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
35 resultados
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- Neuropsychiatric symptoms in the prodromal stages of dementia(2014) STELLA, Florindo; RADANOVIC, Marcia; BALTHAZAR, Marcio L. F.; CANINEU, Paulo R.; SOUZA, Leonardo C. de; FORLENZA, Orestes V.Purpose of reviewTo critically discuss the neuropsychiatric symptoms in the prodromal stages of dementia in order to improve the early clinical diagnosis of cognitive and functional deterioration.Recent findingsCurrent criteria for cognitive syndrome, including Alzheimer's disease, comprise the neuropsychiatric symptoms in addition to cognitive and functional decline. Although there is growing evidence that neuropsychiatric symptoms may precede the prodromal stages of dementia, these manifestations have received less attention than traditional clinical hallmarks such as cognitive and functional deterioration. Depression, anxiety, apathy, irritability, agitation, sleep disorders, among other symptoms, have been hypothesized to represent a prodromal stage of dementia or, at least, they increase the risk for conversion from minor neurocognitive disorder to major neurocognitive disorder. Longitudinal investigations have provided increased evidence of progression to dementia in individuals with minor neurocognitive disorder when neuropsychiatric symptoms also were present.SummaryAlthough neuropsychiatric symptoms are strongly associated with a higher risk of cognitive and functional deterioration, frequently the clinician does not acknowledge these conditions as increasing the risk of dementia. When the clinician accurately diagnoses neuropsychiatric symptoms in the prodromal stage of dementia, he could early establish appropriate treatment and, may be, delay the beginning of clinical and functional deterioration.
- 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.
- 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.
- Decision tree-based classification as a support to diagnosis in the Alzheimer's disease continuum using cerebrospinal fluid biomarkers: insights from automated analysis(2022) COSTA, Alana; PAIS, Marcos; LOUREIRO, Julia; STELLA, Florindo; RADANOVIC, Marcia; GATTAZ, Wagner; FORLENZA, Orestes; TALIB, LedaObjective: Cerebrospinal fluid (CSF) biomarkers add accuracy to the diagnostic workup of cognitive impairment by illustrating Alzheimer's disease (AD) pathology. However, there are no universally accepted cutoff values for the interpretation of AD biomarkers. The aim of this study is to determine the viability of a decision-tree method to analyse CSF biomarkers of AD as a support for clinical diagnosis. Methods: A decision-tree method (automated classification analysis) was applied to concentrations of AD biomarkers in CSF as a support for clinical diagnosis in older adults with or without cognitive impairment in a Brazilian cohort. In brief, 272 older adults (68 with AD, 122 with mild cognitive impairment [MCI], and 82 healthy controls) were assessed for CSF concentrations of A beta(1-42), total-tau, and phosphorylated-tau using multiplexed Luminex assays; biomarker values were used to generate decision-tree algorithms (classification and regression tree) in the R statistical software environment. Results: The best decision tree model had an accuracy of 74.65% to differentiate the three groups. Cluster analysis supported the combination of CSF biomarkers to differentiate AD and MCI vs. controls, suggesting the best cutoff values for each clinical condition. Conclusion: Automated analyses of AD biomarkers provide valuable information to support the clinical diagnosis of MCI and AD in research settings.
- 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.
- Cognitive impairment in late-life bipolar disorder is not associated with Alzheimer's disease pathological signature in the cerebrospinal fluid(2016) FORLENZA, Orestes V.; APRAHAMIAN, Ivan; RADANOVIC, Marcia; TALIB, Leda L.; CAMARGO, Marina Z. A.; STELLA, Florindo; MACHADO-VIEIRA, Rodrigo; GATTAZ, Wagner F.ObjectivesCognitive impairment is a common feature of late-life bipolar disorder (BD). Yet, there is limited information on the biological mechanisms associated with this process. It is uncertain whether cognitively impaired patients with BD may present the Alzheimer's disease (AD) bio-signature in the cerebrospinal fluid (CSF), defined as a combination of low concentrations of the amyloid-beta peptide (A(1-42)) and high concentrations of total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau). In this study, we sought to determine whether cognitive impairment in elderly patients with BD is associated with the AD CSF bio-signature. MethodsSeventy-two participants were enrolled in the study. The test group comprised older adults with BD and mild cognitive impairment (BD-MCI; n=16) and the comparison groups comprised patients with dementia due to AD (n=17), patients with amnestic MCI (aMCI; n=14), and cognitively healthy older adults (control group; n=25). CSF samples were obtained by lumbar puncture and concentrations of A(1-42), T-tau and P-tau were determined. ResultsCSF concentrations of all biomarkers were significantly different in the AD group compared to all other groups, but did not differentiate BD-MCI subjects from aMCI subjects and controls. BD-MCI patients had a non-significant reduction in CSF A(1-42) compared to controls, but this was still higher than in the AD group. Concentrations of T-tau and P-tau in BD-MCI patients were similar to those in controls, and significantly lower than those in AD. ConclusionsCognitively impaired patients with BD do not display the so-called AD bio-signature in the CSF. We therefore hypothesize that cognitive deterioration in BD is not associated with the classical pathophysiological mechanisms observed in AD, i.e., amyloid deposition and hyperphosphorylation of microtubule-associated tau protein.
