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Depression Doubles Dementia Risk in Diabetic Patients
« on: April 21, 2012, 05:58:58 PM »
Depression Doubles Dementia Risk in Diabetic Patients

Deborah Brauser

Authors and Disclosures

December 5, 2011 — Depression coupled with diabetes has been linked to a significantly increased risk of developing dementia compared with diabetes alone.

A large study of more than 19,000 adults with type 2 diabetes showed that those with comorbid depression had a 2-fold higher risk of developing dementia over 5 years compared with their counterparts who did not experience depression.

In addition, younger participants with depression also had a significantly higher risk for dementia compared with patients who were older, whereas those who took insulin had a significantly lower risk compared with those were not on insulin.

"Clinicians who treat diabetes, such as primary care doctors and endocrinologists, already realize that there are comorbidities and behaviors that can worsen risks," lead author Wayne Katon, MD, professor and vice chair in the Department of Psychiatry and Behavioral Sciences at the University of Washington Medical School in Seattle, told Medscape Medical News.

"Our study found that depression is an important comorbidity that needs to be screened for among diabetic patients and treated effectively. This might decrease the risk of developing a very serious complication, such as dementia," he added.

Dr. Katon noted that the finding that younger patients were more affected than older patients was also significant because past research has suggested that depressed people develop diabetes 5 to 6 years earlier than those who are not depressed.

"Given that depression is potentially modifiable, future studies are needed to further evaluate whether effective depression interventions reduce the risk of dementia and identify the mechanisms that may explain our observation," write the investigators.

The study was published online December 5 in the Archives of General Psychiatry.

Poor Glycemic Control

According to the investigators, there is a significant link between depression and diabetes that appears to be bi-directional. Not only can depression lead to an increased risk for diabetes, but adult-onset diabetes can lead to an increased risk for depression, they write.

Dr. Katon said that previous research suggests diabetes is also a risk factor for dementia, as is depression. However, to his knowledge, only 1 other study has looked at whether having both disorders may lead to an even greater risk for dementia.

In a cohort study of 3837 patients with diabetes, published in 2010 in the Journal of General Internal Medicine in 2010 and reported by Medscape Medical News at that time, Dr. Katon and colleagues found that patients with comorbid depression and diabetes were twice as likely to develop dementia as those who had diabetes only.

"That study included participants with limited diversity. So we wanted to do a much bigger study with a more diverse population that would also let us do some innovative things in our analysis, including examining interactions between depression and insulin treatment and controlling for health risk behaviors."

Dr. Katon noted that patients with comorbid depression and diabetes often have poor glycemic control and take worse care of themselves in terms of diet and not taking prescribed medications.

He added that this poor glycemic control, in addition to increased pro-inflammatory factors and increased cortisol levels often found in both disorders, could be factors contributing to an increased risk of dementia.

Risk Even Higher in Younger Patients

The Diabetes Study of Northern California (also known as DISTANCE) was created to assess patients living with diabetes, as found through the Kaiser Permanente Northern California Diabetes Registry. Baseline information was collected through surveys from May 2005 to December 2006.

The Diabetes and Aging Study is an ongoing cohort trial of DISTANCE, focusing specifically on medical issues experienced by DISTANCE's older participants. For the current analysis, the investigators evaluated data on 19,239 of the participants between the ages of 30 and 75 years (mean age, 58.8 years; 51% men; 22% white, 19% Latino, 17% black, and 12% each for Asian and for Filipino).

Depression symptoms were determined by a score of 10 or more on the Patient Health Questionnaire 8 (PHQ-8); a clinical diagnosis based on the International Classification of Diseases, Ninth Revision; and/or past-year prescriptions of antidepressants.

Dementia risk was determined according to a clinical diagnosis of the disorder given 3 to 5 years after the baseline assessments.

Results showed that 3766 (19.6%) of the participants had both depression and diabetes.

Of these patients, 2.1% received 1 or more diagnoses of dementia during the follow-up period compared with 1.0% of those with diabetes alone (incidence rates, 5.5 per 1000 person-years vs 2.6 per 1000 person-years, respectively).

After adjustment for age, sex, and other demographic factors, the participants who had a diagnosis of comorbid depression at baseline had a 2.02 greater risk of developing dementia (95% confidence interval [CI], 1.73 - 2.35) during the 3 to 5 years after baseline assessments than those without depression (P < .001).

In addition, patients who were younger than 65 years had a significantly higher risk for dementia associated with depression compared with those who were older (hazard ratios [HRs], 4.42 [95% CI, 3.11 - 6.29] vs 2.01 [95% CI, 1.65 - 2.45]; P < .001).

Finally, those who took insulin were at a decreased risk for dementia associated with depression compared with those who did not take this treatment (HRs, 1.59 [95% CI, 1.17 - 2.18] vs 2.82 [95% CI, 2.33 - 3.42]; P = .005).

