Evidence
What the research shows
These pages summarise 26 studies and reviews drawn from the literature by the Graham lab. The four tables appear in the order Professor Graham set out: first, olfactory dysfunction in disease; then olfactory training; then training and cognition; and finally the proposed mechanisms.
A note on reading them: some of these are small trials, proof-of-concept studies, or reviews rather than large randomised trials. The summaries are reported as the source documents describe them.
1. Olfactory dysfunction in disease
Literature summary highlighting studies that show olfactory dysfunction is an early feature of Mild Cognitive Impairment (MCI) and Alzheimer disease (AD).
| Authors (Year) | Study Population | Study Design | Main Findings | Clinical Significance |
|---|---|---|---|---|
| Devanand, D. P. et al. (2000) | Patients with MCI and AD | Cross-sectional | Odor identification was impaired in MCI and low test scores predicted the later diagnosis of AD | Olfactory impairment appears before overt dementia and may assist early diagnosis. |
| Wilson, R. S. et al. (2007) | Community-dwelling older adults | Prospective cohort | Poor odor identification predicted future development of MCI. | Olfactory testing may identify individuals at increased risk for cognitive decline. |
| Wilson, R. S. et al. (2009) | Older adults without dementia | Longitudinal | Individuals with poorer olfactory function had higher risk of developing AD at follow-up. | Smell dysfunction is an independent predictor of AD. |
| Roberts, R. O. et al. (2016) | Population-based elderly cohort | Longitudinal | Impaired olfaction increased the likelihood of developing amnestic MCI. | Olfactory dysfunction precedes measurable cognitive impairment. |
| Attems, J. et al. (2015) | Review of neuropathological studies | Systematic review | Olfactory bulb and olfactory cortex are among the earliest brain regions affected in AD. | Explains why smell loss often occurs before memory symptoms. |
| Albers, M. W. et al. (2015) | Review | Comprehensive review | Olfactory impairment is consistently associated with MCI, AD, and disease progression. | Recommends olfactory assessment as part of early neurodegenerative evaluation. |
| Murphy, C. (2019) | Review | Comprehensive review | Olfactory deficits reflect degeneration within the olfactory bulb, entorhinal cortex, and hippocampus. | Smell testing may serve as a practical, non-invasive biomarker for early AD. |
| Li, X. et al. (2026) | Research trends and mechanisms of olfactory deficits in AD | Bibliometric analysis | 1,916 publications identified, overview of research done on olfactory deficits in disease. | Early olfactory risk assessment, diagnosis, and intervention may be critical components in prevention, management in AD |
| Bouhaben, J. et al. (2024) | Subjective cognitive decline and MCI | Cross-sectional | Olfactory identification deficits distinguished early AD from healthy aging and were already detectable in MCI. | Findings suggest olfactory tests could improve the early detection of individuals at risk for cognitive impairment. |
This table can be scrolled sideways. 9 rows.
Overall conclusions
- Olfactory dysfunction is one of the earliest manifestations of Alzheimer disease and is frequently detectable during the Mild Cognitive Impairment stage.
- Smell loss correlates with degeneration in the olfactory bulb, entorhinal cortex, hippocampus, and related limbic structures, which are affected early in Alzheimer disease.
- Numerous longitudinal studies demonstrate that impaired olfactory function predicts progression from normal cognition → MCI → Alzheimer’s disease.
- Because smell testing is non-invasive, inexpensive, rapid, and easy to administer, it is increasingly being investigated as an early screening biomarker when combined with cognitive assessment, imaging, and fluid biomarkers.
2. Olfactory therapy and olfactory function
Literature summary: scientific evidence on the effects of olfactory therapy (olfactory training) on olfactory function in neurodegenerative diseases.
