LEDA LEME TALIB
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
102 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 102
conferenceObject Increased GDNF but not BDNF Plasma Levels in Type II Compared to Type I Bipolar Disorder(2013) ZANETTI, Marcus V.; TEIXEIRA, Antonio L.; CHAIM, Tiffany M.; SOUSA, Rafael T. de; TALIB, Leda L.; GATTAZ, Wagner F.; BUSATTO, Geraldo F.; MACHADO-VIEIRA, RodrigoBackground: The brain-derived neurotrophic factor (BDNF) is a neurotrophin important for synaptic plasticity and neurogenesis, whereas the glial cell-line derived neurotrophic factor (GDNF) modulates the activity of monoaminergic neurons and glial cells. Previous works have suggested that abnormal peripheral levels of these proteins might relate to different mood states in bipolar disorder (BD), but none study so far have evaluated it with regard to potential differences between the types I (BD-I) and II (BD-II) subtypes of the disorder. Methods: Eighteen BD-I and 19 BD-II patients presenting with an acute mood episode (depressive, manic or mixed), and 23 healthy controls were studied. Plasma levels of BDNF and GDNF were measured using enzyme-linked immunosorbent assay (ELISA). Results: BD-II individuals showed significantly increased levels of GDNF compared to both BD-I patients and controls (ANOVA, df=2, F= 5.74, p=0.005; Tukey for post hoc comparisons). When we focused our analysis on the treatment-naïve patients only (14 BD-I and 13 BD-II), this result became even more significant (ANOVA, df=2, F= 7.33, p=0.002). No significant between-groups differences were observed on BDNF levels. Also, no significant correlation was observed between BDNF or GDNF levels and depressive and manic symptoms. Conclusions: BD-II at an acute phase of the illness is associated with increased plasma levels of GDNF. Previous use of mood stabilizer and antipsychotic agents might produce a chronic effect on GDNF production.- Hippocampal serotonin depletion is related to the presence of generalized tonic-clonic seizures, but not to psychiatric disorders in patients with temporal lobe epilepsy(2015) FONSECA, Natascha C. da; JOAQUIM, Helena P. G.; TALIB, Leda L.; VINCENTIIS, Silvia de; GATTAZ, Wagner F.; VALENTE, Kette D.Objective: Previous studies suggest that concentration of serotonin ([5-HT]) plays a pathogenic role in various types of epilepsy inhibiting seizures. However, most have not considered the clinical variables of epilepsy, and all of these studies included small and heterogeneous samples with refractory epilepsy, regardless of etiology. In this work, we measured [5-HT]s in hippocampal tissues from a large series of patients with refractory temporal lobe epilepsy caused by hippocampal sclerosis who underwent epilepsy surgery and evaluated the relationship between [5HT] and epilepsy-related clinical variables and psychiatric disorders. Methods: We included 44 patients with refractory unilateral TLE-HS who underwent surgical treatment for epilepsy. Hippocampal samples were collected, and serotonin concentrations were measured with high-pressure liquid chromatography (HPLC). Results: Lower [5-HT]s were correlated with a history of GTC seizures (Student's t-test: p0.041). There were no differences in [5-HT]s according to the other clinical variables and the presence of psychiatric disorders. Significance: Our findings demonstrated that serotonin depletion in the hippocampus play an important role in some aspects of the severity of epilepsy (i.e., the presence of GTC seizures) in a homogeneous sample of patients with refractory temporal lobe epilepsy determined by hippocampal sclerosis, but not with the presence of psychiatric disorders.
- 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.
- Is cerebral microbleed prevalence relevant as a biomarker in amnestic mild cognitive impairment and mild Alzheimer's disease?(2017) RABELO, A. G. B.; TEIXEIRA, C. V. L.; MAGALHAES, T. N. C.; CARLETTI-CASSANI, A. F. M. K.; AMATO FILHO, A. C. S.; JOAQUIM, H. P. G.; TALIB, L. L.; FORLENZA, O.; RIBEIRO, P. A. O.; SECOLIN, R.; LOPES-CENDES, I.; CENDES, F.; BALTHAZAR, M. L. F.Introduction The search for a reliable neuroimaging biomarker in Alzheimer's disease is a matter of intense research. The presence of cerebral microbleeds seems to be a potential biomarker. However, it is not clear if the presence of microbleeds has clinical usefulness to differentiate mild Alzheimer's disease and amnestic mild cognitive impairment from normal aging. We aimed to verify if microbleed prevalence differs among three groups: mild Alzheimer's disease, amnestic mild cognitive impairment due to Alzheimer's disease, and normal controls. Moreover, we studied whether microbleeds were associated with apolipoprotein E allele ϵ4 status, cerebrospinal fluid amyloid-beta, total and phosphorylated tau protein levels, vascular factors, and cognition. Methods Twenty-eight mild Alzheimer's disease patients, 34 with amnestic mild cognitive impairment and 36 cognitively normal elderly subjects underwent: magnetic resonance imaging with a susceptibility-weighted imaging sequence on a 3T scanner, apolipoprotein E genotyping and a full neuropsychological evaluation. Only amnestic mild cognitive impairment and mild Alzheimer's disease underwent cerebrospinal fluid analysis. We compared the groups and verified if microbleeds were predicted by all other variables. Results Mild Alzheimer's disease presented a higher prevalence of apolipoprotein E allele ϵ4 in relation to amnestic mild cognitive impairment and control group. No significant differences were found between groups when considering microbleed presence. Logistic regression tests failed to find any relationship between microbleeds and the variables. We performed three different regression models using different independent variables: Model 1 - amyloid-beta, phosphorylated tau protein, total tau, apolipoprotein E allele ϵ4 status, age, and sex; Model 2 - vascular risk factors, age, and sex; Model 3 - cognitive scores sex, age, and education. Conclusion Although microbleeds might be related to the Alzheimer's disease process, their presence is not a good candidate for a neuroimaging biomarker of the disease, especially in its early phases. © 2017 SAGE Publications.
