APOE and Alzheimer's disease neuropathologic change: 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.