P2-176: Are cortical sources of auditory oddball event-related potentials an early diagnostic marker of Alzheimer's disease?

Mild cognitive impairment (MCI) subjects were previously characterized by abnormal auditory oddball event-related potentials (AO-ERPs) but it is unclear the specificity of this result with reference to Alzheimer's disease (AD). To address this issue, IMI PharmaCog project (Grant Agreement n°115009, www.pharmacog.org) evaluated whether cortical sources of AO-ERPs are related to cerebrospinal fluid β amyloid (CSF Aβ) level in amnesic MCI (aMCI) subjects. The research data (including human biological samples) were sourced ethically and their research use was in accord with the terms of the international ethical standards. Artifact free AO-ERPs (19 electrodes) were recorded in 104 aMCI subjects in the framework of WP5 PharmaCog project. Individual data sets were broken down into those with high CSF Aβ level (61 Aβ negative, CSF Aβ > 550 pg/ml) and those with low CSF Aβ level (43 Aβ negative, CSF Aβ < 550 pg/ml). Cortical sources of late positive frontal (P3a; novelty of rare targets; Brodmann areas) and posterior (P3b; attention and reaction to rare targets) were estimated by LORETA package. Compared to the Aβ-negative aMCI group, the Aβ-positive aMCI group showed the following abnormalities of the ERP markers possibly related to brain amyloidosis in a prodromal form of the typical amnesic presentation of AD: (i) higher amplitude of prefrontal sources (Brodmann area BA 10, BA 11) at P3a peak as possible neural correlate of an abnormal alerted perception of novelty during the repetition of the rare (oddball) stimuli along the experiment; and (ii) lower amplitude of P3b parietal (BA 5, BA 7) and posterior cingulate (BA 23, BA31) sources as possible neural correlate of a poor attention and short-term memory of the rare (oddball) stimuli (see Figure 1). The present results suggest that specific EEG markers may enrich the discrimination of aMCI subjects in an early stage of prodromal AD for early diagnosis and preventive treatment with Achetylcholinesterase inhibitors or future disease-modifying molecules.