- Physical Exercise Improves Peripheral BDNF Levels and Cognitive Functions in Mild Cognitive Impairment Elderly with Different BDNF Val66Met Genotypes(2015) NASCIMENTO, Carla Manuela Crispim; PEREIRA, Jessica Rodrigues; ANDRADE, Larissa Pires de; GARUFFI, Marcelo; AYAN, Carlos; KERR, Daniel Shikanai; TALIB, Leda Leme; COMINETTI, Marcia Regina; STELLA, FlorindoThe benefits of physical exercise on improvements in brain-derived neurotrophic factor (BDNF) levels and cognitive functioning have been reported in the literature. However, the variability of individual responses may be linked to genetic differences. BDNF is considered one of the most plausible factors involved in the cognitive benefits associated with physical activity practice. A single nucleotide polymorphism localized in the gene that codes BDNF results in a missense mutation that promotes an amino acid substitution (Val66Met) in the protein. This process has been associated with decreased levels of BDNF secretion, with corresponding impairments in specific cognitive functions. Therefore, the objective of this study was to analyze the effects of a multimodal physical exercise program on peripheral BDNF levels and cognitive functions in elderly individuals with mild cognitive impairment (MCI). The participants were genotyped for the BDNF Val66Met polymorphism. Cognitive functions were assessed by the Montreal Cognitive Assessment (MoCA) prior to and after the intervention. Forty-five participants were assigned to the control and trained groups. The trained group participated in a multimodal physical training for a 16-week period. The results showed a significant between-subjects interaction (p < 0.05), which indicates the beneficial contribution of training on cognitive functions independent of the BDNF genotype. However, only participants with BDNF-Met genotypes exhibited significant improvements in peripheral BDNF levels. The BDNF genotype appears to modulate the effects of physical exercise on BDNF secretion, but it does not influence cognition. This is the first study that evaluated the influence of a BDNF polymorphism on physical activity and cognition performance in elderly MCI individuals.
conferenceObject Distinct Glycogen Synthase Kinase 3 beta and Phospholipase A2 Expression Profiles in Bipolar I and II Disorders(2016) ZANETTI, Marcus V.; MACHADO-VIEIRA, Rodrigo; JOAQUIM, Helena P. G.; CHAIM, Tiffany M.; SERPA, Mauricio H.; SOUSA, Rafael T. de; GATTAZ, Wagner F.; BUSATTO, Geraldo F.; TALIB, Leda L.- Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial(2019) FORLENZA, Orestes V.; RADANOVIC, Marcia; TALIB, Leda L.; GATTAZ, Wagner F.Background Experimental studies indicate that lithium may facilitate neurotrophic/protective responses in the brain. Epidemiological and imaging studies in bipolar disorder, in addition to a few trials in Alzheimer's disease support the clinical translation of these findings. Nonetheless, there is limited controlled data about potential use of lithium to treat or prevent dementia. Aims To determine the benefits of lithium treatment in patients with amnestic mild cognitive impairment (MCI), a clinical condition associated with high risk for Alzheimer's disease. Method A total of 61 community-dwelling, physically healthy, older adults with MCI were randomised to receive lithium or placebo (1:1) for 2 years (double-blind phase), and followed-up for an additional 24 months (single-blinded phase) (trial registration at clinicaltrials.gov: NCT01055392). Lithium carbonate was prescribed to yield subtherapeutic concentrations (0.25-0.5 mEq/L). Primary outcome variables were the cognitive (Alzheimer's Disease Assessment Scale - cognitive subscale) and functional (Clinical Dementia Rating - Sum of Boxes) parameters obtained at baseline and after 12 and 24 months. Secondary outcomes were neuropsychological test scores; cerebrospinal fluid (CSF) concentrations of Alzheimer's disease-related biomarkers determined at 0, 12 and 36 months; conversion rate from MCI to dementia (0-48 months). Results Participants in the placebo group displayed cognitive and functional decline, whereas lithium-treated patients remained stable over 2 years. Lithium treatment was associated with better performance on memory and attention tests after 24 months, and with a significant increase in CSF amyloid-beta peptide (A beta(1-42)) after 36 months. Conclusions Long-term lithium attenuates cognitive and functional decline in amnestic MCI, and modifies Alzheimer's disease-related CSF biomarkers. The present data reinforces the disease-modifying properties of lithium in the MCI-Alzheimer's disease continuum. Declaration of interest None.
- Increased platelet glycogen sysnthase kinase 3beta in first-episode psychosis(2018) JOAQUIM, Helena P. G.; ZANETTI, Marcus V.; SERPA, Mauricio H.; BILT, Martinus T. Van de; SALLET, Paulo C.; CHAIM, Tiffany M.; BUSATTO, Geraldo F.; GATTAZ, Wagner F.; TALIB, Leda L.Past studies have linked intracellular pathways related to psychotic disorders to the GSK3B enzyme. This study aimed to investigate GSK3B protein expression and phosphorylation in drug-naive first-episode psychosis patients (n = 43) at baseline and following symptom remission, and in healthy controls (n = 77). At baseline GSK3B total level was higher in patients (p < 0.001). In schizophrenia spectrum patients (n = 25) GSK3B total and phosphorylated levels were higher than in controls and patients with other non-affective psychotic disorders (n = 18) (p < 0.001; p = 0.027; p = 0.05 respectively). No enzyme changes were found after clinical remission. The implication of this finding for the biology of psychoses warrants further studies to clarify whether increased GSK3B may be useful as a biomarker for psychosis in general, and schizophrenia in particular.
- 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.