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

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.

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).

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.

In older adults with T2D, APOE-ε4 carriers have less depressive symptoms in successive measurements suggesting they may be less susceptible to depression.