Using olfactory task functional magnetic resonance imaging (fMRI) to investigate the difference in brain olfactory activation between patients with subjective cognitive decline and normal elderly subjects, and to explore the objective image markers for early identification and evaluation the progression from SCD to Alzheimer′s disease (AD).

Twenty patients with SCD (SCD group) and twenty matched normal elderly subjects (NC group) were recruited from the community from March 2017 to December 2018. A full neuropsychological scale tests battery, olfactory behavioral tests and olfactory task-fMRI were performed. The differences between olfactory behavior, neuropsychological scales, and task-fMRI brain activation between the two groups were tested. Further, brain regions, which had significantly different activations under task-fMRI, were used as seeds for resting state functional connectivity (FC) analysis. Finally, the correlations between brain activation and olfactory behavior along with clinical neuropsychological scale tests were examined.

The results of this study showed SCD had a significant decrease in olfactory behavior (olfactory recognition ability) compared with NC (t=-3.042, P<0.01), and there was no statistically significant difference in olfactory threshold. Significant declines were also observed in the SCD self-rating scale (t=6.973, P<0.01), the immediate (t=-4.623, P<0.01) and delayed (t=-2.746, P<0.01) testing of Philadelphia word learning, while the remaining neuropsychological scales were normal. In the olfactory task-fMRI, activation of bilateral primary olfactory cortical regions was significantly reduced in SCD patients, including bilateral entorhinal cortex, amygdala, piriform cortex, anterior olfactory nucleus, and head of the hippocampus. The resting state functional connectivity with the primary olfactory cortex (POC) as the seed showed that the functional connectivity between the olfactory system and the default model network (DMN) of SCD patients was significantly weakened (AlphaSim correction with voxel level P<0.01 and cluster level P<0.05). The Beta value of the left POC was significantly positively correlated with the olfactory threshold and Montreal cognitive assessment (MoCA) (r=0.329, P=0.041; r=0.317, P=0.046). Partial correlation analysis indicated that there was a significantly positive correlation between the FC of the left POC with the right/left inferior frontal gyrus, the left frontal middle gyrus and the right inferior parietal, and the score of immediate Philadelphia word learning test(r=0.411, P=0.008; r=0.400, P=0.011; r=0.329, P=0.003; r=0.454, P=0.003). The FC between the left POC and the right inferior temporal gyrus was negatively correlated with the score of trail making test (TMT) B, and the FC between the left POC and the right inferior was negatively correlated with score of language fluency test (r=-0.317, P=0.047; r=-0.333, P=0.036). The FC between the right POC and the left inferior parietal was positively correlated with the score of immediate Philadelphia word learning (r=0.315, P=0.048), while the FC between right POC and left middle occipital gyrus was negatively corrected with Language Fluency Test (r=-0.403, P=0.01).

Olfactory function has been impaired in SCD patients with normal standard cognition and phychiatric rating scales, and the changes in the activation of the primary olfactory cortex, such as the entorhinal cortex, may be an early neural circuit damage biomarker for objective evaluation of SCD.

Subjective cognitive decline; Olfactory perception; Magnetic resonance imaging