Published online Aug 19, 2026. doi: 10.5498/wjp.122295
Revised: June 25, 2026
Accepted: July 20, 2026
Published online: August 19, 2026
Processing time: 71 Days and 22.4 Hours
Comorbid anxiety and depression are common among patients with Alzheimer’s disease (AD), significantly impacting these individuals’ disease trajectory and quality of life. Serum inflammatory markers and phosphorylated tau protein appear to be key predictors of these psychiatric disturbances emerging in our population of AD patients, although the mechanisms governing their combined predictive capacity have yet to be determined.
To examine the predictive effects of p-tau181 and serum inflammatory markers [interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α)] on anxiety and depres
Retrospective data were collected from 125 patients diagnosed with AD, who were admitted to the neurology department of our center from January 2022 to December 2024. Based on the results of Hospital Anxiety and Depression Scale (HADS) anxiety and depression status, patients were stratified into two groups: Anxiety-depression group (HADS-A ≥ 8 or HADS-D ≥ 8, n = 56), and non-anxiety-depression group (HADS-A < 8 and HADS-D < 8, n = 69). The concentrations of serum IL-6, TNF-α and plasma p-tau181 were measured using enzyme-linked immunosorbent assay and single-molecule array technology. Receiver operating characteristic curve analysis and logistic regression were conducted to assess the predictive capacity of these biomarkers in anxiety and depression.
The study population included 125 AD patients (mean age 72.8 ± 8.6 years, males: Females ratio of 44.8%:55.2%). Out of the 125 patients, anxiety and/or depression developed in 56 (44.8%) during the observation period. The anxiety-depression group (n = 56) had significantly increased serum IL-6 levels (15.8 ± 4.2 pg/mL vs 9.6 ± 3.1 pg/mL, P < 0.001), TNF-α levels (28.4 ± 6.8 pg/mL vs 18.2 ± 5.4 pg/mL, P < 0.001) and p-tau181 concentrations (24.6 ± 5.8 pg/mL vs 16.4 ± 4.2 pg/mL, P < 0.001) compared with non-anxiety-depression group (n = 69). From multivariate logistic regression, three independent risk factors were identified: Increased IL-6 [odds ratio (OR) = 2.86, 95% confidence interval (CI): 1.42-5.76, P = 0.003], increased TNF-α (OR = 2.54, 95%CI: 1.28-5.04, P = 0.008) and increased p-tau181 (OR = 3.12, 95%CI: 1.56-6.24, P = 0.001). Overall prediction model performance was excellent (area under curve = 0.892, 95%CI: 0.834-0.950) with sensitivity of 82.1% and specificity of 85.5%, far better than that for predictors on an individual biomarker basis (P < 0.001).
We found that the combination of serum inflammatory markers (IL-6, TNF-α) as well as p-tau181 showed excellent predictive for anxiety and depression on AD patients. Conclusion: This multimarker panel shows promising preliminary predictive performance for identifying AD patients at higher risk for anxiety and depression; however, these findings are hypothesis-generating and require prospective external validation in multicenter cohorts before clinical implementation.
Core Tip: Anxiety and depression are common neuropsychiatric complications that markedly worsen the prognosis, as well as the quality of life in patients with Alzheimer’s disease. This study uncovers that the predictive value for anxiety and depression is improved by combining serum inflammatory markers (interleukin-6 and tumor necrosis factor alpha) with p-tau181 instead of individual biomarkers. These findings highlight the importance of comprehensive biomarker assessment as part of standard of care in Alzheimer’s disease to identify at-risk patients for early treatment.