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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: 19/14971-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2019
Effective date (End): July 31, 2021
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Marcio Luiz Figueredo Balthazar
Grantee:Adriel dos Santos Moraes
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:18/15571-7 - Mapping the progression of subjective cognitive decline to mild cognitive impairment and Alzheimer´s disease dementia with multimodal biomarkers, AP.JP2

Abstract

Alzheimer´s Disease (AD) is the most common neurodegenerative disorder and itsprevalence is increasing mainly due to the aging of the population. Recent clinical trials withanti-amyloid and other drugs in AD Dementia and Mild Cognitive Impairment (MCI) havefailed, and one possible explanation is that diagnosis is made too late, when subjects havealready relevant clinical symptoms. Thus, the concept of Subjective Cognitive Decline (SCD), when subjects have cognitive complaints but normal neuropsychological performance, hasemerged and gained more relevance over the last few years. Recently, Jack et al. (2018) proposed a new descriptive classification for AD biomarkers, AT(N) (alterations in amyloid,tau and neurodegeneration), that can be used in the whole spectrum of the ADpathophysiology continuum (including SCD). In this project, our objective is to determinewhich are the best biomarkers to predict the conversion from SCD to MCI and from MCI todementia. We will longitudinally follow normal aging, SCD, and MCI subjects, subclassifying the patients according to AT(N) classification: normal AD biomarkers (AD-) (AT-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 2 years: : a) structural and functional MRI; b) CSF and plasmatic high-sensitive analyses of: AD markers: A²40, A²42, p-Tau, t-Tau, ADAM-10; CSF analyses of synaptic dysfunctionmarkers: VILIP-1 and neurogranin; CSF and plasmatic analyses of neurofilament light chain; CSF and plasmatic analyses of inflammation: YKL-40, MCP-1, IL-6, IL-10, IL-12, IL-18and TNF-±; d) genetic factors: APOE; e) cognitive reserve. (AU)