We determined whether serum cystatin C, a novel measure of kidney function that colocalizes with brain beta-amyloid, is associated with cognition among 3,030 elders. Those with high cystatin C (n = 445; 15%) had worse baseline scores on Modified Mini-Mental State Examination or Digit Symbol Substitution Test (p <or= 0.02) compared with those with intermediate/low level and 7 years greater decline (p <or= 0.04). Incident cognitive impairment (decline >or=1.0 standard deviation) was greatest among those with high cystatin C (Modified Mini-Mental State Examination: 38 vs 25%; adjusted odds ratio, 1.92; 95% confidence interval, 1.37-2.69; Digit Symbol Substitution: 38 vs 26%; odds ratio, 1.54; 95% confidence interval, 1.10-2.15).