- Medical cannabinoids for treatment of neuropsychiatric symptoms in dementia: a systematic review(2021) STELLA, Florindo; VALIENGO, Leandro C. Lane; PAULA, Vanessa J. R. de; LIMA, Carlos Augusto de Mendonca; FORLENZA, Orestes V.Introduction: Neuropsychiatric symptoms are an integral component of the natural history of dementia, occurring from prodromal to advanced stages of the disease process and causing increased burden and morbidity. Clinical presentations are pleomorphic and clinical management often requires combinations of pharmacological and non-pharmacological interventions. However, limited efficacy and a non-negligible incidence of adverse psychotropic drug events emphasize the need for novel therapeutic options. Objectives: To review the evidence supporting use of medical cannabinoids for treatment of neuropsychiatric symptoms (NPS) of dementia. Methods: We conducted a systematic review of the medical literature to examine scientific publications reporting use of medical cannabinoids for treatment of NPS. Medical Subject Headings (MeSH) were used to search for relevant publications and only papers reporting original clinical information were included. A secondary search was performed within selected publications to capture relevant citations that were not retrieved by the systematic review. The papers selected were categorized according to the level of evidence generated by the studies in relation to this clinical application, i.e. (1) controlled clinical trials; (2) open-label or observational studies; and (3) case reports. Results: Fifteen publications with original clinical data were retrieved: five controlled clinical trials, three open-label/observational studies, and seven case reports. Most studies indicated that use of medical cannabinoids engendered favorable outcomes for treatment of NPS related to moderate and advanced stages of dementia, particularly agitation, aggressive behavior, sleep disorder, and sexual disinhibition. Conclusion: Medical cannabinoids constitute a promising pharmacological approach to treatment of NPS with preliminary evidence of benefit in at least moderate to severe dementia. Controlled trials with longitudinal designs and larger samples are required to examine the long-term efficacy of these drugs in different types and stages of dementia, in addition to their adverse events and risk of interactions with other drugs. Many pharmacological details are yet to be determined, such as dosing, treatment duration, and concentrations of active compounds (e.g., cannabidiol [CBD]/Delta(9)-tetrahydrocannabinol [THC] ratio) in commercial preparations of medical cannabinoids.
article 141 Citação(ões) na Scopus Physical Exercise in MCI Elderly Promotes Reduction of Pro-Inflammatory Cytokines and Improvements on Cognition and BDNF Peripheral Levels(2014) NASCIMENTO, Carla Manuela Crispim; PEREIRA, Jessica Rodrigues; ANDRADE, Larissa Pires de; GARUFFI, Marcelo; TALIB, Leda Leme; FORLENZA, Orestes Vicente; CANCELA, Jose Maria; COMINETTI, Marcia Regina; STELLA, FlorindoThe benefits of physical exercise to reduce low-grade inflammation and improve Brain-Derived Neurotrophic Factor (BDNF) levels and cognitive function became a growing field of interest. Low-grade inflammation is common during aging and seems to be linked to neurodegenerative process. Regular physical exercises can help to reduce pro-inflammatory cytokines levels and to improve BDNF peripheral concentrations. The main goal of this research was to analyze the effects of a 16-week multimodal physical exercise program on peripheral BDNF levels and on Tumor Necrosis-alpha (TNF-alpha) and Interleukin-6 (IL-6) as pro-inflammatory markers in cognitive healthy elderly individuals and in elderly with mild cognitive impairment (MCI). Cognitive functions were assessed by the Montreal Cognitive Assessment (MoCA) prior to and after the intervention. Thirty cognitively healthy participants and thirty-seven MCI participants were assigned to the control (CG) and trained (TG) groups. The TG participated in a multimodal physical training program for a 16-week period. The results showed a significant between-subjects interaction, which indicates the beneficial contribution of training on the reduction of TNF-alpha (p= 0.001) and IL-6 (p<0.001) and on the improvement of BDNF (p<0.001) peripheral concentrations. Cognitive functions also presented significant improvements for MCI trained group (p= 0.03). In conclusion, physical exercise was effective to reduce pro-inflammatory cytokines and to improve BDNF peripheral levels, with positive reflexes on cognition. To the best of our knowledge, this is the first study that evaluated longitudinally the effects of a multimodal physical exercises protocol on peripheral concentrations of pro-inflammatory cytokines and cognition performance in elderly MCI individuals.