CASSIO MACHADO DE CAMPOS BOTTINO
Projetos de Pesquisa
Unidades Organizacionais
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Validation of a treatment algorithm for major depression in an older Brazilian sample(2013) RIBEIZ, Salma R. I.; AVILA, Renata; MARTINS, Camila B.; MOSCOSO, Marco A. A.; STEFFENS, David C.; BOTTINO, Cassio M. C.Objective The aim of this study was to investigate the effectiveness of a modified version of the Duke Somatic Algorithm Treatment for Geriatric Depression (STAGED) in a Brazilian sample of older patients with major depression. Besides, we aimed to investigate possible baseline predictive factors for remission in this sample. Methods Sixty-seven depressed individuals were treated according to STAGED over 24 weeks in a prospective cohort design with follow-up. All patients had criteria for major depression and were at least 60 years of age at baseline enrollment. Results During this follow-up, 56 patients could be classified in remitted or not remitted group, 42.85% reached remission, and 57.14% did not reach remission. These results are even better than those found in the original study, probably due to the lower baseline depression severity of our sample. When baseline characteristics were compared between remitted and not remitted groups, scores of Mini Mental State Examination and Cambridge Cognitive Examination (CAMCOG) were the only variables with statistical significant difference (p<0.05) between groups. Logistic regression analysis was carried out to try to predict remission and statistical significance (p<0.05) was found only for baseline MMSE scores. It may mean that patients with mixed cognitive disorders and mood disorders have a worse course of depression. Conclusions This version of STAGED seems to be a useful strategy for treatment of depression in late life. Baseline general cognitive performance might be useful to predict remission of depression in older patients with mild to moderate depression. Further research with different population characteristics should be conducted in order to evaluate its usefulness and feasibility in different settings.
- Amnestic and non-amnestic symptoms of dementia: An international study of Alzheimer's disease in people with Down's syndrome(2020) FONSECA, Luciana M.; PADILLA, Concepcion; JONES, Elizabeth; NEALE, Natalie; HADDAD, Glenda G.; MATTAR, Guilherme P.; BARROS, Eriton; CLARE, Isabel C. H.; BUSATTO, Geraldo F.; BOTTINO, Cassio M. C.; HOEXTER, Marcelo Q.; HOLLAND, Anthony J.; ZAMAN, ShahidThe presence of age-related neuropathology characteristic of Alzheimer's disease (AD) in people with Down syndrome (DS) is well-established. However, the early symptoms of dementia may be atypical and appear related to dysfunction of prefrontal circuitry. Objective To characterize the initial informant reported age-related neuropsychiatric symptoms of dementia in people with DS, and their relationship to AD and frontal lobe function. Methods Non-amnestic informant reported symptoms (disinhibition, apathy, and executive dysfunction) and amnestic symptoms from the CAMDEX-DS informant interview were analyzed in a cross-sectional cohort of 162 participants with DS over 30 years of age, divided into three groups: stable cognition, prodromal dementia, and AD. To investigate age-related symptoms prior to evidence of prodromal dementia we stratified the stable cognition group by age. Results Amnestic and non-amnestic symptoms were present before evidence of informant-reported cognitive decline. In those who received the diagnosis of AD, symptoms tended to be more marked. Memory impairments were more marked in the prodromal dementia than the stable cognition group (OR = 35.07; P < .001), as was executive dysfunction (OR = 7.16; P < .001). Disinhibition was greater in the AD than in the prodromal dementia group (OR = 3.54; P = .04). Apathy was more pronounced in the AD than in the stable cognition group (OR = 34.18; P < .001). Conclusion Premorbid amnestic and non-amnestic symptoms as reported by informants increase with the progression to AD. For the formal diagnosis of AD in DS this progression of symptoms needs to be taken into account. An understanding of the unique clinical presentation of DS in AD should inform treatment options.
