Evaluation of the NIH Toolbox Odor Identification Test across normal cognition, amnestic mild cognitive impairment, and dementia due to Alzheimer's disease

INTRODUCTION: Olfactory decline is associated with cognitive decline in aging, amnestic mild cognitive impairment (aMCI), and amnestic dementia associated with Alzheimer's disease neuropathology (ADd). The National Institutes of Health Toolbox Odor Identification Test (NIHTB-OIT) may distinguish between these clinical categories. METHODS: We compared NIHTB-OIT scores across normal cognition (NC), aMCI, and ADd participants (N = 389, ≥65 years) and between participants positive versus negative for AD biomarkers and the APOE ε4 allele. RESULTS: NIHTB-OIT scores decreased with age (p < 0.001) and were lower for aMCI (p < 0.001) and ADd (p < 0.001) compared to NC participants, correcting for age and sex. The NIHTB-OIT detects aMCI (ADd) versus NC participants with 49.4% (56.5%) sensitivity and 88.8% (89.5%) specificity. NIHTB-OIT scores were lower for participants with positive AD biomarkers (p < 0.005), but did not differ based on the APOE ε4 allele (p > 0.05). DISCUSSION: The NIHTB-OIT distinguishes clinically aMCI and ADd participants from NC participants. Highlights: National Institutes of Health Toolbox Odor Identification Test (NIHTB-OIT) discriminated normal controls from mild cognitive impairment. NIHTB-OIT discriminated normal controls from Alzheimer's disease dementia. Rate of olfactory decline with age was similar across all diagnostic categories. NIHTB-OIT scores were lower in participants with positive Alzheimer's biomarker tests. NIHTB-OIT scores did not differ based on APOE genotype.