MRI-Driven Longitudinal Studies of Hippocampal Alterations During the Initial Cognitive Decline

Area of Science:

• Neuroimaging
• Biomarker Discovery
• Cognitive Decline Research

Background:

• Hippocampal alterations are key indicators of cognitive decline.
• Longitudinal changes in hippocampal morphology during early cognitive decline remain unclear.
• There is an urgent need for validated biomarkers with high clinical relevance.

Purpose of the Study:

• To develop an automated MRI-driven system for longitudinal hippocampal alteration analysis (LHAAS).
• To identify subtle morphometric and volumetric changes in the hippocampus during preclinical stages of cognitive decline.
• To provide insights for early intervention in Alzheimer's disease (AD).

Main Methods:

• Developed LHAAS including segmentation, reconstruction, registration, and feature extraction.
• Applied LHAAS to cognitive unimpaired (CU) participants, distinguishing progressors to MCI from non-progressors.
• Analyzed longitudinal morphometric and volumetric differences in hippocampal subregions.

Main Results:

• LHAAS detected subtle bilateral hippocampal deformations in CU progressors four years before cognitive decline onset.
• Hippocampal atrophy in progressors started in the CA1 subregion, spreading to CA2-3 and Subiculum, with a left-greater-than-right trend.
• Identified hippocampal subregions highly correlated with clinical measurements, reflecting preclinical AD atrophy.

Conclusions:

• LHAAS accurately detects subtle hippocampal subregional atrophy in preclinical AD.
• The system tracks longitudinal hippocampal alterations in early AD stages.
• LHAAS facilitates early detection, pathological research, and timely interventions for improved patient outcomes.