Heterogeneity of odorant identification impairment in patients with Alzheimer's Disease

Abstract

Alzheimer's disease (AD) patients exhibit olfactory dysfunction. However, the olfactory declineti precise nature is not fully understood. One hundred patients (60 AD, 28 amnestic mild cognitive impairment (aMCI), 12 Normal) were enrolled. All participants underwent olfactory function testing using an odour stick identification test for Japanese (OSIT-J). OSIT-J scores were significantly correlated with recall. We classified OSIT-J odorants into three groups: Category I, odorants that were difficult for normal aged subjects to identify; Category II, odorants that became harder to accurately identify with cognitive decline; and Category III, odorants that even AD patients could identify. We defined a "cognitive subset" consisting of six Category II OSIT-J odorants (perfume, rose, Japanese cypress, curry, India ink and gas leak odour). The ability to identify "cognitive subset" odours was significantly better indicator of cognitive status than the ability to identify "non-cognitive subset", which consisted of the six remaining items. The ability to identify the gas leak odorant was decreased early in the aMCI stage, suggesting a need to reconsider the odours used to signal gas leaks. The "cognitive subset" would provide a more convenient and effective biomarker for diagnosing dementia in clinical settings.

Figure 1

MMSE subsets and cognitive status. (a) MMSE recall and orientation 13-item subset for each cognitive status. (b) MMSE subset of 17 other items for each cognitive status. Error bars are standard deviations. ***denotes significant (p < 0.001) difference with Bonferroni correction. Abbreviations: MMSE, Mini-Mental State Examination.

Figure 2

Accuracy of identification of each odorant by cognitive status. Odorants in the upper column became harder to accurately identify with declining cognitive status. Green, black and red odour names indicate Category I, Category II and Category III, respectively. (See Discussion).

Figure 3

OSIT-J and cognitive status. (a) OSIT-J “cognitive subset” score (6 items: perfume, rose, Japanese cypress (hinoki), curry, India ink and gas leak odour) for each cognitive status. (b) OSIT-J “non-cognitive subset” score (6 items: sweaty socks, roasted garlic, condensed milk, wood, Japanese orange and menthol) for each cognitive status. The ability to identify the “cognitive subset” was a better indicator of cognitive status. Error bars are standard deviation. *, ** and *** denote significant (p < 0.05, p < 0.01 and p < 0.001, respectively) differences with Bonferroni correction. Abbreviations: OSIT-J, Odour Stick Identification Test for Japanese.

Figure 4

ROC curves of “cognitive” and “non-cognitive” OSIT-J subsets. Red line and blue line indicate the “cognitive subset” and “non-cognitive subset”, respectively. (a) ROC curves to discriminate AD vs (aMCI + Normal). The AUCs of “cognitive subset” and “non-cognitive subset” were 0.758 and 0.617, respectively. The difference was significant (p = 0.008). (b) ROC curves to discriminate (AD + aMCI) vs Normal. The AUCs of “cognitive subset” and “non-cognitive subset” were 0.879 and 0.654, respectively. The difference was significant (p = 0.005). Abbreviations: ROC, receiver operating characteristic; AUC, area under the curve; OSIT-J, Odour Stick Identification Test for Japanese; AD, Alzheimer’s disease; aMCI, amnestic mild cognitive impairment.