Episodic memory of odors stratifies Alzheimer biomarkers in normal elderly

Abstract

Objective: The objective of this study was to relate a novel test of identifying and recalling odor percepts to biomarkers of Alzheimer's disease (AD) in well-characterized elderly individuals, ranging from cognitively normal to demented.

Methods: One hundred eighty-three participants (cognitively normal: n = 70; subjective cognitive concerns: n = 74; mild cognitive impairment [MCI]: n = 29, AD dementia: n = 10) were administered novel olfactory tests: the Odor Percept IDentification (OPID) and the Percepts of Odor Episodic Memory (POEM) tests. Univariate cross-sectional analyses of performance across diagnoses; logistic regression modeling, including covariates of age, sex, education, APOE genotype, and neuropsychological test scores; and linear mixed modeling of longitudinal cognitive scores were performed. Amyloid deposition and MRI volumetrics were analyzed in a subset of participants.

Results: Accuracy of identification and episodic memory of odor percepts differed significantly across diagnosis and age, with progressively worse performance across degrees of impairment. Among the participants who were cognitively normal or had subjective cognitive concerns, poorer than expected performance on the POEM test (based on the same individual's performance on the OPID and odor discrimination tests) was associated with higher frequencies of the APOE ε4 allele, thinner entorhinal cortices, and worse longitudinal trajectory of Logical Memory scores.

Interpretation: Selective impairment of episodic memory of odor percepts, relative to identification and discrimination of odor percepts revealed by this novel POEM battery, is associated with biomarkers of AD in a well-characterized pre-MCI population. These affordable, noninvasive olfactory tests offer potential to identify clinically normal individuals who have greater likelihood of future cognitive decline. Ann Neurol 2016;80:846-857.

Conflict of interest statement

Potential Conflicts of Interest: Dr. Hastings is the founder, owns stock, and receives a salary for serving as President of Osmic Enterprises, Inc., which markets the OPID and POEM tests. Dr. M. Albers receives consulting fees from International Flavors and Fragrances. All other authors do not have relationships with commercial enterprises that are of direct relevance to the current research.

© 2016 American Neurological Association.

Figures

Figure 1

Schematics of Olfactory Tests. (A) 10-item Qdor Percept IDentification (OPID-10) test: The participant was cued on each trial by the software to prepare to sniff bilaterally and sample the 2 s delivery of an odor. Following odor presentation, participants were asked if they were familiar with the odor (Yes/No). During the instruction phase of the test, the research assistant explicitly indicated that familiarity with the odor percept did not require a semantic label. Following the odor familiarity response, participants were presented with 4 odor names and asked to choose which odor name associated with their memory of the odor percept experienced at the start of the trial. (B) 20-item percept of odor episodic memory (POEM) and identification (OPID-20) tests were administered after a 10 minute delay. Odor presentation is as described for the OPID-10. Immediately following odor presentation, participants were asked if the odor had been presented in the earlier odor percept identification test (Yes/No). During the instruction phase of the test, the research assistant explicitly indicated that New/Old designation referred to the testing session and not to a broader lifetime exposure. Following this measure of episodic odor percept memory, the naming is as described in A. (C) The 12-item odor discrimination (OD) test. The participant was cued on each trial to prepare to sniff bilaterally and sample the delivery of two odors presented consecutively for 2 seconds each. Participants were then asked if the two odors presented were the same or different. Half of the trials were the “Same”, and the odors included were a predetermined selection of the odors listed above.

Figure 2

Odor Percept Identification, POEM index, and Odor Discrimination Across Disease Categories. (A) Proportion of the 20-item odor percepts identified correctly and S.E.Ms for each diagnosis. (B) POEM Performance Index ((# correct “New” or “Old” responses) - (# of incorrect responses) / 20 total responses) for each diagnosis. A score of 0 corresponds to participants performing at chance. (C) Proportion of odors correctly discriminated. Means and S.E.M. are shown. Bars indicate significant differences between diagnoses. * p

Figure 3

Adjusted hippocampal volume and entorhinal cortical thickness correlates with OPID-20 score. (A) Bilateral hippocampal volumes determined from MRI were averaged and adjusted for head size. Scores on the OPID-20 test are plotted against the adjusted hippocampal volume, (r = 0.534.; p

Figure 4

Poor performance on the POEM normalized to the OPID-20 and OD outcomes identifies CN/SCC participants enriched with AD biomarkers. (A) The CN/SCC participants who were good POEM performers (n = 87) had significantly less frequency of the ApoE ε4 allele (18%) relative the PPPs (45%; n =20; p = 0.011) (B) In the subset of olfactory tested CN/ SCC participants who underwent volumetric MRI, average entorhinal thickness of good POEM performers (n = 23) was greater than the poor POEM performers (n = 5) (p = 0.098).