Olfactory Impairment and Frailty: A Systematic Review and Meta-Analysis.

Importance: Olfactory impairment (OI) and frailty are prevalent conditions associated with aging, but studies investigating their association with each other have been discordant.

Objective: To summarize current evidence surrounding the association between OI and frailty.

Data sources: PubMed, Embase, Cochrane Library, SCOPUS, and CINAHL from inception to November 28, 2023.

Study selection: This study included observational studies investigating the association between objectively or subjectively assessed OI and objectively evaluated frailty among adults.

Data extraction and synthesis: Two independent authors extracted data into a structured template. Maximally adjusted estimates were pooled using a random-effects model, and statistical heterogeneity was evaluated using I2 values. Additional prespecified subgroup and sensitivity analyses were performed. This study used the Newcastle-Ottawa Scale for bias assessment and the Grading of Recommendations Assessment, Development and Evaluation framework for overall evidence quality evaluation.

Main outcomes and measures: The primary outcome was the cross-sectional association between OI and frailty, for which the odds of frailty were compared between participants with and without OI. The secondary outcome was the cross-sectional association between frailty and OI, for which the odds of OI were compared between participants with and without frailty.

Results: This study included 10 studies with 10 624 patients (52.9% female; mean [SD] age, 62.9 [9.6] years). The Newcastle-Ottawa Scale score of studies ranged from low to moderate. Grading of Recommendations Assessment, Development and Evaluation scores ranged from low to moderate. OI was associated with a 2.32-fold (odds ratio [OR], 2.32; 95% CI, 1.63-3.31; I2 = 0%) greater odds of frailty compared with individuals with healthy olfactory function. The odds of OI was progressively greater with categorical frailty status, with a 1.55-fold (OR, 1.55; 95% CI, 1.32-1.82; I2 = 0%), 2.28-fold (OR, 2.28; 95% CI, 1.96-2.65; I2 = 0%), and 4.67-fold (OR, 4.67; 95% CI, 2.77-7.86; I2 = 0%) increase in odds for individuals with prefrailty, frailty, and the most frailty, respectively, compared with robust individuals. The results demonstrated stability in subgroup analyses (geographical continent of study, objective vs subjective olfactory assessment) and sensitivity tests.

Conclusions and relevance: The results of this systematic review and meta-analysis suggest that there is an association between OI and frailty, with an increase in the odds of OI with worsening categorical frailty status among individuals with prefrailty, frailty, and the most frailty. OI may be a potential biomarker for frailty. Future studies could delve into whether OI may be a modifiable risk factor for frailty.