Neuroscience and psychology
Low olfactory sensitivity is associated with a higher risk of mortality
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Ainhoa Pérez
Alumni
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MPH, MSc.
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A systematic review and meta-analysis published in JAMA Otolaryngology examined the relationship between olfactory dysfunction and all-cause mortality, finding that olfactory dysfunction is correlated with increased mortality.
These findings underscore the need to consider hyposmia not merely as an isolated sensory disturbance, but as a relevant clinical indicator in the comprehensive assessment of older adults. However, methodological heterogeneity across studies, the paucity of longitudinal data with repeated measures, the possibility of residual confounding, and the observational nature of the evidence preclude establishing causality. Future work should clarify the directionality of this association, its prognostic value in younger populations, and its usefulness in combination with other markers of biological aging.
PATHOPHYSIOLOGY AND MECHANISMS
The human olfactory system plays a crucial role in survival, participating in sensory, affective, memory, appetitive, avoidant, and other aspects of functioning through its connection with limbic and hypothalamic structures. Olfactory sensitivity has been proposed as a biomarker of aging, and its deterioration, common in people over 65 years of age, is associated with neurodegenerative and systemic diseases. Furthermore, loss of smell can increase emotional disconnection and social isolation, which in turn are associated with greater cognitive decline, depression, and lack of self-care, leading to a higher risk of malnutrition, dementia, frailty, and more. Therefore, the relationship between the olfactory system and health is bidirectional.STUDY
A systematic review and meta-analysis (Pang et al., 2022) evaluated the relationship between olfactory dysfunction and all-cause mortality. Eleven observational studies were included, mostly prospective, with more than 21,000 participants, predominantly over 60 years of age. Olfactory function was assessed using standardized objective tests (such as the Brief Smell Identification Test and the San Diego Odor Identification Test) or by self-report, with a mean follow-up of between 4 and 13 years depending on the study.MAIN RESULTS
Olfactory dysfunction was associated with a 52% increased risk of mortality. This association persisted after various adjustments and was consistent across countries and assessment methods. Studies using objective tests showed a higher association with mortality, albeit with high heterogeneity. Meta-regression analysis identified follow-up duration as an effect modifier, suggesting that factors influencing mortality increase over time, decreasing the statistical weight of the olfactory relationship. The overall quality of the evidence was moderate.CONCLUSION AND CLINICAL RELEVANCE
Smell shows an independent association with mortality, suggesting that it is an indicator of biological aging and the early manifestation of neurodegenerative disorders and frailty. The olfactory nerve, the only cranial nerve directly exposed to the environment, has a high turnover rate and is especially vulnerable to toxins and pathogens, making this pathway a region particularly sensitive to neurodegenerative damage. Furthermore, early accumulation of β-amyloid and α-synuclein has been detected in olfactory structures, even before the clinical symptoms of diseases such as Alzheimer's and Parkinson's. Systemic immune, metabolic, and other systemic alterations can also affect it. A relationship with mental health has also been found. A recent cohort study (Ruane et al., 2025) expands this evidence by finding that loss of smell predicts both overall and cause-specific mortality, highlighting a strong association with neurodegenerative deaths. This work also provides a mediation analysis that reveals that dementia, frailty, and malnutrition explain a significant portion of this short-term association, underscoring the importance of smell as an early sign of systemic deterioration. In the long term, frailty remains the main mediator. Additionally, the study identified a significant interaction with the ε4 allele of the APOE gene, a genetic risk marker for dementia, observing higher mortality associated with olfactory impairment in carriers of this allele, especially at six-year follow-up.These findings underscore the need to consider hyposmia not merely as an isolated sensory disturbance, but as a relevant clinical indicator in the comprehensive assessment of older adults. However, methodological heterogeneity across studies, the paucity of longitudinal data with repeated measures, the possibility of residual confounding, and the observational nature of the evidence preclude establishing causality. Future work should clarify the directionality of this association, its prognostic value in younger populations, and its usefulness in combination with other markers of biological aging.
#smell #anosmia #neurodegenerativediseases #dementia #alzheimer #elderlypeople
References:
Pang, N. Y.-L et al, 2022. Association of olfactory impairment with all-cause mortality: A systematic review and meta-analysis. JAMA Otolaryngology-Head & Neck Surgery, 148(5), 436-445. https://doi.org/10.1001/jamaoto.2022.0263
Ruane R et al, 2025. Olfactory Deficits and Mortality in Older Adults. JAMA Otolaryngol Head Neck Surg. Published online April 10, 2025. https://doi.org/10.1001/jamaoto.2025.0174
* The news published on studies do not represent an official position of ICNS, nor a clinical recommendation.
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