Brain event-related potentials: diagnosing early-stage Alzheimer's disease

Abstract

A pattern of components from brain event-related potentials (ERPs) (cognitive non-invasive electrical brain measures) performed well in separating early-stage Alzheimer's disease (AD) subjects from normal-aging control subjects and shows promise for developing a clinical diagnostic for probable AD. A Number-Letter task elicited brain activity related to cognitive processes. In response to the task stimuli, brain activity was recorded as ERPs, whose components were measured by principal components analysis (PCA). The ERP component scores to relevant and irrelevant stimuli were used in discriminant analyses to develop functions that successfully classified individuals as belonging to an early-stage Alzheimer's disease group or a like-aged Control group, with probabilities of an individual belonging to each group. Applying the discriminant function to the developmental half of the data showed 92% of the subjects were correctly classified into either the AD group or the Control group with a sensitivity of 1.00. The two crossvalidation results were good with sensitivities of 0.83 and classification accuracies of 0.75-0.79. P3 and CNV components, as well as other, earlier ERP components, e.g. C145 and the memory "Storage" component, were useful in the discriminant functions.

Figure 1

Event-Related Potentials (ERPs) averaged over 12 Alzheimer’s disease (AD) participants (early stage) and over 12 like-aged control (CON) participants, graphically displaced. ERPs from the central-midline electrode (CZ) to relevant (solid red) and irrelevant (dashed blue) stimuli are superimposed.

Figure 2

Event-Related Potential components derived from Principal Components Analysis across 48 subjects. The top waveform (AV) is the grand average ERP at electrode CZ for all experimental conditions and subjects. The remaining waveforms are the first 8 components from the PCA after Varimax rotation, in order of variance accounted for, from top to bottom. SW = Slow Wave. CNV = Contingent Negative Variation (negative prior to stimulus). P3 = P300, maximum at 415 msec. C250, C145, C540, C325, and C185 are components with maxima at the poststimulus time (msec) given in their labels. Each component is offset here with its baseline shown as a dashed line. In these component waveforms, the metric has been restored by multiplying the loading at each time point by the standard deviation of the data set at the corresponding time point [7]. The amplitudes depicted are for a component score of 1.0.