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
18 resultados
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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.- 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.
- A creative approach to increase social inclusion and reduce stigmatization of people with dementia(2019) OLIVEIRA, Alexandra M.; FORLENZA, Orestes V.
- An intervention to reduce neuropsychiatric symptoms and caregiver burden in dementia: Preliminary results from a randomized trial of the tailored activity program-outpatient version(2019) OLIVEIRA, Alexandra Martini de; RADANOVIC, Marcia; MELLO, Patricia Cotting Homem de; BUCHAIN, Patricia Cardoso; VIZZOTTO, Adriana Dias; HARDER, Janaina; STELLA, Florindo; PIERSOL, Catherine Verrier; GITLIN, Laura N.; FORLENZA, Orestes VicenteObjective To evaluate the efficacy of the tailored activity program-outpatient version (TAP-O) and to reduce neuropsychiatric symptoms (NPS) in patients with dementia and caregiver burden compared with a control group (psychoeducation intervention). Methods Twenty-one persons with dementia and their caregivers were recruited and randomized. The intervention group received TAP-O, designed for outpatients with dementia and their caregivers. TAP-O consisted of eight sessions in which an occupational therapist assessed the patient's abilities and interests; prescribed tailored activities; and educated caregivers about dementia, NPS, and how to implement meaningful activities in the daily routine. The control group received eight sessions of a psychoeducation intervention about dementia and NPS. Results Compared with controls, patients receiving TAP-O had a significant decrease in hallucination (P = 0.04), agitation (P = 0.03), anxiety (P = 0.02), aggression (P = 0.01), sleep disorder (P = 0.02), aberrant motor behavior (P = 0.02), and in caregiver burden (P = 0.003). Conclusions Findings suggest that TAP-O may be an effective nonpharmacological strategy to reduce NPS of outpatients with dementia and to minimize caregiver burden.
conferenceObject Effect of lithium at therapeutic and subtherapeutic doses in GSK3beta autonomous pathways at primary hippocampal neurons cell culture(2019) DE-PAULA, Vanessa; BARBOSA, Andre; FORLENZA, Orestes; BRENTANI, Helena- Correlation between CSF biomarkers of Alzheimer's disease and global cognition in a psychogeriatric clinic cohort(2019) RADANOVIC, Marcia; OSHIRO, Carlos A.; FREITAS, Thiago Q.; TALIB, Leda L.; FORLENZA, Orestes V.Objective: The relationship between biomarkers of amyloid-beta aggregation (A beta(1-42)) and/or neurodegeneration (Tau protein) in cerebrospinal fluid (CSF) and cognitive decline is still unclear. We aimed to ascertain whether CSF biomarkers correlate with cognitive performance in healthy and cognitively impaired subjects, starting from clinical diagnoses. Methods: We tested for correlation between CSF biomarkers and Mini-Mental State Examination (MMSE) scores in 208 subjects: 54 healthy controls, 82 with mild cognitive impairment (MCI), 46 with Alzheimer's disease (AD), and 26 with other dementias (OD). Results: MMSE correlated weakly with all CSF biomarkers in the overall sample (r = 0.242, p < 0.0006). A beta(1-42) and MMSE correlated weakly in MCI (r = 0.247, p = 0.030), and moderately in OD (r = 0.440, p = 0.027). t-Tau showed a weak inverse correlation with MMSE in controls (r = -0.284, p = 0.043) and MCI (r = -0.241, p = 0.036), and a moderate/strong correlation in OD (r = 0.665), p = 0.0003). p-Tau correlated weakly with MMSE in AD (r = -0.343, p = 0.026) and moderately in OD (r = -0.540, p = 0.0005). The A beta(1-42)/p-Tau ratio had a moderate/strong correlation with MMSE in OD (r = 0.597, p = 0.001). Conclusion: CSF biomarkers correlated best with cognitive performance in OD. t-Tau correlated weakly with cognition in controls and patients with MCI. In AD, only p-Tau levels correlated with cognitive performance. This pattern, which has been reported previously, seems to indicate that CSF biomarkers might not be reliable as indicators of disease severity.
