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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- 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.
- 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.
- Structural Brain Changes as Biomarkers and Outcome Predictors in Patients with Late-Life Depression: A CrossSectional and Prospective Study(2013) RIBEIZ, Salma R. I.; DURAN, Fabio; OLIVEIRA, Melaine C.; BEZERRA, Diana; CASTRO, Claudio Campi; STEFFENS, David C.; BUSATTO FILHO, Geraldo; BOTTINO, Cassio M. C.The relationship between structural changes in grey matter and treatment response in patients with late-life depression remains an intriguing area of research. This magnetic resonance imaging (MRI) study compares the baseline grey matter volume of elderly people with and without major depression (according to the DSM-IV-TR criteria) and assesses its association with antidepressant treatment response. Brain MRI scans were processed using statistical parametric mapping and voxel-based morphometry. The sample consisted of 30 patients with depression and 22 healthy controls. We found a significant volumetric reduction in the orbitofrontal cortex bilaterally in patients in comparison with controls. According to their remission status after antidepressant treatment, patients were classified as remitted or not remitted. Compared with controls, remitted patients showed a volumetric reduction in the orbitofrontal cortex bilaterally and in another cluster in the right middle temporal pole. Non-remitted patients showed an even greater volumetric reduction in the orbitofrontal cortex bilaterally compared with controls. To investigate predictive factors of remission after antidepressant treatment, we used a logistic regression. Both baseline Mini Mental State Examination score and baseline left superior lateral orbitofrontal cortex volume (standardized to the total grey matter volume) were associated with remission status. Our findings support the use of regional brain atrophy as a potential biomarker for depression. In addition, baseline cognitive impairment and regional grey matter abnormalities predict antidepressant response in patients with late-life depression.
- Cognitive and Brain Activity Changes After Mnemonic Strategy Training in Amnestic Mild Cognitive Impairment: Evidence From a Randomized Controlled Tria(2018) SIMON, Sharon S.; HAMPSTEAD, Benjamin M.; NUCCI, Mariana P.; DURAN, Fabio L. S.; FONSECA, Luciana M.; MARTINO, Maria da Graca M.; AVILA, Renata; PORTO, Fabio H. G.; BRUCKI, Sonia M. D.; MARTINS, Camila B.; TASCONE, Lyssandra S.; JR, Edson Amaro; BUSATTO, Geraldo F.; BOTTINO, Cassio M. C.Background: Mnemonic strategy training (MST) has been shown to improve cognitive performance in amnestic mild cognitive impairment (a-MCI), however, several questions remain unresolved. The goal of the present study was to replicate earlier pilot study findings using a randomized controlled design and to evaluate transfer effects and changes in brain activation. Methods: Thirty patients with a-MCI were randomized into MST or education program. At baseline, participants completed clinical and neuropsychological assessments as well as structural and functional magnetic resonance imaging (fMRI). Interventions were administered individually and comprised four sessions, over 2 weeks. MST taught patients to use a three-step process to learn and recall face-name associations. Post-treatment assessment included fMRI, a separate face-name association task, neuropsychological tests, and measures of metamemory. Behavioral (i.e., non-fMRI) measures were repeated after one and 3-months. Results: Participants in the MST condition showed greater improvement on measures of face-name memory, and increased associative strategy use; effects that were accompanied by increased fMRI activation in the left anterior temporal lobe. While all participants reported greater contentment with their everyday memory following intervention, only the MST group reported significant improvements in their memory abilities. There was no clear indication of far-transfer effects to other neuropsychological tests. Conclusion: Results demonstrate that patients with a-MCI not only show stimulus specific benefits of MST, but that they appear capable of transferring training to at least some other cognitive tasks. MST also facilitated the use of brain regions that are involved in face processing, episodic and semantic memory, and social cognition, which are consonant with the cognitive processes engaged by training.
