Hypertension has been suspected of being associated with Alzheimer disease (AD). To study this problem, a case-control study investigating the association between hypertension and cognitive decline was conducted as a secondary analysis of data from more than 700 patients diagnosed with AD who had been randomly assigned to the placebo arm of a clinical trial. Additional analyses were undertaken to investigate the effects of baseline disease severity, age, gender, apolipoprotein genotype, and the use of antihypertensive medication in this population. This study found evidence of an association between hypertension and increased cognitive decline in AD patients over a 6-month period. After controlling for baseline disease severity, a pooled odds ratio (OR) was estimated to be 1.6 (95% confidence interval, 1.0-2.7) and found to be statistically significant (p = 0.048). Secondary analyses controlling for gender and apolipoprotein genotype showed no significant effect on the association between hypertension and cognitive decline. With regard to age, patients younger than 65 years with hypertension were more likely to have increased cognitive decline than patients of the same age without hypertension (odds ratio = 6.9, 95% confidence interval, 1.5-31.1; p = 0.005). Treatment with antihypertensives did not appear to provide protection from cognitive decline. Increased cognitive decline among those older than 65 years was comparable for hypertensive and normotensive subjects. This study, examining a large population of patients with AD, provides evidence that the rate in cognitive decline measured over a period of 6 months is accelerated by a state of hypertension in patients younger than 65 years.