Biomarker and neuropsychological correlates of the N400 event-related potential in Alzheimer's disease

Objective: The current study sought to characterize the relationship of the N400 (N4) effect event-related potential to Alzheimer's disease (AD) biomarkers and broader cognition in older adults on the late-life cognitive continuum.

Method: Participants who were cognitively intact (n = 43), or had amnestic mild cognitive impairment (MCI; n = 19), or mild AD (n = 12), completed a word-pair judgement task during concurrent EEG recording to elicit the N400. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and biomarker data (PET-imaged beta-amyloid (aβ) deposition, apolipoprotein-E ε4 (APOE4) allele status, hippocampal volumes) were collected as part of a larger study.

Results: The AD group had slower response times and poorer accuracy on the word-pair judgement task than the intact group. The N4 effect was smaller and occurred later in AD relative to intact participants. MCI participants' values were intermediate. N4 effect amplitudes were not associated with RBANS scores but were positively associated with aβ deposition. Conversely, poorer performance across most RBANS Indexes and the Total score was associated with longer N4 latencies. There was also a negative association between hippocampal volumes and the N4 latency and a positive association between aβ deposition and latency. Finally, the latency of the N4 independently predicted variance in RBANS Total scores, above and beyond aβ deposition, hippocampal volumes, and APOE4 allele status.

Conclusions: These findings support the relevance of the N4 effect in individuals along the late-life cognitive continuum, and motivate future studies into its potential as a longitudinal predictor in AD.