ARTUR MARTINS NOVAES COUTINHO
Projetos de Pesquisa
Unidades Organizacionais
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
35 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 35
- From clinical phenotype to proteinopathy: molecular neuroimaging in neurodegenerative dementias(2022) STUDART-NETO, Adalberto; COUTINHO, Artur MartinsNeurodegenerative dementias are characterized by the abnormal accumulation of misfolded proteins. However, its diagnostic criteria are still based on the clinical phenotype. The development of biomarkers allowed in vivo detection of pathophysiological processes. This article aims to make a non-systematic review of the use of molecular neuroimaging as a biomarker. Molecular neuroimaging is based on the use of radiotracers for image acquisition. The radiotracer most used in PET is F-18-fluorodeoxyglucose (FDG), with which it is possible to study the regional brain glucose metabolism. The pattern of regional hypometabolism provides neuroanatomical information on the neurodegenerative process,which, in turn, has a good specificity for each type of proteinopathy. FDG is very useful in the differential diagnosis of neurodegenerative dementias through the regional pattern of involvement, including dementia with Lewy bodies and the spectrum of frontotemporal dementia. More recently, radiotracers with specific ligands to some of the pathological proteins have been developed. Pittsburgh compound B (PIB) labeled with C-11 and the ligands that use F-18 (florbetapir, florbetaben and flutemetamol) are the most used radiotracers for the detection of insoluble beta-amyloid peptide in Alzheimer's disease (AD). A first generation of ligands for tau protein has been developed, but it has some affinity for other non-tau protein aggregates. A second generation has the advantage of having a higher affinity for hyperphosphorylated tau protein, including in primary tauopathies.
- Evaluation of 10-minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer's disease(2022) CARNEIRO, Camila de Godoi; FARIA, Daniele de Paula; COUTINHO, Artur Martins; ONO, Carla Rachel; DURAN, Fabio Luis de Souza; COSTA, Naomi Antunes da; GARCEZ, Alexandre Teles; SILVEIRA, Paula Squarzoni da; FORLENZA, Orestes Vicente; BRUCKI, Sonia Maria Dozzi; NITRINI, Ricardo; FILHO, Geraldo Busatto; BUCHPIGUEL, Carlos AlbertoObjective: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F] fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease.Methods: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early -phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or-negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping.Results: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early -phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration.Conclusions: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.
- 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.
- Long-Term Lithium Treatment Reduces Glucose Metabolism in the Cerebellum and Hippocampus of Nondemented Older Adults: An [F-18]FDG-PET Study(2014) FORLENZA, Orestes V.; COUTINHO, Artur Martins Novaes; APRAHAMIAN, Ivan; PRANDO, Silvana; MENDES, Luciana Lucas; DINIZ, Breno S.; GATTAZ, Wagner F.; BUCHPIGUEL, Carlos A.Lithium modulates several intracellular pathways related to neuroplasticity and resilience against neuronal injury. These properties have been consistently reported in experimental models, and involve the up-regulation of neurotrophic response and autophagy, and down-regulation of apoptosis, oxidative stress, and inflammation. Clinical and epidemiological studies in bipolar disorder show that acute treatment with lithium increases plasma concentrations of brain-derived neurotrophic factor, and long-term treatment lowers the risk of dementia. Neuroimaging studies indicate that lithium use is further associated with increased cortical thickness and larger hippocampal volumes. The objective of the present study was to evaluate whether these neurobiological properties of lithium reflect in increased regional brain glucose metabolism, as shown by [F-18]FDG-PET. Participants (n = 19) were nondemented older adults recruited at the end point of a controlled trial addressing clinical and biological effects of lithium in a sample of patients with amnestic mild cognitive impairment. Twelve patients who had received low-dose lithium carbonate for 4 years were compared to seven matched controls. Chronic lithium treatment was not associated with any significant increase in brain glucose metabolism in the studied areas. Conversely, we found a significant reduction in glucose uptake in several clusters of the cerebellum and in both hippocampi. These findings were not associated with any clinical evidence of toxicity. The clinical implications of the present findings need to be clarified by future controlled studies, particularly in the light of the potential use of lithium as a disease-modifying treatment approach for certain neurodegenerative disorders, namely, Alzheimer's disease and amyotrophic lateral sclerosis.
