Structural correlates of early and late onset Alzheimer's disease: voxel based morphometric study

Objective: To examine the brain structural correlates of age at onset in patients with Alzheimer's disease. Methods: We studied nine patients with early onset ( age less than or equal to65 years), nine with late onset (age >65) Alzheimer's disease (EOAD and LOAD, respectively) of mild-moderate severity, and 26 controls who were stratified into younger (YC, age less than or equal to65, n = 9) and older (OC, age >65, n = 17) subjects. The patients were closely matched for clinical severity: 3/2/3/1 patients had clinical dementia rating of 0.5/1/2/3, respectively, in both the groups. High resolution magnetic resonance images of the brain of the EOAD and YC groups and the LOAD and OC groups were compared on a voxel by voxel basis with statistical parametric mapping to detect areas specifically atrophic. Results: The patients with EOAD showed greater neocortical atrophy at the temporoparietal junction while the patients with LOAD showed greater hippocampal atrophy. The results could not be accounted for by the apolipoprotein E genotype. Conclusions: Since genetic factors are believed to play a relevant pathogenetic role in EOAD and environmental factors in LOAD, genetic and environmental factors may differentially predispose the neocortical and limbic areas to the development of Alzheimer's neuropathology.