Brain volumetry and functional connectivity patterns of hippocampal subfields in normal and pathological aging

Resumen

Alzheimer's disease remains the most common dementia, affecting 55 million people globally. It is estimated that nearly 10 million people worldwide are diagnosed each year, making it one of the most common neurodegenerative diseases. This alarming statistic intensifies by the fact that there is no medical cure for Alzheimer's patients. Moreover, the evolution of treatments has not found the key to conclusively curbing the disease, making Alzheimer's disease a major health problem and a challenge for medical research. The hippocampus is the basic brain area linked to Alzheimer's disease and has a great impact on its debut and evolution, since its structure and function may be related to the progression of the disease. Our group has found that the volume and functional connectivity patterns vary with normal and pathological aging, which could lead to an early diagnosis of the disease. In this thesis we study hippocampal subfields from a medical perspective, using fMRI, to assess its potential as an early indicator of pathology versus the presence of mild cognitive impairment associated with early stages of Alzheimer's disease. To this end, we analyzed the functional connectivity networks of the hippocampus, its subfields and the rest of the brain in young and elderly participants, as well as the volume of subfields in healthy elderly participants and Alzheimer's patients by age group. Our functional results showed that there is a consistency in the functional connectivity of the hippocampus, mainly in the subiculum and CA4 subfield in resting-state networks, with brain aging. Structural results revealed that both aging and Alzheimer's disease affect the volume of hippocampal subfields. Specifically, a three-way interaction was observed between the age of the individual, the hippocampal longitudinal axis section (head, body) and the subfield analyzed. Our correlation has potential to be employed in mathematical estimates of hippocampal volumetric decline associated with normal human aging, as well as with the onset of Alzheimer's disease in its early stages. This work provides an integrated view for the differentiation between normal brain aging and pathological aging, and can lay the foundation for early diagnosis of Alzheimer's disease by correlating the volumetric loss of hippocampal subfields, which occurs naturally during aging, with the pathological study sample.