ADALBERTO STUDART NETO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
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- 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.
- 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.
- 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.
- Adult-onset subacute sclerosing panencephalitis manifesting as slowly progressive dementia(2015) STUDART NETO, Adalberto; NOBREGA, Paulo Ribeiro; DUARTE, Maria Irma Seixas; LUCATO, Leandro Tavares; CASTRO, Luiz Henrique Martins; NITRINI, Ricardo
- The Brain Metabolic Signature in Superagers Using In Vivo H-1-MRS: A Pilot Study(2021) GODOY, L. L. de; STUDART-NETO, A.; WYLEZINSKA-ARRIDGE, M.; TSUNEMI, M. H.; MORAES, N. C.; YASSUDA, M. S.; COUTINHO, A. M.; BUCHPIGUEL, C. A.; NITRINI, R.; BISDAS, S.; LEITE, C. da CostaBACKGROUND AND PURPOSE: Youthful memory performance in older adults may reflect an underlying resilience to the conventional pathways of aging. Subjects having this unusual characteristic have been recently termed ?superagers.? This study aimed to explore the significance of imaging biomarkers acquired by H-1-MRS to characterize superagers and to differentiate them from their normal-aging peers. MATERIALS AND METHODS: Fifty-five patients older than 80?years of age were screened using a detailed neuropsychological protocol, and 25 participants, comprising 12 superagers and 13 age-matched controls, were statistically analyzed. We used state-of-the-art 3T H-1-MR spectroscopy to quantify 18 neurochemicals in the posterior cingulate cortex of our subjects. All H-1-MR spectroscopy data were analyzed using LCModel. Results were further processed using 2 approaches to investigate the technique accuracy: 1) comparison of the average concentration of metabolites estimated with Cramer-Rao lower bounds?<20%; and 2) calculation and comparison of the weighted means of metabolites? concentrations. RESULTS: The main finding observed was a higher total N-acetyl aspartate concentration in superagers than in age-matched controls using both approaches (P =?.02 and P =?.03 for the weighted means), reflecting a positive association of total N-acetyl aspartate with higher cognitive performance. CONCLUSIONS: H-1-MR spectroscopy emerges as a promising technique to unravel neurochemical mechanisms related to cognitive aging in vivo and providing a brain metabolic signature in superagers. This may contribute to monitoring future interventional therapies to avoid or postpone the pathologic processes of aging.
- FDG-PET Patterns Predict Amyloid Deposition and Clinical Profile in Corticobasal Syndrome(2021) PARMERA, Jacy Bezerra; COUTINHO, Artur Martins; ARANHA, Mateus Rozalem; STUDART-NETO, Adalberto; CARNEIRO, Camila de Godoi; ALMEIDA, Isabel Junqueira de; SOLLA, Davi J. Fontoura; ONO, Carla Rachel; BARBOSA, Egberto Reis; NITRINI, Ricardo; BUCHPIGUEL, Carlos Alberto; BRUCKI, Sonia Maria DozziBackground Corticobasal syndrome (CBS) is an atypical parkinsonian syndrome related to multiple underlying pathologies. Objective To investigate if individual brain [F-18]fluorodeoxyglucose-positron emission tomography (FDG-PET) patterns could distinguish CBS due to Alzheimer's disease (AD) from other pathologies based on [C-11]Pittsburgh Compound-B (PIB)-PET. Methods Forty-five patients with probable CBS were prospectively evaluated regarding cognitive and movement disorders profile. They underwent FDG-PET and were distributed into groups: likely related to AD (CBS FDG-AD) or likely non-AD (CBS FDG-nonAD) pathology. Thirty patients underwent PIB-PET on a hybrid PET-magnetic resonance imaging equipment to assess their amyloid status. FDG and PIB-PET images were classified individually based on visual and semi-quantitative analysis, blinded to each other. Quantitative group analyses were