CASSIO MACHADO DE CAMPOS BOTTINO
Projetos de Pesquisa
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LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Líder
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conferenceObject ASSOCIATION BETWEEN BEREAVEMENT AND COGNITIVE DECLINE IN DOWN SYNDROME: GROUND FOR FURTHER STUDIES ON PERSISTENT COMPLEX BEREAVEMENT DISORDER AS PROPOSED BY DSM-5?(2015) FONSECA, L. M.; OLIVEIRA, M. C.; GUILHOTO, L. M. F. F.; CAVALHEIRO, E. A.; BOTTINO, C. M. C.- 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.
- 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.
- Frontal Lobe Degeneration in Adults with Down Syndrome and Alzheimer's Disease: A Review(2016) FONSECA, Luciana Mascarenhas; YOKOMIZO, Juliana Emy; BOTTINO, Cassio Machado; FUENTES, DanielBackground: There is a proven link between Down syndrome and the early development of the neuropathological features of Alzheimer's disease (AD). Changes in the personality and behavior of adults with Down syndrome might indicate the early stages of dementia or of frontotemporal lobar degeneration. The objective of this study was to investigate the executive functions and changes in behavior associated with frontal lobe degeneration in individuals with Down syndrome who develop AD. We conducted a systematic review selecting studies employing cognitive assessments. Summary: We identified few studies using objective measurements to determine whether cognitive aspects associated with the frontal lobe correlate with dementia in this population. We observed a tendency toward such correlations. (C) 2016 S. Karger AG, Basel
- 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.
- Cognitive Rehabilitation of Dementia in Adults with Down Syndrome: A Review of Non-Pharmacological Interventions(2015) FONSECA, Luciana Mascarenhas; NAVATTA, Anna Carolina Rufino; BOTTINO, Cassio M. C.; MIOTTO, Eliane CorreaBackground: There is a close genetic relationship between Alzheimer's disease (AD) and Down syndrome (DS), AD being the most severe mental disorder affecting ageing individuals with DS. The objective of the present study was to evaluate the efficacy of cognitive rehabilitation interventions in DS patients with AD by means of a critical literature review. Summary: Because AD is progressive and irreversible, treatment is aimed at delaying and reducing the cognitive and functional decline in order to preserve or improve quality of life. The effects that pharmacological treatments and cognitive interventions have on elderly individuals with AD are well documented. Recent clinical trials have investigated the use of pharmacological treatment in DS patients with AD, generating preliminary results that have been unfavourable. Key Messages: There is a clear lack of studies addressing the efficacy of cognitive rehabilitation interventions in DS patients with AD, and there is an urgent need for studies providing evidence to inform decisions regarding the appropriate choice of treatment strategies. (C) 2015 S. Karger AG, Basel
- Mnemonic strategy training modulates functional connectivity at rest in mild cognitive impairment: Results from a randomized controlled trial(2020) SIMON, Sharon Sanz; HAMPSTEAD, Benjamin M.; NUCCI, Mariana P.; FERREIRA, Luiz Kobuti; DURAN, Fabio L. S.; FONSECA, Luciana M.; MARTIN, 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.Introduction: Mnemonic strategy training (MST) has been shown to improve cognitive performance and increase brain activation in those with mild cognitive impairment (MCI). However, little is known regarding the effects of MST on functional connectivity (FC) at rest. The aim of the present study was to investigate the MST focused on face-name associations effect on resting-state FC in those with MCI Methods: Twenty-six amnestic MCI participants were randomized in MST (N = 14) and Education Program (active control; N = 12). Interventions occurred twice a week over two consecutive weeks (ie, four sessions). Resting-state functional magnetic resonance imaging was collected at pre- and post-intervention. Regions of interest (ROIs) were selected based on areas that previously showed task-related activation changes after MST. Changes were examined through ROI-to-ROI analysis and significant results were corrected for multiple comparisons. Results: At post-intervention, only the MST group showed increased FC, whereas the control group showed decreased or no change in FC. After MST, there was an increased FC between the left middle temporal gyrus and right orbitofrontal cortex. In addition, a time-by-group interaction indicated that the MST group showed greater increased FC between the right inferior frontal gyrus and left brain regions, such as fusiform gyrus, temporal pole, and orbitofrontal cortex relative to controls. Discussion: MST enhanced FC in regions that are functionally relevant for the training; however, not in all ROIs investigated. Our findings suggest that MST-induced changes are reflected in task-specific conditions, as previously reported, but also in general innate connectivity. Our results both enhance knowledge about the mechanisms underlying MST effects and may provide neurophysiological evidence of training transfer.