Olfactory identification impairment in cerebral small-vessel disease indicates cognitive network disconnection and predicts accelerated cognitive decline.

Abstract

Background: Olfactory identification impairment is a well-established early screening index for cognitive decline in neurodegenerative disorders. However, whether this simple sensory test can similarly detect or predict cognitive deficits in cerebral small vessel disease (CSVD)-a leading cause of vascular cognitive impairment-remains unclear.

Methods: All participants-including 193 CSVD patients and 164 normal controls (NC)-completed the University of Pennsylvania Smell Identification Test (UPSIT) and a comprehensive neuropsychological battery. Multimodal MRI analyses were conducted to identify structural and functional abnormalities associated with UPSIT performance. A cognitive follow-up assessment was performed 24 months post-baseline, and the rate of cognitive decline was annualized.

Results: Compared to NC, CSVD patients exhibited significantly lower UPSIT scores (p < 0.001). UPSIT performance correlated strongly with cognition. Local structural and functional abnormalities in primary and secondary olfactory cortices did not reliably predict UPSIT performance in CSVD patients. In contrast, dorsolateral prefrontal cortex functional connectivity strength was significantly associated with odor-identification performance. Mediation models further demonstrated that greater white matter lesion burden indirectly impaired olfactory identification via disrupted inter-network connectivity between the salience network (SN) and posterior default mode network (pDMN). CSVD patients with baseline UPSIT < 20 exhibited a steeper annual MMSE decline than those with UPSIT ≥ 20 (1.0 vs. 0.5 points per year; p < 0.001).

Conclusion: Olfactory identification impairment in patients with CSVD reflects disruption of higher-order cognitive networks, and a baseline UPSIT score below 20 predicts accelerated cognitive decline.