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
68 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 68
conferenceObject Mixed mood states and optimizing generalizability: An update from the global aging & geriatric experiments in bipolar disorder database (GAGE-BD)(2021) SAJATOVIC, Martha; DOLS, Annemiek; REJ, Soham; BLUMBERG, Hilary; BRIGGS, Farren; FORESTER, Brent; FORLENZA, Orestes; GILDENGERS, Ariel; MULSANT, Benoit; SCHOUWS, Sigfried; SUTHERLAND, Ashley; TSAI, Shang-Ying; VIETA, Eduard; EYLER, Lisa- 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.
- Lower Cerebrospinal Fluid Concentration of Brain-Derived Neurotrophic Factor Predicts Progression from Mild Cognitive Impairment to Alzheimer's Disease(2015) FORLENZA, Orestes Vicente; DINIZ, Breno Satler; TEIXEIRA, Antonio Lucio; RADANOVIC, Marcia; TALIB, Leda Leme; ROCHA, Natalia Pessoa; GATTAZ, Wagner FaridThere is little information on the dynamics of BDNF in the CSF in the continuum between healthy aging, MCI and AD. We included 128 older adults (77 with amnestic MCI, 26 with AD and 25 healthy controls). CSF BDNF level was measured by ELISA assay, and AD biomarkers (A beta(42), T-Tau and P-Tau(181)) were measured using a Luminex xMAP assay. CSF BDNF levels were significantly reduced in AD subjects compared to MCI and healthy controls (p = 0.009). Logistic regression models showed that lower CSF BDNF levels (p = 0.008), lower CSF A beta(42) (p = 0.005) and lower MMSE scores (p = 0.007) are significantly associated with progression from MCI to AD. The present study adds strong evidence of the involvement of BDNF in the pathophysiology of neurodegenerative changes in AD. Interventions aiming to restore central neurotrophic support may represent future therapeutic targets to prevent or delay the progression from MCI to AD.
- Mitochondrial dysfunction in Alzheimer's disease: Therapeutic implications of lithium(2021) SINGULANI, Monique P.; PAULA, Vanessa J. R. De; FORLENZA, Orestes V.Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by the accumulation of abnormal tau proteins within neurons and amyloid plaques in the brain parenchyma, which leads to progressive loss of neurons in the brain. While the detailed mechanism of the pathogenesis of AD is still unknown, evidence suggests that mitochondrial dysfunction likely plays a fundamental role in the pathogenesis of this disease. Due to the relevance of mitochondrial alterations in AD, recent works have suggested the therapeutic potential of mitochondrial-targeted lithium. Lithium has been shown to possess neuroprotective and neurotrophic properties that could also be related to the upregulation of mitochondrial function. In the current work, we perform a comprehensive investigation of the significance of mitochondrial dysfunction in AD and pharmacological treatment with lithium as imperative in this pathology, through a brief review of the major findings on the effects of lithium as a therapeutic approach targeting mitochondria in the context of AD.
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- 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.
- Regulation of leukocyte tricarboxylic acid cycle in drug-naive Bipolar Disorder(2015) SOUSA, Rafael T. de; STRECK, Emilio L.; FORLENZA, Orestes V.; BRUNONI, Andre R.; ZANETTI, Marcus V.; FERREIRA, Gabriela K.; DINIZ, Breno S.; PORTELA, Luis V.; CARVALHO, Andre F.; ZARATE JR., Carlos A.; GATTAZ, Wagner F.; MACHADO-VIEIRA, RodrigoSeveral lines of evidence suggest a role for mitochondrial dysfunction in the pathophysiology of bipolar disorder (BD). The tricarboxylic acid cycle (TCA cycle) is fundamental for mitochondrial energy production and produces substrates used in oxidative phosphorylation by the mitochondrial electron transport chain. The activity of the key TCA cycle enzymes citrate synthase, malate dehydrogenase, and succinate dehydrogenase has never been evaluated in BD. In the present study, these enzymes were assayed from leukocytes of drug-naive BD patients in a major depressive episode (n = 18) and compared to 24 age-matched healthy controls. Drug-naive BD patients did not show differences in activities of citrate synthase (p = 0.79), malate dehydrogenase (p = 0.17), and succinate dehydrogenase (p = 0.35) compared with healthy controls. No correlation between any TCA cycle enzyme activity and severity of depressive symptoms was observed. Overall, these data suggest that the activities of the TCA cycle enzymes are not altered in major depressive episodes of recent-onset BD, which may support the concept of illness staging and neuroprogression in BD.
conferenceObject A comparison of caregivers of patients with bipolar disorder and Alzheimer's disease: similar levels of burden and greater distress in bipolar disorder(2015) SANTOS, G. D.; LADEIRA, R. B.; ALMEIDA, J. G.; APRAHAMIAN, I.; FORLENZA, O. V.; LAFER, B.; NUNES, P.- Systemic Inflammation and Multimodal Biomarkers in Amnestic Mild Cognitive Impairment and Alzheimer's Disease(2018) MAGALHAES, T. N. C.; WEILER, M.; TEIXEIRA, C. V. L.; HAYATA, T.; MORAES, A. S.; BOLDRINI, V. O.; SANTOS, L. M. dos; CAMPOS, B. M. de; REZENDE, T. J. R. de; JOAQUIM, H. P. G.; TALIB, L. L.; FORLENZA, O. V.; CENDES, F.; BALTHAZAR, Marcio L. F.There is increasing evidence suggesting that one of the most relevant pathophysiological features of Alzheimer's disease (AD) is neuroinflammation, which plays an important role in the production and regulation of AD-related proteins (amyloid beta (A beta) and Tau) and exacerbates AD pathology. Neuroinflammation can also be induced by systemic influences (factors from outside the central nervous system). However, the role of systemic inflammation in AD pathophysiology is much less understood. Thus, our main objective in this study was to verify whether the presence of serum cytokines (IL-1 beta, IL-6, IL-10, IL-12, and TNF-alpha) affects different AD biomarkers: A beta(1-42) and Tau protein levels, hippocampal volumes (HV), and default mode network functional connectivity (DMN FC) in healthy elderly controls, amnestic mild cognitive impairment (aMCI) patients due to AD, and mild AD patients. To accomplish this, we acquired 3-T MRI, blood, and cerebrospinal fluid (CSF) samples from 42 healthy controls, 55 aMCI patients due to AD, and 33 mild AD patients. Comparing the groups, we found that the mild AD patients presented smaller HV, disrupted DMN FC, and proportionally less IL-1 beta than the controls. The aMCI patients only differed from the controls in DMN FC. In intra-group comparison, aMCI and mild AD with detectable levels of cytokines (TNF-alpha, IL-1 beta, IL-10, and IL-12) had decreased DMN FC. On the other hand, patients with detectable levels of IL-10 and IL-12 presented a more favorable AD biomarkers profile (larger HV, more CSF A beta(1-42), and less p-Tau), indicating a possible protective role of these ILs. Our findings indicate a possible relationship between systemic inflammation with DMN FC disruption, hippocampal atrophy, and CSF protein levels in the subjects with mild AD and aMCI.
- 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.