Table 3 Ability of the odor identification score to discriminate between categories of the A/T/N classification and corresponding cut-off values.

Analysis No	Group 1	Versus Group 2	Comparative pathological stage	Mean (SD) (Group 1/Group 2)	P-value (t-test)	AUC	95% CI (De Long)	Cut-off	Specificity	Sensitivity
1	A−/T−/N−	A+/T−/N− A+/T+/N− A+/T+/N+	Normal vs. after amyloidogenesis	6.7(2.2)/4.5(2.1)	< 0.0001	0.761	0.658–0.864	5.5	0.676	0.659
2	A−/T−/N− A+/T−/N−	A+/T+/N− A+/T+/N+	Normal to amyloidogenesis vs. after p-Tau accumulation	6.3(2.3)/4.5(2.1)	0.0006	0.717	0.604–0.83	4.5	0.830	0.514
3	A−/T−/N− A+T−/N− A+/T+/N−	A+/T+/N+	Normal to p-Tau accumulation vs. AD neurodegeneration	6.1(2.2)/2.2(2.3)	0.0011	0.716	0.588–0.844	4.5	0.786	0.545
4	A−/T−/N−	A−/T+/N− A−/T+/N+	Normal vs. p-Tau accumulation without amyloidogenesis	6.7(2.2)/5.1(2.6)	0.0049	0.670	0.546–0.794	4.5	0.892	0.486
5	A−/T−/N−	A−/T+/N− A−/T+/N+ A−/T−/N+	Normal vs. SNAP	6.7(2.2)/5.2(2.5)	0.0050	0.653	0.538–0.768	4.5	0.892	0.429

The discriminative ability of odor identification scores according to the A/T/N classification was evaluated. Regardless of the presence or absence of neurodegeneration, the AUC for odor identification scores was high when amyloidogenesis occurred (Analysis 1). Analyses 2 and 3 were less sensitive, making it difficult to differentiate the processes leading to p-Tau accumulation and neurodegenerative stages after amyloidogenesis. The AUC and sensitivity were low in the normal to p-Tau accumulation stage without amyloidogenesis regardless of the presence or absence of neurodegeneration (Analysis 4). After setting odor cut-off values for each A/T/N stage (A−/T−/N−, A+/T−/N−, A+/T+/N−, and A+/T+/N+), a post hoc power analysis was conducted; all stages met the criteria of a significance level of 5%, and a power of 80% at an AUC value ≥ 0.652. The results indicated that the sample size was sufficient to determine the cutoff value. Therefore, odor identification scores are excellent for differentiating amyloidogenesis but not p-Tau accumulation.
A (+) amyloid-positive individuals with A/T/N classification; A (−) amyloid-negative; T (+) p-Tau positive; T (−) p-Tau negative; N (+) t-Tau positive; N (−) t-Tau negative; SD standard deviation; AUC area under the curve; CI confidence interval; p-Tau phosphorylated Tau; SNAP suspected non-AD pathophysiology.

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