MARCIA RADANOVIC
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
78 resultados
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- White matter abnormalities associated with Alzheimer's disease and mild cognitive impairment: a critical review of MRI studies(2013) RADANOVIC, Marcia; PEREIRA, Fabricio Ramos Silvestre; STELLA, Florindo; APRAHAMIAN, Ivan; FERREIRA, Luiz Kobuti; FORLENZA, Orestes Vicente; BUSATTO, Geraldo F.In this article, the authors aim to present a critical review of recent MRI studies addressing white matter (WM) abnormalities in Alzheimer's disease (AD) and mild cognitive impairment (MCI), by searching PubMed and reviewing MRI studies evaluating subjects with AD or MCI using WM volumetric methods, diffusion tensor imaging and assessment of WM hyperintensities. Studies have found that, compared with healthy controls, AD and MCI samples display WM volumetric reductions and diffusion tensor imaging findings suggestive of reduced WM integrity. These changes affect complex networks relevant to episodic memory and other cognitive processes, including fiber connections that directly link medial temporal structures and the corpus callosum. Abnormalities in cortico-cortical and cortico-subcortical WM interconnections are associated with an increased risk of progression from MCI to dementia. It can be concluded that WM abnormalities are detectable in early stages of AD and MCI. Degeneration of WM networks causes disconnection among neural cells and the degree of such changes is related to cognitive decline.
- Cognitive-communication disorder following right hemisphere damage: Narrative production(2022) RODRIGUEZ, E.; BELAN, A. F. R.; RADANOVIC, M.Background: Cognitive-communication disorder (CCD) results from the association of language and cognition impairment that may follow right hemisphere (RH) damage and impair the quality of life of affected persons. Objective: We studied a set of 1,625 narratives produced by a cohort of 125 individuals (50 with a single right vascular lesion in the MCA territory and 75 cognitively healthy controls) using a task of picture-based discourse production. Discourse production was analyzed in its macro-and microlinguistic aspects to characterize better the linguistic mechanisms underlying RH patients' performance. Results: The RH group produced more words and elocutions than controls, with a lower rate of informational content and a higher percentage of global coherence errors (all p-values <0.0001). Conclusion: Individuals with RH lesions showed formal lexical and syntactic aspects of discourse mostly preserved. Alterations in the macrostructure of discourse prevailed over microstructural alterations in our sample, according to most literature studies. The group of individuals with RH lesions produced narratives containing more words and utterances, with a lesser degree of lexical information and more global coherence errors. © 2022
- screening for cognitive impairment in late onset depression in a Brazilian sample using the BBRC-edu(2012) NOVARETTI, Tânia Maria da Silva; RADANOVIC, Marcia; NITRINI, RicardoABSTRACT Depression and dementia are the most prevalent neuropsychiatric disorders in the elderly population. Alzheimer's disease is the leading cause of dementia in most countries, being responsible for more than half of all dementia cases. Late-onset depression is a frequent cause of cognitive decline in the elderly. Differentiating between cognitive impairment secondary to depression and incipient dementia poses a challenge in the clinical setting. Objective: To evaluate the performance of elderly depressed patients using the BBRC-Edu. Methods: We studied 25 patients with late onset depression (mean age: 73.6 y (6.6); schooling: 9.1 y (5.7)) and 30 patients with mild AD (mean age 76.6 y (5.4); schooling: 7.5 y (7.1)), who were compared to a control group of 30 healthy elderly (mean age 73.8 y (5.8); schooling: 9.1 y (5.4)) using the CERAD and BBRC-Edu batteries. Results: For the CERAD battery, depressed patients performed better than AD patients on all tasks (p<0.0001) except for Constructional Praxis (p>0.05), and performed poorer than controls on verbal fluency (animals) and Word List Recall tasks (p<0.0001). For the BBRC-Edu, depressed patients performed better than AD patients on all tasks (p<0.0001) except for Digit Span (direct order) (p=0.076) and Incidental Memory (p>0.05), and performed worse than controls on Learning (second presentation) and verbal fluency (fruits) tasks (p<0.0001). Conclusion: Overall performance on the BBRC-Edu allowed differentiation of controls and depressed patients from AD patients.