- Theranostics in Nuclear Medicine: Emerging and Re-emerging Integrated Imaging and Therapies in the Era of Precision Oncology(2020) MARIN, Jose Flavio Gomes; NUNES, Rafael F.; COUTINHO, Artur M.; ZANIBONI, Elaine C.; COSTA, Larissa B.; BARBOSA, Felipe G.; QUEIROZ, Marcelo A.; CERRI, Giovanni G.; BUCHPIGUEL, Carlos A.Theranostics refers to the pairing of diagnostic biomarkers with therapeutic agents that share a specific target in diseased cells or tissues. Nuclear medicine, particularly with regard to applications in oncology, is currently one of the greatest components of the theranostic concept in clinical and research scenarios. Theranostics in nuclear medicine, or nuclear theranostics, refers to the use of radioactive compounds to image biologic phenomena by means of expression of specific disease targets such as cell surface receptors or membrane transporters, and then to use specifically designed agents to deliver ionizing radiation to the tissues that express these targets. The nuclear theranostic approach has sparked increasing interest and gained importance in parallel to the growth in molecular imaging and personalized medicine, helping to provide customized management for various diseases; improving patient selection, prediction of response and toxicity, and determination of prognosis; and avoiding futile and costly diagnostic examinations and treatment of many diseases. The authors provide an overview of theranostic approaches in nuclear medicine, starting with a review of the main concepts and unique features of nuclear theranostics and aided by a retrospective discussion of the progress of theranostic agents since early applications, with illustrative cases emphasizing the imaging features. Advanced concepts regarding the role of fluorine 18-fluorodeoxyglucose PET in theranostics, as well as developments in and future directions of theranostics, are discussed. (C) RSNA, 2020
- Subjective sleep parameters in prodromal Alzheimer's disease: a case-control study(2021) BORGES, Conrado R.; PIOVEZAN, Ronaldo D.; POYARES, Dalva R.; FILHO, Geraldo Busatto; STUDART-NETO, Adalberto; COUTINHO, Artur M.; TUFIK, Sergio; NITRINI, Ricardo; BRUCKI, Sonia M.Objective: People with Alzheimer's disease (AD) dementia have impaired sleep. However, the characteristics of sleep in the early stages of AD are not well known, and studies with the aid of biomarkers are lacking. We assessed the subjective sleep characteristics of non-demented older adults and compared their amyloid profiles. Methods: We enrolled 30 participants aged >= 60 years, with no dementia or major clinical and psychiatric diseases. They underwent [C-11]PiB-PET-CT, neuropsychological evaluations, and completed two standardized sleep assessments (Pittsburgh Sleep Quality Inventory and Epworth Sleep Scale). Results: Comparative analysis of subjective sleep parameters across the two groups showed longer times in bed (p = 0.024) and reduced sleep efficiency (p = 0.05) in individuals with positive amyloid. No differences in other subjective sleep parameters were observed. We also found that people with multiple-domain mild cognitive impairment (MCI) had shorter self-reported total sleep times (p = 0.034) and worse overall sleep quality (p = 0.027) compared to those with single-domain MCI. Conclusions: Older adults testing positive for amyloid had a longer time in bed and lower sleep efficiency, regardless of cognitive status. In parallel, individuals with multiple-domain MCI reported shorter sleep duration and lower overall sleep quality.
- 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.
- Changes in Neuropsychological Tests and Brain Metabolism After Bariatric Surgery(2014) MARQUES, Emerson Leonildo; HALPERN, Alfredo; MANCINI, Marcio Correa; MELO, Maria Edna de; HORIE, Ndia Celeste; BUCHPIGUEL, Carlos Alberto; COUTINHO, Artur Martins Novaes; ONO, Carla Rachel; PRANDO, Silvana; SANTO, Marco Aurelio; CUNHA-NETO, Edecio; FUENTES, Daniel; CERCATO, CintiaContext: The mechanisms by which obesity alters the cerebral function and the effect of weight loss on the brain have not been completely clarified. Objective: The objective of the study was to assess the effect of bariatric surgery on the cognitive function and cerebral metabolism. Design: Seventeen obese women were studied prior to and 24 weeks after bariatric surgery using neuropsychological tests and positron emission tomography. Setting: The study was conducted in a reference center for the treatment of obesity of a Brazilian public university. Participants: Thirty-three women paired by age and level of education made up two groups: 17 severely obese patients and 16 lean patients. They did not have diabetes mellitus or a family history of dementia. Main Outcome Measures: Comparison of performance in neuropsychological tests and cerebral metabolism of the obese women before and after bariatric surgery was measured. The results found at the two moments were compared with those of the women of normal weight. Results: Women with a mean age of 40.5 years and mean body mass index of 50.1 kg/m(2) when compared with women with mean body mass index of 22.3 kg/m(2) showed increased cerebral metabolism, especially in the posterior cingulate gyrus (P <.004). No difference was found between the groups for the neuropsychological tests. After 24 weeks the cerebral metabolism of the obese women was lower, similar to the lean women, and there was an improvement of executive function, accompanying changes of metabolic and inflammatory parameters. Conclusions: Obese women may have increased cerebral metabolism when compared with women of normal weight, and this appears to reverse after weight loss induced by bariatric surgery, accompanied by improved executive function.
- Paraneoplastic limbic encephalitis with prominent neuropsychiatric apathy(2014) PORTO, Fabio Hernique de Gobbi; COUTINHO, Artur Martins Novaes; LUCATO, Leandro Tavares; SPINDOLA, Livia; ONO, Carla Rachel; BRUCKI, Sonia Maria Dozzi; BUCHPIGUEL, Carlos Alberto; NITRINI, RicardoThe spectrum of paraneoplastic neurologic syndromes has increased with the description of encephalitis associated with antibodies against cell surface and synaptic proteins. Subacute cognitive impairment, movement disorders, late onset epilepsy and neuropsychiatric syndromes were recently linked to paraneoplastic encephalitis. Despite that, probably some syndromes and antibodies are yet to be reported. Herein we reported the clinical and neuroimaging pictures of a patient with late onset medial temporal lobe epilepsy, subtle cognitive impairment, psychosis and severe apathy diagnosed with antibody-negative paraneoplastic encephalitis due to colonic adenocarcinoma. The apathy markedly improved after removal of the tumor, without concomitant immunotherapy (steroids, intravenous immunoglobulins, immunosuppressants, plasmapheresis, etc). Our report highlights the importance of a full clinical and neurologic investigation in cases of atypical neuropsychiatric presentations, particularly in the elderly and with the concomitance of epilepsy and cognitive decline. Even chronic presentations must be considered. Neuroimaging is an important tool to demonstrate structural and functional brain dysfunction in these cases. Colonic adenocarcinoma should be searched for in cases in which a typical tumor related to paraneoplastic neurologic syndromes is not found.