Longitudinal brain structural changes in preclinical Alzheimer's disease.

Area of Science:

• Neuroscience
• Neurology
• Biomarker Research

Background:

• Brain structural changes in preclinical Alzheimer's disease (AD) are not well understood.
• Investigating early AD pathology is crucial for timely intervention.
• Cerebrospinal fluid (CSF) biomarkers are key indicators of AD progression.

Purpose of the Study:

• To compare cortical thickness changes across preclinical AD stages defined by CSF biomarkers.
• To analyze the relationship between baseline CSF biomarkers and rates of brain atrophy.
• To elucidate the trajectory of brain structural changes in early Alzheimer's disease.

Main Methods:

• Utilized the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.
• Compared 2-year longitudinal changes in cortical thickness.
• Defined preclinical AD stages based on NIA-AA criteria using CSF biomarker levels (Aβ1-42, tau).

Main Results:

• Stage 1 preclinical AD showed reduced atrophy in medial frontal and precuneus regions compared to stage 0.
• Stage 2/3 preclinical AD exhibited accelerated atrophy in medial temporal structures.
• Low CSF Aβ1-42 correlated with reduced atrophy in normal tau subjects; high tau correlated with accelerated atrophy in low Aβ1-42 subjects.

Conclusions:

• Longitudinal data confirm a biphasic pattern of brain structural changes in preclinical AD.
• Findings have implications for patient selection in AD clinical trials.
• MRI may serve as a surrogate marker for treatment efficacy in AD studies.