Biphasic cortical macro- and microstructural changes in autosomal dominant Alzheimer's disease

Area of Science:

• Neuroimaging
• Neuropathology
• Alzheimer's Disease Research

Background:

• Conflicting findings in Alzheimer's disease (AD) observational studies and anti-amyloid trials may stem from a lack of dynamic models for brain changes.
• Understanding preclinical AD progression is crucial for developing effective early interventions.

Purpose of the Study:

• To test a biphasic model of brain structural changes in preclinical Alzheimer's disease (AD).
• To determine the timing of inflection points in cortical thickness and diffusivity changes.
• To reconcile paradoxical findings in AD research.

Main Methods:

• Utilized a cohort of 389 participants from the Dominantly Inherited Alzheimer Network (DIAN).
• Applied linear and quadratic trajectory models to analyze vertexwise changes in cortical thickness and cortical diffusivity.
• Calculated the timing of inflection points relative to estimated symptom onset.

Main Results:

• Identified a biphasic trajectory for brain structural changes in early preclinical AD.
• Observed initial increases in cortical thickness and decreases in cortical diffusivity (20-15 years before symptom onset).
• Detected subsequent cortical thinning and increased diffusivity in later preclinical and symptomatic stages, with inflection points aligning with tau biomarker alterations.

Conclusions:

• The study confirms a biphasic trajectory for brain structural changes in preclinical AD.
• Findings provide a framework for interpreting MRI measures in AD prevention trials.
• The biphasic model offers insights into the dynamic nature of neurodegeneration in AD.