- Topography of C-11-Pittsburgh compound B uptake in Alzheimer's disease: a voxel-based investigation of cortical and white matter regions(2019) FARIA, Daniele de P.; DURAN, Fabio L.; SQUARZONI, Paula; COUTINHO, Artur M.; GARCEZ, Alexandre T.; SANTOS, Pedro P.; BRUCKI, Sonia M.; OLIVEIRA, Maira O. de; TRES, Eduardo S.; FORLENZA, Orestes V.; NITRINI, Ricardo; BUCHPIGUEL, Carlos A.; BUSATTO FILHO, GeraldoObjective: To compare results of positron emission tomography (PET) with carbon-11-labeled Pittsburgh compound B (C-11-PIB) obtained with cerebellar or global brain uptake for voxel intensity normalization, describe the cortical sites with highest tracer uptake in subjects with mild Alzheimer's disease (AD), and explore possible group differences in C-11-PIB binding to white matter. Methods: C-11-PIB PET scans were acquired from subjects with AD (n=17) and healthy elderly controls (n=19). Voxel-based analysis was performed with statistical parametric mapping (SPM). Results: Cerebellar normalization showed higher C-11-PIB uptake in the AD group relative to controls throughout the cerebral cortex, involving the lateral temporal, orbitofrontal, and superior parietal cortices. With global uptake normalization, greatest cortical binding was detected in the orbitofrontal cortex; decreased C-11-PIB uptake in white matter was found in the posterior hippocampal region, corpus callosum, pons, and internal capsule. Conclusion: The present case-control voxelwise C-11-PIB PET comparison highlighted the regional distribution of amyloid deposition in the cerebral cortex of mildly demented AD patients. Tracer uptake was highest in the orbitofrontal cortex. Decreased C-11-PIB uptake in white-matter regions in this patient population may be a marker of white-matter damage in AD.
- Protein levels of ADAM10, BACE1, and PSEN1 in platelets and leukocytes of Alzheimer's disease patients(2019) BRAM, Jessyka Maria de Franca; TALIB, Leda Leme; JOAQUIM, Helena Passarelli Giroud; SARNO, Tamires Alves; GATTAZ, Wagner Farid; FORLENZA, Orestes VicenteThe clinical diagnosis of Alzheimer's disease (AD) is a probabilistic formulation that may lack accuracy particularly at early stages of the dementing process. Abnormalities in amyloid-beta precursor protein (APP) metabolism and in the level of APP secretases have been demonstrated in platelets, and to a lesser extent in leukocytes, of AD patients, with conflicting results. The aim of the present study was to compare the protein level of the APP secretases A-disintegrin and metalloprotease 10 (ADAM10), Beta-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PSEN1) in platelets and leukocytes from 20 non-medicated older adults with AD and 20 healthy elders, and to determine the potential use of these biomarkers to discriminate cases of AD from controls. The protein levels of all APP secretases were significantly higher in platelets compared to leukocytes. We found statistically a significant decrease in ADAM10 (52.5%, p < 0.0001) and PSEN1 (32%, p = 0.02) in platelets from AD patients compared to controls, but not in leukocytes. Combining all three secretases to generate receiver-operating characteristic (ROC) curves, we found a good discriminatory effect (AD vs. controls) when using platelets (the area under the curve-AUC-0.90, sensitivity 88.9%, specificity 66.7%, p = 0.003), but not in leukocytes (AUC 0.65, sensitivity 77.8%, specificity 50.0%, p = 0.2). Our findings indicate that platelets represent a better biological matrix than leukocytes to address the peripheral level of APP secretases. In addition, combining the protein level of ADAM10, BACE1, and PSEN1 in platelets, yielded a good accuracy to discriminate AD from controls.
- Noninvasive brain stimulation for behavioural and psychological symptoms of dementia: A systematic review and meta-analysis(2019) VACAS, Sara M.; STELLA, Florindo; LOUREIRO, Julia C.; COUTO, Frederico Simoes do; OLIVEIRA-MAIA, Albino J.; FORLENZA, Orestes V.Background Pharmacological and conventional nonpharmacological treatments for behavioural and psychological symptoms of dementia (BPSD) have only modest efficacy. Furthermore, pharmacotherapy carries the risk of important side effects. Noninvasive brain stimulation (repetitive transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS)) are valuable and safe for cognitive function in Alzheimer disease (AD). However, there have been few studies, and there is no consensus, regarding the use of these techniques to treat BPSD. Methods We performed a systematic review of the literature and meta-analysis of studies reporting the effect of rTMS or tDCS on BPSD. Results Seven articles were included: five randomized, controlled clinical trials and two open-label clinical trials. Five studies investigated the effects of rTMS and two the effects of tDCS. Both studies using tDCS reported no evidence of efficacy on BPSD, while two of the three RCTs using rTMS found statistically significant benefits. In an exploratory meta-analysis with four of the RCT studies, we did not find evidence of efficacy of noninvasive brain stimulation techniques, with an overall effect of -0.02 (95% CI = -0.90, 0.94; I-2 = 85%). However, when we used only the data from the studies that applied rTMS, we found a positive effect on BPSD, with an overall effect of -0.58 (95% CI = -1.02, -0.14; I-2 = 0%). With regards to the adverse effects reported, these were mild and not clinically relevant. Conclusions Our results establish a tendency for efficacy of rTMS protocols on BPSD, while corroborating their safety and tolerability, suggesting the need for further research.
conferenceObject SYMPTOMS OF DEPRESSION IN ADULTS AND ELDERS WITH DOWN SYNDROME: DATA FROM A PILOT STUDY IN BRAZIL(2019) NOGUEIRA, C.; CARVALHO, C. L.; GONCALVES, A.; BELAN, A.; BRAM, J.; SANTANA, L.; RADANOVIC, M.; BECKER, A.; FORLENZA, O.