic intake is necessary to achieve the best therapeutic results.
- Subjective memory and strategy use in mild cognitive impairment and healthy aging(2013) BRUM, Paula Schimidt; YASSUDA, Mônica Sanches; FORLENZA, Orestes VicenteLimited information is available about subjective memory and strategy use in seniors with mild cognitive impairment (MCI). We investigated whether differences exist in the perception of changes in memory, perceived frequency of forgetting, overall memory evaluation, and strategy use between seniors with MCI and unimpaired older adults. The study included 56 participants, aged 60 years and older, including 28 normal controls (NC) and 28 MCI patients. The participants completed the Short Cognitive Performance Test, the Story and Grocery list recall tasks, the 15-item Geriatric Depression Scale, the Memory Complaint Questionnaire for the perception of changes in episodic memory, the McNair Frequency of Forgetting Questionnaire, and a single question that evaluated overall memory. The Bousfield semantic clustering measure was calculated to assess semantic clustering for list recall. The number of underlined words during story encoding was calculated to assess strategy use. Participants with MCI had significantly worse scores on Story and Grocery list recall, semantic clustering, and overall memory evaluation. No differences were found in the number of underlined words. List recall was significantly correlated with semantic clustering in both groups (NC: r = .58, p = .001; MCI: r = .57, p = .002). Participants with MCI appeared to be less efficacious when using memory strategies, which may be associated with poor memory performance.
- Neuronal-Glial Interaction in a Triple-Transgenic Mouse Model of Alzheimer's Disease: Gene Ontology and Lithium Pathways (vol 14, 579984, 2020)(2021) ROCHA, Nicole Kemberly R.; THEMOTEO, Rafael; BRENTANI, Helena; FORLENZA, Orestes V.; PAULA, Vanessa De Jesus Rodrigues De
- Bipolar symptoms, somatic burden and functioning in older-age bipolar disorder: A replication study from the global aging & geriatric experiments in bipolar disorder database (GAGE-BD) project(2024) SAJATOVIC, Martha; REJ, Soham; ALMEIDA, Osvaldo P.; ALTINBAS, Kursat; BALANZA-MARTINEZ, Vicent; BARBOSA, Izabela G.; BEUNDERS, Alexandra J. M.; BLUMBERG, Hilary P.; BRIGGS, Farren B. S.; DOLS, Annemiek; FORESTER, Brent P.; FORLENZA, Orestes V.; GILDENGERS, Ariel G.; JIMENEZ, Esther; KLAUS, Federica; LAFER, Beny; MULSANT, Benoit; MWANGI, Benson; NUNES, Paula Villela; OLAGUNJU, Andrew T.; OLUWANIYI, Stephen; ORHAN, Melis; PATRICK, Regan E.; RADUA, Joaquim; RAJJI, Tarek; SARNA, Kaylee; SCHOUWS, Sigfried; SIMHANDL, Christian; SEKHON, Harmehr; SOARES, Jair C.; SUTHERLAND, Ashley N.; TEIXEIRA, Antonio L.; TSAI, Shangying; VIDAL-RUBIO, Sonia; VIETA, Eduard; YALA, Joy; EYLER, Lisa T.Objectives: The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232, mean +/- standard deviation age 47.2 +/- 13.5, 65% women, 49% aged over 50) dataset. Design/Methods: Using mixed models with random effects for cohort, we examined associations between BD symptoms, somatic burden and age and the contribution of these to functioning in W2 and the combined W1 + W2 sample (n = 2601). Results: Compared to W1, the W2 sample was younger (p < 0.001), less educated (p < 0.001), more symptomatic (p < 0.001), lower functioning (p < 0.001) and had fewer somatic conditions (p < 0.001). In the full W2, older individuals had reduced manic symptom severity, but age was not associated with depression severity. Age was not associated with functioning in W2. More severe BD symptoms (mania p <= 0.001, depression p <= 0.001) were associated with worse functioning. Older age was significantly associated with higher somatic burden in the W2 and the W1 + W2 samples, but this burden was not associated with poorer functioning. Conclusions: In a large, independent sample, older age was associated with less severe mania and more somatic burden (consistent with previous findings), but there was no association of depression with age (different from previous findings). Similar to previous findings, worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning.
- 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.