Olfactory Dysfunction Is Already Present With Subjective Cognitive Decline And Deepens With Disease Severity In The Alzheimer'S Disease Spectrum

Background: Odor identification dysfunction occurs early in Alzheimer's disease (AD) and is considered a preclinical symptom along with subjective cognitive decline (SCD). Nevertheless, whether subjects with SCD are co-symptomatic with odor identification dysfunction remains unclear.Objective: To compare the degree of odor identification dysfunction and assess the relation between odor identification and cognitive performance in the AD spectrum (including SCD, mild cognitive impairment (MCI), and AD).Methods: Patients (84 SCD, 129 MCI, 52 AD) and 35 controls underwent the Sniffin' Sticks Screen 16 test and comprehensive neuropsychological examination.Results: Odor identification scores were progressively lower moving from normal older adult to SCD, MCI, and AD. Additionally, the proportion of odor identification dysfunction were increasingly higher in the AD spectrum (p for trend <0.001), but no significant difference was found in the proportion of subjective olfactory dysfunction. No significant correlation was found between odor identification and cognition in the normal older adults and SCD subjects, but odor identification correlated with global cognition in the MCI (r= 0.199, p = 0.033) and in the AD (r= 0.300, p = 0.036) patients. Multiple linear regression showed that odor identification dysfunction was most strongly associated with memory among different cognitive subdomains and was most strongly associated with immediate verbal recall among different memory subdomains.Conclusion: Odor identification dysfunction is already present with SCD and deepens with disease severity in the AD spectrum, and it may contribute to predicting cognitive decline and identifying SCD subjects who are at risk of developing AD.