Comorbid Diabetes and Depression Increase Dementia Risk
By Pauline Anderson
Medscape Medical News
March 11, 2010 — Patients with diabetes who also have major depression have almost a 3-fold increased risk of developing dementia compared with patients with diabetes alone, according to a new study.
This finding is important because as the population ages, it is becoming increasingly important to uncover clues about what is contributing to the "epidemic" rates of dementia, said lead study author Wayne J. Katon, MD, professor and vice chair, Department of Psychiatry Behavioral Sciences, University of Washington School of Medicine, Seattle.
"We’re moving into an era where we have a much larger aging population than ever before and the rates for dementia increase with each decade. That’s certainly going to cost the Medicare system a huge amount of money, not to mention the suffering to families," Dr. Katon told Medscape Psychiatry.
Both diabetes and depression are treatable conditions, and both are risk factors for dementia, said Dr. Katon. "If we’re able to treat those risk factors, we may be able to decrease the prevalence of this illness," he said.
The results of the study underline the importance of screening for depression among patients with diabetes and for diabetes in patients with depression, said Dr. Katon.
The study was published online January 28 in the Journal of General Internal Medicine.
The prospective cohort Pathways Epidemiologic Follow-Up Study included 3837 patients with diabetes enrolled in Group Health, a mixed-model capitated health plan in the state of Washington. At baseline, the subjects completed the Patient Health Questionnaire, which gathers information on the 9 Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) major depressive symptoms.
Dementia Codes
After about 5 years, the presence of dementia in surviving subjects who had no dementia at baseline was determined from both outpatient and inpatient databases using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, which include senile dementia uncomplicated, Alzheimer’s disease, vascular dementia, and dementia not otherwise specified.
During the follow-up period, 199 participants (5.2%), representing more than 15,468 person-years of follow-up, met the primary definition of dementia with at least 1 ICD-9-CM dementia diagnosis for an incidence rate of 12.9 per 1000 person-years.
Of the 455 patients with major depression at baseline, 7.9% had a new diagnosis of dementia during follow-up during 1671 person-years, for an incidence rate of 21.5 per 1000 person-years. This compared with 163 of 3382 patients (4.8%) without major depression during 13,797 person-years, for an incidence rate of 11.8 per 1000 person-years.
After adjusting for sex, age, race, education, diabetes duration, diabetes complications, hypertension, health habits, and other variables, the hazard ratio (HR) for developing dementia for patients with major depression compared with those without depression was 2.69 (95% confidence interval, 1.77 – 4.07).
Excluding patients who developed dementia during the first 2 years of the study had similar results (HR = 2.05 in an adjusted model), as did using the more conservative definition of dementia that requires 2 or more ICD-9-CM codes (adjusted HR = 2.77).
Bidirectional Relationship
Depression and diabetes are closely linked in a "bidirectional" relationship, said Dr. Katon. Between 15% and 20% of people with diabetes will have a significant clinical depression, and depression is 2 to 3 times more common among people with diabetes compared with those without diabetes, he said.
One way depression may raise the risk for developing diabetes is that it leads to poor self-care. "Depressed diabetics don’t follow their diet, they smoke more, they’re more obese, have higher blood sugars, and are more apt to be nonadherent to their medications," said Dr. Katon.
But poor self-care does not appear to explain the increased risk for dementia among diabetic patients who have depression. The current study adjusted for baseline physical activity, smoking, and other health habits.
Biological Explanation More Potent
"This suggests that maybe the biological parts of depression, such as its effect on the hypothalamic pituitary axis and higher cortisol levels, its effect on the autonomic nervous system, and the effect on proinflammatory factors, may be more salient, more potent, reasons for why depression is associated with increased risk for dementia," said Dr. Katon.
It is also possible that depression could be a prodromal symptom of early-stage dementia. But the finding that depression remained associated with an increased risk for dementia after excluding a diagnosis of dementia in the first 2 years of the study suggests that this is likely not the case, the study authors write.
Diabetes may also increase depression risk through complications such as loss of eyesight or amputation, which can have a profound impact on mood.
Importance of Screening
Primary care physicians should screen patients with diabetes for depression just as they would screen such patients for smoking, said Dr. Katon. But it is also important for psychiatrists to screen their patients for diabetes.
"People with psychiatric illnesses like schizophrenia and bipolar disorder have a much higher prevalence of diabetes; among the chronically mentally ill, the rates of diabetes are 2- to 3-fold higher," he said.
Psychiatry residents are being trained to diagnose chronic medical illnesses and to monitor patients’ weight and blood pressure, said Dr. Katon, adding that some psychiatric medications can cause obesity.
A limitation of the study was that a diagnosis of depression was not made through a structured psychiatric interview and was only measured at baseline. Other limitations include the study's reliance on self-reports of health habits only at baseline and that identification of dementia was based on dementia codes and therefore relied on physician recognition of the condition.
Approached for a comment on the study, William Thies, PhD, chief medical and scientific officer, Alzheimer’s Association, said it was interesting but does not sort out the "confusion" surrounding the issue of a possible link between depression and dementia. He noted that some studies have found such a link, whereas others have not.
"I think this study is interesting but it would not immediately solidify the discussion of the relationship of depression and dementia," said Dr. Thies. "It doesn’t ring any huge bells for me.”
On the other hand, the research linking diabetes to dementia is "fairly well established," he said.
Dr. Thies noted that although the study initially included 3837 patients, only 36 of those with major depression at baseline had a new diagnosis of dementia during follow-up.
"Ultimately, their data about depression and diabetes and dementia sit on the shoulders of 36 people," said Dr. Thies. "So if you add enough caveats, the numbers get smaller and smaller. My rough calculation is that a difference of 10 patients is going to make the rates about equal."
Dr. Katon reports that he has received honoraria for lectures from Wyeth, Eli Lilly, Forest, and Pfizer pharmaceutical companies and serves on the Advisory Board for Eli Lilly and Wyeth. Disclosures of the study coauthors are available in the original study.
J Gen Intern Med. Published online January 28, 2010.
