Depression was associated with accelerated cognitive decline among patients with type 2 diabetes in the prospective ACCORD-MIND study.
Of 2,977 adults with type 2 diabetes and a high risk of cardiovascular events who participated in the 40-month cohort ACCORD-MIND (Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes) study, 531 (18%) were considered to have depression based on a score of 10 or greater on the 9-item Patient Health Questionnaire (PHQ-9). Those patients showed greater cognitive decline than did nondepressed patients on a rigorous battery of cognitive tests, Dr. Mark D. Sullivan of the University of Washington, Seattle, and his colleagues reported online Aug. 14 in JAMA Psychiatry.
For example, estimated least squares means for decline in cognitive function were consistently greater among the depressed patients, compared with nondepressed patients, for the Digit Symbol Substitution Test (DSST), which is an omnibus test of psychomotor speed (0.72); the Rey Auditory Verbal Learning Test, which assesses memory (0.18); and the modified Stroop Test, which assesses executive function (–1.06).
Dr. Mark D. Sullivan
"Adjustment for progressively more extensive lists of demographic and clinical covariates did little to change the differences in means or statistical significance," the investigators said, noting that when the PHQ-9 score was entered into the models as a continuous variable, the score remained significantly associated with cognitive decline on all three tests (JAMA Psychiatry 2013 Aug. 14 [doi:10.1001/jamapsychiatry.2013.1965]).
The effect of depression on cognitive decline did not differ based on insulin levels, previous cardiovascular disease, baseline cognition or age, intensive vs. standard glucose-lowering treatment, blood pressure treatment, or lipid treatment, the investigators said.
Furthermore, the effects of depression on cognitive decline were greater when the initial cognition level was included in the models for change.
"Additional exploratory analyses revealed that subjects with PHQ-9 scores 10 or more at both baseline and 20 months showed the greatest cognitive decline on the DSST during both the 0- to 20-month (mean decline, –2.0) and 20- to 40-month (mean decline, –2.7) intervals. The group with a PHQ-9 score less than 10 at baseline but 10 or more at 20 months showed nearly as large a decline (mean decline, –2.5) in the 20- to 40-month interval," Dr. Sullivan and his associates wrote.
Patients included in the study were middle-aged and older adults who had type 2 diabetes for a mean duration of 9 years and who were at high risk for cardiovascular disease.
The findings support those of prior studies that also showed a link between depression and dementia in patients with type 2 diabetes and expand those findings to show that the association exists across cognitive domains and patient groups.
"To our knowledge, this is the clearest demonstration to date that depression constitutes a risk factor for cognitive decline in the population of patients with type 2 diabetes. It also demonstrates that this effect is not limited to specific cognitive tests or specific subgroups," the investigators said.
The findings also suggest that the interaction between cognition and depression develops over relatively short periods, as it was apparent in this study in the first 40 months of follow-up, they added, noting that the interaction needs monitoring over time.
As for why depression is associated with cognitive decline in type 2 diabetes, the authors suggested several possible mechanisms, including the association between depression and poor adherence to recommendations regarding diet, exercise, smoking and medication, as well as between depression and poor glycemic control in patients with diabetes – all of which can contribute to the increased risk of dementia.
Additionally, both depression and type 2 diabetes are associated with signs of systemic inflammation, decreased insulin sensitivity, and autonomic dysfunction. These also might mediate the effects of depression on dementia risk.
Depression also is associated with "an array of biologic abnormalities that may mediate the effect of depression on cognitive decline," Dr. Sullivan and his colleagues said.
The findings are limited by numerous factors, such as the lack of a control population of patients without diabetes and the use of a self-report measure for assessing depression.
Also, since the study was observational, the investigators were not able to determine whether treatment of depression would reduce the risk of cognitive decline among patients with type 2 diabetes – a possibility that should be addressed in future studies, they said.
Despite the limitations, the findings suggest that "a potentially reversible factor may be promoting general cognitive decline in the broad population of patients with type 2 diabetes," the investigators said.
"Since dementia is one of the fastest growing and most dreaded complications of diabetes, our findings may be important for public health," they concluded.