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
56 resultados
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- Evaluation of 10-minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer's disease(2022) CARNEIRO, Camila de Godoi; FARIA, Daniele de Paula; COUTINHO, Artur Martins; ONO, Carla Rachel; DURAN, Fabio Luis de Souza; COSTA, Naomi Antunes da; GARCEZ, Alexandre Teles; SILVEIRA, Paula Squarzoni da; FORLENZA, Orestes Vicente; BRUCKI, Sonia Maria Dozzi; NITRINI, Ricardo; FILHO, Geraldo Busatto; BUCHPIGUEL, Carlos AlbertoObjective: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F] fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease.Methods: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early -phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or-negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping.Results: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early -phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration.Conclusions: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.
- 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.
- Caregiver burden regarding elderly with bipolar disorder: An underrecognized problem(2018) SANTOS, Glenda D.; LADEIRA, Rodolfo B.; ALMEIDA, Jouce G.; APRAHAMIAN, Ivan; FORLENZA, Orestes V.; LAFER, Beny; NUNES, Paula V.
- Caregiver burden in older adults with bipolar disorder: relationship to functionality and neuropsychiatric symptoms(2017) SANTOS, Glenda D. dos; FORLENZA, Orestes V.; LADEIRA, Rodolfo B.; APRAHAMIAN, Ivan; ALMEIDA, Jouce G.; LAFER, Beny; NUNES, Paula V.Background: There are few studies addressing caregivers of bipolar disorder (BD) patients, especially patients who are older adults with an increased need for care, often given by a relative. The aim of this study was to describe which factors increase caregiver burden among caregivers of elderly BD outpatients. Methods: Patients were older than 60 years and met the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, criteria for BD. They were evaluated for current mood, cognitive and other neuropsychiatric symptoms, functionality, medical comorbidities, quality of life, years since BD diagnosis, and number of psychiatric admissions. The caregiver who spent the greatest time with each patient was evaluated with the Zarit Caregiver Burden Interview. The caregivers' global health, mood symptoms, quality of life, and tasks performed for the patient were also assessed. Results: Thirty-six BD patients and their caregivers were assessed. The Zarit Caregiver Burden Interview was positively correlated with patients' neuropsychiatric symptoms (r = 0.508, P = 0.002) and functional impairment (r = 0.466, P = 0.004). The Zarit Caregiver Burden Interview was also correlated with caregivers' own depression (r = 0.576, P < 0.001), anxiety (r = 0.360, P = 0.031), quality of life (r = -0.406, P = 0.014), medical comorbidities (r = 0.387, P = 0.020), and number of tasks that they completed for the patient (r = 0.480, P = 0.003). Conclusions: In this group of elderly BD patients, caregiver burden was more associated with symptoms frequently seen in others diseases as in dementia than with depressive, manic, or anxiety symptoms, which are often used as treatment outcomes measures goals in BD. Potential treatable and modifiable factors associated with caregiver burden could be caregivers' depression, anxiety, and medical comorbidities, as well as support for caregivers in terms of services and social relationships.
- 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.
- 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.
- 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.
- 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.
- Whole-brain DTI parameters associated with tau protein and hippocampal volume in Alzheimer's disease(2023) MAGALHAES, Thamires Naela Cardoso; CASSEB, Raphael Fernandes; GERBELLI, Christian Luiz Baptista; PIMENTEL-SIVA, Luciana Ramalho; NOGUEIRA, Mateus Henrique; TEIXEIRA, Camila Vieira Ligo; CARLETTI, Ana Flavia Mac Knight; REZENDE, Thiago Junqueira Ribeiro de; JOAQUIM, Helena Passarelli Giroud; TALIB, Leda Leme; FORLENZA, Orestes Vicente; CENDES, Fernando; BALTHAZAR, Marcio Luiz FigueredoThe causes of the neurodegenerative processes in Alzheimer's disease (AD) are not completely known. Recent studies have shown that white matter (WM) damage could be more severe and widespread than whole-brain cortical atrophy and that such damage may appear even before the damage to the gray matter (GM). In AD, Amyloid-beta (A beta(42)) and tau proteins could directly affect WM, spreading across brain networks. Since hippocampal atrophy is common in the early phase of disease, it is reasonable to expect that hippocampal volume (HV) might be also related to WM integrity. Our study aimed to evaluate the integrity of the whole-brain WM, through diffusion tensor imaging (DTI) parameters, in mild AD and amnestic mild cognitive impairment (aMCI) due to AD (with A beta(42) alteration in cerebrospinal fluid [CSF]) in relation to controls; and possible correlations between those measures and the CSF levels of A beta(42), phosphorylated tau protein (p-Tau) and total tau (t-Tau). We found a widespread WM alteration in the groups, and we also observed correlations between p-Tau and t-Tau with tracts directly linked to mesial temporal lobe (MTL) structures (fornix and hippocampal cingulum). However, linear regressions showed that the HV better explained the variation found in the DTI measures (with weak to moderate effect sizes, explaining from 9% to 31%) than did CSF proteins. In conclusion, we found widespread alterations in WM integrity, particularly in regions commonly affected by the disease in our group of early-stage disease and patients with Alzheimer's disease. Nonetheless, in the statistical models, the HV better predicted the integrity of the MTL tracts than the biomarkers in CSF.
- Cognitive impairment and dementia in late-life bipolar disorder(2013) APRAHAMIAN, Ivan; NUNES, Paula V.; FORLENZA, Orestes V.Purpose of review This work aims to review the most recent publications on cognitive impairment and dementia associated with bipolar disorder (BPD), especially in the elderly. Recent findings In the last years, a growing number of studies aiming at better understanding of cognitive impairment in BPD were found. Impairments found in BPD were compared with other psychiatric disorders and primary cognitive diseases. The impact of cognitive impairment on functionality was also recently highlighted. With respect to neurobiology, studies that explored inflammatory, neurotrophic and pathological cascades possibly associated with BPD and cognition were published. Finally, the first study covering treatment of cognitive impairment was carried out with pramipexole, and it raised important methodological issues for future research in BPD. Summary Cognitive impairment and dementia in BPD should be better explored with cognitive and functionality protocols along with biological and neuroimaging markers.