- Neuropsychiatric Symptoms of Alzheimer's Disease in Down Syndrome and Its Impact on Caregiver Distress(2021) FONSECA, Luciana Mascarenhas; MATTAR, Guilherme Prado; HADDAD, Glenda Guerra; BURDULI, Ekaterina; MCPHERSON, Sterling M.; GUILHOTO, Laura Maria de Figueiredo Ferreira; YASSUDA, Monica Sanches; BUSATTO, Geraldo Filho; BOTTINO, Cassio Machado de Campos; HOEXTER, Marcelo Queiroz; CHAYTOR, Naomi SageBackground: Neuropsychiatric symptoms (NPS) are non-cognitive manifestations common to dementia and other medical conditions, with important consequences for the patient, caregivers, and society. Studies investigating NPS in individuals with Down syndrome (DS) and dementia are scarce. Objective: Characterize NPS and caregiver distress among adults with DS using the Neuropsychiatric Inventory (NPI). Methods: We evaluated 92 individuals with DS (>= 30 years of age), divided by clinical diagnosis: stable cognition, prodromal dementia, and AD. Diagnosis was determined by a psychiatrist using the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). NPS and caregiver distress were evaluated by an independent psychiatrist using the NPI, and participants underwent a neuropsychological assessment with Cambridge Cognitive Examination (CAMCOG-DS). Results: Symptom severity differed between-groups for delusion, agitation, apathy, aberrant motor behavior, nighttime behavior disturbance, and total NPI scores, with NPS total score being found to be a predictor of AD in comparison to stable cognition (OR for one-point increase in the NPI = 1.342, p = 0.012). Agitation, apathy, nighttime behavior disturbances, and total NPI were associated with CAMCOG-DS, and 62% of caregivers of individuals with AD reported severe distress related to NPS. Caregiver distress was most impacted by symptoms of apathy followed by nighttime behavior, appetite/eating abnormalities, anxiety, irritability, disinhibition, and depression (R-2 = 0.627, F(15,76) = 8.510, p < 0.001). Conclusion: NPS are frequent and severe in individuals with DS and AD, contributing to caregiver distress. NPS in DS must be considered of critical relevance demanding management and treatment. Further studies are warranted to understand the biological underpinnings of such symptoms.
- The validity and reliability of the CAMDEX-DS for assessing dementia in adults with Down syndrome in Brazil(2019) FONSECA, Luciana M.; HADDAD, Glenda G.; MATTAR, Guilherme P.; OLIVEIRA, Melaine C. de; SIMON, Sharon S.; GUILHOTO, Laura M.; BUSATTO, Geraldo F.; ZAMAN, Shahid; HOLLAND, Anthony J.; HOEXTER, Marcelo Q.; BOTTINO, Cassio M.Objective: Alzheimer's disease occurs at a higher prevalence and an earlier age in individuals with Down syndrome (DS) than typically developing individuals. However, diagnosing dementia in individuals with intellectual disability remains a challenge due to pre-existing cognitive deficits. The aim of this study was to investigate the validity and reliability of the Brazilian version of the Cambridge Examination for Mental Disorders of Older People with Down's syndrome and Others with Intellectual Disabilities (CAMDEX-DS) for individuals with DS. Methods: Two psychiatrists, working independently, evaluated 92 adults with DS >= 30 years of age. The concurrent validity of the CAMDEX-DS was analyzed in relation to the gold standard of established international criteria. In a subgroup of 20 subjects, the concurrent validity of the CAM DEX-DS was analyzed in relation to an independent objective assessment of cognitive decline over three years. We analyzed the inter-rater reliability of cognitive assessment. Results: The diagnostic accuracy of the CAMDEX-DS compared to the gold standard was 96.7%. CAMDEX-DS-based diagnosis was considered consistent with cognitive decline. The probability of a participant with dementia having cognitive decline was 83%. Inter-rater reliability for the participant assessment was good, with a kappa of > 0.8 for 93% of the CAMDEX-DS items. Conclusion: The CAMDEX-DS can be considered the first valid and reliable instrument for evaluating dementia in adults with DS in Brazil. Its use in such individuals could improve clinical practice and research.
- Screening for Dementia and Cognitive Decline in Adults With Down Syndrome A Novel Approach Using the Informant Questionnaire on Cognitive Decline in the Elderly(2022) MATTAR, Guilherme Prado; UCHIDA, Ricardo R.; HADDAD, Glenda G.; SHIOZAWA, Pedro; SILVA, Maria de Fatima Reboucas da; HOEXTER, Marcelo Q.; BUSATTO, Geraldo F.; BOTTINO, Cassio M. de Campos; FONSECA, Luciana M.; V, Orestes ForlenzaObjective: The aim was to examine the psychometric properties of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a diagnostic tool to screen for dementia in aging individuals with Down syndrome (DS). Methods: This was a cross-sectional study of 92 individuals with DS 30 y or above of age) evaluated with the IQCODE. Using the informant questionnaire of the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities, we divided the subjects into 3 diagnostic groups: stable cognition; prodromal dementia; and dementia. The ability of the IQCODE to discriminate between diagnostic groups was analyzed by calculating the areas under the receiver operator characteristic curves (AUCs). Results: The optimal IQCODE cutoffs were 3.14 for dementia versus stable cognition (AUC= 0.993; P< 0.001) and 3.11 for prodromal dementia+dementia versus stable cognition (AUC= 0.975; P< 0.001), with sensitivity/specificity/accuracy of 100%/96.8%/97.3%, and 93.3%/ 91.9%/92.4%, respectively. The IQCODE showed a weak-to-moderate correlation with cognitive performance (P< 0.05). Conclusion: The IQCODE is a useful tool to screen for cognitive decline in individuals with DS and is suitable for use in a primary care setting.
