Cerebral amyloid angiopathy (CAA) is a vascular neuropathology commonly reported in non-cognitively impaired (NCI), mild cognitive impairment, and Alzheimer's disease (AD) brains. However, it is unknown whether similar findings are present in non-demented elderly subjects. This study determined the association between CAA and cognition among elderly NCI subjects with varying levels of AD pathology. Data from 182 cases that received a diagnosis of NCI at their first clinical assessment were obtained from the Rush Religious Orders study (RROS). A cognitive composite score was used to measure cognitive decline. CAA was dichotomized as present or absent. Cases were also dichotomized according to CERAD neuropathological diagnosis and Braak staging. A mixed model-repeated measures analysis assessed decline on the cognitive composite score. CAA, alone, was not associated with cognitive decline [-0.87 (95% CI: -3.33, 1.58), p = 0.49]. However, among those with CAA, the High CERAD group had significantly greater decline relative to the Low CERAD group [-4.08 (95% CI: -7.10, -1.06), p = 0.008]. The High and Low CERAD groups were not significantly different [-1.77 (95% CI: -6.14, 2.60), p = 0.43] in those without CAA. Composite score decline in the High and Low Braak groups with [-1.32 (95% CI: -4.40, 1.75), p = 0.40] or without [0.27 (95% CI: -4.01, 4.56), p = 0.90] CAA was not significantly different. The current data shows that an interaction between CAA and plaque load is associated with greater decline on a cognitive composite score used to test non-cognitively impaired elderly participants in AD prevention trials.