Predictive value of serum inflammatory factors combined with p-tau181 for anxiety and depression in Alzheimer’s disease patients

Table 1 Baseline characteristics of study subjects, n (%)/mean ± SD

Characteristics	Total (n = 125)	Non-anxiety-depression group (n = 69)	AD group (n = 56)	P value
Age (years)	72.8 ± 8.6	71.9 ± 8.2	73.9 ± 9.0	0.198
Male gender	56 (44.8)	32 (46.4)	24 (42.9)	0.696
MMSE score	18.4 ± 4.2	19.4 ± 4.2	17.2 ± 4.0	0.004
IL-6 (pg/mL)	12.4 ± 4.8	9.6 ± 3.1	15.8 ± 4.2	< 0.001
TNF-α (pg/mL)	22.8 ± 7.6	18.2 ± 5.4	28.4 ± 6.8	< 0.001
p-tau181 (pg/mL)	20.1 ± 6.2	16.4 ± 4.2	24.6 ± 5.8	< 0.001

AD: Anxiety-depression; MMSE: Mini-Mental State Examination; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; p-tau181: Phosphorylated tau-181.

Table 2 Correlation between biomarker levels and Hospital Anxiety and Depression Scale scores

Biomarker	HADS-A (r)	P value	HADS-D (r)	P value	HADS-Total (r)
IL-6 (pg/mL)	0.418	< 0.001	0.524	< 0.001	0.486
TNF-α (pg/mL)	0.445	< 0.001	0.556	< 0.001	0.512
p-tau181 (pg/mL)	0.482	< 0.001	0.598	< 0.001	0.558

HADS-A: Hospital Anxiety and Depression Scale-Anxiety subscale; HADS-D: Hospital Anxiety and Depression Scale-Depression subscale; HADS: Hospital Anxiety and Depression Scale; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; p-tau181: Phosphorylated tau-181; r: Spearman correlation coefficient.

Table 3 Univariate analysis of risk factors for anxiety and depression

Risk factor	Odds ratio	95%CI	P value
Age ≥ 75 years	1.86	0.92-3.76	0.086
Female gender	1.72	0.88-3.36	0.112
MMSE ≤ 18	2.24	1.12-4.48	0.022
Elevated IL-6 (> 10 pg/mL)	3.24	1.58-6.65	0.001
Elevated TNF-α (> 20 pg/mL)	2.92	1.44-5.92	0.003
Elevated p-tau181 (> 18 pg/mL)	3.56	1.72-7.38	< 0.001

CI: Confidence interval; MMSE: Mini-Mental State Examination; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; p-tau181: Phosphorylated tau-181.

Table 4 Risk stratification based on number of elevated biomarkers

Number of elevated biomarkers	n	AD incidence (%)	OR (95%CI)	P value
0 (low risk)	24	12.5	Reference	-
1 (low-intermediate risk)	31	25.8	2.42 (0.68-8.62)	0.172
2 (intermediate-high risk)	32	50.0	6.84 (2.08-22.52)	0.002
3 (high risk)	38	78.9	26.32 (7.24-95.68)	< 0.001
P for trend	-	-	-	< 0.001

Elevated biomarkers defined as: IL-6 > 10 pg/mL, TNF-α > 20 pg/mL, p-tau181 > 18 pg/mL. AD: Anxiety-depression; OR: Odds ratio; CI: Confidence interval.

Table 5 Sensitivity analysis and subgroup analysis

Analysis type	Subgroup	AUC (95%CI)	P value
Primary analysis	Overall (n = 125)	0.892 (0.834-0.950)	-
Stricter criteria	HADS ≥ 10	0.876 (0.812-0.940)	-
Gender-stratified	Male (n = 56)	0.884 (0.802-0.966)	0.724
Gender-stratified	Female (n = 69)	0.898 (0.828-0.968)	-
Cognitive severity	Moderate (MMSE 10-18)	0.912 (0.856-0.968)	0.048
Cognitive severity	Mild (MMSE 19-26)	0.856 (0.772-0.940)	-

AUC: Area under curve; CI: Confidence interval; HADS: Hospital Anxiety and Depression Scale; MMSE: Mini-Mental State Examination.