Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia
Roberts RO, Christianson TJ, Kremers WK, Mielke MM, Machulda MM, Vassilaki M, Alhurani RE, Geda YE et al.. JAMA neurology, 2016-01-01
Topic: Amyloid, tau and blood-test diagnosis
Importance To increase the opportunity to delay or prevent mild cognitive impairment (MCI) or Alzheimer disease (AD) dementia, markers of early detection are essential. Olfactory impairment may be an important clinical marker and predictor of these conditions and may help identify persons at increased risk. Objective To examine associations of impaired olfaction with incident MCI subtypes and progression from MCI subtypes to AD dementia. Design, setting, and participants Participants enrolled in the population-based, prospective Mayo Clinic Study of Aging between 2004 and 2010 were clinically evaluated at baseline and every 15 months through 2014. Participants (N = 1630) were classified as having normal cognition, MCI (amnestic MCI [aMCI] and nonamnestic MCI [naMCI]), and dementia. We administered the Brief Smell Identification Test (B-SIT) to assess olfactory function. Main outcomes and measures Mild cognitive impairment, AD dementia, and longitudinal change in cognitive performance measures. Results Of the 1630 participants who were cognitively normal at the time of the smell test, 33 died before follow-up and 167 were lost to follow-up. Among the 1430 cognitively normal participants included, the mean (SD) age was 79.5 (5.3) years, 49.4% were men, the mean duration of education was 14.3 years, and 25.4% were APOE ε4 carriers. Over a mean 3.5 years of follow-up, there were 250 incident cases of MCI among 1430 cognitively normal participants. We observed an association between decreasing olfactory identification, as measured by a decrease in the number of correct responses in B-SIT score, and an increased risk of aMCI. Compared with the upper B-SIT quartile (quartile [Q] 4, best scores), hazard ratios (HRs) (95% CI) were 1.12 (0.65-1.92) for Q3 (P = .68); 1.95 (1.25-3.03) for Q2 (P = .003); and 2.18 (1.36-3.51) for Q1 (P = .001) (worst scores; P for trend Conclusions and relevance Olfactory impairment is associated with incident aMCI and progression from aMCI to AD dementia. These findings are consistent with previous studies that have reported associations of olfactory impairment with cognitive impairment in late life and suggest that olfactory tests have potential utility for screening for MCI and MCI that is likely to progress.
Key findings
- Olfactory impairment may be an important clinical marker and predictor of these conditions and may help identify persons at increased risk.
- Results Of the 1630 participants who were cognitively normal at the time of the smell test, 33 died before follow-up and 167 were lost to follow-up.
- We observed an association between decreasing olfactory identification, as measured by a decrease in the number of correct responses in B-SIT score, and an increased risk of aMCI.
- Compared with the upper B-SIT quartile (quartile [Q] 4, best scores), hazard ratios (HRs) (95% CI) were 1.12 (0.65-1.92) for Q3 (P = .68); 1.95 (1.25-3.03) for Q2 (P = .003); and 2.18 (1.36-3.51) for Q1 (P = .001) (worst scores; P for trend <.001) after adjustment for sex and education, with age as the time scale.
- These findings are consistent with previous studies that have reported associations of olfactory impairment with cognitive impairment in late life and suggest that olfactory tests have potential utility for screening for MCI and MCI that is likely to progress.
Why it matters
In this longitudinal study, decreasing ability to identify smells was associated with an increased risk of amnestic mild cognitive impairment. This suggests that a smell identification test may help identify people at higher risk, though it does not show that treating smell loss would prevent or delay dementia.
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Study details
- Study designlongitudinal study
- Participants1,630
- Effect size49.4%; 25.4%
- Evidence strengthModerate
How this study scored 69/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,630 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 431 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 35.9 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 4 / 6 | Cited 18.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 12 other studies in this library |
| Still being cited | 3 / 4 | Cited 124 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Ronald Carl Petersen: h-index 209 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26569387) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 69 / 100 | — |
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Read the original
- DOI: 10.1001/jamaneurol.2015.2952
- PubMed: 26569387
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Roberts, R. O., Christianson, T. J., Kremers, W. K., Mielke, M. M., Machulda, M. M., Vassilaki, M., et al. (2016). Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia. JAMA neurology. https://doi.org/10.1001/jamaneurol.2015.2952
Vancouver
Roberts RO, Christianson TJ, Kremers WK, Mielke MM, Machulda MM, Vassilaki M, et al. Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia. JAMA neurology. 2016. doi:10.1001/jamaneurol.2015.2952. PMID: 26569387.
BibTeX
@article{roberts2016-26569387,
author = {Roberts, R. O. and Christianson, T. J. and Kremers, W. K. and Mielke, M. M. and Machulda, M. M. and Vassilaki, M. and Alhurani, R. E. and Geda, Y. E. and others},
title = {{Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia}},
journal = {JAMA neurology},
year = {2016},
doi = {10.1001/jamaneurol.2015.2952},
pmid = {26569387},
url = {https://doi.org/10.1001/jamaneurol.2015.2952}
}
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