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<p>Alzheimer’s disease (AD) has multiple potential etiologies such as genetic factors and environmental exposure. It has been hypothesized that environmental exposure to toxicants may contribute to the pathophysiological processes of AD. However, previous studies yielded conflicting results. To assess this discrepancy, we conducted a literature review and a meta-analysis. A comprehensive systematic search was carried out across electronic databases (Google Scholar, PubMed, Scopus, and the Comparative Toxicogenomics Database) to identify eligible studies. Meta-analyses, using random-effects models, were performed to calculate the pooled estimated effects reported as standardized mean differences (SMD), Odds Ratio (OR), and Hazard Ratio (HR). According to our strategy, 137 studies were identified regarding aluminum (n = 72), arsenic(n = 9), cadmium (n = 17), mercury (n = 22), lead (n = 26), pesticides (n = 12), solvents (n = 7), and air pollution (n = 24). Meta-analyses showed significantly elevated circulatory levels of pesticide metabolites (SMD = 1.08; 95% CI [0.65,1.51]; <i>p</i> &lt; 10<sup>–5</sup>), aluminum (SMD = 0.87; 95% CI[0.58,1.17]; <i>p</i> &lt; 10<sup>–5</sup>), arsenic (SMD = 0.39; 95% CI[0.04,0.75]; <i>P</i> = 0.03), and cadmium (SMD = 0.45; 95% CI [0.19, 0.7]; <i>p</i> = 0.0006) in AD patients than in controls. In contrast, neither lead levels (SMD = 0.02; 95% CI [-0.12, 0.15]; <i>p</i> = 0.82) nor mercury levels significantly differ between the two groups (SMD = 0.17; 95% CI [-0.08, 0.42]; <i>p</i> = 0.17). Moreover, air pollution increases by 3% the risk of developing AD (HR = 1.03; 95% CI [1.01, 1.03]; <i>p</i> &lt; 0.00001). Most notably, our meta-analysis revealed a significant association between AD and exposure to pesticides (OR = 1.59; 95% CI [1.40, 1.81]; <i>p</i> &lt; 0.00001) and solvents (OR = 1.29; 95% CI [1.02, 1.64]; <i>p</i> = 0.04). These findings suggest that chronic exposure to some toxic metals, atmospheric pollution, solvents, and pesticides could potentially contribute to AD progression.</p>

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Alzheimer’s disease and exposome: is there really a connection? Literature review and meta-analysis

  • 期刊论文

  • 发表日期：

    2026年2月12日

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  • Chiraz Zayani,
  • Rania Abdelhedi,
  • Imed Gargouri

摘要

Alzheimer’s disease (AD) has multiple potential etiologies such as genetic factors and environmental exposure. It has been hypothesized that environmental exposure to toxicants may contribute to the pathophysiological processes of AD. However, previous studies yielded conflicting results. To assess this discrepancy, we conducted a literature review and a meta-analysis. A comprehensive systematic search was carried out across electronic databases (Google Scholar, PubMed, Scopus, and the Comparative Toxicogenomics Database) to identify eligible studies. Meta-analyses, using random-effects models, were performed to calculate the pooled estimated effects reported as standardized mean differences (SMD), Odds Ratio (OR), and Hazard Ratio (HR). According to our strategy, 137 studies were identified regarding aluminum (n = 72), arsenic(n = 9), cadmium (n = 17), mercury (n = 22), lead (n = 26), pesticides (n = 12), solvents (n = 7), and air pollution (n = 24). Meta-analyses showed significantly elevated circulatory levels of pesticide metabolites (SMD = 1.08; 95% CI [0.65,1.51]; p < 10–5), aluminum (SMD = 0.87; 95% CI[0.58,1.17]; p < 10–5), arsenic (SMD = 0.39; 95% CI[0.04,0.75]; P = 0.03), and cadmium (SMD = 0.45; 95% CI [0.19, 0.7]; p = 0.0006) in AD patients than in controls. In contrast, neither lead levels (SMD = 0.02; 95% CI [-0.12, 0.15]; p = 0.82) nor mercury levels significantly differ between the two groups (SMD = 0.17; 95% CI [-0.08, 0.42]; p = 0.17). Moreover, air pollution increases by 3% the risk of developing AD (HR = 1.03; 95% CI [1.01, 1.03]; p < 0.00001). Most notably, our meta-analysis revealed a significant association between AD and exposure to pesticides (OR = 1.59; 95% CI [1.40, 1.81]; p < 0.00001) and solvents (OR = 1.29; 95% CI [1.02, 1.64]; p = 0.04). These findings suggest that chronic exposure to some toxic metals, atmospheric pollution, solvents, and pesticides could potentially contribute to AD progression.