Worsening Sense of Smell Linked to Mild Cognitive Impairment, Dementia

woman flowers smell
woman flowers smell
Worsening scores on the smell test were associated with greater risk of mild cognitive impairment and Alzheimer's disease dementia.

An impaired sense of smell may be linked to the development of amnestic mild cognitive impairment and the progression to Alzheimer’s disease dementia, according to research published in JAMA Neurology.

Previous research has suggested an association between loss of sense of smell and cognitive decline, mild cognitive impairment (MCI), and Alzheimer’s disease (AD) dementia, so Rosebud Roberts, MB, ChB, from the Mayo Clinic in Rochester, Minnesota and colleagues aimed to replicate these findings in a large study. They also sought to more closely examine the relationship between impairment of smell with the risk of MCI and specific MCI subtypes, as well as the progression to either AD or non-AD dementia.

The researchers examined 1,430 participants (49.4% men) between 2004 and 2010 with a mean (SD) age of 79.5 (5.3) years who had normal cognition. They were clinically evaluated at baseline and every 15 months through 2014 as either having normal cognition, amnestic MCI, nonamnestic MCI, or dementia.

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To assess their sense of smell, the researchers administered the Brief Smell Identification Test (B-SIT). Participants identified 6 food smells (banana, chocolate, cinnamon, lemon, onion, and pineapple) and 6 non-food smells (gasoline, paint thinner, rose, soap, smoke, and turpentine.)

Over an average follow-up of 3.5 years, there were 250 new cases of MCI among the 1,430 participants. The researchers found an association between decreasing ability to identify smells and an increased risk of amnestic MCI. Compared with the best B-SIT scores (quartile [Q]4), the lower scores had increasing hazard ratios (95% CI): Q3 had a hazard ratio of 1.12 (0.65-1.92) (P = .68), Q2 had a hazard ratio of 1.95 (1.25-3.03) (P = .003), and Q1 had a hazard ratio of 2.18 (1.36-3.51) (P = .001). There was no association between smell scores and nonamnestic MCI.

There were also 64 new cases of dementia among 221 MCI cases. The researchers found a significant association between worsening smell scores and progression to AD dementia. Compared with Q4, Q3 had a hazard ratio of 3.02 (1.06-8.57) (P = .04), Q2 had a hazard ratio of 3.63 (1.19-11.10) (P = .02) and Q1 had a hazard ratio of 5.20 (1.90-14.20) (P = .001).

These results “suggest that impaired olfaction is associated with worse cognitive performance among cognitively normal individuals, and predicts decline in cognitive performance in nearly all cognitive domains. The greater declines in memory, executive function, and language suggest that brain regions that mediate performance in these domains may be involved early in the disease process,” the authors write.

The researchers note that because the B-SIT test is easily administered, does not require administration or interpretation by trained personnel, is non-invasive, and is relatively inexpensive, it may be beneficial for screening cognitively normal patients and patients with CMI to identify those who might benefit from early interventions to modulate the risk of progression.


  1. Roberts RO, Christianson TJH, Kremers WK, et al. Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia. JAMA Neurol. 2015; doi:10.1001/jamaneurol.2015.2952.