Olfactory network variability is associated with odor identification and cognitive performance in mild cognitive impairment

BackgroundOdor identification impairment is an early marker of Alzheimer's disease pathology and predicts dementia conversion in mild cognitive impairment (MCI). However, the pathophysiological role of dynamic functional connectivity (dFC) variability within olfactory networks remains unclear.ObjectiveTo characterize seed-based dFC variability across olfactory pathways in MCI with odor identification impairment (MCI-OII) and examine its associations with olfactory and cognitive performance.MethodsNinety-seven patients with MCI were recruited and subdivided into MCI-OII and those without odor identification impairment (MCI-NOII), along with 97 age-matched healthy controls (HC). All participants underwent neuropsychological assessment, olfactory testing, and resting-state functional magnetic resonance imaging. Seed-based dFC variability was computed using a sliding window approach. Correlation and exploratory mediation analyses examined associations among abnormal dFC, odor identification, and cognition.ResultsCompared to MCI-NOII and HC, MCI-OII exhibited increased dFC variability between the left piriform cortex/right insula and right caudate nucleus, and between the left insula and left middle frontal gyrus. For the connection between the left insula and left cerebellar lobule VI, dFC variability showed a graded pattern from MCI-OII to HC to MCI-NOII. Increased caudate-centered dFC variability was associated with poorer odor identification, memory, and executive performance. Furthermore, exploratory mediation analyses suggested indirect associations involving odor identification, caudate-centered dFC variability, and memory or executive function.ConclusionsMCI-OII is characterized by increased olfactory-network dFC variability, particularly in caudate-centered pathways. These findings suggest that dFC variability may serve as a candidate network-level marker of concurrent olfactory impairment and cognitive dysfunction in MCI.