Coronary artery disease is associated with cognitive decline independent of changes on magnetic resonance imaging in cognitively normal elderly adults.

Objectives: To examine in cognitively normal elderly adults whether vascular factors predict cognitive decline and whether these associations are mediated by magnetic resonance imaging (MRI) measures of subclinical vascular brain injury.

Design: Prospective multisite longitudinal study of subcortical ischemic vascular diseases.

Setting: Memory and aging centers in California.

Participants: Seventy-four participants who were cognitively normal at entry and underwent at least two neuropsychological evaluations and two MRI examinations over an average follow-up of 6.9 years.

Measurements: Item response theory was used to create composite scores of global, verbal memory, and executive functioning. Volumetric MRI measures included white matter hyperintensities (WMHs), silent brain infarcts (SBIs), hippocampus, and cortical gray matter (CGM). Linear mixed-effects models were used to examine the associations between vascular factors, MRI measures, and cognitive scores.

Results: History of coronary artery disease (CAD) was associated with greater declines in global cognition, verbal memory, and executive function. The CAD associations remained after controlling for changes in WMHs, SBIs, and hippocampal and CGM volumes.

Conclusion: History of CAD may be a surrogate marker for clinically significant atherosclerosis, which also affects the brain. Structural MRI measures of WMHs and SBIs do not fully capture the potential adverse effects of atherosclerosis on the brain. Future longitudinal studies of cognition should incorporate direct measures of atherosclerosis in cerebral arteries, as well as more sensitive neuroimaging measures.