LAUSR

Background Lead (Pb) exposure has been associated with poorer cognitive function cross‐sectionally in aging adults, however the association between cumulative Pb exposure and longitudinal changes in cognition is little characterized. Methods In a 1993–2007 subcohort of the VA Normative Aging Study (Mini‐mental status exam (MMSE) n=741; global cognition summary score n=715), we used linear mixed effects models to test associations between cumulative Pb exposure (patella or tibia bone Pb) and repeated measures of cognition (MMSE, individual cognitive tests, and global cognition summary). Cox proportional hazard modeling assessed the risk of an MMSE score falling below 25. Results Among men 51–98 at baseline, higher patella Pb concentration (IQR: 21 &mgr;g/g) was associated with −0.13 lower baseline MMSE (95% CI: −0.25, −0.004) and faster longitudinal MMSE decline (−0.016 units/year, 95% CI: −0.032, −0.0004) over 15 years. Each IQR increase in patella Pb was associated with increased risk of a MMSE score below 25 (HR=1.21, 95% CI: 0.99, 1.49; p=0.07). There were no significant associations between Pb and global cognition (both baseline and longitudinal change). Patella Pb was associated with faster longitudinal decline in Word List Total Recall in the language domain (0.014 units/year, 95% CI: −0.026, −0.001) and Word List Delayed Recall in the memory domain (0.014 units/year, 95% CI: −0.027, −0.002). We found weaker associations with tibia Pb. Conclusions Cumulative Pb exposure is associated with faster declines in MMSE and Word List Total and Delayed Recall tests. These findings support the hypothesis that Pb exposure accelerates cognitive aging. HighlightsCognitive data collected over 15 years was used to study how lead affects cognitive trajectories.Cumulative lead exposure measured by bone lead levels was associated with faster decline in mini‐mental status exam scores.This suggests that exposure to lead accelerates cognitive aging, and possibly functional status.