title: Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota2Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Rosebud O
authors.initials: RO
authors.lastname: Roberts
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Teresa J H
authors.initials: TJ
authors.lastname: Christianson
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Walter K
authors.initials: WK
authors.lastname: Kremers
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Machulda
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Maria
authors.initials: M
authors.lastname: Vassilaki
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Rabe E
authors.initials: RE
authors.lastname: Alhurani
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Scottsdale, Arizona6Department of Neurology, Mayo Clinic, Scottsdale, Arizona.
authors.forename: Yonas E
authors.initials: YE
authors.lastname: Geda
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota2Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology; D000647:Amnesia / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D000857:Olfaction Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology; D011159:Population Surveillance / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors