Cognitive event-related potentials: longitudinal changes in mild cognitive impairment.

OBJECTIVE: To measure changes over time in the latency and amplitude of the major waves of auditory event-related potentials (AERP) and their correlation with the memory status of patients with mild cognitive impairment (MCI). METHODS: AERPs were recorded in 22 MCI patients (mean±SD age=67.4±7.8, median (interquartile range-IQR) MMSE score=28 (27-29) in three consecutive exams and in 30 age-matched controls at baseline. During this time period, 3 patients converted to Alzheimer disease (AD). Latencies and amplitudes of N200, P300 and Slow Wave and the N200-P300 peak-to-peak amplitudes and latencies were determined, and correlation coefficients (CC) between them and MMSE scores were calculated. RESULTS: A significant increase in the P300 latency and a decrease in the N200 amplitude were observed between the exams. Only N200 latency correlated with baseline MMSE scores, whereas P300 and Slow Wave latencies correlated with age. CONCLUSIONS: N200 amplitude is more sensitive in identifying differences over time at the early stages of the disease, whereas P300 latency at later stages. SIGNIFICANCE: A new N2-P3 inter-peak index that incorporates changes in N200 and P300 latencies and amplitudes into a single parameter is introduced in order to adequately describe the gradual progress of MCI and its transition to AD.

Combination of P300 and CSF ß-amyloid(1-42) assays may provide a potential tool in the early diagnosis of Alzheimer's disease.

BACKGROUND/AIMS: The aim of this study was to investigate the diagnostic role of CSF beta amyloid(1-42) levels and auditory event-related potentials (AERPs) in the progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD). METHODS: In fifty three MCI patients a lumbar puncture was performed and beta amyloid(1-42) levels were determined. Twenty patients were re-examined after 11 months. During this period five of them progressed to AD. Neuropsychological and ERP examinations were performed in all patients at both exams. RESULTS: Compared to MCI stable patients, AD-converters showed significantly lower beta-amyloid(1-42) values both for group 1 (Mann Whitney test, Z=-2.952, p=0.003, effect size r=-0.41) and group 2 (Z=-2.458, p=0.011; effect size r=-0.55). On the other hand, the patients of group 1 who converted to AD had prolonged latencies and lower amplitudes of the P300 wave compared to those of the MCI-stable patients, although the differences were not significant. CONCLUSIONS: Compared to the separate use of CSF beta-amyloid(1-42) and AERPs, higher values of sensitivity and specificity were achieved by the combined use of beta-amyloid(1-42) levels and P300 latencies (80% and 98%) or amplitudes (100% and 89%) in the discrimination between AD converters and MCI stable patients. Therefore the combination of an electrophysiological and a biological marker is potentially of high diagnostic value for the early diagnosis of AD converters.

Prediction of conversion from mild cognitive impairment to Alzheimer's disease by CSF cytochrome c levels and N200 latency.

The aim of the present study was to investigate the role of CSF cytochrome c levels and auditory event-related potentials (AERPs) on the progress of mild cognitive impairment (MCI) to Alzheimer's disease (AD). Fifty one patients diagnosed with MCI and fourteen healthy individuals underwent lumbar puncture at baseline and their CSF cytochrome c levels were determined. A follow-up examination of cytochrome c levels took place in 20 patients after 11 months and in this period five of the patients progressed to AD. ERP examinations were also performed in all patients both at baseline and follow-up. MCI patients had significantly higher cytochrome c levels compared to healthy controls (Mann-Whitney test, Z=-2.110, p=0.018). Compared to MCI patients who remained stable, the AD-converters, had a higher increase over time in cytochrome c levels (Mann-Whitney test, p=0.002; effect size r=0.63) and significantly prolonged N200 latency (Mann-Whitney test, p<0.001; effect size r=0.50). Amongst investigated ERP variables, only N200 amplitude was significantly correlated with CSF cytochrome c levels (rs=0.310, p=0.03). Both parameters were proved capable of discriminating AD converters from those MCI patients who remained stable, with sensitivity and specificity >75%. Our results suggest that conversion from MCI to AD is associated with a marked elevated N200 latency at baseline and a high increase in cytochrome c levels during a relatively short period of time, and that both parameters could be possibly considered as candidate markers for the discrimination between MCI patients who convert to AD and those who remain stable.