A quantitative meta-analysis of olfactory dysfunction in mild cognitive impairment

Background The connection between Alzheimer's disease (AD) and olfactory deficits is well documented and further, alterations in olfactory functioning may signal declines in functions associated with dementia. The aim of the present comprehensive meta-analysis was to investigate the nature of olfactory deficits in mild cognitive impairment (MCI). Methods Articles were identified through computerised literature search from inception to 30 June 2016 using PubMed, MEDLINE and PsychInfo databases. In order to control for differences in sample size during effect size computation, studies were weighted according to their inverse variance estimates. Results 31 articles (62 effects) were identified, which included 1993 MCI patients and 2861 healthy older adults (HOA). Included studies contrasted odour identification, discrimination, detection threshold and/or memory between cases and controls. Moderate to large and heterogeneous effects were seen for olfactory deficits in MCI relative to HOA (d=-0.76, 95% CI -0.87<-0.64). Moderator analysis revealed that tests of odour identification yielded larger effect sizes than those of odour detection threshold or memory. In addition, a potential interaction between age and sex was observed, with male patients carrying a larger burden of olfactory deficit and older female patients performing better on olfactory tests. Conclusions and relevance Olfactory deficits are present and robust in MCI. Odour identification is most impaired in MCI, which parallels the most prominent sensory deficit seen in AD. As such, a simple-to-administer test of odour identification warrants inclusion in the screening of individuals at risk for developing AD.