Chronic Cerebral Hypoxia and Cognitive Impairment: A Systematic Review and Meta-Analysis Based on Chronic Mountain Sickness, Anemia, Chronic Obstructive Pulmonary Disease, and Obstructive Sleep Apnea.

Abstract

Background: Chronic hypoxia, a key pathological feature of chronic mountain sickness (CMS), anemia, Chronic Obstructive Pulmonary Disease (COPD), and Obstructive Sleep Apnoea (OSA), impairs cognitive function; however, their association strength, shared mechanisms, and disease-specific differences remain unsystematized, hindering early interventions.

Objective: This study aimed to quantify these via a systematic review and meta-analysis to clarify the deficits and mechanisms for clinical guidance.

Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library for relevant studies, assessed the quality using the Newcastle-Ottawa Scale, and analyzed the data using Stata 18.0.

Results: Forty-one studies involving 18 countries, 369, 619 participants (5 on CMS, 8 on anemia, 11 on OSA, and 17 on COPD) demonstrated that all four diseases were associated with an increased risk of cognitive impairment, with OR ranging from 1.370 to 6.892. In dichotomous analyses, anemia was epidemiologically linked to elevated cognitive impairment risk but showed nonsignificant, heterogeneous effects on continuous cognitive scores and no associations with specific cognitive domains, indicating its impact is moderated by population traits and measurement approaches. The other three diseases impaired global and domain-specific cognition with SMD ranging from -0.6352 to -0.2000, each with unique deficit profiles. Notably, correction for publication bias eliminated the statistical significance of the overall pooled OR for cognitive impairment risk.

Conclusion: Hypoxia is the core shared mechanism linking these four diseases to cognitive impairment, involving mitochondrial dysfunction and neuroinflammation, with additional modulation by genetic and adaptive factors. However, current evidence is limited by publication bias and inconsistent findings (e.g., for anemia). These conclusions must be interpreted with extreme caution, and high-quality longitudinal studies are needed to confirm causality.