Can a failure in the error monitoring system explain unawareness of memory deficits in Alzheimer’s disease?

Abstract Unawareness of memory deficits is an early manifestation in patients with Alzheimer’s disease (AD). This intriguing behavior constitutes a form of anosognosia and has neural mechanisms that remain largely unknown. Here, we hypothesized that it may result from a failure in the error-monitoring system, which would prevent AD patients from being aware of their own memory impairment. To investigate, we measured event-related potentials (ERPs) evoked by erroneous responses during a memory task in two groups of amyloid positive individuals who had only subjective memory complaints at study entry: those who progressed to AD within the five-year study period (PROG group); and those who remained cognitively normal throughout the study (CTRL group). A significant reduction in the amplitude of the positivity error (Pe), an ERP related to error awareness, was observed in the PROG group at the time of AD diagnosis, in intra-group analysis, as well as when compared with the CTRL group, in inter-group analysis. To our knowledge, the results of this study reveal for the first time the emergence of a failure in the error-monitoring system from the very early stages of AD, strongly suggesting that a neurophysiological impairment in this system may be critical for the lack of awareness of memory deficits that often delays AD diagnosis. Hence, this study further suggests that a reduced Pe amplitude may constitute a potential neural biomarker of prodromal AD.