Leonardo · Frontiers in aging neuroscience 2023 · systematic review and meta-analysis of observational studies · n=79 studies

Association of inflammation and cognition in the elderly: A systematic review and meta-analysis.

Cited 108 times in the scientific literature.

Level 3 - non-randomized controlled study

Systematic review and meta-analysis of observational (cohort and cross-sectional) studies

PubMed 36815174 · doi:10.3389/fnagi.2023.1069439 · record verified 2026-08-29

What was done

A systematic literature search on MEDLINE, PubMed, Embase, Web of Science, and Scopus identified 79 prospective longitudinal and cross-sectional studies evaluating the relationship between systemic inflammatory markers and cognitive impairment (mild cognitive impairment [MCI] and Alzheimer's disease [AD]).

What was found

Cross-sectional pooled estimates showed higher levels of inflammatory markers in AD versus controls: CRP (Hedges's g 0.35, 95% CI 0.16 to 0.55), IL-1β (g 0.94, 95% CI -0.04 to 1.92), IL-6 (g 0.46, 95% CI 0.05 to 0.88), TNF-α (g 0.22, 95% CI -0.24 to 0.68), and sTNFR-1 (g 0.74, 95% CI 0.46 to 1.02). In MCI versus controls, elevations were reported for IL-1β (g 0.17, 95% CI 0.05 to 0.28), IL-6 (g 0.13, 95% CI 0.08 to 0.18), TNF-α (g 0.28, 95% CI 0.07 to 0.49), and sTNFR-1 (g 0.21, 95% CI 0.05 to 0.48). Longitudinally, high IL-6 was associated with cognitive decline (OR 1.34, 95% CI 1.13 to 1.56), but intermediate IL-6 was not (OR 1.06, 95% CI 0.80 to 1.32). CRP, antichymotrypsin, albumin, and TNF-α did not demonstrate longitudinal prognostic utility.

Why it matters

This review differentiates cross-sectional associations from longitudinal predictors, suggesting elevated IL-6 specifically may flag risk for progressive cognitive deterioration.

Limits

All pooled data stem from observational designs, precluding causal inference. Total participant count, study heterogeneity, and adjustment for systemic comorbidities or medications are not reported in the abstract. CIs for AD cross-sectional IL-1β and TNF-α cross zero despite reported p < 0.05.

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