ARTUR MARTINS NOVAES COUTINHO
Projetos de Pesquisa
Unidades Organizacionais
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
13 resultados
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- Probable 4-Repeat Tauopathy Criteria Predict Brain Amyloid Negativity, Distinct Clinical Features, and FDG-PET/MRI Neurodegeneneration Patterns in Corticobasal Syndrome(2024) PARMERA, Jacy Bezerra; CARNEIRO, Camila de Godoi; ALMEIDA, Isabel Junqueira de; OLIVEIRA, Marcos Castello Barbosa de; BARBOSA, Pedro Melo; STUDART-NETO, Adalberto; ONO, Carla Rachel; NITRINI, Ricardo; BUCHPIGUEL, Carlos Alberto; BARBOSA, Egberto Reis; BRUCKI, Sonia Maria Dozzi; COUTINHO, Artur MartinsBackgroundCorticobasal syndrome (CBS) is associated with diverse underlying pathologies, including the four-repeat (4R)-tauopathies. The Movement Disorders Society (MDS) criteria for progressive supranuclear palsy (PSP) proposed the novel category ""probable 4R-tauopathy"" to address the phenotypic overlap between PSP and corticobasal degeneration (CBD).ObjectivesTo investigate the clinical ability of the MDS-PSP criteria for probable 4R-tauopathy in predicting a negative amyloid-PET in CBS. Additionally, this study aims to explore CBS patients classified as 4R-tauopathy concerning their clinical features and neuroimaging degeneration patterns.MethodsThirty-two patients with probable CBS were prospectively evaluated and split into those who fulfilled or did not fulfill the 4R-tauopathy criteria (CBS-4RT+ vs. CBS-4RT-). All patients underwent positron emission tomographies (PET) with [18F]fluorodeoxyglucose and [11C]Pittsburgh Compound-B (PIB) on a hybrid PET-MRI scanner to perform multimodal quantitative comparisons with a control group.ResultsEleven patients were clinically classified as CBS-4RT+, and only one had a positive PIB-PET. The CBS-4RT+ classification had 92% specificity, 52% sensitivity, and 69% accuracy in predicting a negative PIB-PET. The CBS-4RT+ group presented with dysarthria and perseveration more often than the CBS-4RT- group. Moreover, the CBS-4RT+ group showed a prominent frontal hypometabolism extending to the supplementary motor area and striatum, and brain atrophy at the anterior cingulate and bilateral striata.ConclusionsThe 4R-tauopathy criteria were highly specific in predicting a negative amyloid-PET in CBS. Patients classified as 4R-tauopathy presented distinct clinical aspects, as well as brain metabolism and atrophy patterns previously associated with tauopathies.
- Foot-Hand Synkinesis in Corticobasal Syndrome: Single Clinical Feature with Distinct Molecular Imaging Biomarkers(2021) PARMERA, Jacy Bezerra; BRUCKI, Sonia Maria Dozzi; COUTINHO, Artur Martins; NITRINI, Ricardo
conferenceObject Metabolic and Structural Signatures in Corticobasal Syndrome: A Multimodal PET/MRI Study(2021) CARNEIRO, G. C.; PARMERA, J. B.; ALMEIDA, I. J.; OLIVEIRA, M. C. B.; SILAGI, M. L.; STUDART-NETO, A.; ONO, C. R.; BARBOSA, E. R.; NITRINI, R.; BUCHPIGUEL, C. A.; BRUCKI, S. M. D.; COUTINHO, A. M.- Metabolic and Structural Signatures of Speech and Language Impairment in Corticobasal Syndrome: A Multimodal PET/MRI Study(2021) PARMERA, Jacy Bezerra; ALMEIDA, Isabel Junqueira de; OLIVEIRA, Marcos Castello Barbosa de; SILAGI, Marcela Lima; CARNEIRO, Camila de Godoi; STUDART-NETO, Adalberto; ONO, Carla Rachel; BARBOSA, Egberto Reis; NITRINI, Ricardo; BUCHPIGUEL, Carlos Alberto; BRUCKI, Sonia Maria Dozzi; COUTINHO, Artur MartinsIntroduction: Corticobasal syndrome (CBS) is a progressive neurological disorder related to multiple underlying pathologies, including four-repeat tauopathies, such as corticobasal degeneration and progressive supranuclear palsy, and Alzheimer's disease (AD). Speech and language are commonly impaired, encompassing a broad spectrum of deficits. We aimed to investigate CBS speech and language impairment patterns in light of a multimodal imaging approach. Materials and Methods: Thirty-one patients with probable CBS were prospectively evaluated