Event-related potential as biomarkers for preclinical Alzheimer's disease

Abstract

Event Related Potentials (ERPs) are useful cognitive biomarker for the diagnosis of dementia, tracking disease progression, and evaluating the pro-cognitive effect of therapeutics. Nowadays there is a real need for improved electrophysiological markers to asses' neurplastic changes for the differentiation of Preclinical Alzheimer's Disease (AD) from normal aging. The aim of this study is to asses the value of ERP as potential marker of cognitive decline in frail elderly subjects at risk to develop AD. 100 subjects were eligible for the study. ERPs were obtained in an auditory oddball paradigm with 200 tones: the frequent stimulus (tones at 1000Hz) and around 20% of rare or target stimulus (tones at 1500Hz). Electrical brain activities were recorded from four scalp derivations (frontal: Fz, central: Cz, parietal: Pz, occipital: Oz) according to the international 10/20 standards. Subject was instructed to mentally count the number of rare stimulus. ERP and neuropsychological battery performed at baseline and follow up. 3 subgroups of subjects were identified according to their ERP risk profile (high, mild, lower). Latency of P3b in parietal region strongly discriminated between high ERP risk group and lower ERP risk group (p< 0.0001). Amplitude of P3b in frontal region discriminated high risk group from lower risk group (p<0.01). Pattern of frontal activity in elderly subjects with ERP high risk profile may reflect neural compensation process requires to recruit more attention resources to perform the cognitive task. Frail elderly subjects with high ERP risk profile showed more decline in executive task (Verbal Fluency) than other groups (p< 0.05) and might reflect a faster cognitive decline especially as executive tasks requires high level of attentional resources. Early modifications of ERP components appears early in frail elderly subjects in the absence of global cognitive deficit.