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

Abstract

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. 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. 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. 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. Alzheimer's disease (AD) appears to be caused by complex interactions. Environment, genetics, lifestyle, educational level, are all factors that can affect disease occurrence and progression. Of the multiple environmental factors that may play a role in AD, heavy metals exposure has been shown to have an important correlation to this disease. In this research we evaluated the blood levels of four heavy metals, arsenic, lead, mercury, and lithium in AD patients and healthy subjects. Our results showed that Arsenic is correlated to the disease while lithium could play a protective role! These findings need to be validated on other populations then translated into public health policies. Othman et al. measure blood concentrations of arsenic, lead, mercury, and lithium in 50 Alzheimer’s disease patients and 50 cognitively healthy controls across multiple centres in Egypt. They show that blood arsenic is associated with increased Alzheimer’s disease risk and lower cognitive scores surviving false discovery rate correction.