PAPER

The relationship between cerebral Alzheimer’s disease pathology and odour identification in old age

R S Wilson^1,3, S E Arnold⁶, J A Schneider^1,4, Y Tang^2,5 and D A Bennett¹

¹ Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois, USA
² Rush Institute for Healthy Aging, Chicago, Rush University Medical Center, Chicago, Illinois, USA
³ Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois, USA
⁴ Department of Pathology, Rush University Medical Center, Chicago, Illinois, USA
⁵ Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA
⁶ The Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Correspondence to:
Correspondence to:
Dr R S Wilson
Rush Alzheimer’s Disease Center, Rush University Medical Center, 600 South Paulina, Suite 1038, Chicago, IL 60612, USA; rwilson{at}rush.edu

Background: Olfactory dysfunction is common in old age, but its basis is uncertain.

Objective: To test the hypothesis that difficulty in identifying odours in old age is related to the accumulation of Alzheimer’s disease pathology.

Methods: As part of the Rush Memory and Aging Project, participants completed the 12-item Brief Smell Identification Test, a standard measure of odour identification. During a mean (standred deviation (SD)) of 2.2 (1.2) years of follow-up (range 0.2–4.9), 166 people died, with brain autopsies performed on 129 (77.7%) people and neuropathological examinations completed on 77 (mean (SD) age at death 87.5 (5.9) years; median postmortem interval 6.1 h). From a uniform postmortem examination of multiple brain regions, summary measures of plaque and tangle pathology were derived on the basis of silver staining, and those of amyloid ß burden, tangle density and Lewy bodies on the basis of immunohistochemistry.

Results: Odour identification performance ranged from 0 to 12 correct (mean (SD) 8.0 (2.6)). In analyses adjusted for age, sex and education, a composite measure of plaques and tangles accounted for >12% of the variation in odour identification. The association remained after controlling for dementia or semantic memory. Density of tangles was inversely related to odour identification. A similar effect for amyloid burden was attenuated after controlling for tangles. The association with odour identification was robust for tangles in the entorhinal cortex and CA1/subiculum area of the hippocampus, but not for tangles in other cortical sites. Lewy bodies, identified in 12.5%, were not related to odour identification, probably partly due to to their relative infrequency.

Conclusion: The results suggest that difficulty in identifying familiar odours in old age is partly due to the accumulation of neurofibrillar pathology in central olfactory regions.

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