EEG abnormalities in early and late onset Alzheimer's disease: understanding heterogeneity

Objective To compare differences in severity and type of electroencephalography (EEG) abnormalities between early and late onset Alzheimer's disease (AD) and to assess the influence of APOE genotype on this association, in order to understand the biological differences in AD according to age at onset Method Of 460 probable AD patients and 336 patients with subjective complaints, serving as controls, EEG and APOE genotype were obtained. Subjects were categorised by age into a younger (≤65 years) and an older group (>65 years), based on age at diagnosis. Severity and type of EEG abnormalities were visually assessed. Severity of EEG abnormalities ranged from normal to slightly abnormal to moderately severe. EEG abnormalities were characterised as only focal abnormalities, only diffuse abnormalities or both focal and diffuse abnormalities. Results Logistic regression revealed that younger AD patients more often had EEG abnormalities, which were more severe, with a predominance of both focal and diffuse abnormalities. In controls, we observed the opposite, as older controls more often had EEG abnormalities than younger controls. Furthermore, APOE ε4 negative AD patients had more severe EEG abnormalities than APOE ε4 positive AD patients, while no such effect was observed in controls. There was no interaction between age at onset and APOE ε4 genotype. Conclusion Early onset and APOE ε4 negative AD patients present with more severe EEG abnormalities than late onset and APOE ε4 positive AD patients. These results suggest that in younger patients, AD manifests with more prominent functional brain changes.