Problems with the sense of smell are well established as an early biomarker of Alzheimer disease (AD) and Mild Cognitive Impairment (MCI). Most evidence comes from pilot clinical trials, proof-of-concept studies, and studies of olfactory enrichment in older adults. Collectively, the findings support that repeated olfactory stimulation may improve olfactory function and may also positively influence cognition.
| Authors (Year) | Population | Study Design | Intervention | Duration | Main Findings | Conclusion |
|---|---|---|---|---|---|---|
| Woo, C. C. et al. (2023) | Healthy older adults (60–85 years) | Not stated | Nightly olfactory enrichment using rotating essential oil scents during sleep | 6 months | Participants receiving odor enrichment showed a marked improvement in verbal memory compared with controls, along with imaging evidence of improved integrity in memory-related white matter pathways. | Demonstrated that long-term olfactory stimulation can enhance memory and brain connectivity, supporting its potential application in MCI and AD prevention. |
| Cha, H. et al. (2021) | Patients with dementia | Not stated | Intensive olfactory training | 15 days | Repeated exposure to odors alleviated depression and improved some cognitive functions | OT may be an effective non-pharmacological approach for improving the symptoms of dementia |
| Murphy, C. (2019) | Review of aging and AD | Review | Not stated | Not stated | Highlighted that olfactory pathways directly connect to the hippocampus and amygdala, making smell training biologically plausible as a cognitive intervention. | Proposed olfactory rehabilitation as a promising adjunct therapy requiring further validation. |
| Hummel, T. et al. (2009) Laryngoscope | Patients with olfactory dysfunction (various causes) | Not stated | Classical olfactory training (rose, eucalyptus, lemon, cloves) twice daily | 12 weeks | Significant improvement in odor identification and discrimination after structured smell training. | Established the standard olfactory training protocol now widely adopted in smell rehabilitation. |
| Sorokowska, A. et al. (2017) | Patients with chronic smell disorders | Systematic review and meta-analysis | Not stated | Multiple studies | Olfactory training significantly improved olfactory function, particularly odor identification. | Supports olfactory training as intervention for smell loss in neurodegenerative diseases. |
| Pekala, K. et al. (2016) | Individuals with olfactory dysfunction | Systematic review | Not stated | Multiple studies | Repeated odor exposure improved olfactory sensitivity and identification across etiologies. | Suggests olfactory training may represent a promising intervention for patients. |
| Birte-Antina, W. et al. (2018) | Older adults | Not stated | Extended olfactory training | 5 months | OT showed a positive effect on olfaction, verbal fluency and emotional well-being | OT is an inexpensive and simple way to improve quality of life in older people. |
| Kollndorfer, K. et al. (2015) | Anosmic patients | Not stated | Olfactory training | 12 weeks | Post OT sensitivity to detect odors increased, which was also manifested in modifications of functional connections in all three investigated cerebral networks. | Recovery of olfactory-specific functional connections in the brain post olfactory training |
| Leon, M. et al. (2022) | Depression | Review | Not stated | Not stated | Olfactory loss is a predisposing factor for depression | Olfactory enrichment could be a critical treatment for depression |
| Vance, D. et al. (2023) Neuropsychol Rev | Healthy adults and patients with olfactory dysfunction | Systematic review (18 studies) | Olfactory training | Not stated | OT was associated with improvements in olfaction and in global cognition. | Emerging evidence supports cognitive benefits beyond smell recovery. |
| Pieniak, M. et al. (2022) | Individuals with olfactory dysfunction | Review (47 studies) | Olfactory training | Not stated | Compelling evidence shows that OT has beneficial effects for people experiencing olfactory loss with different etiologies. | OT can now be considered an established method for smell rehabilitation and support in developmental and aging process engaging cognitive functions. |
This table can be scrolled sideways. 11 rows.
Overall conclusions
The available literature supports the concept that olfactory therapy/training is a promising non-pharmacological, affordable intervention for individuals with MCI and Alzheimer disease. While robust evidence already demonstrates its effectiveness for improving olfactory function in chronic smell disorders, emerging research indicates that repeated olfactory stimulation may also strengthen memory-related neural networks through neuroplasticity and neurogenesis. The strongest evidence for cognitive benefit currently comes from olfactory enrichment studies in older adults rather than patients with established AD or MCI.
3. Olfactory therapy and cognitive function
Literature summary: scientific evidence on the effects of olfactory therapy (olfactory training) on cognitive function in neurodegenerative diseases.
