PAULA VILLELA NUNES
Projetos de Pesquisa
Unidades Organizacionais
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
34 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 34
- Low brain-derived neurotrophic factor levels in post-mortem brains of older adults with depression and dementia in a large clinicopathological sample(2018) NUNES, Paula Villela; NASCIMENTO, Camila Fernandes; KIM, Helena Kyunghee; ANDREAZZA, Ana Cristina; BRENTANI, Helena Paula; SUEMOTO, Claudia Kimie; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; GRINBERG, Lea Tenenholz; YONG, Lionel Trevor; JACOB-FILHO, Wilson; LAFER, BenyBackground: Disturbances in peripheral brain-derived neurotrophic factor (BDNF) have been reported in major depressive disorder (MDD). However, there are no studies measuring BDNF levels directly in post-mortem brains of older subjects with MDD and dementia. We aimed to verify if brain BDNF levels were lower in older adults with lifetime history of MDD with and without dementia. Methods: BDNF levels of post-mortem brains from 80 community-dwelling older individuals with lifetime MDD with and without dementia were compared with levels from 80 controls without lifetime MDD. Participants with no reliable close informant, or with prolonged agonal state were excluded. Lifetime MDD was defined as at least one previous episode according to the Structured Clinical Interview for DSM (SCID). Results: BDNF levels were lower in the MDD group with dementia than in participants with dementia and without MDD as confirmed by multivariate analysis adjusted for clinical and cardiovascular risk factors (beta = - 0.106, 95%CI = - 0.204; - 0.009, p = 0.034). No difference was found in the group with MDD without dementia compared with their controls. Limitations: The retrospective assessment of a lifetime history of depression may be subject to information bias and this study only establishes a cross-sectional association between lifetime history of MDD and lower levels of BDNF in patients with dementia. Conclusions: In this community sample of older individuals, lower brain BDNF levels were found in cases with both lifetime MDD and dementia. Low BDNF levels could be a moderator to accelerated brain aging observed in MDD with dementia.
- Neuropsychiatric symptoms in community-dwelling older Brazilians with mild cognitive impairment and dementia(2022) SUEMOTO, Claudia Kimie; NUNES, Paula Villela; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; RODRIGUEZ, Roberta Diehl; GRINBERG, Lea Tenenholz; JACOB-FILHO, Wilson
- Increased levels of TAR DNA-binding protein 43 in the hippocampus of subjects with bipolar disorder: a postmortem study(2022) NASCIMENTO, Camila; V, Paula Nunes; KIM, Helena K.; LEITE, Renata E. P.; RODRIGUEZ, Roberta D.; OLIVEIRA, Katia Cristina De; BRENTANI, Helena P.; JACOB-FILHO, Wilson; NITRINI, Ricardo; PASQUALUCCI, Carlos A.; GRINBERG, Lea T.; SUEMOTO, Claudia K.; LAFER, BenyBipolar disorder shares symptoms and pathological pathways with other neurodegenerative diseases, including frontotemporal dementia (FTD). Since TAR DNA-binding protein 43 (TDP-43) is a neuropathological marker of frontotemporal dementia and it is involved in synaptic transmission, we explored the role of TDP-43 as a molecular feature of bipolar disorder (BD). Homogenates were acquired from frozen hippocampus of postmortem brains of bipolar disorder subjects. TDP-43 levels were quantified using an ELISA-sandwich method and compared between the postmortem brains of bipolar disorder subjects and age-matched control group. We found higher levels of TDP-43 protein in the hippocampus of BD (n = 15) subjects, when compared to controls (n = 15). We did not find associations of TDP-43 with age at death, postmortem interval, or age of disease onset. Our results suggest that protein TDP-43 may be potentially implicated in behavioral abnormalities seen in BD. Further investigation is needed to validate these findings and to examine the role of this protein during the disease course and mood states.
- 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.
- 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.
- A review on shared clinical and molecular mechanisms between bipolar disorder and frontotemporal dementia(2019) NASCIMENTO, Camila; NUNES, Paula Villela; RODRIGUEZ, Roberta Diehl; TAKADA, Leonel; SUEMOTO, Claudia Kimie; GRINBERG, Lea Tenenholz; NITRINI, Ricardo; LAFER, BenyMental disorders are highly prevalent and important causes of medical burden worldwide. Co-occurrence of neurological and psychiatric symptoms are observed among mental disorders, representing a challenge for their differential diagnosis. Psychiatrists and neurologists have faced challenges in diagnosing old adults presenting behavioral changes. This is the case for early frontotemporal dementia (FTD) and bipolar disorder. In its initial stages, FTD is characterized by behavioral or language disturbances in the absence of cognitive symptoms. Consequently, patients with the behavioral subtype of FTD (bv-FTD) can be initially misdiagnosed as having a psychiatric disorder, typically major depression disorder (MDD) or bipolar disorder (BD). Bipolar disorder is associated with a higher risk of dementia in older adults and with cognitive impairment, with a subset of patients presents a neuroprogressive pattern during the disease course. No mendelian mutations were identified in BD, whereas three major genetic causes of FTD have been identified. Clinical similarities between BD and bv-FTD raise the question whether common molecular pathways might explain shared clinical symptoms. Here, we reviewed existing data on clinical and molecular similarities between BD and FTD to propose biological pathways that can be further investigated as common or specific markers of BD and FTD.
