Objective Olfactory Dysfunction May Be Robust Marker for Dementia Risk

Olfactory dysfunction is associated with a higher risk for dementia, especially severe dysfunction when combined with APOE ε4 carriage.

Individuals with olfactory dysfunction may be at increased risk for dementia onset, according to study findings published in the journal Alzheimer’s & Dementia.

Previous research has found olfactory dysfunction to be an early biomarker for dementia and Alzheimer disease (AD). However, olfactory dysfunction can be difficult to quantify and a more nuanced picture of the relationship between olfactory dysfunction and dementia risk is needed.

For this study, researchers from the Karolinska Institutet and Stockholm University in Sweden sourced data from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K). In SNAC-K, older individuals (N=2473) living in Kungsholmen were randomly selected to take part in the study in 2001-2003. Individuals aged 60, 66, and 72 were contacted for follow-up every 6 years and those aged 78 years and older every 3 years up to year 12 of the study.

Risk for onset of dementia was evaluated on the basis of Sniffin’ Sticks odor identification performance. Hyposmia, or mild olfactory dysfunction, was defined as Sniffin’ Sticks scores of 7-10 and anosmia, or severe olfactory dysfunction, as scores of 6 or less.

Severe OD, especially in combination with the APOE ε4 allele, is strongly suggestive of an impending dementia disorder.

These were the following characteristics of individuals in the 3 groups:

  • no olfactory dysfunction (n=1757), hyposmia (n=528), and anosmia (n=188)
  • 62.83%, 58.90%, and 51.06% were women (P =.004);
  • mean age, 69.68, 77.72, and 81.33 years (P <.001);
  • Mini-Mental State Examination (MMSE) scores of 29.14, 28.47, and 28.03 points (P <.001);
  • average Sniffin’ Sticks scores were 13.27, 8.81, and 4.29 points (P <.001); and
  • 72.03%, 66.94%, and 69.94% were not apolipoprotein E (APOE) ε4 carriers, respectively.

A minority of individuals with hyposmia (16.54%) or anosmia (39.25%) self-reported olfactory dysfunction, indicating that affected individuals tended to be unaware of their olfactory dysfunction.

During the follow-up, 348 incident dementia cases occurred. The rate of dementia was lower among individuals with no olfactory dysfunction (8.88%) compared with those who had hyposmia (24.05%) or anosmia (34.57%).

In the fully adjusted model, dementia onset associated with:

  • Sniffin’ Sticks total scores (adjusted hazard ratio [aHR], 0.88; 95% CI, 0.86-0.91),
  • free response scores (aHR, 0.81; 95% CI, 0.76-0.87),
  • multiple choice scores (aHR, 0.93; 95% CI, 0.89-0.97),
  • categorical odor identification score (aHR, 1.85; 95% CI, 1.45-2.36),
  • hyposmia (aHR, 1.60; 95% CI, 1.23-2.08),
  • anosmia (aHR, 2.82; 95% CI, 2.03-3.92),
  • self-reported quite poor or very poor olfactory function (aHR, 1.49; 95% CI, 1.09-2.04), and
  • self-reported very poor olfactory function (aHR, 2.73; 95% CI, 1.40-5.33).

Results were consistent in a sensitivity analysis that considered death without dementia as a competing event.

Combining olfactory dysfunction and APOE ε4 status indicated there was an additive effect of both olfaction and genotype, in which compared with individuals without olfactory dysfunction or APOE ε4 carriage, individuals with anosmia and ε4/ε4 carriage were at greatest risk for dementia (aHR, 17.53), followed by individuals with anosmia and ε4 carriage (aHR, 6.09) and no OD and ε4/ε4 carriage (aHR, 5.82).

These findings may not be generalizable for individuals with no sense of smell.

The researchers acknowledged that olfactory dysfunction could be a marker of dementia. “In contrast, subjective reports underestimate the occurrence of OD and is an insensitive indicator of future dementia risk, underlining the importance of performing objective olfactory testing. “Severe OD, especially in combination with the APOE ε4 allele, is strongly suggestive of an impending dementia disorder,” they concluded.


Laukka EJ, Ekström I, Larsson M, Grande G, Fratiglioni L, Rizzuto D. Markers of olfactory dysfunction and progression to dementia: a 12-year population-based study. Alzheimers Dement. Published online January 23, 2023. doi:10.1002/alz.12932