FABIO HENRIQUE DE GOBBI PORTO
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
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- 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.
- Deficits in short-term memory binding are detectable in individuals with brain amyloid deposition in the absence of overt neurodegeneration in the Alzheimer's disease continuum(2021) CECCHINI, Mario Amore; YASSUDA, Monica Sanches; SQUARZONI, Paula; COUTINHO, Artur Martins; FARIA, Daniele de Paula; DURAN, Fabio Luiz de Souza; COSTA, Naomi Antunes da; PORTO, Fabio Henrique de Gobbi; NITRINI, Ricardo; FORLENZA, Orestes Vicente; BRUCKI, Sonia Maria Dozzi; BUCHPIGUEL, Carlos Alberto; PARRA, Mario A.; BUSATTO, Geraldo F.The short-term memory binding (STMB) test involves the ability to hold in memory the integration between surface features, such as shapes and colours. The STMB test has been used to detect Alzheimer's disease (AD) at different stages, from preclinical to dementia, showing promising results. The objective of the present study was to verify whether the STMB test could differentiate patients with distinct biomarker profiles in the AD continuum. The sample comprised 18 cognitively unimpaired (CU) participants, 30 mild cognitive impairment (MCI) and 23 AD patients. All participants underwent positron emission tomography (PET) with Pittsburgh compound B labelled with carbon-11 ([C-11]PIB) assessing amyloid beta (A beta) aggregation (A) and 18fluorine-fluorodeoxyglucose ([F-18]FDG)-PET assessing neurodegeneration (N) (A -N-[n = 35]); A+N-[n = 11]; A+ N+ [n = 19]). Participants who were negative and positive for amyloid deposition were compared in the absence (A-N vs. A+N-) of neurodegeneration. When compared with the RAVLT and SKT memory tests, the STMB was the only cognitive task that differentiated these groups, predicting the group outcome in logistic regression analyses. The STMB test showed to be sensitive to the signs of AD pathology and may represent a cognitive marker within the AD continuum.
- 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.
- Effects of Aerobic Training on Cognition and Brain Glucose Metabolism in Subjects with Mild Cognitive Impairment(2015) PORTO, Fabio Henrique de Gobbi; COUTINHO, Artur Martins Novaes; PINTO, Ana Lucia de Sa; GUALANO, Bruno; DURAN, Fabio Luis de Souza; PRANDO, Silvana; ONO, Carla Rachel; SPINDOLA, Livia; OLIVEIRA, Maira Okada de; VALE, Patricia Helena Figueredo do; NITRINI, Ricardo; BUCHPIGUEL, Carlos Alberto; BRUCKI, Sonia Maria DozziBackground: Aerobic training (AT) is a promising intervention for mild cognitive impairment (MCI). Objective: To evaluate the effects of AT on cognition and regional brain glucose metabolism (rBGM) in MCI patients. Methods: Subjects performed a twice-a-week, moderate intensity, AT program for 24 weeks. Assessment with ADAS-cog, a comprehensive neuropsychological battery, and evaluation of rBGM with positron emission tomography with F-18-fluorodeoxyglucose ([F-18] FDG-PET) were performed before and after the intervention. Aerobic capacity was compared using the maximal oxygen consumption VO2 max (mL/Kg/min). [F-18] FDG-PET data were analyzed on a voxel-by-voxel basis with SPM8 software. Results: Forty subjects were included, with a mean (M) age of 70.3 (5.4) years and an initial Mini-Mental State Exam score of 27.4 (1.7). Comparisons using paired t-tests revealed improvements in the ADAS-cog (M difference: -2.7 (3.7), p < 0.001) and VO(2)max scores (M difference: 1.8 (2.0) mL/kg/min, p < 0.001). Brain metabolic analysis revealed a bilateral decrease in the rBGM of the dorsal anterior cingulate cortex, pFWE = 0.04. This rBGM decrease was negatively correlated with improvement in a visuospatial function/attentional test (rho = -0.31, p = 0.04). Several other brain areas also showed increases or decreases in rBGM. Of note, there was an increase in the retrosplenial cortex, an important node of the default mode network, that was negatively correlated with the metabolic decrease in the dorsal anterior cingulate cortex (r = -0.51, p = 0.001). Conclusion: AT improved cognition and changed rBGM in areas related to cognition in subjects with MCI.
- Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters(2020) COUTINHO, Artur Martins; BUSATTO, Geraldo F.; PORTO, Fabio Henrique de Gobbi; FARIA, Daniele de Paula; ONO, Carla Rachel; GARCEZ, Alexandre Teles; SQUARZONI, Paula; DURAN, Fabio Luiz de Souza; OLIVEIRA, Maira Okada de; TRES, Eduardo Sturzeneker; BRUCKI, Sonia Maria Dozzi; FORLENZA, Orestes Vicente; NITRINI, Ricardo; BUCHPIGUEL, Carlos AlbertoPurpose [F-18]FDG-PET and [C-11]PIB-PET are validated as neurodegeneration and amyloid biomarkers of Alzheimer's disease (AD). We used a PET staging system based on the 2018 NIA-AA research framework to compare the proportion of amyloid positivity (A+) and hypometabolism ((N)+) in cases of mild probable AD, amnestic mild cognitive impairment (aMCI), and healthy controls, incorporating an additional classification of abnormal [F-18]FDG-PET patterns and investigating the co-occurrence of such with A+, exploring [F-18]FDG-PET to generate hypotheses in cases presenting with clinical-biomarker ""mismatches."" Methods Elderly individuals (N = 108) clinically classified as controls (N = 27), aMCI (N = 43) or mild probable AD (N = 38) were included. Authors assessed their A(N) profiles and classified [F-18]FDG-PET neurodegenerative patterns as typical or non-typical of AD, performing re-assessments of images whenever clinical classification was in disagreement with the PET staging (clinical-biomarker ""mismatches""). We also investigated associations between ""mismatches"" and sociodemographic and educational characteristics. Results AD presented with higher rates of A+ and (N)+. There was also a higher proportion of A+ and (N)+ individuals in the aMCI group in comparison to controls, however without statistical significance regarding the A staging. There was a significant association between amyloid positivity and AD (N)+ hypometabolic patterns typical of AD. Non-AD (N)+ hypometabolism was seen in all A- (N)+ cases in the mild probable AD and control groups and [F-18]FDG-PET patterns classified such individuals as ""SNAP"" and one as probable frontotemporal lobar degeneration. All A- (N)- cases in the probable AD group had less than 4 years of formal education and lower socioeconomic status (SES). Conclusion The PET-based staging system unveiled significant A(N) differences between AD and the other groups, whereas aMCI and controls had different (N) staging, explaining the cognitive impairment in aMCI. [F-18]FDG-PET could be used beyond simple (N) staging, since it provided alternative hypotheses to cases with clinical-biomarker ""mismatches."" An AD hypometabolic pattern correlated with amyloid positivity. Low education and SES were related to dementia in the absence of biomarker changes.
