# Associations between systemic inflammatory markers and cognitive decline in patients with early-stage Alzheimer’s disease: a retrospective clinical study

## TL;DR

This study finds that certain inflammatory markers are linked to cognitive decline in early-stage Alzheimer's disease, suggesting their potential use for monitoring and treatment.

## Contribution

The study identifies specific inflammatory biomarkers associated with cognitive decline in early-stage Alzheimer’s disease.

## Key findings

- AD patients had higher levels of IL-1β, IL-6, TNF-α, and MCP-1 compared to controls.
- IL-6, IL-1β, and TNF-α showed the strongest negative correlations with cognitive scores.
- A multi-marker panel of IL-1β, TNF-α, and IL-6 improved diagnostic accuracy with high sensitivity and specificity.

## Abstract

Emerging evidence implicates systemic inflammation in Alzheimer’s disease (AD)’s development and progression, yet comprehensive clinical data linking specific systemic inflammatory biomarkers to cognitive decline in early-stage AD remain limited.

To evaluate the correlation between key systemic inflammatory biomarkers and cognitive decline in early-stage AD, to identify potential inflammatory indicators for risk screening and disease monitoring.

In this retrospective study, 155 patients with early-stage AD and 100 matched healthy controls were enrolled between March 2020 and March 2025. Peripheral blood levels of inflammatory biomarkers, including IL-1β, IL-6, IL-8, IL-10, TNF-α, MCP-1, and CRP, were measured. Cognitive function was assessed using the MMSE and MoCA. Group comparisons, Spearman correlation analyses, and ROC curves with DeLong tests were performed.

The groups were comparable in baseline demographics (p > 0.05). The AD group exhibited significantly lower MMSE and MoCA scores (p < 0.001). AD patients had significantly elevated plasma levels of IL-1β, IL-6, TNF-α, and MCP-1 (p < 0.001), and decreased levels of IL-8 and IL-10 (p < 0.001). Correlation analyses revealed significant negative correlations between MMSE/MoCA scores and IL-1β, IL-6, TNF-α, and MCP-1 (p < 0.05), and positive correlations with IL-8 and IL-10 (p < 0.05). IL-6, IL-1β, and TNF-α showed the strongest associations. ROC analysis indicated AUCs of 0.766 for IL-1β, 0.716 for TNF-α, and 0.768 for IL-6. A panel combining IL-1β, TNF-α, and IL-6 achieved a significantly higher AUC of 0.894, with 77.42% sensitivity and 86.00% specificity.

Elevated levels of IL-6, IL-1β, and TNF-α are strongly associated with cognitive decline in early-stage AD, suggesting their utility as potential biomarkers for disease progression. A multi-marker inflammatory panel significantly enhances diagnostic accuracy, supporting the exploration of anti-inflammatory strategies for early intervention.