INTRODUCTION

Structural MRI–derived atrophy and FDG-PET–measured hypometabolism are complementary markers of neurodegeneration in Alzheimer’s disease (AD), capturing cumulative tissue loss and synaptic–neuronal dysfunction, respectively.

However, the temporo-spatial evolution of cortical hypometabolism and atrophy patterns from preclinical stages to AD dementia remains incompletely understood.

Aim: In this study, we investigated the temporal evolution of cortical hypometabolism and atrophy using serial FDG-PET and MRI acquisitions in individuals who developed AD dementia.

METHODS

Participants: 208 nondemented individuals (15% CU, 85% MCI) enrolled in the ADNI study who developed biomarker-confirmed AD dementia over clinical follow-up (Table 1).

• All participants underwent serial MRI and [18F]FDG-PET acquisitions spanning from −15 years before to +5 years after dementia onset.

Neuroimaging:

• Cortical thickness on MRI and standardized uptake value ratios on FDG-PET were calculated across 200 cortical regions defined in the Schaefer atlas.

• Region-wise z-scores were calculated to quantify cortical thickness and hypometabolism relative to healthy elderly controls (N(MRI)=218, N(FDG)=56).

Statistical analyses:

• Longitudinal atrophy and hypometabolism progression of each brain region was calculated using linear mixed-effects models adjusted for age and sex.

• Predicted z-scores were generated at 2-year intervals spanning from −10 years before dementia onset to +2 years after.

• Inter-modality z-score differences quantified the relative predominance of regional hypometabolism versus atrophy over the course of disease progression.