The hippocampus as a structural and functional network epicentre for distant cortical thinning in neurocognitive aging

Abstract

Alterations in grey matter (GM) and white matter (WM) are associated with memory impairment across the neurocognitive aging spectrum and theorised to spread throughout brain networks. Functional and structural connectivity (FC,SC) may explain widespread atrophy. We tested the effect of SC and FC to the hippocampus on cortical thickness (CT) of connected areas. In 419 (223 F) participants (age_mean=73 ± 8) from the Alzheimer's Disease Neuroimaging Initiative, cortical regions associated with memory (Rey Auditory Verbal Learning Test) were identified using Lasso regression. Two structural equation models (SEM), for SC and resting-state FC, were fitted including CT areas, and SC and FC to the left and right hippocampus (LHIP,RHIP). LHIP (β=-0.150,p=<.001) and RHIP (β=-0.139,p=<.001) SC predicted left temporopolar/rhinal CT; RHIP SC predicted right temporopolar/rhinal CT (β=-0.191,p=<.001). LHIP SC predicted right fusiform/parahippocampal (β=-0.104,p=.011) and intraparietal sulcus/superior parietal CT (β=0.101,p=.028). Increased RHIP FC predicted higher left inferior parietal CT (β=0.132,p=.042) while increased LHIP FC predicted lower right fusiform/parahippocampal CT (β=-0.97; p=.023). The hippocampi may be epicentres for cortical thinning through disrupted connectivity.

Keywords: Alzheimer’s disease; Connectivity; DTI; FMRI; Mild cognitive impairment; Network.