The mismatch negativity as an index of cognitive decline for the early detection of Alzheimer's disease (original) (raw)

Evidence suggests that Alzheimer's disease (AD) is part of a continuum, characterized by long preclinical phases before the onset of clinical symptoms. In several cases, this continuum starts with a syndrome, defined as mild cognitive impairment (MCI), in which daily activities are preserved despite the presence of cognitive decline. The possibility of having a reliable and sensitive neurophysiological marker that can be used for early detection of AD is extremely valuable because of the incidence of this type of dementia. In this study, we aimed to investigate the reliability of auditory mismatch negativity (aMMN) as a marker of cognitive decline from normal ageing progressing from MCI to AD. We compared aMMN elicited in the frontal and temporal locations by duration deviant sounds in short (400 ms) and long (4000 ms) inter-trial intervals (ITI) in three groups. We found that at a short ITI, MCI showed only the temporal component of aMMN and AD the frontal component compared to healthy elderly who presented both. At a longer ITI, aMMN was elicited only in normal ageing subjects at the temporal locations. Our study provides empirical evidence for the possibility to adopt aMMN as an index for assessing cognitive decline in pathological ageing. Auditory mismatch negativity (aMMN) is an event-related potential (ERP) component occurring approximately 100–200 ms after a detectable change (deviant stimulus) in a repetitive and predictive sequence of sounds (standard stimuli) 1. aMMN appears maximal at the central-frontal electrodes with an inversion of polarity at the mas-toids, which is consistent with neural generators located in the temporo-frontal network 2,3. aMMN recorded from temporal electrodes is associated with the encoding of the physical features of the stimuli and the maintenance of the sensory memory trace; while aMMN recorded from frontal electrodes has been linked to involuntary capture of attention triggered by the occurrence of the deviant tone 4–7. The aMMN elicitation arises from an automatic comparison between the deviant sensory input and the sensory-memory trace representing the preceding stimuli 8. MMN is also considered an index of the efficiency of the auditory system to extract regularities in a sequence of sounds and to detect abnormalities based on predictions, according to the predictive coding theoretical framework 9. aMMN is commonly used in clinical settings for indexing (i) auditory discrimination accuracy, (ii) sen-sory–memory duration 5 , and (iii) general cognitive decline 10. Recording aMMN at different inter-stimulus intervals (ISI) (typically, short ISI are less than 500 ms, whereas long ISI are more than 2 sec) is an experimental modulation used to investigate the accuracy of sensory memory encoding (short ISI) and the integrity of maintenance of sensory information (long ISI). By gradually extending ISI, the aMMN eventually vanishes, which enables one to assess sensory-memory duration. It has been found that in healthy participants, acoustic memory decays after a few seconds because aMMN is no longer elicited if the ISI is longer than 10 seconds 11,12. Because aMMN is elicited in the absence of direct control of voluntary attention, it is considered an automatic orienting towards salient events, and for this reason, it is particularly useful for the investigation of clinical populations in which prolonged sustained attention tasks are difficult to perform. Interestingly, Näätänen and colleagues have recently proposed MMN as an index of the cognitive decline occurring in a large number of