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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- 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.