Auditory brain-stem, middle- and long-latency evoked potentials in mild cognitive impairment

Abstract

Objective

Mild cognitive impairment (MCI) is a selective episodic memory deficit in the elderly with a high risk of Alzheimer's disease. The amplitudes of a long-latency auditory evoked potential (P50) are larger in MCI compared to age-matched controls. We tested whether increased P50 amplitudes in MCI were accompanied by changes of middle-latency potentials occurring around 50 ms and/or auditory brain-stem potentials.

Methods

Auditory evoked potentials were recorded from age-matched controls (n=16) and MCI (n=17) in a passive listening paradigm at two stimulus presentation rates (2/s, 1/1.5 s). A subset of subjects also received stimuli at a rate of 1/3 s.

Results

Relative to controls, MCI subjects had larger long-latency P50 amplitudes at all stimulus rates. Significant group differences in N100 amplitude were dependent on stimulus rate. Amplitudes of the middle-latency components (Pa, Nb, P1 peaking at approximately 30, 40, and 50 ms, respectively) did not differ between groups, but a slow wave between 30 and 49 ms on which the middle-latency components arose was significantly increased in MCI. ABR Wave V latency and amplitude did not differ significantly between groups.

Conclusions

The increase of long-latency P50 amplitudes in MCI reflects changes of a middle-latency slow wave, but not of transient middle-latency components. There was no evidence of group difference at the brain-stem level.

Significance

Increased slow wave occurring as early as 50 ms may reflect neurophysiological consequences of neuropathology in MCI.

Introduction

Mild cognitive impairment (MCI) describes elderly individuals having a decline in episodic memory function relative to other cognitive abilities (Collie and Maruff, 2000, Morris, 2003, Petersen et al., 1999, Smith et al., 1996). MCI patients are approximately 6-fold more likely to progress to Alzheimer's disease relative to healthy older individuals (Morris et al., 2001, Petersen et al., 1999). Alzheimer's disease has a long preclinical period where neuropathological deposits (i.e. β-amyloid plaques, neurofibrillary tangles) gradually accumulate in the brain without sufficient neuronal damage to cause clinically detectable dementia (Giannakopoulos et al., 2003, Morris and Price, 2001, Ohm et al., 1995). Neuropathological studies report that both the extent of neuronal loss (Kordower et al., 2001) and the regional accumulation of β-amyloid plaques and neurofibrillary tangles (Dekosky et al., 2002, Morris and Price, 2001, Mufson et al., 1999) in MCI are similar to early Alzheimer's disease. Taken together, the greater risk of Alzheimer's disease in MCI and the similarity in neuropathological features to early Alzheimer's disease suggests that MCI can be a transition state between normal aging and Alzheimer's disease.

A previous study in MCI using auditory long-latency cortical potentials in a target detection, or ‘oddball’ task, demonstrated an increased amplitude and delayed latency for a component having a peak latency of ∼50 ms (P50) (Golob et al., 2002). P50 amplitude increases in MCI are not specific to the use of an auditory discrimination task as P50 amplitudes are also increased relative to controls when passively listening to tones (Golob et al., 2001). P50 is thought to reflect neural activity in primary/secondary auditory cortex (Yoshiura et al., 1995, Liegeois-Chauvel et al., 1994, Reite et al., 1988) and the definition of large P50 amplitudes in MCI compared to controls may reflect group differences at auditory sensory cortex.

It is well known that the amplitude of sensory cortical potentials is affected by rate of stimulation (Picton et al., 1974). We examined 3 variables that could influence the amplitudes of auditory long-latency P50 component. First, stimulus rate affects P50 amplitudes. Amplitudes decrease as stimulus rate increases, a process known as a ‘refractory effect’ (Butler, 1973, Davis et al., 1966, Naatanen and Picton, 1987, Nelson and Lassman, 1973, Roth et al., 1976). The amplitude differences between MCI and controls might be due to differences in refractory effects in the two groups. We therefore measured the effects of stimulus rate on P50 amplitudes differences in MCI and controls to define if (a) MCI subjects exhibit an overall increase in auditory P50 amplitudes that is independent of stimulus presentation rate or (b) P50 amplitudes may vary as a function of stimulus rate differently in MCI than controls.

The second variable that could affect long-latency P50 amplitudes involves changes in middle-latency responses with latencies between ∼20 and 60 ms, a time domain that overlaps that of the long-latency P50 component. The middle-latency responses are typically high-pass filtered (>10 Hz) attenuating slow potentials and enhancing 3 transient components, Pa, Nb, and P1, also known as P30, N40, and P50, respectively (Picton et al., 1974).

The third variable that could affect long-latency P50 amplitudes involves an increase of activity in the ascending auditory pathway in MCI. We measured auditory brain-stem responses (ABRs) to identify if there were changes that accounted for the long-latency P50 amplitude increases in MCI.