Depression and type 2 diabetes mellitus can separately increase the risk for dementia, but that risk is even greater when both conditions are present. Further, the increased risk was greatest in younger patients, increasing almost fivefold among those under 65 years, compared with those with neither depression nor diabetes, researchers said in a study published April 15.

In the largest study to date that examined dementia risk in those with comorbid depression and diabetes, Dr. Wayne Katon of the University of Washington, Seattle, and his colleagues found an enhancement of risk for dementia in those with both conditions. The finding is worrisome, because diabetes is occurring at ever-younger ages, and people are living longer than ever.

Knowing from previous studies that depression increases the risk of all-cause dementia and taking into account that depression is associated with increased risk for diabetes, Dr. Katon and his colleagues examined both separate and summed all-cause dementia risks for depression and diabetes They said their study was the first to assess the excess risk of these two diagnoses over that of the general population (JAMA Psychiatry 2015 April 15 [ doi:10.1001/jamapsychiatry.2015.0082 ]).

Drawing on large and comprehensive Danish national health registries, the population-based cohort study included a total of 2,454,532 adults who were at least 50 years old and without dementia at enrollment. Of these, 477,133 (19.4%) had depression; 223,174 (9.1%) had diabetes; 95,691 (3.9%) had both. Patient group allocations, as well as incident dementia diagnoses, were determined by tracking physician-assigned diagnosis codes and by interrogating a prescription registry. Statistical analysis adjusted for the effect of other comorbidities, as well as for potentially confounding demographic variations.

During the 7 years of the follow-up period, the hazard ratio for developing dementia among those with comorbid depression and diabetes was 2.17 (95% confidence interval, 2.10-2.24); for those with depression alone, 1.20 (95% CI, 1.17-1.23), and for those with diabetes alone, 1.83 (95% CI, 1.80-1.87). For those younger than age 65 years, the hazard ratio for dementia with both DM and depression was 4.84 (95% CI, 4.21-5.55).

The study’s strengths included the large sample size and the very small attrition rate inherent in the robust Danish database. However, the population’s homogeneity limits generalizability. Additionally, only those who sought treatment for depression or diabetes were included, creating a selection bias toward more severe disease.

Though the study’s overall findings are clear, the causality is not. However, Dr. Katon and his coauthors observed, “Although underlying causal mechanisms are unclear, one explanation could be that depression and [diabetes] have many shared risk factors for dementia,” including obesity, inflammation, and vascular disease.