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Mapping the progression of subjective cognitive decline to mild cognitive impairment and Alzheimer´s disease dementia with multimodal biomarkers

Grant number: 18/15571-7
Support Opportunities:Research Grants - Young Investigators Grants - Phase 2
Duration: May 01, 2019 - April 30, 2025
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Marcio Luiz Figueredo Balthazar
Grantee:Marcio Luiz Figueredo Balthazar
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated researchers:Fernando Cendes ; Iscia Teresinha Lopes Cendes ; Márcia Regina Cominetti ; Monica Sanches Yassuda
Associated research grant:11/17092-0 - Biomarkers in Alzheimer's Disease and mild cognitive impairment: evaluation of functional magnetic resonance imaging methods, plasmatic and cerebrospinal fluid markers, AP.JP
Associated scholarship(s):23/10675-7 - EVALUATION OF SLEEP AND CSF BLOOD BIOMARKERS IN INDIVIDUALS WITH MILD COGNITIVE IMPAIRMENT AND SUBJECTIVE COGNITIVE DECLINE, BP.IC
21/11729-8 - Biomarkers of Alzheimer's Disease as predictors of neuropsychiatric symptoms in patients with Subjective Cognitive Decline and Mild Cognitive Impairment, BP.IC
19/23028-4 - Characterization of individuals with suspected non-Alzheimer pathophysiology (SNAP) through multimodal biomarkers, BP.PD
+ associated scholarships 19/26933-0 - Structural covariance of white matter by diffusion tensor imaging on patients with mild cognitive impairment and Alzheimer Disease, BP.IC
20/02140-8 - Correlations between cognitive performance and cortical gray matter in patients with subjective cognitive decline and mild cognitive impairment according to AT(N) classification, BP.MS
19/14971-4 - Mapping the progression of subjective cognitive decline to mild cognitive impairment and Alzheimer´s Disease Dementia with multimodal biomarkers, BP.PD - associated scholarships

Abstract

Alzheimer´s disease (AD) is the most common neurodegenerative disorder and its prevalence is increasing mainly due to the aging of the population. Recent clinical trials with anti-amyloid and other drugs in AD dementia and Mild Cognitive Impairment (MCI) have failed, and one possible explanation is that diagnosis is made too late, when subjects have already relevant clinical symptoms. Thus, the concept of Subjective Cognitive Decline (SCD), when subjects have cognitive complaints but normal neuropsychological performance, has emerged and gained more relevance over the last few years. Recently, Jack et al. (2016) proposed a new descriptive classification for AD biomarkers, A/T/N (alterations in amyloid, tau and neurodegeneration), that can be used in the whole spectrum of the AD pathophysiology continuum (including SCD). In this project, our objective is to determine which are the best biomarkers to predict the conversion from SCD to MCI and from amnestic MCI (aMCI) to dementia. We will longitudinally follow normal aging, SCD, and aMCI subjects, sub classifying the patients according to A/T/N classification: normal AD biomarkers (AD-) (A-T-N-); suspected non-Alzheimer pathophysiology (SNAP) (A-T+N-, A-T-N+, or A-T+N+) and AD pathophysiologic continuum (AD+) (any A+ combination). We will longitudinally evaluate new and well-established multimodal biomarkers in baseline and annually for 4 years: : a) structural and functional MRI; b) FDG-PET brain glucose metabolism; c) CSF analyses of: - AD markers: A²40, A²42, A² oligomers, p-Tau, t-Tau, ADAM-10; - Synaptic dysfunction markers: VILIP-1 and neurogranin; neurofilament light chain; - Neuroinflammation: YKL-40, MCP-1, IL-6, IL-10, IL-12, IL-18 and TNF-±; d) genetic factors: APOE, CLU, PICALM and CR1; e) cognitive reserve; f) white matter disease observed in MRI. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RIZZI, LIARA; AVENTURATO, ITALO KARMANN; BALTHAZAR, MARCIO L. F.. Neuroimaging Research on Dementia in Brazil in the Last Decade: Scientometric Analysis, Challenges, and Peculiarities. FRONTIERS IN NEUROLOGY, v. 12, . (18/15571-7, 19/23028-4)
PROTA, JOANA; RIZZI, LIARA; BONADIA, LUCIANA; DE SOUZA, LEONARDO CRUZ; CARAMELLI, PAULO; SECOLIN, RODRIGO; LOPES-CENDES, ISCIA; BALTHAZAR, MARCIO L. F.. Slowly progressive behavioral frontotemporal dementia syndrome in a family co-segregating the C9orf72 expansion and a Synaptophysin mutation. ALZHEIMERS & DEMENTIA, . (18/15571-7, 13/07559-3)
LOURENCO, RAFAEL BRANDES; DE CAMPOS, BRUNNO MACHADO; RIZZI, LIARA; DE SOUZA, MILENE SAKZENIAN; FORLENZA, ORESTES VICENTE; JOAQUIM, HELENA GIROUD; TALIB, LEDA LEME; CENDES, FERNANDO; FIGUEREDO BALTHAZAR, MARCIO LUIZ. Functional Connectome Analysis in Mild Cognitive Impairment: Comparing Alzheimer's Disease Continuum and Suspected Non-Alzheimer Pathology. BRAIN CONNECTIVITY, v. 12, n. 9, p. 10-pg., . (17/13906-9, 11/17092-0, 18/15571-7)
ALEXANDRE MOTTA MECÊ; VITOR CORSALETTI ABREU; GUSTAVO MANGINELLI LAMAS; RAFAELLA DO ROSÁRIO TACLA; THAIS BENÍCIO MINEKAWA; CELSO DARIO RAMOS; MARCIO LUIZ FIGUEIREDO BALTHAZAR. INTOXICAÇÃO POR LÍTIO COMO CAUSA DE DEMÊNCIA RAPIDAMENTE PROGRESSIVA: UM RELATO DE CASO E REVISÃO DA LITERATURA. Dement. Neuropsychol., . (18/15571-7)
DE OLIVEIRA, TASSIA R.; ERBERELI, CAMILA R.; MANZINE, PATRICIA R.; MAGALHAES, THAMIRES N. C.; BALTHAZAR, MARCIO L. F.; COMINETTI, MARCIA R.; FARIA, RONALDO C.. Early Diagnosis of Alzheimer's Disease in Blood Using a Disposable Electrochemical Microfluidic Platform. ACS SENSORS, v. 5, n. 4, p. 1010-1019, . (14/22401-0, 15/26084-1, 18/15571-7, 17/24839-0, 17/24053-7, 15/19890-1)
ALEXANDRE MOTTA MECÊ; VITOR CORSALETTI ABREU; GUSTAVO MANGINELLI LAMAS; RAFAELLA DO ROSÁRIO TACLA; THAIS BENÍCIO MINEKAWA; CELSO DARIO RAMOS; MARCIO LUIZ FIGUEIREDO BALTHAZAR. INTOXICAÇÃO POR LÍTIO COMO CAUSA DE DEMÊNCIA RAPIDAMENTE PROGRESSIVA: UM RELATO DE CASO E REVISÃO DA LITERATURA. Dement. Neuropsychol., v. 16, n. 2, p. 249-252, . (18/15571-7)
RIZZI, LIARA; BALTHAZAR, MARCIO L. F.. Mini-review: The suspected non-Alzheimer's disease pathophysiology. Neuroscience Letters, v. 764, . (18/15571-7, 19/23028-4)

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