The transitional association between β-amyloid pathology and regional brain atrophy

Area of Science:

• Neuroscience
• Biomarkers
• Medical Imaging

Background:

• Alzheimer's disease (AD) is linked to β-amyloid (Aβ) accumulation, brain atrophy, and cognitive decline.
• The relationship between Aβ levels and regional brain atrophy requires precise modeling.
• Current methods often dichotomize cerebrospinal fluid (CSF) Aβ into positive/negative groups.

Purpose of the Study:

• To compare a trilinear spline model of CSF Aβ with dichotomous models for assessing Aβ and regional atrophy.
• To identify nonlinear associations and acceleration points of atrophy relative to CSF Aβ levels.

Main Methods:

• Analysis of longitudinal MRI data from 183 individuals with mild cognitive impairment and 108 controls.
• Application of mixed-effects regression and piecewise-linear splines to model CSF Aβ and regional atrophy.
• Comparison of different CSF Aβ parameterizations using likelihood ratio tests and AIC.

Main Results:

• Spline models provided superior fits for temporal and parietal regions compared to dichotomous models.
• The trilinear model revealed regional variations in atrophy acceleration.
• Accelerated atrophy was observed in regions like the insula, amygdala, and hippocampus before reaching the CSF Aβ positivity threshold.

Conclusions:

• Piecewise-linear splines offer a more accurate model for the nonlinear relationship between CSF Aβ and regional atrophy in AD-implicated areas.
• Accelerated brain atrophy occurs in certain regions prior to the conventional CSF Aβ42 threshold.
• These findings suggest that brain atrophy signs may precede the current definition of preclinical AD.