APOE Genotypes and Brain Imaging Classes in Normal Cognition, Mild Cognitive Impairment, and Alzheimer's Disease: A Longitudinal Study

Objective: To evaluate in 419 stroke-free cognitively normal subjects (CN) aged 45-82 years covering during a long prospective study (11.54 ± 1.47 years) the preclinical to dementia spectrum: 1) the distribution of small vessel disease (V) and brain atrophy (A) aggregated as following: V−/A−, V−/A+, V+/A−, V+/A+; 2) the relationship of these imaging classes with individual apolipoprotein E (APOE) genotypes; 3) the risk of progression to Alzheimer Disease (AD) of the individual APOE genotypes. Methods: Participants underwent one baseline (t0), and 4 clinical and neuropsychological assessments (t1,t2,t3, and t4). Brain MRI was performed in all subjects at t0, t2, t3 and t4.. White matter hyperintensities were assessed through two visual rating scales. Lacunes were also rated. Subcortical and global brain atrophy were determined through the bicaudate ratio and the lateral ventricle to brain ratio, respectively. APOE genotypes were determined at t0 in all subjects. Cox proportional hazard model was used to evaluate the risk of progression to AD. Results: The imaging class of mixed type was very common in AD, and in non amnestic mild cognitive impaired APOE ɛ4 non carriers. In these subjects, frontal and parieto-occipital regions were most affected by small vessel disease. Conclusion: Our findings suggest that the APOE ɛ3 allele is probably linked to the brain vascular pathology.