- Support vector machine-based classification of neuroimages in Alzheimer's disease: direct comparison of FDG-PET, rCBF-SPECT and MRI data acquired from the same individuals(2018) FERREIRA, Luiz K.; RONDINA, Jane M.; KUBO, Rodrigo; ONO, Carla R.; LEITE, Claudia C.; SMID, Jerusa; BOTTINO, Cassio; NITRINI, Ricardo; BUSATTO, Geraldo F.; DURAN, Fabio L.; BUCHPIGUEL, Carlos A.Objective: To conduct the first support vector machine (SVM)-based study comparing the diagnostic accuracy of T1-weighted magnetic resonance imaging (T1-MRI), F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and regional cerebral blood flow single-photon emission computed tomography (rCBF-SPECT) in Alzheimer's disease (AD). Method: Brain T1-MRI, FDG-PET and rCBF-SPECT scans were acquired from a sample of mild AD patients (n=20) and healthy elderly controls (n=18). SVM-based diagnostic accuracy indices were calculated using whole-brain information and leave-one-out cross-validation. Results: The accuracy obtained using PET and SPECT data were similar. PET accuracy was 68 similar to 71% and area under curve (AUC) 0.77 similar to 0.81; SPECT accuracy was 68 similar to 74% and AUC 0.75 similar to 0.79, and both had better performance than analysis with T1-MRI data (accuracy of 58%, AUC 0.67). The addition of PET or SPECT to MRI produced higher accuracy indices (68 similar to 74%; AUC: 0.74 similar to 0.82) than T1-MRI alone, but these were not clearly superior to the isolated neurofunctional modalities. Conclusion: In line with previous evidence, FDG-PET and rCBF-SPECT more accurately identified patients with AD than T1-MRI, and the addition of either PET or SPECT to T1-MRI data yielded increased accuracy. The comparable SPECT and PET performances, directly demonstrated for the first time in the present study, support the view that rCBF-SPECT still has a role to play in AD diagnosis.
- Effect of temporal lobe structure volume on memory in elderly depressed patients(2011) AVILA, Renata; RIBEIZ, Salma; DURAN, Fabio L. S.; ARRAIS, Jony P. J.; MOSCOSO, Marco A. A.; BEZERRA, Diana M.; JALUUL, Omar; CASTRO, Claudio C.; BUSATTO, Geraldo F.; BOTTINO, Cassio M. C.Objective: To compare the volume of the hippocampus and parahippocampal gyrus in elderly individuals with and without depressive disorders, and to determine whether the volumes of these regions correlate with scores on memory tests. Method: Clinical and demographic differences, as well as differences in regional gray matter volumes, were assessed in 48 elderly patients with depressive disorders and 31 control subjects. Brain (structural MRI) scans were processed using statistical parametric mapping and voxel-based morphometry. Cognitive tests were administered to subjects in both groups. Results: There were no between-group gray matter volume differences in the hippocampus or parahippocampal gyrus. In the elderly depressed group only, the volume of the left parahippocampal gyrus correlated with scores on the delayed naming portion of the visual verbal learning test. There were also significant direct correlations in depressed subjects between the volumes of the left hippocampus, right and left parahippocampal gyrus and immediate recall scores on verbal episodic memory tests and visual learning tests. In the control group, there were direct correlations only between overall cognitive performance (as assessed with the MMSE) and the volume of right hippocampus, and between the total score on the visual verbal learning test and the volume of the right and left parahippocampal gyrus. Conclusions: These findings highlight different patterns of relationship between cognitive performance and volumes of medial temporal structures in depressed individuals and healthy elderly subjects. The direct correlation between delayed visual verbal memory recall scores with left parahippocampal volumes specifically in elderly depressed individuals provides support to the view that depression in elderly populations may be a risk factor for dementia.