Altered temporal dynamics of intrinsic brain activity in mild cognitive impairment with olfactory dysfunction

Background Odor identification (OI) impairment in mild cognitive impairment (MCI) elevates the risk for Alzheimer's disease (AD). The present study was designed to clarify the underlying neural mechanisms by investigating brain network aberrations in MCI patients with OI impairment using dynamic resting-state functional magnetic resonance imaging (rs-fMRI). Objective This study aimed to delineate the profile of dynamic intrinsic brain activity in MCI patients with and without OI impairment. It further aimed to establish the clinical relevance of these dynamic neural signatures by linking them to cognitive and olfactory function. Methods In 194 participants (97 MCI and 97 healthy controls [HC]), we analyzed dynamic metrics including dynamic fractional Amplitude of Low-Frequency Fluctuations (dfALFF), dynamic Amplitude of Low-Frequency Fluctuations (dALFF), dynamic Degree Centrality (dDC), and dynamic Regional Homogeneity (dReHo), and their correlation with cognitive performance and OI. Results The MCI with OI impairment (MCI-OII) group (n = 22) performed worse across all cognitive domains than both HC and the MCI without OI impairment (MCI-NOII) group (n = 75, p < 0.001). These patients exhibited elevated dALFF, dfALFF, dDC, and dReHo variability in regions including the fusiform gyrus, insula, precuneus, and cingulate cortex ( p < 0.001). These dynamic metrics correlated with olfactory and cognitive scores ( p < 0.05). Additionally, dReHo in the right precuneus partially mediated the relationship between olfactory function and delayed recall memory. Conclusions This study demonstrates that MCI patients with OI impairment exhibit widespread disruptions in dynamic brain activity. These alterations correlate with clinical deficits, and precuneus dReHo may partially link olfactory and cognitive decline in MCI.