Does reported sex modify the association between ambient air pollution exposure and Alzheimer's disease and related dementias? A systematic review and meta-analysis

Abstract

Air pollution has been recognized as a modifiable risk factor for Alzheimer's disease and related dementia. The evidence on whether reported sex modifies this association remains unclear. PubMed, Scopus, and Web of Science were searched up to September 2025 for longitudinal studies on reported sex-specific associations between air pollution and dementia. Female to male Ratio of Risk Ratios (RRR) was calculated as the metric for association modification. Publication bias was assessed using funnel plots and Egger's test. Meta-regression was performed to explore sources of between-study heterogeneity. Certainty of evidence was evaluated using a GRADE framework. Twenty-four cohort studies on more than 126 million participants were included. Associations were reported for 12 air pollutants, most frequently PM(2).(5) (n= 17) and NO(2) (n= 11). Dementia (n= 18) was the most reported outcome, followed by Alzheimer's disease (n= 12) and vascular dementia (n= 5). No statistically significant female to male RRR was found for Alzheimer's disease (e.g., PM(2.5): n =8, pooled RRR: 0.963, 95 CI: 0.919-1.009), vascular dementia (e.g., PM(2.5): n-= 3, pooled RRR: 1.003, 95 CI: 0.954-1.054), and most of the pollutants in overall dementia, except for PM(2.5) (n= 12, pooled RRR: 1.046, 95 CI: 1.024-1.069). Heterogeneity in most of the meta-analyses was negligible to low except for PM(10) in Alzheimer's disease (I(2) = 73). No evidence of publication bias was detected. The certainty of evidence was moderate. The current evidence does not provide sufficient support for reported sex-specific air pollution-dementia risk reduction policies, and should be interpreted with caution as the methodological heterogeneity and biases may mask true differences.