- Relationship Between PET-Assessed Amyloid Burden and Visual and Verbal Episodic Memory Performance in Elderly Subjects(2020) SQUARZONI, Paula; FARIA, Daniele de Paula; YASSUDA, Monica Sanches; PORTO, Fabio Henrique de Gobbi; COUTINHO, Artur Martins; COSTA, Naomi Antunes da; NITRINI, Ricardo; FORLENZA, Orestes Vicente; DURAN, Fabio Luiz de Souza; BRUCKI, Sonia Maria Dozzi; BUCHPIGUEL, Carlos Alberto; BUSATTO, Geraldo F.Background: Studies of elderly subjects using biomarkers that are proxies for Alzheimer's disease (AD) pathology have the potential to document meaningful relationships between cognitive performance and biomarker changes along the AD continuum. Objective: To document cognitive performance differences across distinct AD stages using a categorization based on the presence of PET-assessed amyloid-beta (A beta) burden and neurodegeneration. Methods: Patients with mild dementia compatible with AD (n = 38) or amnestic mild cognitive impairment (aMCI; n = 43) and a cognitively unimpaired group (n = 27) underwent PET with Pittsburgh compound-B (PiB) assessing A beta aggregation (A+) and [F-18]FDG-PET assessing neurodegeneration ((N)+). Cognitive performance was assessed with verbal and visual episodic memory tests and the Mini-Mental State Examination. Results: The A+(N)+ subgroup (n = 32) showed decreased (p < 0.001) cognitive test scores compared to both A+(N)-(n = 18) and A-(N)- (n = 49) subjects, who presented highly similar mean cognitive scores. Despite its modest size (n = 9), the A-(N)+ subgroup showed lower (p < 0.043) verbal memory scores relative to A-(N)- subjects, and trend lower (p = 0.096) scores relative to A+(N)- subjects. Continuous A beta measures (standard uptake value ratios of PiB uptake) were correlated most significantly with visual memory scores both in the overall sample and when analyses were restricted to dementia or (N)+ subjects, but not in non-dementia or (N)- groups. Conclusion: These results demonstrate that significant A beta-cognition relationships are highly salient at disease stages involving neurodegeneration. The fact that findings relating A beta burden to memory performance were detected only at (N)+ stages, together with the similarity of test scores between A+(N)- and A-(N)- subjects, reinforce the view that A beta-cognition relationships during early AD stages may remain undetectable unless substantially large samples are evaluated.
- Hippocampal subregional volume changes in elders classified using positron emission tomography-based Alzheimer's biomarkers of beta-amyloid deposition and neurodegeneration(2021) BUSATTO FILHO, Geraldo; DURAN, Fabio Luiz de Souza; SQUARZONI, Paula; COUTINHO, Artur Martins Novaes; ROSA, Pedro Gomes Penteado; TORRALBO, Leticia; PACHI, Clarice Gameiro da Fonseca; COSTA, Naomi Antunes da; PORTO, Fabio Henrique de Gobbi; CARVALHO, Cleudiana Lima; BRUCKI, Sonia Maria Dozzi; NITRINI, Ricardo; FORLENZA, Orestes Vicente; LEITE, Claudia da Costa; BUCHPIGUEL, Carlos Alberto; FARIA, Daniele de PaulaChanges in hippocampal subfield volumes (HSV) along the Alzheimer's disease (AD) continuum have been scarcely investigated to date in elderly subjects classified based on the presence of beta-amyloid aggregation and signs of neurodegeneration. We classified patients (either sex) with mild dementia compatible with AD (n = 35) or amnestic mild cognitive impairment (n = 39), and cognitively unimpaired subjects (either sex;n = 26) using [C-11]PIB-PET to assess beta-amyloid aggregation (A+) and [F-18]FDG-PET to account for neurodegeneration ((N)+). Magnetic resonance imaging-based automated methods were used for HSV and white matter hyperintensity (WMH) measurements. Significant HSV reductions were found in A+(N)+ subjects in the presubiculum/subiculum complex and molecular layer, related to worse memory performance. In both the A+(N)+ and A+(N)- categories, subicular volumes were inversely correlated with the degree of A beta deposition. The A-(N)+ subgroup showed reduced HSV relative to the A-(N)- subgroup also in the subiculum/presubiculum. Combining all (N)- subjects, HSV were lower in subjects presenting significant cognitive decline irrespective of A+/A- classification (controlling for WMH load); these between-group differences were detected again in the presubiculum, but also involved the CA4 and granular layer. These findings demonstrate that differential HSV reductions are detectable both in (N)+ and (N)- categories along the AD continuum, and are directly related to the severity of cognitive deficits. HSV reductions are larger both in A+(N)+ and A+(N)- subjects in direct proportion to the degree of A beta deposition. The meaningful HSV reductions detected in the A-(N)+ subgroup highlights the strength of biomarker-based classifications outside of the classical AD continuum.