APOE and major depressive disorder: Furthermore, several population-based studies have suggested that APOE ε4 allele may modify the association of depression with risk of dementia and cognitive decline, such that people with both depression and the ε4 allele have a markedly increased risk of cognitive decline and dementia (Irie et al., 2008; Niti et al., 2009; Köhler et al., 2010; Kim et al., 2011; Pink et al., 2015).