[Alterations in olfactory and spatial navigation abilities and their neural mechanisms in subjective cognitive...

Objective: To investigate the characteristics and neural mechanisms of altered olfactory and spatial navigation abilities in individuals with subjective cognitive decline (SCD). Methods: A total of 44 cognitively normal participants and 69 participants meeting diagnostic criteria for SCD were recruited from Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from September 2023 to October 2025. All participants underwent neuropsychological assessments, olfactory testing, spatial navigation testing, 3.0 T resting-state functional MRI (rs-fMRI), task-based functional MRI (task-fMRI), and high-resolution T1-weighted imaging. Independent samples t-tests and Mann-Whitney U tests were used to compare olfactory and spatial navigation behavioral differences between the two groups. Left and right anterior lateral entorhinal cortex (alEC), posterior medial entorhinal cortex (pmEC), and primary olfactory cortex (POC) were selected as seeds to analyze functional connectivity (FC) under resting state and during odor stimulation, with multiple comparisons corrected using false discovery rate (FDR). Partial correlation analysis was performed to explore the relationship between olfactory and spatial navigation and FC metrics in the SCD group, controlled age, gender and years of education. Results: No significant differences were found between the two groups regarding age, gender and years of education. Compared with the NC group, SCD participants showed reduced olfactory memory (old) (Z=-3.05, P=0.005), lower composite olfactory memory Z-score (t=3.53, P=0.001), and lower overall olfactory Z-score (t=2.48, P=0.014). They also exhibited increased average error distances in allo-egocentric navigation (AEN) (Z=-9.17, P=0.001), egocentric navigation (EN) (Z=-8.84, P=0.003), and allocentric navigation (AN) (Z=-8.09, P=0.024), along with a decreased composite spatial navigation Z-score (t=3.84, P<0.001). rs-fMRI results revealed that, SCD participants showed significantly reduced resting-state FC within EC and POC related pathways, but enhanced FC with frontal, cingulate, and parietal regions during odor stimulation (all q<0.05, FDR-corrected). Partial correlation analysis indicated that in the SCD group, the FC between left alEC and left angular gyrus (ANG) positively correlated with EN average error distance (r=0.26, P=0.033), while the FC between right POC and right posterior cingulate cortex(PCC) positively correlated with AEN average error distance (r=0.29, P=0.028). Conclusion: SCD individuals already exhibit deficits in olfactory memory and spatial navigation, suggesting possible coexistence of impaired baseline network connectivity and compensatory network activation during tasks, or inefficient and abnormal recruitment due to diminished network integration efficiency. Abnormal functional connectivity between alEC and ANG, and between POC and PCC, is associated with spatial navigation performance and may represent key neural substrates underlying olfactory and spatial navigation changes in SCD.