Olfactory dysfunction is one of the earliest symptoms of several neurodegenerative diseases, including Mild Cognitive Impairment (MCI), Alzheimer disease (AD) and Parkinson disease. Because the olfactory system has direct anatomical connections with the hippocampus, amygdala, entorhinal cortex, and orbitofrontal cortex, researchers have proposed that olfactory training (OT) may promote cognitive function through neuroplasticity, neurogenesis, and strengthening of memory-related neural networks. Evidence suggests olfactory stimulation has measurable effects on cognition and brain structure.
| Authors (Year) | Population | Study Design | Intervention | Cognitive Findings | Major Conclusion |
|---|---|---|---|---|---|
| Hummel, T. et al. (2009) Laryngoscope | Patients with chronic olfactory dysfunction | Prospective clinical trial | Classical olfactory training | Significant improvement in odor identification and discrimination | Established the modern olfactory training protocol. |
| Pekala, K. et al. (2016) Int Forum Allergy Rhinol | Patients with olfactory disorders | Systematic review | Olfactory training | Improved olfactory function across multiple etiologies | Strong evidence supporting OT as a rehabilitation strategy. |
| Murphy, C. (2019) Nature Rev Neurology | Aging and Alzheimer disease | Narrative review | Review | Highlighted direct olfactory projections to the hippocampus and amygdala and their role in episodic memory. | Provides biological rationale for cognitive benefits of OT. |
| Woo, C. C. et al. (2023) | Healthy adults aged 60–85 years | Randomized controlled trial | Nightly olfactory enrichment using rotating pleasant scents for 6 months | Participants showed markedly greater verbal memory improvement than controls, accompanied by improved integrity of the uncinate fasciculus on MRI. | Demonstrated that sustained olfactory stimulation can enhance memory and structural brain connectivity. |
| Leon, M. et al. (2024) Frontiers in Mol Neurosci | Review of neurodegenerative conditions | Mechanistic review | Olfactory enrichment | Reported associations between olfactory loss and more than 100 neurological disorders and proposed olfactory enrichment as a strategy to preserve cognition through sensory stimulation. | Suggests olfactory stimulation may become a preventive or adjunctive therapy. |
| Vance, D. et al. (2023) Neuropsychol Rev | Healthy adults and patients with olfactory dysfunction | Systematic review (18 studies) | Olfactory training | OT was associated with improvements in global cognition, verbal learning, verbal fluency, hippocampal volume, olfactory bulb volume, and functional brain connectivity. | Emerging evidence supports cognitive benefits beyond smell recovery. |
This table can be scrolled sideways. 6 rows.
Overall conclusions
Olfactory training is a safe, inexpensive, and non-invasive intervention with well-established benefits for improving olfactory function. Emerging evidence indicates that repeated olfactory stimulation may also improve memory, verbal learning, verbal fluency, and global cognition, likely by enhancing neuroplasticity within hippocampal and limbic networks. The strongest cognitive evidence currently comes from studies of older adults and individuals with olfactory dysfunction, rather than patients with established neurodegenerative disease. However, there is emerging evidence that this can also help those with diseases.
Despite these limitations, the biological rationale and early clinical findings suggest that olfactory training is a promising adjunctive intervention for promoting cognitive health and potentially slowing cognitive decline in neurodegenerative diseases.
4. Proposed mechanisms
Experimental and clinical evidence suggests that olfactory training may improve brain function through several complementary mechanisms.
| Mechanism | Evidence |
|---|---|
| Neuroplasticity | Repeated olfactory stimulation strengthens synaptic connectivity within the olfactory bulb, piriform cortex, orbitofrontal cortex, and hippocampus. |
| Neurogenesis | Animal studies indicate increased generation and survival of interneurons within the olfactory bulb following odor enrichment. |
| Enhanced hippocampal activity | Olfactory pathways project directly to the hippocampus and entorhinal cortex, supporting memory processing. |
| Increased cognitive reserve | Continuous multisensory stimulation may reinforce neural networks involved in attention, executive function, and episodic memory. |
| Improved emotional processing | Because olfactory pathways connect closely with the amygdala, smell training may positively influence mood and emotional well-being. |
This table can be scrolled sideways. 5 rows.