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Description
Possession of ApoE4 is a primary genetic risk factor for late onset Alzheimer's disease (AD). Homozygote carriers (E4/E4) have a higher risk and a lower mean age of onset than heterozygote carriers (E4/E3 or E4/E2), though additional genetic as well as environmental factors have impacted treatment and diagnosis. It is necessary to develop measures that are more sensitive to the earliest presence of AD pathology so that individuals at risk might be studied across larger periods of time. The event related potential (ERP) technique, which involves isolating neural responses to stimuli from electroencephalograph recordings, has shown healthy adults generate large negative amplitudes following semantically mismatched stimulus pairs. Individuals experiencing early AD pathogenesis generate a similar but weakened response. This inhibited "priming effect" implies deficient semantic organization may precede clinical diagnosis. Behavioral measures including odor identification and memory confirm the semantic deficit, but earlier than comparable verbal-only measures. This study measured subjects' neural responses following matched or mismatched odor-image pairings through electrophysiological changes in 24 older (ages 65+) (M=69.4, SD= 3.86) ApoE4 male (n=6) and female (n=6) carriers as well as male (n=6) and female (n=6) non-carriers. The subjects were matched for age, education level, and prescreened for olfactory and verbal performance. A monitor displayed a randomized sequence of 28 images; each appeared for 2000ms, followed by one of 14 odors. Every odor was presented once matched and mismatched across the 28 images. Odors were delivered through a continuous air olfactometer for 200ms, with a 30s inter stimulus interval (ISI). Subjects were asked for feedback regarding the congruency of the pairings after one sequence. Hedonic judgments were also recorded at this time through the general labeled magnitude scale (GLMS). The average amplitude occurring within 600-1300ms post odor at 52 electrodes, divided into 8 regions, was subjected to a repeated measures ANOVA. Intra-class correlations compared amplitude and waveshape similarities between subjects. Mismatch trials were more negative than match trials during the 600-1300 ms post odor interval, distributed primarily at posterior electrode sites. The average amplitude on mismatch trials was weakest at right dorsal sites while strongest at right ventral sites in E4 carriers, consistent with a right hemispheric compensatory mechanism. Intra-class correlations indicated that ERPs recorded from male E4 carriers were least correlated with ERPs from females at posterior electrode sites on mismatch trials. Both male and female E4 carriers had strong correlations at right frontal sites on mismatch trials. The OERP data support the hypothesis that metabolic disturbances occur in E4 carriers within brain regions related to AD pathological load. They suggest ApoE status influences processing mechanisms evoked by stimulus congruency, and gender differences contribute.