also performed. Results CBS FDG-AD group demonstrated worse cognitive performances, mostly concerning attention, memory, visuospatial domains, and displayed more myoclonus and hallucinations. The non-AD metabolic group presented more often limb dystonia, ocular motor dysfunction, motor perseveration, and dysarthria. All patients classified as CBS FDG-AD tested positive at PIB-PET compared to 3 of 20 in the non-AD group. The individual FDG-PET classification demonstrated 76.92% of sensitivity, 100% of specificity and positive predictive value and 88.5% of balanced accuracy to detect positive PIB-PET scans. Individuals with positive and negative PIB-PET showed hypometabolism in posterior temporoparietal areas and in thalamus and brainstem, respectively, mainly contralateral to most affected side, disclosing possible metabolic signatures of CBS variants. Conclusion FDG-PET was useful to predict AD and non-AD CBS variants depicting their specific degeneration patterns, different clinical features, and brain amyloid deposition. (c) 2020 International Parkinson and Movement Disorder Society
- Neurological consultations and diagnoses in a large, dedicated COVID-19 university hospital(2020) STUDART-NETO, Adalberto; GUEDES, Bruno Fukelmann; TUMA, Raphael de Luca e; CAMELO FILHO, Antonio Edvan; KUBOTA, Gabriel Taricani; IEPSEN, Bruno Diogenes; MOREIRA, Gabriela Pantaleao; RODRIGUES, Julia Chartouni; FERRARI, Maira Medeiros Honorato; CARRA, Rafael Bernhart; SPERA, Raphael Ribeiro; OKU, Mariana Hiromi Manoel; TERRIM, Sara; LOPES, Cesar Castello Branco; PASSOS NETO, Carlos Eduardo Borges; FIORENTINO, Matheus Dalben; SOUZA, Julia Carvalhinho Carlos De; BAIMA, Jose Pedro Soares; SILVA, Tomas Fraga Ferreira Da; MORENO, Cristiane Araujo Martins; SILVA, Andre Macedo Serafim; HEISE, Carlos Otto; MENDONCA, Rodrigo Holanda; FORTINI, Ida; SMID, Jerusa; ADONI, Tarso; GONCALVES, Marcia Rubia Rodrigues; PEREIRA, Samira Luisa Apostolos; PINTO, Lecio Figueira; GOMES, Helio Rodrigues; ZANOTELI, Edmar; BRUCKI, Sonia Maria Dozzi; CONFORTO, Adriana Bastos; CASTRO, Luiz Henrique Martins; NITRINI, RicardoBackground: More than one-third of COVID-19 patients present neurological symptoms ranging from anosmia to stroke and encephalopathy. Furthermore, pre-existing neurological conditions may require special treatment and may be associated with worse outcomes. Notwithstanding, the role of neurologists in COVID-19 is probably underrecognized. Objective: The aim of this study was to report the reasons for requesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. Methods: This retrospective study was carried out at Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Brazil, a 900-bed COVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosis was confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurology consultations between March 23rd and May 23rd, 2020 were analyzed. Neurologists performed the neurological exam, assessed all available data to diagnose the neurological condition, and requested additional tests deemed necessary. Difficult diagnoses were established in consensus meetings. After diagnosis, neurologists were involved in the treatment. Results: Neurological consultations were requested for 89 out of 1,208 (7.4%) inpatient COVID admissions during that period. Main neurological diagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurological diseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brain lesions (3.4%), and other mild nonspecific symptoms (11.2%). Conclusions: Most neurological consultations in a COVID-19-dedicated hospital were requested for severe conditions that could have an impact on the outcome. First-line doctors should be able to recognize neurological symptoms; neurologists are important members of the medical team in COVID-19 hospital care.
