Odor identification score as an alternative method for early identification of amyloidogenesis in Alzheimer's disease

Abstract

A simple screening test to identify the early stages of Alzheimer's disease (AD) is urgently needed. We investigated whether odor identification impairment can be used to differentiate between stages of the A/T/N classification (amyloid, tau, neurodegeneration) in individuals with amnestic mild cognitive impairment or AD and in healthy controls. We collected data from 132 Japanese participants visiting the Toranomon Hospital dementia outpatient clinic. The odor identification scores correlated significantly with major neuropsychological scores, regardless of apolipoprotein E4 status, and with effective cerebrospinal fluid (CSF) biomarkers [amyloid β 42 (Aβ42) and the Aβ42/40 and phosphorylated Tau (p-Tau)/Aβ42 ratios] but not with ineffective biomarkers [Aβ40 and the p-Tau/total Tau ratio]. A weak positive correlation was observed between the corrected odor identification score (adjusted for age, sex, ApoE4 and MMSE), CSF Aβ42, and the Aβ42/40 ratio. The odor identification score demonstrated excellent discriminative power for the amyloidogenesis stage , according to the A/T/N classification, but was unsuitable for differentiating between the p-Tau accumulation and the neurodegeneration stages. After twelve odor species were analyzed, a version of the score comprising only four odors-India ink, wood, curry, and sweaty socks-proved highly effective in identifying AD amyloidogenesis, showing promise for the screening of preclinical AD.

Figure 1

Flowchart of participants from examination to A/T/N classification and evaluation of olfactory discrimination. CSF cerebrospinal fluid; DLB diffuse Lewy body disease; FTD frontotemporal dementia; MCI mild cognitive impairment; AD Alzheimer's disease; ROC receiver operating characteristic; Aβ amyloid-β; p-Tau phosphorylated Tau; t-Tau total Tau; A+ amyloid-positive individuals; A− amyloid-negative individuals; T+ phosphorylated Tau-positive individuals; T− phosphorylated Tau-negative individuals; T+ total Tau-positive individuals; T− total Tau-negative individuals; SNAP suspected non-Alzheimer’s disease pathophysiology; ApoE apolipoprotein E; MMSE Mini-Mental State Examination; AUC area under the curve.