Smell Loss Linked to Higher Mortality Risk Through Neurodegeneration and Frailty: JAMA

Olfactory ability, or sense of smell, has come to be seen more and more as a critical predictor of health. The capacity for odor identification accuracy could indicate neural pathway integrity and brain health overall. As the population ages, determining how deficits in olfactory ability are linked with mortality may provide insights on how to enhance quality of life and survival among older individuals.

The SNAC-K study is a population-based, longitudinal cohort study that was initiated between 2001 and 2004 in Kungsholmen, Stockholm, Sweden. A total of 2,524 participants aged between 60 and 99 years (mean age 71.9 years, 61.2% women) were included. Participants had baseline assessments of olfactory function with the 16-item Sniffin' Sticks Odor Identification test, which assesses the capacity to identify particular odors.

Participants were under observation for 12 years, and mortality information was obtained from the Swedish National Cause of Death Register. Mortality due to all causes at 6 years and 12 years was tested for association with olfactory function using Cox proportional hazards models, and competing hazard risk regression analyses tested cause-specific mortality. Mediators under consideration, such as dementia, frailty, and malnutrition, were identified using generalized structural equation models.

Key Findings

Mortality Rates

• 445 participants (17.6%) had died at 6 years of follow-up.

• 969 participants (38.4%) had died at 12 years of follow-up.

Increased Risk of Mortality with Olfactory Deficits:

• Every incorrect response on the odor identification test was linked to a 6% increased risk of all-cause mortality at 6 years (HR 1.06, 95% CI: 1.03-1.08).

• At 12 years, every incorrect response was associated with a 5% increased risk of mortality (HR 1.05, 95% CI: 1.03-1.08).

Cause-Specific Mortality:

• The greatest relation between odor deficiency and mortality was found to occur for neurodegenerative illness.

Mediators of Olfaction-Mortality Association:

• For 6-year-olds, the most significant mediators were:

• Dementia (23% of the association overall).

• Frailty (11% of the association overall).

• Malnutrition (5% of the association overall).

• In children aged 12 years, frailty continued as a main mediator (9% of the overall association).

The SNAC-K study concludes that olfactory impairment is an important predictor of mortality in older age, especially from neurodegenerative disease and frailty. Olfactory impairment is identified as a marker of risk of mortality and highlights the importance of more research and the possible clinical application of smell testing in geriatric practice. Routine olfactory screening may aid in identifying higher-risk patients, thereby facilitating prompt interventions to enhance their survival and quality of life.

Reference:

Ruane R, Lampert O, Larsson M, Vetrano DL, Laukka EJ, Ekström I. Olfactory Deficits and Mortality in Older Adults. JAMA Otolaryngol Head Neck Surg. Published online April 10, 2025. doi:10.1001/jamaoto.2025.0174