Lead (Pb) in Alzheimer's Dementia: A Systematic Review of Human Case- Control Studies.

BACKGROUND

Alzheimer's Dementia (AD) has a complex pathophysiology that is incompletely understood. Chronic, low-level environmental lead (Pb) exposure is associated with cognitive impairment, hypertension and mortality, and has been proposed as a potential cause of AD.

OBJECTIVE

We aimed to review the literature to clarify the potential role of Pb in AD and to guide future research.

METHODS

Through a series of systematic reviews, we identified case-control studies comparing AD to controls on 6 measures of Pb exposure or accumulation: blood, bone, cerebrospinal fluid, hair/nail, postmortem pathology, and urine. We completed meta-analyses where possible.

RESULTS

The number of identified case-control studies of AD, by measurement method, was: 15 by blood, 0 by bone, 5 by Cerebrospinal Fluid (CSF), 3 by hair/nail, 3 by postmortem, and 1 by urine. Two meta-analyses were possible for 7 studies reporting whole blood Pb and for 8 studies of serum Pb. Both were negative. The largest study of CSF Pb showed lower levels in AD. Similarly, lower hair Pb levels were found in AD.

CONCLUSION

The available case-control studies are insufficient to draw conclusions on the role of Pb in AD. Most methods do not address long-term or early-life exposure. The preferred measure of chronic Pb is in bone, which has not been utilized in case-control AD studies. Future research should measure bone Pb in AD, together with other biomarkers, such as amyloid and tau imaging, and markers of cerebrovascular pathology.