Altered mismatch response precedes gray matter atrophy in subjective cognitive decline

The cross-sectional identification of subjective cognitive decline (SCD) in cognitively normal adults is particularly important for the early effective prevention or intervention of the future development of mild cognitive impairments (MCI) or Alzheimer's disease (AD). A pre-attentive neurophysiological signal that reflects the brain's ability to detect the changes of the environment is called mismatch negativity (MMN) or its magnetic counterpart (MMNm). It has been shown that patients with MCI or AD demonstrate reduced MMN/MMNm responses, while the exact profile of MMN/MMNm in SCD is substantially unknown. We applied magnetoencephalographic recordings to interrogate MMNm activities in healthy controls (HC, n = 29) and individuals with SCD (n = 26). Furthermore, we analyzed gray matter (GM) volumes in the MMNm-related regions through voxel-based morphometry and performed apolipoprotein E4 (APOE4) genotyping for all the participants. Our results showed that there were no significant differences in GM volume and proportions of APOE4 carriers between HC and SCD groups. However, individuals with SCD exhibited weakened z-corrected MMNm responses in the left inferior parietal lobule and right inferior frontal gyrus (IFG) as compared to HC. Based on the regions showing significant between-group differences, z-corrected MMNm amplitudes of the right IFG significantly correlated with the memory performance among the SCD participants. Our data suggest that neurophysiological changes of the brain, as indexed by MMNm, precede structural atrophy in the individuals with SCD compared to those without SCD.