After including all the subsyndromes in one multivariate model (with family-level as random-effects, adjusted for gender, APOE, education and family mutation type), only the interaction of the neuropsychiatric subsyndromes agitation, disinhibition, irritability and depression with shorter EYO was associated with the decline of global [18F]FDG uptake (β = − 0.044, 95% CI − 0.071 to − 0.017, p = 0.001) in the DIAD mutation carriers (Table 5). This evidence concerns the gene APOE and major depressive disorder.