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Adult type 2 diabetes is associated with accelerated cognitive decline, but the predictors of cognitive decline including treatment intensification remain unclear.The Veterans Affairs Diabetes Trial randomized 1791 middle-and olderaged adults with advanced type 2 diabetes to standard (STD) vs intensive (INT) glycemic treatment lasting 5-7.5 years.Cognitive function was assessed at the baseline and 5 year follow-up visits in 1190 subjects using the digit span (DS), digit symbol (Dsymb) and Trail Making Test-Part B (Tr-B) tests of working memory, processing speed and executive function, respectively.Subjects (INT vs STD) did not differ significantly in their baseline characteristics, mean (SD): age 60 + 9 yrs, hemoglobin A1c 9.4 + 1.5%, systolic blood pressure 132 + 17 mm Hg or scaled cognitive scores, DS 10.2 + 3.0, Dsymb 8.8 +3.3, Tr-B 7.2 + 2.3.Mean 5-year scaled cognitive test scores (year 5-baseline) declined modestly: DS-0.003, Tr-B-0.44, Dsymb-0.92 and the changes were significant (P<.001) for Tr-B and Dsymb.In multivariable regression analysis, baseline risk factors significantly associated with 5-year decline in TrB included: age (P<.001), systolic blood pressure (P =.0l), diabetes duration (P =.001), baseline aspirin (P =.004) and baseline metformin use (P =.003).Baseline risk factors significantly associated with 5-year decline in Dsymb included: age (P=.002), diabetes duration (P =.02), and baseline aspirin use (P=.02).Baseline diastolic blood pressure (P <.0001) or baseline sulfonylurea use (P =.02) were predictive of significant 5-year improvement in Tr-B or Dsymb, respectively.Any baseline hypoglycemia was not a significant predictor of cognitive change.When specific classes of anti-hypertensive medications were included as variables, the final models for 5-year cognitive decline (using multivariable regression analysis) included as significant baseline predictors, Dspan: age, African-American race;Tr-B: diabetes duration, diastolic blood pressure, education, baseline calcium channel blocker (CCB)use;Dsymb: age, baseline CCB, baseline thiazide diuretic use.Glycemic treatment group was not a significant predictor of 5-year change in cognitive function, however, post-baseline triglyceride-lowering or diastolic blood pressure-lowering (year 5-baseline level) was significantly associated with improved Dsymb (P =.04) or Tr-B (P =.001) performance, respectively.Post-baseline systolic blood pressure-lowering was significantly associated with worsening executive function, Trails B (P =.0006).Taken together, these data suggest a multi-factorial etiology for cognitive decline in middle-or older-aged adult type 2 diabetes that may include systolic hypertension, insulin resistance or deficiency, and underlying vasculopathy as potentially modifiable risk factors.The effect of blood pressure-lowering on cognitive function in older adult type 2 diabetes with underlying small vessel disease is likely to be complex and requires more study.