N200 Latency and CSF Cytochrome C Levels as Biomarkers for Early Detection of Progression to Alzheimer's Disease in Mild Cognitive Impairment Patients

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The role of CSF cytochrome c levels and auditory event-related potentials (AERPs) in the progress of mild cognitive impairment (MCI) to Alzheimer's disease (AD) is investigated. A study sample that consisted of fifty one MCI patients and fourteen healthy individuals that underwent lumbar puncture at baseline was used and their CSF cytochrome c levels were determined. CSF cytochrome c levels were reexamined in 20 patients after a time period of 11 months. During this period five patients progressed to AD. All patients underwent AERP examinations both at baseline and follow-up. MCI patients were found to have significantly higher cytochrome c levels compared to healthy controls (Mann-Whitney test, Z=-2.110, p=0.018). ADconverters, 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) compared to MCI stable patients. Amongst the ERP wave characteristics that were studied, only N200 amplitude was significantly correlated with CSF cytochrome c levels (rs=0.310, p=0.03). Both parameters could discriminate AD converters from MCI stable patients, with sensitivity and specificity >75%. When both N200 latency and cytochrome c increase were applied, the prediction of the MCI patients who converted to AD was 100%. Our results suggest that MCI to AD conversion 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 AD converters and MCI stable patients.