Hippocampal Asymmetry Captures Non-Amyloid-Related Risk of Memory Decline and Clinical Progression

Area of Science:

• Neuroimaging
• Neurodegeneration
• Alzheimer's Disease Research

Background:

• Hippocampal atrophy is a key marker of Alzheimer's disease (AD) neurodegeneration.
• Hippocampal volume alone may not fully capture cognitive decline heterogeneity.
• The prognostic value of hemispheric hippocampal asymmetry is unclear.

Purpose of the Study:

• To investigate the prognostic value of total hippocampal volume and hemispheric asymmetry for cognitive decline and clinical progression.
• To determine if hippocampal asymmetry provides complementary information to total volume in Alzheimer's disease.

Main Methods:

• Studied 1,142 dementia-free participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI).
• Analyzed baseline structural MRI, CSF biomarkers (Aβ42, p-tau-181), and longitudinal cognitive data.
• Modeled total hippocampal volume and hemispheric asymmetry, assessing associations with cognitive performance, decline, and dementia risk.

Main Results:

• Larger total hippocampal volume correlated with better baseline cognition and slower decline across all domains.
• Greater hippocampal asymmetry was linked to worse baseline memory and faster memory decline.
• Hippocampal asymmetry predicted dementia risk in amyloid-negative individuals, while smaller total volume predicted risk across all groups.

Conclusions:

• Hippocampal total volume and asymmetry reflect distinct aspects of neurodegeneration.
• Hippocampal asymmetry offers additional prognostic information for memory decline and clinical progression, especially in amyloid-negative individuals.