Odor Identification: Marker for Early Alzheimer Disease?

Cross-sectional study of OI as biomarker of presymptomatic AD
274 healthy individuals ≥60 years
   Parent or multiple siblings with AD
   Seen at McGill University (Montreal)
AD biomarkers measured in 101 CSF donors: total tau, phospho-tau, and their ratios with Alzheimer β-amyloid
OI tested with standardized scratch and sniff booklets

Overall unadjusted results showed impaired OI linked to:
   Lower cognitive score (P<.02)
   Older age (p<.02)
Increased ratios of total tau and phospho-tau to β-amyloid (p < 0.02)
OI known to be impaired in aging and dementia, link between OI, age and cognition expected

Analyses restricted to CSF donors:
   Results adjusted for age, cognition, APOE Ɛ4, education, and sex
   Links between impaired OI, older age and lower cognition disappeared
   Link between impaired OI and total tau/β-amyloid remained (p=0.005)
Suggests impaired OI may be an early indicator of AD pathology before symptom onset

OI test may be affected by nasal congestion
High percentage of women with high levels of education, results may not generalize
CSF puncture by volunteer, may introduce bias
Small sample, cross-sectional design:  cannot determine if results reflect change over time
   Longitudinal studies in progress

“While impaired OI may in fact help identify persons who could for various reasons eventually have cognitive impairment, we strongly urge that our present cross-sectional results not be regarded as rationale for clinical use of olfactory testing as an AD diagnostic. We suggest, however, that OI may serve for research purposes as a simple and inexpensive indicator of evolving AD pathology. Indeed, we are exploring its use as a biomarker in clinical trials among asymptomatic persons at risk of later dementia symptoms,” lead author John C.S. Breitner, MD, MPH. for the PREVENT-AD Research Group (McGill, University, Montreal)

Small Canadian study in healthy aging individuals at high risk for AD found decreased OI was linked to increased CSF biomarkers of AD pathology, after adjusting for important confounders.
Impaired OI may be a simple, inexpensive biomarker of early AD pathology in the research setting.
Longitudinal studies evaluating OI as a biomarker in asymptomatic individuals at risk for AD are ongoing.

Reference
1. Lafaille-Magnan ME, Poirier J, Etienne P, et al. Odor identification as a biomarker of preclinical AD in older adults at risk. Neurology. 2017;89(4):327-335.