- Metamemory and aging: Psychometric properties of the Brazilian version of the Multifactorial Memory Questionnaire for elderly(2016) SIMON, Sharon Sanz; ÁVILA, Renata Thomas; VIEIRA, Gilson; BOTTINO, Cássio Machado de CamposABSTRACT Metamemory measures provide subjective memory information and are relevant to investigate memory ability in aging. However, there is a lack of metamemory instruments available in Brazil. Objective: The aim of this study was to examine the psychometric properties of the Brazilian version of the Multifactorial Memory Questionnaire (MMQ), which evaluates different dimensions of subjective memory functioning, such as Feelings, Abilities and Strategies used in everyday life. Methods: The MMQ was translated into Portuguese and administered to 30 Brazilian elderly subjects. The participants underwent cognitive tests, mood scales and metamemory instruments. Results: Analyses revealed good internal consistency (Cronbach's a coefficient ranged from 0.75 to 0.89) and test-retest validity for each MMQ dimensions (positive correlations between two applications ranged from 0.75 to 0.8). Convergent validity evidence for the MMQ was confirmed by significant positive correlations (0.47 to 0.68) with dimensions of the Metamemory in Adulthood scale (MIA) (i.e., the Ability, Control, Self-efficacy and Strategy dimensions). Discriminant validity revealed no associations between the MMQ and cognitive performance, suggesting a weak metamemory-objective memory correspondence. Moreover, there was a negative correlation between MMQ-Ability subscale scores and mood symptoms (-0.63 for anxious symptoms, and -0.54 for depressive symptoms); and the Brazilian MMQ was comparable with MMQ translations to other languages. Conclusion: The Brazilian MMQ exhibits good psychometric properties and appears promising for clinical and research purposes. Additional studies are needed to further examine the psychometric properties of the Brazilian MMQ in a larger sample.
- Neuropsychiatric Symptoms, Caregiver Burden and Distress in Behavioral-Variant Frontotemporal Dementia and Alzheimer's Disease(2015) LIMA-SILVA, Thais Bento; BAHIA, Valeria Santoro; CARVALHO, Viviane Amaral; GUIMARAES, Henrique Cerqueira; CARAMELLI, Paulo; BALTHAZAR, Marcio Luiz; DAMASCENO, Benito; BOTTINO, Cassio Machado; BRUCKI, Sonia Maria; NITRINI, Ricardo; YASSUDA, Monica SanchesBackground/Aims: We aimed to compare caregiver burden and distress in behavioral-variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) and to investigate which factors contribute to caregivers' burden and distress. Methods: Fifty patients and their care-givers were invited to participate. Among the patients, 20 had a diagnosis of bvFTD and 30 had AD. Caregivers and patients were statistically equivalent for age, sex, education and dementia severity according to Clinical Dementia Rating. The protocol included the Short Zarit Burden Inventory, the Neuropsychiatric Inventory (NPI), Disability Assessment for Dementia (DAD), the Cornell Scale for Depression in Dementia (CSDD), Addenbrooke's Cognitive Examination-Revised, the Executive Interview with 25 Items, Direct Assessment of Functional Status and the Geriatric Anxiety Inventory (GAI). Results: In the NPI, caregivers of bvFTD patients reported a higher presence and severity of neuropsychiatric symptoms and caregiver distress compared to caregivers of AD patients. There was no significant difference in the perceived burden. In bvFTD, DAD and GAI scores were significantly correlated with burden, whereas in AD, burden was correlated with CSDD and NPI scores. Psychiatric symptoms were associated with distress in both groups. Conclusions: Caregivers of bvFTD patients experienced higher levels of distress than caregivers of AD patients. Patients' functional limitations were associated with burden of caregivers of bvFTD patients, whereas neuropsychiatric symptoms were associated with caregiver strain in both groups. (C) 2015 S. Karger AG, Basel
- Analysis of the posterior cingulate cortex with [ 18 F]FDG-PET and Naa/mI in mild cognitive impairment and Alzheimer's disease: Correlations and differences between the two methods(2015) COUTINHO, Artur M.N.; PORTO, Fábio H.G.; ZAMPIERI, Poliana F.; OTADUY, Maria C.; PERROCO, Tíbor R.; OLIVEIRA, Maira O.; NUNES, Rafael F.; PINHEIRO, Toulouse Leusin; BOTTINO, Cassio M.C.; LEITE, Claudia C.; BUCHPIGUEL, Carlos A.ABSTRACT Reduction of regional brain glucose metabolism (rBGM) measured by [18F]FDG-PET in the posterior cingulate cortex (PCC) has been associated with a higher conversion rate from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Magnetic Resonance Spectroscopy (MRS) is a potential biomarker that has disclosed Naa/mI reductions within the PCC in both MCI and AD. Studies investigating the relationships between the two modalities are scarce. OBJECTIVE To evaluate differences and possible correlations between the findings of rBGM and NAA/mI in the PCC of individuals with AD, MCI and of cognitively normal volunteers. METHODS Patients diagnosed with AD (N=32) or MCI (N=27) and cognitively normal older adults (CG, N=28), were submitted to [18F]FDG-PET and MRS to analyze the PCC. The two methods were compared and possible correlations between the modalities were investigated. RESULTS The AD group exhibited rBGM reduction in the PCC when compared to the CG but not in the MCI group. MRS revealed lower NAA/mI values in the AD group compared to the CG but not in the MCI group. A positive correlation between rBGM and NAA/mI in the PCC was found. NAA/mI reduction in the PCC differentiated AD patients from control subjects with an area under the ROC curve of 0.70, while [18F]FDG-PET yielded a value of 0.93. CONCLUSION rBGM and Naa/mI in the PCC were positively correlated in patients with MCI and AD. [18F]FDG-PET had greater accuracy than MRS for discriminating AD patients from controls.
