Olfactory function in mild cognitive impairment and Alzheimer's disease: A meta‐analysis

Abstract

Objective Olfactory function is altered in mild cognitive impairment (MCI) and Alzheimer's disease (AD); therefore, it may serve as a useful tool for the early detection of MCI before its advancement to AD. The aim of this meta‐analysis was to investigate olfactory deficits in patients with MCI and AD. Study Design Literature search. Methods A search was conducted of the electronic databases PubMed, Embase, and Web of Science from their inception until 2017. We included original articles with adequate data on the identification, threshold, and/or discrimination of olfactory function in MCI or AD. The standard mean difference and 95% confidence interval (CI) were calculated. The studies were weighted according to inverse variance estimates. The effect sizes were categorized as small [Cohen's d = 0.2], medium (d = 0.5), or large (d ≥ 0.8) based on these methods. Subgroup analyses were performed based on mean age and sex differences between the groups. Results Twelve articles (reporting 21 effects) examining 563 patients with MCI and 788 patients with AD, were included in the meta‐analysis. Compared to MCI, AD had moderate to large heterogeneous effects on olfactory function (Cohen's d = 0.64, 95% CI: 0.50, 0.78). Olfactory identification tests demonstrated larger effects (d = 0.71, 95% CI: 0.51, 0.91) than did tests of other olfactory domains. Conclusions Meta‐analysis results revealed that olfactory identification was more profoundly impaired in patients with AD than in those with MCI. These findings suggest that a simple test of odor identification is valuable in differentiating individuals at a risk of AD. Level of Evidence NA Laryngoscope, 129:362–369, 2019

Mechanisms Linking Olfactory Impairment and Risk of Mortality

“…It is known that approximately 70% of MCI patients will ultimately convert to AD (Gauthier et al, 2006). Yet, recent data converge toward the idea that olfactory-impaired MCI patients are more prone to develop AD than those without OI (Conti et al, 2013;Devanand, 2016;Adams et al, 2018;Jung et al, 2019). Overall, these findings make OI a potential early predictor for AD development.…”

Predictive value of olfactory impairment for cognitive decline among cognitively normal adults

“…Although the literature is well established on the cross‐sectional association between OI and cognitive impairment, there has not been a systematic review examining the predictive value of olfactory impairment for future cognitive decline among cognitively normal adults. A systematic review conducted in 2012 including cross‐sectional and longitudinal studies supports the association between decreased olfaction and Alzheimer's disease.…”

“…The identification of cognitively normal adults who are at risk for MCI may facilitate additional research by allowing for risk stratification prior to the onset of clinically detectable cognitive decline. 15 Although the literature is well established on the crosssectional association between OI and cognitive impairment, 16 there has not been a systematic review examining the predictive value of olfactory impairment for future cognitive decline among cognitively normal adults. A systematic review conducted in 2012 including cross-sectional and longitudinal studies supports the association between decreased olfaction and Alzheimer's disease.…”

Taste and smell function in Wolfram syndrome

“…One important clinical marker and one of the earliest signs of common neurodegenerative diseases such as Alzheimer [12,13] and Parkinson disease [14,15] is olfactory dysfunction. Although olfactory dysfunction has been associated with Wolfram syndrome in clinical reports [16][17][18][19] [20,21].…”