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DNA oxidative stress has been suggested as an important pathogenic mechanism in cognitive impairment and dementia. With baseline data collected from 2004 to 2008, the authors examined whether urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of global DNA oxidation, was associated with cognitive function in a sample of 1,003 Puerto Rican adults, aged 45–75 years, living in Boston, Massachusetts, and the surrounding area. Cognitive function was measured by using a battery of 7 tests: the Mini-Mental State Examination, word list learning, digit span, clock drawing and figure copying, Stroop, and verbal fluency tests. The primary outcome was a global cognitive score, averaging standardized scores across all cognitive tests. A higher 8-OHdG concentration was significantly associated with lower global cognitive scores, after adjustment for age, education, status of the gene for apolipoprotein E (APOE), and other covariates (Ptrend = 0.01). The difference in the global score, comparing participants in the 2 extreme 8-OHdG quartiles, was −0.11 (95% confidence interval: −0.20, −0.02), which was equivalent to accelerating cognitive aging by about 4 years, as observed in this population. Prospective studies are needed to elucidate whether elevated urinary 8-OHdG concentrations can predict the rate of cognitive decline and incident dementia. [ABSTRACT FROM PUBLISHER]