Smell identification function as a severity and progression marker in Alzheimer's disease

Int Psychogeriatr. 2013 Jul;25(7):1157-66. doi: 10.1017/S1041610213000446. Epub 2013 Apr 19.


Background: Olfactory dysfunction, impaired smell identification in particular, is known as a diagnostic and a marker of conversion in Alzheimer's disease (AD). We aimed to evaluate the associations of olfactory identification impairments with cognition, illness severity, and progression in AD patients.

Methods: Fifty-seven outpatients with late onset mild to moderate AD and 24 elderly non-demented controls (NDC) were assessed, at baseline and after three months, for Mini-Mental State Examination (MMSE), University of Pennsylvania Smell Identification Test (UPSIT), and Bristol Activities of Daily Living and Neuropsychiatry Inventory. AD participants were classified as Rapid Cognitive Decliners (RCD) defined on a priori with a loss of ≥2 points in MMSE within the previous six months.

Results: AD participants had lower olfactory scores than NDC. RCD had lower olfaction scores compared with Non-Rapid Cognitive Decliners (NRCD). Although the baseline UPSIT scores were associated with baseline MMSE scores, it did not interact significantly with change in MMSE over the follow-up period. Using a median split for olfactory scores, the AD participants were classified as Rapid Olfactory Progressors (ROP) (UPSIT ≤ 15) and Slow Olfactory Progressors correlating significantly with RCD/NRCD groups. The ROP group with higher olfactory impairment indicated more symptomatic illness or severity, i.e. lower cognition, higher functional dependence, and presence of behavioral symptoms.

Conclusions: Our study supports association of smell identification function with cognition and its utility as an adjunct clinical measure to assess severity in AD. Further work, including larger longitudinal studies, is needed to explore its value in predicting AD progression.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / physiopathology*
  • Alzheimer Disease / psychology
  • Biomarkers / analysis
  • Case-Control Studies
  • Cholinesterase Inhibitors / therapeutic use
  • Cognition*
  • Disease Progression
  • Female
  • Humans
  • Male
  • Mental Status Schedule
  • Neuropsychological Tests
  • Olfaction Disorders / drug therapy
  • Olfaction Disorders / etiology
  • Olfaction Disorders / physiopathology*
  • Severity of Illness Index
  • Smell*
  • Socioeconomic Factors


  • Biomarkers
  • Cholinesterase Inhibitors