Olfactory Impairment and Incident Cognitive Decline: A Systematic Review and Meta-Analysis

Olfactory impairment (OI) is associated with poor ageing outcomes. While cross-sectional studies found a high prevalence of OI among patients with neurodegenerative diseases, the temporal relationship remains unclear. This meta-analysis aims to synthesise the longitudinal association of OI with cognitive decline (CD).

PubMed, Embase and Web of Science were searched through August 9, 2024 for longitudinal studies reporting on self-reported and objectively measured OI in adults, in association with CD, measured using validated methods. The outcome of interest was incident CD. Independent authors extracted data, assessed for bias and graded the strength of evidence. A mixed-effects meta-analysis with subgroup, sensitivity and bias analyses was conducted. The population-attributable fraction (PAF) of OI-associated CD was calculated.

This study included 48 articles and 37,783 participants. OI patients had a 2.06-fold greater risk of any CD (risk ratio [RR] = 2.06; 95% CI = 1.87‒2.26, I² = 0%), compared to individuals with normal olfaction. Patients with severe OI had a higher risk of any CD (RR = 2.60; 95% CI = 2.12‒3.20, I² = 0%) than patients with moderate OI (RR = 1.51; 95% CI = 1.23‒1.85, I² = 0%). The risk of any CD increased by 18% per 10% decrease in olfactory score (RR = 1.18; 95% CI = 1.14‒1.22, I² = 24%) and by 15% per point decrement on the Sniffin' Sticks Odor Identification Test (RR = 1.15; 95% CI = 1.11‒1.18, I² = 0%). These results remained robust to supplementary analyses. The PAF of OI-associated incident CD was 18%.

OI may increase the risk of CD, with poorer olfaction linked to greater risks. OI should be assessed as a potential cognitive screening tool, and cognitive screening should be considered in patients with long-standing OI.