- 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.
- Bipolar symptoms, somatic burden and functioning in older-age bipolar disorder: A replication study from the global aging & geriatric experiments in bipolar disorder database (GAGE-BD) project(2024) SAJATOVIC, Martha; REJ, Soham; ALMEIDA, Osvaldo P.; ALTINBAS, Kursat; BALANZA-MARTINEZ, Vicent; BARBOSA, Izabela G.; BEUNDERS, Alexandra J. M.; BLUMBERG, Hilary P.; BRIGGS, Farren B. S.; DOLS, Annemiek; FORESTER, Brent P.; FORLENZA, Orestes V.; GILDENGERS, Ariel G.; JIMENEZ, Esther; KLAUS, Federica; LAFER, Beny; MULSANT, Benoit; MWANGI, Benson; NUNES, Paula Villela; OLAGUNJU, Andrew T.; OLUWANIYI, Stephen; ORHAN, Melis; PATRICK, Regan E.; RADUA, Joaquim; RAJJI, Tarek; SARNA, Kaylee; SCHOUWS, Sigfried; SIMHANDL, Christian; SEKHON, Harmehr; SOARES, Jair C.; SUTHERLAND, Ashley N.; TEIXEIRA, Antonio L.; TSAI, Shangying; VIDAL-RUBIO, Sonia; VIETA, Eduard; YALA, Joy; EYLER, Lisa T.Objectives: The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232, mean +/- standard deviation age 47.2 +/- 13.5, 65% women, 49% aged over 50) dataset. Design/Methods: Using mixed models with random effects for cohort, we examined associations between BD symptoms, somatic burden and age and the contribution of these to functioning in W2 and the combined W1 + W2 sample (n = 2601). Results: Compared to W1, the W2 sample was younger (p < 0.001), less educated (p < 0.001), more symptomatic (p < 0.001), lower functioning (p < 0.001) and had fewer somatic conditions (p < 0.001). In the full W2, older individuals had reduced manic symptom severity, but age was not associated with depression severity. Age was not associated with functioning in W2. More severe BD symptoms (mania p <= 0.001, depression p <= 0.001) were associated with worse functioning. Older age was significantly associated with higher somatic burden in the W2 and the W1 + W2 samples, but this burden was not associated with poorer functioning. Conclusions: In a large, independent sample, older age was associated with less severe mania and more somatic burden (consistent with previous findings), but there was no association of depression with age (different from previous findings). Similar to previous findings, worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning.
- Factors associated with brain volume in major depression in older adults without dementia: results from a large autopsy study(2018) NUNES, Paula Villela; SUEMOTO, Claudia Kimie; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; FARFEL, Jose Marcelo; OLIVEIRA, Katia Cristina de; GRINBERG, Lea Tenenholz; COSTA, Nicole Rezende da; NASCIMENTO, Camila Fernandes; SALMASI, Faraz; KIM, Helena Kyunghee; YOUNG, Lionel Trevor; JACOB-FILHO, Wilson; LAFER, BenyObjectiveWe examined brain volume and atrophy in individuals with major depressive disorder (MDD) without dementia that were referred to a large autopsy service. We also examined potential risk factors for brain atrophy, including demographics and clinical variables. MethodsIn this study, 1373 participants (787 male) aged 50years or older who died from natural causes were included. Participants with no reliable informant, with cognitive impairment or dementia, with a medical history of severe chronic disease, or with prolonged agonal state were excluded. Presence of MDD at least once in their lifetime was defined according to the Structured Clinical Interview for DSM. Brain volume was measured immediately after removal from the skull. ResultsMean age at death was 68.611.6, and MDD was present in 185 (14%) individuals. Smaller brain volume was associated with older age (p<0.001), lower education (years; p<0.001), hypertension (p=0.001), diabetes (p=0.006), and female gender (p<0.001). In the multivariate analysis adjusted for sociodemographics and cardiovascular risk factors, smaller brain volume was not associated with major depression (=-0.86, 95% CI=-26.50 to 24.77, p=0.95). ConclusionsIn this large autopsy study of older adults, MDD was not associated with smaller brain volumes. Regardless of the presence of MDD, in this sample of older adults without dementia, we found that smaller brain volumes were associated with risk factors for brain neurodegeneration such as older age, diabetes, hypertension, and lower education.
- 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.