Individuals with diabetes who also have depression have a greater risk of developing dementia than do diabetes patients without concurrent depression.

That was the finding of a study that surveyed a racially and ethnically stratified random sample of patients with type 2 diabetes in a large managed-care setting in California.

Patients with comorbid depression and diabetes had a 100 percent increased risk of dementia during a period three to five years after onset of the study.

“Up to 20 percent of people with diabetes have clinically significant depression,” lead author Wayne Katon, M.D., told Psychiatric News. “This study shows that comorbid depression has an added increased risk of macro- and micro-complications and an increased risk for dementia. It speaks to the importance of providing integrated quality mental health and general health care.” Katon is a professor of psychiatry at the University of Washington.

In the study, cases of depression were identified among a sample of 19,239 diabetes registry members aged 30 to 75 enrolled in Kaiser Permanente Northern California using the Patient Health Questionnaire-8, International Classification of Diseases, Ninth Revision (ICD-9) diagnoses of depression, and/or antidepressant prescriptions in the 12 months prior to baseline.

Because depression is sometimes a prodromal symptom of early dementia itself (as opposed to an antecedent condition), dementia diagnoses were based only on ICD-9-CM diagnoses identified in years 3 to 5 postbaseline.

The risk of dementia for patients with depression and diabetes compared with patients with diabetes alone was estimated using statistical models that adjusted for sociodemographic, clinical, and health-risk factors.

A total of 3,766 (19.6 percent) of the patients with diabetes met criteria for clinically significant depression. Katon and colleagues found that 80 of the 3,766 patients (2.1 percent) with comorbid depression and diabetes had dementia in years 3 to 5; in contrast, 158 of 15,473 participants (1.0 percent) without depression developed dementia during the follow-up period.

“Although the bidirectional associations between depression and diabetes—and between both disorders and dementia—are well known, the study adds important new knowledge about the added impact of depression and diabetes on incident dementia that has important implications for public health, clinical-care delivery, and potentially our understanding of the pathogenesis of dementia,” said geriatric psychiatrist Yeates Conwell, M.D., who reviewed the report.

“This carefully conducted study shows that the combination of the two increases the risk of developing dementia two-fold over those who have diabetes alone,” he told Psychiatric News. “The public-health significance lies in the fact that older adults are the most rapidly growing segment of the population, and the increasing prevalence of diabetes in the population is reaching crisis proportions. In coming decades the impact of these demographic and clinical shifts may combine to cause further increases in the number and proportion of older adults with dementia, and consequently place even greater burden on health care systems and their financing.”

“The clinical implications are important as well,” Conwell said, “adding further impetus to the need for early diagnosis and aggressive treatment of depression in people with diabetes.”

Conwell is vice chair of psychiatry and director of the geriatric psychiatry program at the University of Rochester Medical Center. His research has focused on the incorporation of community-based services into a more comprehensive collaborative-care model for older adults.

Katon told Psychiatric News that the study also looked at other variables that may affect the association between comorbid depression and diabetes and later development of dementia. Among the key findings is that depression seemed to have a greater impact on younger patients with diabetes in terms of later development of dementia. “It suggests that we may be seeing the development of dementia earlier in patients with comorbid depression,” he said.

Also noteworthy is the finding that treatment with insulin appears to have a protective effect against development of dementia. “Data have emerged recently that the brain may have insulin receptors in areas implicated in memory,” Katon said. “And some new studies have indicated that intranasal insulin gets immediately to the brain and may help prevent cognitive decline. But our findings of a protective effect need to be replicated.”

Finally, the study also looked at whether lifestyle characteristics that sometimes accompany diabetes influenced the risk for dementia. “We found that actually when we adjusted for those factors they had very little effect,” Katon said.

That finding suggests that biological factors associated with depression may be at work in dementia risk in these patients. “We know that dysregulation of the pituitary axis and cortisol levels—which can be caused by depression—have effects on the brain that can also contribute to dementia,” Katon noted. “There is also evidence that depression is associated with inflammatory factors that increase the risk for dementia and that depression is also associated with decreased insulin sensitivity.”