Diffusion Changes in Hippocampal Cingulum in Early Biologically Defined Alzheimer's Disease

Area of Science:

• Neuroimaging
• Neuropathology
• Alzheimer's Disease Research

Background:

• Alzheimer's disease (AD) diagnosis now reflects underlying neuropathology, with amyloid deposition defining the AD continuum.
• Tau positivity further specifies AD within this continuum.

Purpose of the Study:

• To investigate white matter (WM) alterations in patients within the Alzheimer's continuum.
• To assess the relationship between WM changes, amyloid and tau burden, and diagnostic potential.

Main Methods:

• Included 236 subjects stratified by amyloid and tau status (A/T) using PET scans.
• Utilized diffusion tensor imaging (DTI) to measure WM alteration.
• Evaluated group differences, correlations with A/T status, and diagnostic performance of DTI measures.

Main Results:

• Widespread WM alterations were observed across the Alzheimer's continuum, notably in the hippocampal cingulum (CGH).
• Early diffusion changes (decreased FA) in CGH were detected in amyloid-positive, tau-positive cognitively normal individuals (A+T+ CN).
• CGH FA correlated with tau burden and showed moderate diagnostic performance for distinguishing early AD continuum stages.

Conclusions:

• White matter alteration is prevalent throughout the Alzheimer's continuum.
• Early diffusion changes in the CGH are linked to tau pathology.
• CGH diffusion alteration may serve as a promising biomarker for preclinical Alzheimer's disease.