concerning their speech-language, cognitive, and motor profiles. They underwent positron emission tomography with [F-18]fluorodeoxyglucose (FDG-PET) and [C-11]Pittsburgh Compound-B (PIB-PET) on a hybrid PET-MRI machine to assess their amyloid status. PIB-PET images were classified based on visual and semi-quantitative analyses. Quantitative group analyses were performed on FDG-PET data, and atrophy patterns on MRI were investigated using voxel-based morphometry (VBM). Thirty healthy participants were recruited as imaging controls. Results: Aphasia was the second most prominent cognitive impairment, presented in 67.7% of the cases, following apraxia (96.8%). We identified a wide linguistic profile, ranging from nonfluent variant-primary progressive aphasia to lexical-semantic deficits, mostly with impaired verbal fluency. PIB-PET was classified as negative (CBS-A- group) in 18/31 (58%) and positive (CBS-A+ group) in 13/31 (42%) patients. The frequency of dysarthria was significantly higher in the CBS-A- group than in the CBS-A+ group (55.6 vs. 7.7%, p = 0.008). CBS patients with dysarthria had a left-sided hypometabolism at frontal regions, with a major cluster at the left inferior frontal gyrus and premotor cortex. They showed brain atrophy mainly at the opercular frontal gyrus and putamen. There was a positive correlation between [F-18]FDG uptake and semantic verbal fluency at the left inferior (p = 0.006, R-2 = 0.2326), middle (0.0054, R-2 = 0.2376), and superior temporal gyri (p = 0.0066, R-2 = 0.2276). Relative to the phonemic verbal fluency, we found a positive correlation at the left frontal opercular gyrus (p = 0.0003, R-2 = 0.3685), the inferior (p = 0.0004, R-2 = 0.3537), and the middle temporal gyri (p = 0.0001, R-2 = 0.3993). Discussion: In the spectrum of language impairment profile, dysarthria might be helpful to distinguish CBS patients not related to AD. Metabolic and structural signatures depicted from this feature provide further insights into the motor speech production network and are also helpful to differentiate CBS variants.
- Analysis of the posterior cingulate cortex with [ 18 F]FDG-PET and Naa/mI in mild cognitive impairment and Alzheimer's disease: Correlations and differences between the two methods(2015) COUTINHO, Artur M.N.; PORTO, Fábio H.G.; ZAMPIERI, Poliana F.; OTADUY, Maria C.; PERROCO, Tíbor R.; OLIVEIRA, Maira O.; NUNES, Rafael F.; PINHEIRO, Toulouse Leusin; BOTTINO, Cassio M.C.; LEITE, Claudia C.; BUCHPIGUEL, Carlos A.ABSTRACT Reduction of regional brain glucose metabolism (rBGM) measured by [18F]FDG-PET in the posterior cingulate cortex (PCC) has been associated with a higher conversion rate from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Magnetic Resonance Spectroscopy (MRS) is a potential biomarker that has disclosed Naa/mI reductions within the PCC in both MCI and AD. Studies investigating the relationships between the two modalities are scarce. OBJECTIVE To evaluate differences and possible correlations between the findings of rBGM and NAA/mI in the PCC of individuals with AD, MCI and of cognitively normal volunteers. METHODS Patients diagnosed with AD (N=32) or MCI (N=27) and cognitively normal older adults (CG, N=28), were submitted to [18F]FDG-PET and MRS to analyze the PCC. The two methods were compared and possible correlations between the modalities were investigated. RESULTS The AD group exhibited rBGM reduction in the PCC when compared to the CG but not in the MCI group. MRS revealed lower NAA/mI values in the AD group compared to the CG but not in the MCI group. A positive correlation between rBGM and NAA/mI in the PCC was found. NAA/mI reduction in the PCC differentiated AD patients from control subjects with an area under the ROC curve of 0.70, while [18F]FDG-PET yielded a value of 0.93. CONCLUSION rBGM and Naa/mI in the PCC were positively correlated in patients with MCI and AD. [18F]FDG-PET had greater accuracy than MRS for discriminating AD patients from controls.
