Blood metal signatures and their association with Alzheimer's disease risk and cognitive decline in an Egyptian cohort.

BACKGROUND

Alzheimer's disease (AD) is a multifactorial disease in which environmental exposures may contribute to disease risk. This study aimed to investigate associations between blood concentrations of arsenic, lead, mercury, and lithium with AD risk and cognitive performance in an Egyptian cohort.

METHODS

We conducted a cross-sectional study in 50 AD patients and 50 cognitively healthy controls recruited across multiple centres in Egypt. Blood metal concentrations were measured by inductively coupled plasma optical emission spectrometry. A tiered analytical strategy addressed variable left-censoring: group-stratified Kaplan-Meier imputation was applied for arsenic, lead, and lithium, followed by logistic and linear regression adjusted for age and sex, with a binary detection sensitivity analysis for lithium, lead, and mercury. Multiple testing was corrected using the Benjamini-Hochberg false discovery rate method.

RESULTS

Here we show that higher arsenic concentrations are strongly associated with increased odds of AD (OR = 1321.61, p = 3.48×10⁻⁶) and lower cognitive scores (β = -16.44, p = 1.46×10⁻⁸), both surviving false discovery rate correction. Higher lithium is associated with reduced disease odds (OR = 0.634, FDR-adjusted p = 0.022) and better cognitive performance (β = 1.21, FDR-adjusted p = 0.020), corroborated in sensitivity analyses. Mercury detection is markedly more frequent in patients than controls (24% vs. 2%, p = 0.002) and associates with lower cognitive scores (β = -7.08, p = 0.0003). Lead shows a borderline association with disease (OR = 1.53, p = 0.046) that does not survive correction.

CONCLUSIONS

These findings support arsenic neurotoxicity and lithium deficiency as potentially important contributors to AD risk in an Egyptian population, with implications for environmental public health in low- and middle-income settings.