- Clinical and sociodemographic factors in a sample of older subjects experiencing depressive symptoms(2012) BARCELOS-FERREIRA, Ricardo; LOPES, Marcos A.; NAKANO, Eduardo Yoshio; STEFFENS, David C.; BOTTINO, Cassio M. C.Objectives This study aims to determine the frequency of clinically significant depressive symptoms (CSDS) in a community sample of older Brazilians and to examine their relationship with sociodemographic factors, cognitive and functional impairment (CFI), and medical illness. Methods A total of 1145 subjects aged 60?years or older living in the City of Ribeirao Preto, State of Sao Paulo, Brazil, were interviewed. The following instruments were used: a 10-item scale for screening of depressive symptoms in older people, the mini mental state examination, the Fuld Object Memory Evaluation, the Informant Questionnaire on Cognitive Decline in the Elderly, the Bayer Activities of Daily Living Scale, and a sociodemographic and clinical questionnaire. Results The frequency of CSDS was 15.7%. Logistic regression analysis indicated that being previously depressed, having CFI, having lower level of education, using psychotropics, and not engaging in physical exercise were related to CSDS. On the other hand, being a woman, older, medically ill, employed, or married was not associated with CSDS. Conclusions Consistent with previous reports, lower education, lack of physical activity, and CFI were significantly associated with higher frequencies of CSDS. Further investigations are necessary to clarify the occurrence of depression and possible modifiable factors in developing countries such as Brazil.
- Frontal-subcortical behaviors during Alzheimer's disease in individuals with Down syndrome(2019) FONSECA, Luciana Mascarenhas; MATTAR, Guilherme Prado; HADDAD, Glenda Guerra; GONCALVES, Aline Souza; MIGUEL, Andre de Queiroz Constantino; GUILHOTO, Laura Maria; ZAMAN, Shahid; HOLLAND, Anthony J.; BOTTINO, Cassio Machado de Campos; HOEXTER, Marcelo QueirozThere is evidence that frontal-subcortical circuits play an important role in the initial presentation of dementia in Down syndrome (DS), including changes in behavior, a decline in working memory and executive dysfunction. We evaluated 92 individuals with DS (>= 30 years of age), divided into 3 groups by diagnosis-stable cognition, prodromal dementia, and Alzheimer's disease. Each individual was evaluated with an executive protocol developed for people with intellectual disabilities and was rated for behaviors related to frontal lobe dysfunction (disinhibition, executive dysfunction, and apathy) by an informant using the Frontal Systems Behavior Scale. Informant-reported behaviors related to frontal lobe dysfunction were found to correlate negatively with executive function performance. Disinhibition and executive dysfunction were associated with the clinical stage of dementia. The odds of having Alzheimer's disease increased in parallel with increases in the domain and total Frontal Systems Behavior Scale scores (p <= 0.5). Disinhibition, executive dysfunction and apathy should be taken into consideration during the clinical evaluation of adults with DS, and future studies should consider the intersection of neuropathology, brain connectivity, and behavior.
- Translation, cross-cultural adaptation and applicability of the Brazilian version of the Frontotemporal Dementia Rating Scale (FTD-FRS)(2013) LIMA-SILVA, Thais Bento; BAHIA, Valéria Santoro; CARVALHO, Viviane Amaral; GUIMARÃES, Henrique Cerqueira; CARAMELLI, Paulo; BALTHAZAR, Márcio; DAMASCENO, Benito; BOTTINO, Cássio Machado de Campos; BRUCKI, Sônia Maria Dozzi; MIOSHI, Eneida; NITRINI, Ricardo; YASSUDA, Mônica SanchesABSTRACT Background: Staging scales for dementia have been devised for grading Alzheimer's disease (AD) but do not include the specific symptoms of frontotemporal lobar degeneration (FTLD). Objective: To translate and adapt the Frontotemporal Dementia Rating Scale (FTD-FRS) to Brazilian Portuguese. Methods: The cross-cultural adaptation process consisted of the following steps: translation, back-translation (prepared by independent translators), discussion with specialists, and development of a final version after minor adjustments. A pilot application was carried out with 12 patients diagnosed with bvFTD and 11 with AD, matched for disease severity (CDR=1.0). The evaluation protocol included: Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini-Mental State Examination (MMSE), Executive Interview (EXIT-25), Neuropsychiatric Inventory (NPI), Frontotemporal Dementia Rating Scale (FTD-FRS) and Clinical Dementia Rating scale (CDR). Results: The Brazilian version of the FTD-FRS seemed appropriate for use in this country. Preliminary results revealed greater levels of disability in bvFTD than in AD patients (bvFTD: 25% mild, 50% moderate and 25% severe; AD: 36.36% mild, 63.64% moderate). It appears that the CDR underrates disease severity in bvFTD since a relevant proportion of patients rated as having mild dementia (CDR=1.0) in fact had moderate or severe levels of disability according to the FTD-FRS. Conclusion: The Brazilian version of the FTD-FRS seems suitable to aid staging and determining disease progression.
