Rostral-Caudal Hippocampal Functional Convergence Is Reduced Across the Alzheimer's Disease Spectrum

Area of Science:

• Neuroscience
• Medical Imaging
• Neurology

Background:

• Alzheimer's disease (AD) is characterized by reduced functional connectivity between the hippocampus and cortical regions.
• Internal hippocampal connectivity abnormalities in early AD remain poorly understood.
• Synaptic depletion contributes to hippocampal network dysfunction in AD.

Purpose of the Study:

• To investigate rostral-caudal hippocampal convergence (rcHC), a novel metric of hippocampal functional network overlap, across the Alzheimer's disease spectrum.
• To determine if rcHC declines in the early stages of Alzheimer's disease.
• To explore the potential of rcHC as an early biomarker for AD-related connectivity dysfunction.

Main Methods:

• Utilized functional magnetic resonance imaging (fMRI) to generate resting-state hippocampal functional networks.
• Analyzed data from 56 controls, 48 early MCI (EMCI), 35 late MCI (LMCI), and 31 AD patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.
• Employed conjunction analysis and mixed-effects linear models to assess network convergence and differences.

Main Results:

• Demonstrated a significant reduction in rostral-caudal hippocampal convergence strength from early MCI to AD.
• Observed that this decline in convergence was independent of hippocampal atrophy.
• Found a clear parallel between the functional convergence within the hippocampus and the clinical stage of the disease.

Conclusions:

• Reduced rostral-caudal hippocampal convergence is a key finding in the progression of Alzheimer's disease.
• This functional convergence metric shows promise as a biomarker for early connectivity dysfunction in AD, independent of structural changes.
• Findings highlight the importance of investigating intra-hippocampal network integrity for understanding AD pathogenesis.