Associations of event-related brain potentials and Alzheimer's disease severity: A longitudinal study.

So far, no cost-efficient, widely-used biomarkers have been established to facilitate the objectivization of Alzheimer's disease (AD) diagnosis and monitoring. Research suggests that event-related potentials (ERPs) reflect neurodegenerative processes in AD and might qualify as neurophysiological AD markers. First, to examine which ERP component correlates the most with AD severity, as measured by the Mini-Mental State Examination (MMSE). Then, to analyze the temporal change of this component as AD progresses. Sixty-three subjects (31 with possible, 32 with probable AD diagnosis) were recruited as part of the cohort study Prospective Dementia Registry Austria (PRODEM). For a maximum of 18 months patients revisited every 6 months for follow-up assessments. ERPs were elicited using an auditory oddball paradigm. P300 and N200 latency was determined with regard to target as well as difference wave ERPs, whereas P50 amplitude was measured from standard stimuli waveforms. P300 latency exhibited the strongest association with AD severity (e.g., r = –0.512, p < 0.01 at Pz for target stimuli in probable AD subjects). Further, there were significant Pearson correlations for N200 latency (e.g., r = –0.407, p = 0.026 at Cz for difference waves in probable AD subjects). P50 amplitude, as measured by different detection methods and at various scalp sites, did not significantly correlate with disease severity – neither in probable AD, possible AD, nor in both subgroups of patients combined. ERP markers for the group of possible AD patients did not show any significant correlations with MMSE scores. Post-hoc pairwise comparisons between baseline and 18-months follow-up assessment revealed significant P300 latency differences (e.g., p < 0.001 at Cz for difference waves in probable AD subjects). However, there were no significant correlations between the change rates of P300 latency and MMSE score. P300 and N200 latency significantly correlated with disease severity in probable AD, whereas P50 amplitude did not. P300 latency, which showed the highest correlation coefficients with MMSE, significantly increased over the course of the 18 months study period in probable AD patients. The magnitude of the observed prolongation is in line with other longitudinal AD studies and substantially higher than in normal ageing, as reported in previous trials (no healthy controls were included in our study). • Highest number of AD subjects (N = 63) for correlation analysis between ERP markers and AD severity in a prospective study. • ERP study with the highest number of AD patients longitudinally followed (N = 29), considering study periods above 6 months. • First study to investigate correlation coefficients between P50 amplitude and AD severity. • P300 and N200 latency significantly correlate with disease severity in probable AD patients, while P50 amplitude does not. • P300 latency significantly increases over 18 months in probable AD subjects. [ABSTRACT FROM AUTHOR]