Could Early Identification of Changes in Olfactory Function Be an Indicator of Preclinical Neurodegenerative Disease? A Systematic Review

Introduction Alzheimer's disease (AD) is a debilitating neurodegenerative disease that currently affects 850,000 individuals in the UK with estimates continuing to rise. Diagnosis is only available in the presence of significant neuronal pathology and apparent cognitive decline, meaning that treatment avenues are often limited and carry little to no effect on prognosis. Olfactory function has been shown to have a direct correlation with cognitive function and therefore may serve as a potential diagnostic tool for the detection of preclinical disease. The objective was to examine the current literature to establish the accuracy of olfactory function testing in determining current and future cognitive function. Methods A systematic review was performed via Medline on 17 October 2019 using the search terms and Boolean operators 'Dementia OR Alzheimer's AND olfaction AND cognitive impairment' yielding 111 results. These were then screened using inclusion/exclusion criteria alongside a PICO strategy. After titles, abstracts and full text were screened, nine articles were included in the review and critically appraised using the AXIS and CASP tools. Results Significant correlations are demonstrated between olfactory impairment (OI) and cognitive decline. However, there were limitations of many of the studies in that confounders such as head trauma, upper respiratory infection (URTI) and smoking history were not considered. The majority of the studies also used an olfactory screening tool that was not designed for the population being examined. Conclusion Despite improvements in olfactory testing needing to be implemented, OI is clearly impaired in neurodegenerative disease across a multitude of ages and cultures, offering an early marker of future cognitive decline. As a result of the heterogenous nature of the included studies, there is a further need for future research to ensure the sensitivity, validity and reliability of implementing olfactory testing as an early marker of future cognitive decline.