Association between Hippocampal Shape, Neuroinflammation, and Cognitive Decline in Alzheimer's Disease

Background: Alzheimer's disease (AD) is a neurodegenerative condition characterized by memory impairment and general decrease in cognitive functions and daily living competences, that leads to a complete loss of autonomy. The pathogenesis of AD is characterized by the deposition of amyloid-β plaques (Aβ plaques) and neurofibrillary tangles, initially involving cortical and hippocampal structures, and neuroinflammation. To date, no studies have investigated the topological association between neuroinflammation and hippocampal shape in AD. Objective: The aim of the present study is to assess the association between hippocampal shape, cognitive profile, and neuroinflammation in a group of AD patients in the mild stage of the disease. Methods: Thirty-one patients with typical onset AD (mild stage) underwent MRI examination (1.5T scanner); hippocampal structures were segmented using a vertex-wise analysis (FSL-FIRST). Immune parameters were evaluated on peripheral blood mononuclear cells by flow-cytometry. Correlation analyses were performed between hippocampal shape and both cognitive profile (ADAS-Cog and MMSE scores), and neuro-inflammatory variables (i.e., circulating monocytes, cytokines). Results: Statistically significant correlations (p < 0.05 FWE) between right hippocampal shape and cognitive measurements and between left hippocampal shape and inflammatory indices were detected. The hippocampal field mostly involved was the lateral portion of bilateral hippocampi, mainly overlapping with Cornu Ammonis, extending along the entire longitudinal axis. Conclusions: A topological relationship between hippocampal atrophy and both cognitive profile and neuroinflammation is found; the association with neuroinflammatory indices is in line with the pattern of AD-Associated neuronal death, whereas the association with cognitive test might account for residual cognitive functions.