CAA commonly co-occurs with the Alzheimer disease neuropathologic changes (ADNC), and the apolipoprotein E (APOE) e4 allele is a risk factor of both ADNC and CAA severity.16-20 CAA has also been associated with clinically diagnosed dementia, cognitive impairment and functional impairment by us and others.8-16,21 It is estimated that 70–98% of individuals with dementia also have CAA.8,14,21 While it seems likely that CAA, NP and NFT may work together to impact cognition (Fig. 1A), the exact relationships are unknown. This evidence concerns the gene APOE and Cognitive impairment.