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Magnetic resonance brain perfusion (arterial spin labeling) in Alzheimer's disease and mild cognitive impairment patients and its relationship with cognitive performance

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Ana Fl?via Mac Knight Carletti-Cassani
Total Authors: 1
Document type: Master's Dissertation
Defense date:
Advisor: Marcio Luiz Figueredo Balthazar

Dementia in Alzheimer's disease (AD) is a serious public health problem that tends to intensify, mainly due to the aging of the population. Regarding the clinical aspects of the disease, the first symptom usually observed is the difficulty in storing new information, affecting episodic memory, as the disease progresses, other cognitive functions are affected. The pathophysiology of AD is characterized by a series of neuropathological changes that include: senile plaques that contain excess extracellular deposits ß-amyloid peptide (Aß) and intracellular neurofibrillary tangles that contain hyperphosphorylated Tau protein (p-Tau), leading to a massive neuronal death, and functional abnormalities in neural network, such as in the Default Mode Network (DMN). The functional connectivity (FC) of DMN is altered in AD due to the accumulation of Aß in its regions, contributing to the severity of cognitive and clinical symptoms. Structural changes such as brain atrophy, especially hippocampal atrophy, are also seen in the disease. There is increasing evidence that systemic inflammation, through inflammatory mediators, such as cytokines, plays an important role in the production and regulation of these proteins (ßA and Tau) present in cerebrospinal fluid (CSF). There are pathways of communication between the brain and the peripheral immune system that may be altered from the pre-dementia phase, favoring or not the progression of the disease, as a result of which systemic inflammation has also been associated with cerebral cognition and morphology. Our main objective was to verify the hypothesis that sistemic inflammation may be associated with the main biomarkers of AD (CSF proteins and neuroimaging). For this, we acquired magnetic resonance imaging in 3T of 25 healthy controls, 45 amnestic Mild Cognitive Impairment (aMCI) and 28 patients with mild AD. We observed that patients with aMCI in whom we detected IL-12, TNF-'alpha' and IL-6 showed increased FC of the regions of the DMN; the patients in the mild AD group in which we detected IL-12, IL-6, IL-10 and TNF-'alpha' had higher hippocampal volume, less Aß1-42, and decreased FC in DMN. Our results may indicate a possible relationship between the systemic inflammation profile and the biomarkers of AD (AU)

FAPESP's process: 11/17092-0 - Biomarkers in Alzheimer's Disease and mild cognitive impairment: evaluation of functional magnetic resonance imaging methods, plasmatic and cerebrospinal fluid markers
Grantee:Marcio Luiz Figueredo Balthazar
Support type: Research Grants - Young Investigators Grants