- Increased CSF levels of total Tau in patients with subcortical cerebrovascular pathology and cognitive impairment(2017) RADANOVIC, Márcia; STELLA, Florindo; SILVA, Lis Gomes; TALIB, Leda L.; FORLENZA, Orestes V.ABSTRACT. Cognitive impairment includes mild cognitive decline and dementia, such as Alzheimer's disease (AD) and cerebrovascular-related pathologies. Objective: To investigate the profile of AD-related CSF biomarkers in a sample of cognitively impaired and unimpaired older adults with concomitant subcortical cerebrovascular burden. Methods: Seventy-eight older adults attending an outpatient psychogeriatric clinic were enrolled. Diagnoses were based on clinical, neuropsychological, laboratory, and neuroimaging data. Participants were classified into: cognitively normal (controls, n = 30), mild cognitive impairment (MCI, n = 34), and dementia (AD, n = 14). All subjects were submitted to CSF analyses for determination of amyloid-beta (Aβ1-42), total tau (t-tau), phosphorylated tau (p-tau) and Aβ1-42/p-tau ratio according to the Luminex method. MRI was performed in all individuals, and was scored independently by two experts according to Fazekas scale. Statistical analyses were conducted with the aid of general linear model procedures, and the Chi-squared test. Results: T-tau levels were significantly associated with subcortical lesion pattern when Fazekas was considered as a group factor. CSF biomarkers were not associated with MCI, AD, or controls when considered separately. There was a tendency for reduction in CSF Aβ1-42 together with increasing Fazekas scores, but without statistical significance. Comparisons of Aβ1-42 and t-tau with each clinical group or with each neuroimaging pattern did not reach statistical differences. Likewise, Fazekas scores had no impact on CAMCOG scores. Conclusion: We found a significant association between t-tau levels and subcortical lesions when all Fazekas classifications were considered as a single group; comparisons of Fazekas subgroups and CSF biomarkers did not reach significance.
- Caregiver report versus clinician impression: disagreements in rating neuropsychiatric symptoms in Alzheimer's disease patients(2015) STELLA, Florindo; FORLENZA, Orestes Vicente; LAKS, Jerson; ANDRADE, Larissa Pires de; CACAO, Joao de Castilho; GOVONE, Jose Silvio; MEDEIROS, Kate de; LYKETSOS, Constantine G.BackgroundThe measurement of neuropsychiatric symptoms (NPS) in dementia is often based on caregiver report. Challenges associated with providing care may bias the caregiver's recognition and reporting of symptoms. Given potential problems associated with caregiver report, clinicians may improve measurement by drawing from a wider array of available data and by applying clinical judgment. ObjectiveThe objective of this study is to evaluate potential disagreements between caregiver report and clinician impression when rating psychopathological manifestations from the same patient with dementia. MethodsThree hundred twelve participants (156 patients with Alzheimer's disease [AD] and 156 caregivers) were studied using the Neuropsychiatric Inventory-Clinician Rating Scale. We considered disagreement to be present when caregiver ratings were significantly higher or lower (p<0.05) than NPS ratings by clinicians of the same patient. To evaluate whether disagreements were related to dementia severity, we repeated comparisons across levels defined by the clinical dementia rating. ResultsThe most common disagreements involved ratings of agitation, depression, anxiety, apathy, irritability, and aberrant motor behavior especially in patients with mild dementia. There were fewer discrepancies in moderate or severe dementia. The most consistent disagreements involved global ratings of depression where caregiver scores ranged from +22.5 higher to -4.5 lower than clinician rating. ConclusionsCaregivers may have incomplete perception of patient NPS mainly in mild dementia. NPS ratings might be confounded by cultural beliefs, sometimes leading caregiver to interpret symptoms as part of normal aging.