- Brain metabolism and cerebrospinal fluid biomarkers profile of non-amnestic mild cognitive impairment in comparison to amnestic mild cognitive impairment and normal older subjects(2015) COUTINHO, Artur M. N.; PORTO, Fabio H. G.; DURAN, Fabio L. S.; PRANDO, Silvana; ONO, Carla R.; FEITOSA, Esther A. A. F.; SPINDOLA, Livia; OLIVEIRA, Maira O. de; VALE, Patricia H. F. do; GOMES, Helio R.; NITRINI, Ricardo; BRUCKI, Sonia M. D.; BUCHPIGUEL, Carlos A.Introduction: Mild cognitive impairment (MCI) is classically considered a transitional stage between normal aging and dementia. Non-amnestic MCI (naMCI) patients, however, typically demonstrate cognitive deficits other than memory decline. Furthermore, as a group, naMCI have a lower rate of an eventual dementia diagnosis as compared to amnestic subtypes of MCI (aMCI). Unfortunately, studies investigating biomarker profiles of naMCI are scarce. The study objective was to investigate the regional brain glucose metabolism (rBGM) with [F-18]FDG-PET and cerebrospinal fluid (CSF) biomarkers in subjects with naMCI as compared to a control group (CG) and aMCI subjects. Methods: Ninety-five patients were included in three different groups: naMCI (N = 32), aMCI (N = 33) and CG (N = 30). Patients underwent brain MRI and [F-18]FDG-PET. A subsample (naMCI = 26, aMCI = 28) also had an assessment of amyloid-beta, tau, and phosphorylated tau levels in the CSF. Results: Both MCI groups had lower rBGM in relation to the CG in the precuneus. Subjects with naMCI showed decreased right prefrontal metabolism as well as higher levels of CSF amyloid-beta relative to aMCI subjects. Conclusion: While amnestic MCI subjects showed a biomarker profile classically related to MCI due to Alzheimer's disease, naMCI patients illustrated a decrease in both prefrontal hypometabolism and higher CSF amyloid-beta levels relative to the aMCI group. These biomarker findings indicate that naMCI is probably a heterogeneous group with similar precuneus hypometabolism compared to aMCI, but additional frontal hypometabolism and less amyloid-beta deposition in the brain. Clinical follow-up and reappraisal of biomarkers of the naMCI group is needed to determine the outcome and probable etiological diagnosis.
- The Association Between Acquired Color Deficiency and PET Imaging of Neurodegeneration in Mild Cognitive Impairment and Alzheimer Disease(2022) VIDAL, Kallene Summer Moreira; DECLEVA, Diego; BARBONI, Mirella Telles Salgueiro; NAGY, Balazs Vince; MENEZES, Paulo Augusto Hidalgo de; AHER, Avinash; COUTINHO, Artur Martins; SQUARZONI, Paula; FARIA, Daniele de Paula; DURAN, Fabio Luis de Souza; BUCHPIGUEL, Carlos Alberto; KREMERS, Jan; FILHO, Geraldo Busatto; VENTURA, Dora FixPURPOSE. To evaluate color vision changes and retinal processing of chromatic and lumi-nance pathways in subjects with Alzheimer disease (AD) and mild cognitive impairment (MCI) compared with a matched control group and whether such changes are associated with impaired brain glucose metabolism and beta-amyloid deposition in the brain.METHODS. We evaluated 13 patients with AD (72.4 +/- 7.7 years), 23 patients with MCI (72.5 +/- 5.5 years), and 18 controls of comparable age (P = 0.44) using Cambridge color test and the heterochromatic flicker ERG (HF-ERG). The Cambridge color test was performed using the trivector protocol to estimate the protan, deutan and tritan color confusion axes. HF-ERG responses were measured at a frequency of 12 Hz, which ERGs reflect chromatic activity, and at 36 Hz, reflecting luminance pathway. A study subsample was performed using neuropsychological assessments and positron emission tomography.RESULTS. Patients with AD presented higher mean values indicating poorer color discrim-ination for protan (P = 0.04) and deutan (P = 0.001) axes compared with the controls. Along the tritan axis, both patients with AD and patients with MCI showed decreased color vision (P = 0.001 and P = 0.001) compared with controls. The analyses from the HF-ERG protocol revealed no differences between the groups (P = 0.31 and P = 0.41). Diffuse color vision loss was found in individuals with signs of neurodegeneration (protan P = 0.002, deutan P = 0.003 and tritan P = 0.01), but not in individuals with signs of beta-amyloid deposition only (protan P = 0.39, deutan P = 0.48, tritan P = 0.63), regardless of their clinical classification.CONCLUSIONS. Here, patients with AD and patients with MCI present acquired color vision deficiency that may be linked with impaired brain metabolism.
