Molecular and neuroimaging biomarkers in patients with mild cognitive impairment: cross-sectional and longitudinal study

Author(s)

Thamires Naela Cardoso Magalhães

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2021-04-12

Examining board members

Marcio Luiz Figueredo Balthazar; Marcondes Cavalcante Franca Junior; Rachel Paes Guimarães; Geraldo Busatto Filho; Andre Russowsky Brunoni

• Advisor: Marcio Luiz Figueredo Balthazar

Abstract

Neurodegenerative dementias are diseases that affect the individual's cognition, behavior and independence. The most prevalent type is the Alzheimer's disease (AD). Some of the main aspects of the pathophysiology of AD are the excessive extracellular deposition of amyloid-beta peptide (Aß) and intracellular accumulation of phosphorylated Tau protein (p-Tau) in the brain, which can be quantified in cerebrospinal fluid (CSF). Individuals in prodromal phases such as amnestic mild cognitive impairment (aMCI) evolve to probable AD dementia at a rate of ~10-15% per year. The search for biomarkers that can differentiate which of these patients will evolve into AD is a topic of great interest, especially from the perspective of disease-modifying drugs. Regarding neuroimaging markers, there is the hypothesis that AD may be a syndrome of disconnection of neuronal networks involving abnormalities that begin at the synaptic level and progressively result in loss and degeneration of the integrity of the white matter (WM) and gray matter (GM). In the present work we seek to evaluate transversal and longitudinally patients with aMCI in the continuum of DA, that are, with alteration of the Aß (Aß +) peptide in the CSF examination. We analyzed different techniques of Magnetic Resonance Imaging (MRI) (hippocampal volume (HV), measurements by diffusion tensor imaging (DTI) and functional connectivity (FC)) and molecular analyzes (quantification of the A? peptide and Tau protein in the CSF), both transversely and longitudinally (in this case, comparing aMCI Aß + in relation to the conversion or not to AD in a period of 13 months. We used the programs Multi-Atlas, UF2C and Freesurfer to evaluate DTI parameters, FC and HV, respectively. In our cross-sectional study, we found significant differences between patients and controls in the measures of WM integrity in several tracts, we also found significant correlations between these measures with the CSF levels of Tau protein in the medial temporal structures (fornix and the hippocampal tracts of the right cingulate). We showed that in relation to the HV values, the converter group had a lower volume when compared to the control group. And we also observed differences in WM changes in the parahypocampal bundle of the right cingulate when comparing the converter group with the non-converters and with the controls. Structural measures seem to differentiate groups better than other markers. (AU)

• FAPESP's process: 17/13906-9 - Predictors of functional and structural neuroimaging in conversion of mild cognitive impairment to dementia of Alzheimer's Disease according to AT(N) classification
• Grantee: Thamires Naela Cardoso Magalhães
• Support Opportunities: Scholarships in Brazil - Doctorate