- Neuropsychiatric symptoms in the prodromal stages of dementia(2014) STELLA, Florindo; RADANOVIC, Marcia; BALTHAZAR, Marcio L. F.; CANINEU, Paulo R.; SOUZA, Leonardo C. de; FORLENZA, Orestes V.Purpose of reviewTo critically discuss the neuropsychiatric symptoms in the prodromal stages of dementia in order to improve the early clinical diagnosis of cognitive and functional deterioration.Recent findingsCurrent criteria for cognitive syndrome, including Alzheimer's disease, comprise the neuropsychiatric symptoms in addition to cognitive and functional decline. Although there is growing evidence that neuropsychiatric symptoms may precede the prodromal stages of dementia, these manifestations have received less attention than traditional clinical hallmarks such as cognitive and functional deterioration. Depression, anxiety, apathy, irritability, agitation, sleep disorders, among other symptoms, have been hypothesized to represent a prodromal stage of dementia or, at least, they increase the risk for conversion from minor neurocognitive disorder to major neurocognitive disorder. Longitudinal investigations have provided increased evidence of progression to dementia in individuals with minor neurocognitive disorder when neuropsychiatric symptoms also were present.SummaryAlthough neuropsychiatric symptoms are strongly associated with a higher risk of cognitive and functional deterioration, frequently the clinician does not acknowledge these conditions as increasing the risk of dementia. When the clinician accurately diagnoses neuropsychiatric symptoms in the prodromal stage of dementia, he could early establish appropriate treatment and, may be, delay the beginning of clinical and functional deterioration.
- Lower Cerebrospinal Fluid Concentration of Brain-Derived Neurotrophic Factor Predicts Progression from Mild Cognitive Impairment to Alzheimer's Disease(2015) FORLENZA, Orestes Vicente; DINIZ, Breno Satler; TEIXEIRA, Antonio Lucio; RADANOVIC, Marcia; TALIB, Leda Leme; ROCHA, Natalia Pessoa; GATTAZ, Wagner FaridThere is little information on the dynamics of BDNF in the CSF in the continuum between healthy aging, MCI and AD. We included 128 older adults (77 with amnestic MCI, 26 with AD and 25 healthy controls). CSF BDNF level was measured by ELISA assay, and AD biomarkers (A beta(42), T-Tau and P-Tau(181)) were measured using a Luminex xMAP assay. CSF BDNF levels were significantly reduced in AD subjects compared to MCI and healthy controls (p = 0.009). Logistic regression models showed that lower CSF BDNF levels (p = 0.008), lower CSF A beta(42) (p = 0.005) and lower MMSE scores (p = 0.007) are significantly associated with progression from MCI to AD. The present study adds strong evidence of the involvement of BDNF in the pathophysiology of neurodegenerative changes in AD. Interventions aiming to restore central neurotrophic support may represent future therapeutic targets to prevent or delay the progression from MCI to AD.
conferenceObject COGNITIVE PROFILE OF ADULTS AND SENIORS WITH DOWN'S SYNDROME: DATA FROM THE CAMBRIDGE EXAMINATION FOR MENTAL DISORDERS OF OLDER PEOPLE WITH DOWN SYNDROME BRAZILIAN VERSION - CAMDEX-DS ADAPTED AND VALIDATED FOR THE BRAZILIAN POPULATION(2019) CARVALHO, C. L.; ARAUJO, M. C. Cristianini; NOGUEIRA, C.; GONCALVES, A.; BELAN, A.; BRAM, J.; SANTANA, L.; BECKER, A.; RADANOVIC, M.; FORLENZA, O.- Sentence processing in mild cognitive impairment(2022) PEREIRA, Diana Nakamura; SOUZA, Wellington da Cruz; BELAN, Ariella Fornachari Ribeiro; CAMARGO, Marina von Zuben de Arruda; FORLENZA, Orestes Vicente; RADANOVIC, MarciaDifficulties in sentence processing have been reported in patients with Mild Cognitive Impairment (MCI), which may be due to impairment in primary syntactic abilities or short-term memory. In the present study, we investigated the relationship between overt sentence production (SP) and comprehension (SC) with short-term memory performance in MCI. Cognitively healthy elderly (n = 34), amnestic MCI (aMCI,n = 22), non-amnestic MCI (naMCI,n = 45), and Alzheimer's disease (AD,n = 18) patients were asked to complete tests of constrained SP and oral SC. We tested the association between performance in SP and SC with memory tasks and performed a qualitative analysis of the frequency and type of errors in SC. Our results showed that there were no intergroup differences in SC and SP performances. SC scores were associated with delayed recall for words in the naMCI group (p = 0.003), and immediate (p = 0.001) and delayed recall for shapes (p = 0.031) in AD. There were no predictors for NAT scores in any group. In conclusion, the three groups performed similarly in SC and SP tasks. Short-term memory was not associated with performance in the SP task. There was an association between performance in the SC task and verbal memory in naMCI and non-verbal memory in AD; the latter may reflect visuospatial processing demands embedded in the SC task.
- Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial(2019) FORLENZA, Orestes V.; RADANOVIC, Marcia; TALIB, Leda L.; GATTAZ, Wagner F.Background Experimental studies indicate that lithium may facilitate neurotrophic/protective responses in the brain. Epidemiological and imaging studies in bipolar disorder, in addition to a few trials in Alzheimer's disease support the clinical translation of these findings. Nonetheless, there is limited controlled data about potential use of lithium to treat or prevent dementia. Aims To determine the benefits of lithium treatment in patients with amnestic mild cognitive impairment (MCI), a clinical condition associated with high risk for Alzheimer's disease. Method A total of 61 community-dwelling, physically healthy, older adults with MCI were randomised to receive lithium or placebo (1:1) for 2 years (double-blind phase), and followed-up for an additional 24 months (single-blinded phase) (trial registration at clinicaltrials.gov: NCT01055392). Lithium carbonate was prescribed to yield subtherapeutic concentrations (0.25-0.5 mEq/L). Primary outcome variables were the cognitive (Alzheimer's Disease Assessment Scale - cognitive subscale) and functional (Clinical Dementia Rating - Sum of Boxes) parameters obtained at baseline and after 12 and 24 months. Secondary outcomes were neuropsychological test scores; cerebrospinal fluid (CSF) concentrations of Alzheimer's disease-related biomarkers determined at 0, 12 and 36 months; conversion rate from MCI to dementia (0-48 months). Results Participants in the placebo group displayed cognitive and functional decline, whereas lithium-treated patients remained stable over 2 years. Lithium treatment was associated with better performance on memory and attention tests after 24 months, and with a significant increase in CSF amyloid-beta peptide (A beta(1-42)) after 36 months. Conclusions Long-term lithium attenuates cognitive and functional decline in amnestic MCI, and modifies Alzheimer's disease-related CSF biomarkers. The present data reinforces the disease-modifying properties of lithium in the MCI-Alzheimer's disease continuum. Declaration of interest None.
- Heterogeneity of Cerebrospinal Fluid Biomarkers Profiles in Individuals with Distinct Levels of Cognitive Decline: A Cross-Sectional Study(2021) PAIS, Marcos; LOUREIRO, Julia; VALE, Vagner do; RADANOVIC, Marcia; TALIB, Leda; STELLA, Florindo; FORLENZA, OrestesBackground: Decreased cerebrospinal fluid (CSF) concentrations of the amyloid-beta (A beta), along with increased total (T-tau) and phosphorylated tau protein (P-tau), are widely accepted as core biomarkers of Alzheimer's disease (AD) pathology. Nonetheless, there are a few remaining caveats that still preclude the full incorporation of AD biomarkers into clinical practice. Objective: To determine the frequency of clinical-biological mismatches in a clinical sample of older adults with varying degrees of cognitive impairment. Methods: 204 participants were enrolled for a cross-sectional assessment and allocated into diagnostic groups: probable AD (n = 60, 29.4%); MCI (n = 84, 41.2%); or normal cognition (NC, n = 60, 29.4%). CSF concentrations of A beta(42), T-tau, and (181)Thr-P-tau were determined, and A beta(42)/P-tau ratio below 9.53 was used as a proxy of AD pathology. The AT(N) classification was further used as a framework to ascertain the biological evidence of AD. Results: The majority (73.7%) of patients in the AD group had the A beta(42)/P-tau ratio below the cut-off score for AD, as opposed to a smaller proportion in the MCI (42.9%) and NC (23.3%) groups. In the latter, 21 subjects (35%) were classified as A+, 28 (46.7%) as T+, and 23 (38.3%) as N+. In the AD group, 66.7% of the cases were classified as A+, 78.3% as T+, and 80% as N+. Conclusion: Analysis of CSF biomarkers was able to discriminate between AD, MCI, and NC. However, clinical-biological mismatches were observed in a non-negligible proportion of cases.
- Semantic processing and neurobiology in Alzheimer?s disease and Mild Cognitive Impairment(2022) ALMEIDA, Victor N.; RADANOVIC, MarciaIn the present theoretical review we will perform a critical surveillance of linguistic and semantic processing in Mild Cognitive Impairment and Alzheimer???s disease, explicitly favouring a neurobiological prism. We conjecture that most linguistic alterations arise from semantic indiscrimination through inhibitory hypofunction. Specif-ically, a conjoint cluster of cholinergic dysfunction, A?? load and somatostatin-positive cell loss renders the se-mantic network disinhibited and overly noisy: fine discriminatory processes in temporal and medial-frontal regions cannot differentiate semantic representations from baseline unconscious activity, which leads to failures in faithful retrieval (preferentially idiosyncratic lexical-semantic links, e.g., proper names), verbal fluency anomalies, semantic interference, dampened N400 effects, and various semiological deviances.