- Clinical, cerebrospinal fluid, and neuroimaging findings in COVID-19 encephalopathy: a case series(2021) TUMA, Raphael L.; GUEDES, Bruno F.; CARRA, Rafael; IEPSEN, Bruno; RODRIGUES, Julia; CAMELO-FILHO, Antonio Edvan; KUBOTA, Gabriel; FERRARI, Maira; STUDART-NETO, Adalberto; OKU, Mariana Hiromi; TERRIM, Sara; LOPES, Cesar C. B.; PASSOS NETO, Carlos E. B.; FIORENTINO, Matheus D.; SOUZA, Julia C. C.; BAIMA, Jose Pedro S.; SILVA, Tomas; PERISSINOTTI, Iago; MARTIN, Maria da Graca M.; GONCALVES, Marcia; FORTINI, Ida; SMID, Jerusa; ADONI, Tarso; LUCATO, Leandro; NITRINI, Ricardo; GOMES, Helio; CASTRO, Luiz H.Objective To describe the clinical, neurological, neuroimaging, and cerebrospinal fluid (CSF) findings associated with encephalopathy in patients admitted to a COVID-19 tertiary reference center. Methods We retrospectively reviewed records of consecutive patients with COVID-19 evaluated by a consulting neurology team from March 30, 2020 through May 15, 2020. Results Fifty-five patients with confirmed SARS-CoV-2 were included, 43 of whom showed encephalopathy, and were further divided into mild, moderate, and severe encephalopathy groups. Nineteen patients (44%) had undergone mechanical ventilation and received intravenous sedatives. Eleven (26%) patients were on dialysis. Laboratory markers of COVID-19 severity were very common in encephalopathy patients, but did not correlate with the severity of encephalopathy. Thirty-nine patients underwent neuroimaging studies, which showed mostly non-specific changes. One patient showed lesions possibly related to CNS demyelination. Four had suffered an acute stroke. SARS-CoV-2 was detected by RT-PCR in only one of 21 CSF samples. Two CSF samples showed elevated white blood cell count and all were negative for oligoclonal bands. In our case series, the severity of encephalopathy correlated with higher probability of death during hospitalization (OR = 5.5 for each increment in the degree of encephalopathy, from absent (0) to mild (1), moderate (2), or severe (3), p < 0.001). Conclusion In our consecutive series with 43 encephalopathy cases, neuroimaging and CSF analysis did not support the role of direct viral CNS invasion or CNS inflammation as the cause of encephalopathy.
- Phenotyping Superagers Using Resting-State fMRI(2023) GODOY, L. L. de; STUDART-NETO, A.; PAULA, D. R. de; GREEN, N.; HALDER, A.; ARANTES, P.; CHAIM, K. T.; MORAES, N. C.; YASSUDA, M. S.; NITRINI, R.; DRESLER, M.; LEITE, C. da Costa; PANOVSKA-GRIFFITHS, J.; SODDU, A.; BISDAS, S.BACKGROUND AND PURPOSE: Superagers are defined as older adults with episodic memory performance similar or superior to that in middle-aged adults. This study aimed to investigate the key differences in discriminative networks and their main nodes between superagers and cognitively average elderly controls. In addition, we sought to explore differences in sensitivity in detecting these functional activities across the networks at 3T and 7T MR imaging fields. MATERIALS AND METHODS: Fifty-five subjects 80 years of age or older were screened using a detailed neuropsychological protocol, and 31 participants, comprising 14 superagers and 17 cognitively average elderly controls, were included for analysis. Participants underwent resting-state-fMRI at 3T and 7T MR imaging. A prediction classification algorithm using a penalized regression model on the measurements of the network was used to calculate the probabilities of a healthy older adult being a superager. Additionally, ORs quantified the influence of each node across preselected networks. RESULTS: The key networks that differentiated superagers and elderly controls were the default mode, salience, and language networks. The most discriminative nodes (ORs > 1) in superagers encompassed areas in the precuneus posterior cingulate cortex, prefrontal cortex, temporoparietal junction, temporal pole, extrastriate superior cortex, and insula. The prediction classification model for being a superager showed better performance using the 7T compared with 3T resting-state-fMRI data set. CONCLUSIONS: Our findings suggest that the functional connectivity in the default mode, salience, and language networks can provide potential imaging biomarkers for predicting superagers. The 7T field holds promise for the most appropriate study setting to accurately detect the functional connectivity patterns in superagers.