- Does TRODAT-1 SPECT Uptake Correlate with Cerebrospinal Fluid alpha-Synuclein Levels in Mid-Stage Parkinson's Disease?(2023) COUTINHO, Artur M.; GHILARDI, Maria Gabriela; CAMPOS, Ana Carolina P.; ETCHEBEHERE, Elba; FONOFF, Fernanda C.; CURY, Rubens G.; PAGANO, Rosana L.; MARTINEZ, Raquel C. R.; FONOFF, Erich T.Background: Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons with impaired motor and non-motor symptoms. It has been suggested that motor asymmetry could be caused due to an imbalance in dopamine levels, as visualized by dopamine transporter single emission computed tomography test (DAT-SPECT), which might be related to indirect measures of neurodegeneration, evaluated by the Montreal Cognitive Assessment (MOCA) and alpha-synuclein levels in the cerebrospinal fluid (CSF). Therefore, this study aimed to understand the correlation between disease laterality, DAT-SPECT, cognition, and alpha-synuclein levels in PD. Methods: A total of 28 patients in the moderate-advanced stage of PD were subjected to neurological evaluation, TRODAT-1-SPECT/CT imaging, MOCA, and quantification of the levels of alpha-synuclein. Results: We found that alpha-synuclein in the CSF was correlated with global cognition (positive correlation, r(2) = 0.3, p = 0.05) and DAT-SPECT concentration in the putamen (positive correlation, r(2) = 0.4, p = 0.005), and striatum (positive correlation, r(2) = 0.2, p = 0.03), thus working as a neurodegenerative biomarker. No other correlations were found between DAT-SPECT, CSF alpha-synuclein, and cognition, thus suggesting that they may be lost with disease progression. Conclusions: Our data highlight the importance of understanding the dysfunction of the dopaminergic system in the basal ganglia and its complex interactions in modulating cognition.
- Expanding MAPT p.V363I Mutation Phenotype: An Overlapping of PSP-CBS and Posterior Cortical Atrophy(2023) PARMERA, Jacy Bezerra; COUTINHO, Artur Martins; GUIMARAES, Thiago Goncalves; YAMAMOTO, Joyce Yuri Silvestre; TAKADA, Leonel Tadao; NITRINI, Ricardo; BARBOSA, Egberto Reis; BRUCKI, Sonia Maria Dozzi
- The Discourse Profile in Corticobasal Syndrome: A Comprehensive Clinical and Biomarker Approach(2022) ALMEIDA, Isabel Junqueira de; SILAGI, Marcela Lima; CARTHERY-GOULART, Maria Teresa; PARMERA, Jacy Bezerra; CECCHINI, Mario Amore; COUTINHO, Artur Martins; BRUCKI, Sonia Maria Dozzi; NITRINI, Ricardo; SCHOCHAT, ElianeThe aim of this study was to characterize the oral discourse of CBS patients and to verify whether measures obtained during a semi-spontaneous speech production could differentiate CBS patients from controls. A second goal was to compare the performance of patients with CBS probably due to Alzheimer's disease (CBS-AD) pathology and CBS not related to AD (CBS-non-AD) in the same measures, based on the brain metabolic status (FDG-PET) and in the presence of amyloid deposition (amyloid-PET). Results showed that CBS patients were significantly different from controls in speech rate, lexical level, informativeness, and syntactic complexity. Discursive measures did not differentiate CBS-AD from CBS-non-AD. However, CBS-AD displayed more lexical-semantic impairments than controls, a profile that is frequently reported in patients with clinical AD and the logopenic variant of primary progressive aphasia (lvPPA). CBS-non-AD presented mainly with impairments related to motor speech disorders and syntactic complexity, as seen in the non-fluent variant of PPA.