- Cortical brain volume abnormalities associated with few or multiple neuropsychiatric symptoms in Alzheimer's disease(2017) TASCONE, Lyssandra dos Santos; PAYNE, Martha E.; MACFALL, James; AZEVEDO, Dionisio; CASTRO, Claudio Campi de; STEFFENS, David C.; BUSATTO, Geraldo F.; BOTTINO, Cassio M. C.New research on assessing neuropsychiatric manifestations of Alzheimer's Disease (AD) involves grouping neuropsychiatric symptoms into syndromes. Yet this approach is limited by high inter-subject variability in neuropsychiatric symptoms and a relatively low degree of concordance across studies attempting to cluster neuropsychiatric symptoms into syndromes. An alternative strategy that involves dichotomizing AD subjects into those with few versus multiple neuropsychiatric symptoms is both consonant with real-world clinical practice and can contribute to understanding neurobiological underpinnings of neuropsychiatric symptoms in AD patients. The aim of this study was to address whether the number of neuropsychiatric symptoms (i.e., presence of few [<= 2] versus multiple [<= 3] symptoms) in AD would be associated with degree of significant gray matter (GM) volume loss. Of particular interest was volume loss in brain regions involved in memory, emotional processing and salience brain networks, including the prefrontal, lateral temporal and parietal cortices, anterior cingulate gyrus, temporo-limbic structures and insula. We recruited 19 AD patients and 13 healthy controls, which underwent an MRI and neuropsychiatric assessment. Regional brain volumes were determined using voxel-based morphometry and other advanced imaging processing methods. Our results indicated the presence of different patterns of GM atrophy in the two AD subgroups relative to healthy controls. AD patients with multiple neuropsychiatric manifestations showed more evident GM atrophy in the left superior temporal gyrus and insula as compared with healthy controls. In contrast, AD subjects with few neuropsychiatric symptoms displayed more GM atrophy in prefrontal regions, as well as in the dorsal anterior cingulate ad post-central gyri, as compared with healthy controls. Our findings suggest that the presence of multiple neuropsychiatric symptoms is more related to the degree of atrophy in specific brain networks rather than dependent on the global severity of widespread neurodegenerative brain changes.
- The influence of lithium on hippocampal volume in elderly bipolar patients: a study using voxel-based morphometry(2016) ZUNG, S.; SOUZA-DURAN, F. L.; SOEIRO-DE-SOUZA, M. G.; UCHIDA, R.; BOTTINO, C. M.; BUSATTO, G. F.; VALLADA, H.Recent studies have demonstrated that lithium (Li) exerts neuronal protective and regenerative effects both in vitro and in vivo. However, the effects of long-term Li treatment in the brain areas associated with memory impairment of elderly bipolar patients are still unknown. The aim of this study was to compare the hippocampal volumes of elderly bipolar patients using Li, elderly bipolar patients not using Li and healthy controls. Sociodemographic, clinical and magnetic resonance imaging data from 30 elderly euthymic bipolar patients who had been using Li for an average of >61 months; 27 elderly euthymic bipolar patients not taking Li for an average of 45 months; and 22 elderly healthy controls were analyzed. Volumetric differences in the hippocampus between groups were investigated with voxel-based morphometry (VBM) based on the Statistical Parametric Mapping technique. No statistical differences in sociodemographic and clinical characteristics and course of bipolar disorder between the two bipolar groups were observed. Using small volume correction in the VBM analysis (analysis of variance (ANOVA)), one voxel cluster of statistical significance was detected in the left hippocampus (P<0.05 corrected for multiple comparisons, extent threshold >10 voxels). Post hoc unpaired t-tests revealed increased left hippocampal volume in the Li-treated group compared with the non-Li-treated group, and decreased left hippocampal volume in the non-Li group relative to controls. Additional exploratory two-group comparisons indicated trends toward reduced right-hippocampal volumes in the non-Li-treated group relative to both the Li-treated group and controls. The findings suggested that the use of Li may influence the volume of the hippocampus, possibly due to its neuroprotective effects.