We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia

Rosebud O. Roberts, MB, ChB1,2; Teresa J. H. Christianson, BS3; Walter K. Kremers, PhD3; Michelle M. Mielke, PhD1; Mary M. Machulda, PhD4; Maria Vassilaki, MD, PhD1; Rabe E. Alhurani, MBBS2; Yonas E. Geda, MD5,6; David S. Knopman, MD2; Ronald C. Petersen, MD, PhD1,2
[+] Author Affiliations
1Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
2Department of Neurology, Mayo Clinic, Rochester, Minnesota
3Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
4Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota
5Department of Psychiatry and Psychology, Mayo Clinic, Scottsdale, Arizona
6Department of Neurology, Mayo Clinic, Scottsdale, Arizona
JAMA Neurol. 2016;73(1):93-101. doi:10.1001/jamaneurol.2015.2952.
Text Size: A A A
Published online

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 <.001) after adjustment for sex and education, with age as the time scale. There was no association with naMCI. There were 64 incident dementia cases among 221 prevalent MCI cases. The B-SIT score also predicted progression from aMCI to AD dementia, with a significant dose-response with worsening B-SIT quartiles. Compared with Q4, HR (95% CI) estimates were 3.02 (1.06-8.57) for Q3 (P = .04); 3.63 (1.19-11.10) for Q2 (P = .02); and 5.20 (1.90-14.20) for Q1 (P = .001). After adjusting for key predictors of MCI risk, B-SIT (as a continuous measure) remained a significant predictor of MCI (HR, 1.10 [95% CI, 1.04-1.16]; P < .001) and improved the model concordance.

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.

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?





Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles

Care at the Close of Life: Evidence and Experience
Alzheimer Disease: "It's OK, Mama, If You Want to Go, It's OK"

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Supplemental Content