DANIELE DE PAULA FARIA
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject C-11-pib pet showed a distinct cerebrospinal fluid pattern in patients with progressive multiple sclerosis(2020) PITOMBEIRA, M.; DURAN, F.; CAMPANHOLO, K.; SOUZA, A.; APOSTOLOS-PEREIRA, S.; RIMKUS, C. Medeiros; MENDES, M. F.; BUSATTO FILHO, G.; CALLEGARO, D.; BUCHPIGUEL, C.; FARIA, D. De Paula- 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.
- In vivo imaging evidence of poor cognitive resilience to Alzheimer's disease pathology in subjects with very low cognitive reserve from a low-middle income environment(2020) BUSATTO, Geraldo F.; PORTO, Fabio Henrique de Gobbi; FARIA, Daniele de Paula; SQUARZONI, Paula; COUTINHO, Artur Martins; GARCEZ, Alexandre Teles; ROSA, Pedro Gomes Penteado; COSTA, Naomi Antunes da; CARVALHO, Cleudiana Lima; TORRALBO, Leticia; HERNANDES, Jullie Rosana de Almeida; ONO, Carla Rachel; BRUCKI, Sonia Maria Dozzi; NITRINI, Ricardo; BUCHPIGUEL, Carlos Alberto; DURAN, Fabio Luis Souza; FORLENZA, Orestes VicenteINTRODUCTION: Reduced cognitive reserve (CR) due to very low educational (VLE) levels may influence high dementia rates in low-middle income environments, leading to decreased cognitive resilience (RES) to Alzheimers disease (AD) pathology. However, in vivo findings in VLE groups confirming this prediction are lacking. METHODS: Cognitively impaired patients (with clinically defined AD dementia or amnestic mild cognitive impairment) and cognitively unimpaired older adults (n = 126) were recruited for a positron emission tomography (PET) and magnetic resonance imaging (MRI) investigation in Brazil, including 37 VLE individuals (<= 5 years of education). A CR score was generated combining educational attainment and vocabulary knowledge. RES indices to AD pathology were calculated using standardized residuals from linear regression models relating current cognitive performance (episodic memory or overall cognition) to amyloid beta (A beta) burden Pittsburgh compound-B ([11C]PiB-PET). RESULTS: A beta burden was lower in VLE relative to highly-educated subjects (controlling for age, sex, and Mini-Mental Status Exam [MMSE] scores) in the overall cognitively impaired sample, and in dementia subjects when the three clinically defined groups were evaluated separately. In bivariate regression analyses for the overall sample, the RES index based on a composite cognitive score was predicted by CR, socioeconomic status, and hippocampal volume (but not white matter hyperintensities or intracranial volume [ICV]); in the multivariate model, only CR retained significance (and similar results were obtained in the A beta-positive subsample). In the multivariate model for the overall sample using the RES index based on memory performance, CR, hippocampal volume, and ICV were significant predictors, whereas only CR retained significance in A beta-positive subjects. DISCUSSION: Lower CR consistently predicted less resilience to AD pathology in older adults from a low-middle income environment.
- Episodic Memory, Hippocampal Volume, and Function for Classification of Mild Cognitive Impairment Patients Regarding Amyloid Pathology(2022) MIOTTO, Eliane Correa; BRUCKI, Sonia Maria Dozzi; CERQUEIRA, Carlos T.; BAZAN, Paulo R.; SILVA, Geise Aline de Almeida; MARTIN, Maria da Graca M.; SILVEIRA, Paula Squarzoni da; FARIA, Daniele de Paula; COUTINHO, Artur Martins; BUCHPIGUEL, Carlos Alberto; BUSATTO FILHO, Geraldo; NITRINI, RicardoBackground: Previous studies of hippocampal function and volume related to episodic memory deficits in patients with amnestic mild cognitive impairment (aMCI) have produced mixed results including increased or decreased activity and volume. However, most of them have not included biomarkers, such as amyloid-beta (A beta) deposition which is the hallmark for early identification of the Alzheimer's disease continuum. Objective: We investigated the role of A beta deposition, functional hippocampal activity and structural volume in aMCI patients and healthy elderly controls (HC) using a new functional MRI (fMRI) ecological episodic memory task. Methods: Forty-six older adults were included, among them A beta PET PIB positive (PIB+) aMCI (N = 17), A beta PET PIB negative (PIB-) aMCI (N = 15), and HC (N = 14). Hippocampal volume and function were analyzed using Freesurfer v6.0 and FSL for news headlines episodic memory fMRI task, and logistic regression for group classification in conjunction with episodic memory task and traditional neuropsychological tests. Results: The aMCI PIB+ and PIB- patients showed significantly worse performance in relation to HC in most traditional neuropsychological tests and within group difference only on story recall and the ecological episodic memory fMRI task delayed recall. The classification model reached a significant accuracy (78%) and the classification pattern characterizing the PIB+ included decreased left hippocampal function and volume, increased right hippocampal function and volume, and worse episodic memory performance differing from PIB- which showed increased left hippocampus volume. Conclusion: The main findings showed differential neural correlates, hippocampal volume and function during episodic memory in aMCI patients with the presence of A beta deposition.
- 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.