Trajectories of depression symptoms over time differ by APOE4 genotype in older adults with type 2 diabetes

Objectives: The APOE-ε4 genotype has been associated with old-age depression, but this relationship has been rarely investigated in type 2 diabetes (T2D) older adults, who are at significantly increased risk for depression, a major contributor to T2D complications. We examined whether trajectories of depression symptoms over time differ by APOE-ε4 genotype in older adults with T2D. Methods: Participants (n = 754 [13.1% APOE-ε4 carrier]s) were from the longitudinal Israel Diabetes and Cognitive Decline (IDCD) study. They were initially cognitively normal and underwent evaluations of depression approximately every 18 months using the 15-item version of the Geriatric Depression Scale (GDS) and the depression subscale of the Neuropsychiatric Inventory (NPI). APOE was defined as a dichotomy of ε4 carriers and non-carriers. We used Hierarchical Linear Mixed Models (HLMM) that modeled the effects of APOE status on repeated GDS and NPI-depression scores in an unadjusted model (Model 1), adjusting for demographic factors (Model 2) and additionally adjusting for cardiovascular factors and global cognition (Model 3). Results: Participants’ mean age was 71.37 (SD = 4.5); 38.2% female. In comparison to non-carriers, APOE-ε4 carriers had lower mean GDS scores (β = −0.46, p = 0.018) and lower NPI-depression scores (β = −0.170, p = 0.038) throughout all study follow period. The groups did not differ in the slope of change over time in GDS (β = −0.005, p = 0.252) or NPI-depression (β = −0.001, p = 0.994) scores. Additional adjustment for cardiovascular factors and global cognition did not alter these results. Conclusions: In older adults with T2D, APOE-ε4 carriers have less depressive symptoms in successive measurements suggesting they may be less susceptible to depression.