Depression Not Prodromal

The researchers note that "insulin modulates levels of ß-amyloid in the brain" and that past research has suggested that insulin dysregulation may lead to pathophysiology of Alzheimer's disease (AD).

"Moreover, intranasal insulin may preserve memory and general cognitive abilities in patients with mild cognitive impairment or mild to moderate AD."

They write that overall study effect sizes were "quite robust" for both primary and sensitivity assessments, which included examining only diagnoses of dementia in years 4 and 5, or only including a score of 10 or more on the PHQ-8.

In fact, they note that sensitivity analyses showed an even higher risk for dementia in those with depression, "suggesting that these results are not due to depression being a prodromal phase of dementia or the depression definition."

"We were also able to control for factors such as smoking and obesity. And we expected that there would be some mediation on depression causing dementia because of these health risk behaviors that are associated with depression. But in fact, those behaviors had no effect on the risk at all," added Dr. Katon.

"So I think we can conclude that it is probably the psychobiological changes associated with depression that increased this risk more than health risk behaviors."

Equal to 5-Year Earlier Onset

"This study showed a very interesting relationship that we need to understand further," J. Wesson Ashford, MD, PhD, clinical professor (affiliated) of psychiatry and behavioral sciences at Stanford University in Palo Alto, California, told Medscape Medical News.

"The complex relationship between depression and diabetes has been studied for a long time and I would say that the basis of it is not known. So when we're dealing with these complex epidemiological studies, you find relationships that might be important. But it's also important not to confuse them with cause-and-effects," said Dr. Ashford.

"It points you in a direction but it doesn't establish a path."

Still, Dr. Ashford, who is chair of the Memory Screening Advisory Board of the Alzheimer's Foundation of America and clinical editor of the Journal of Alzheimer's Disease, noted that clinicians should screen for this possible risk factor.

"A 2-fold increase of risk would be comparable to a 5-year earlier onset of incidence. This should lead to providing cognitive screenings 5 years earlier than when it otherwise would be started. In other words, screenings should probably begin annually at 60 years of age as opposed to 65 years of age," he said.

"These screenings can improve quality of care because having unrecognized dementia can be a disaster in someone with diabetes as medications are often missed or forgotten."

Insulin Debate

Concerns voiced included that the study did not say whether or not someone treated for depression would be less likely to develop dementia. In fact, because use of an antidepressant was one of the criteria for identifying participants with depression, Dr. Ashford said that it is a possibility that that treatment could have been a risk factor itself.

"So again, you have to be careful with the cause and effect. But it absolutely raises some questions in an area that has huge interest, said Dr. Ashford.

He also noted that there has been considerable debate in the field about whether insulin is good or bad for amyloid production.

"Overall, I'm hearing more and more about how pessimistic the whole field is about finding a treatment for Alzheimer's. There are billions of dollars that have been spent that has led to nothing. And it's been 10 years since anything beneficial has been found," said Dr. Ashford.

"An interesting question from this paper is: does this mean patients with diabetes and depression should be started on medications? There's no evidence that these medications prevent the development of Alzheimer's, so I would say no.

"But on the other hand, there is evidence that as soon as a person does develop dementia, they should be put on a cholinesterase inhibitor. And that does seem to have a long-term benefit in terms of delaying nursing home placement and delaying cognitive progression a little bit. So again, interesting questions have been raised," he said.

The study was supported by grants from the National Institute of Mental Health Services, the National Institute of Diabetes and Digestive and Kidney Disease, and by the Centers for Diabetes Translation Research. Dr. Katon reported board memberships for Eli Lilly and Wyeth and receiving lecture honoraria from both companies, plus Pfizer and Forest. Dr. Ashford reported having an interest in MemTrax, which is a screening test for AD.

Arch Gen Psychiatry. Published online December 5, 2011. Abstract

Association of Depression With Increased Risk of Dementia in Patients With Type 2 Diabetes

The Diabetes and Aging Study

Wayne Katon, MD; Courtney R. Lyles, PhD; Melissa M. Parker, MS; Andrew J. Karter, PhD; Elbert S. Huang, MD, MPH; Rachel A. Whitmer, PhD

Arch Gen Psychiatry. Published online December 5, 2011. doi:10.1001/archgenpsychiatry.2011.154

Context  Although depression is a risk factor for dementia in the general population, its association with dementia among patients with diabetes mellitus has not been well studied.

Objective  To determine whether comorbid depression in patients with type 2 diabetes increases the risk of development of dementia.

Design  The Diabetes and Aging Study was a cohort investigation that surveyed a racially/ethnically stratified random sample of patients with type 2 diabetes.

Setting  A large, integrated, nonprofit managed care setting in Northern California.

Participants  A sample of 19 239 diabetes registry members 30 to 75 years of age.

Main Outcome Measures  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 were used to identify prevalent cases of depression. Clinically recognized dementia was identified among subjects with no prior ICD-9 Clinical Modification (ICD-9-CM) diagnoses of dementia. To exclude the possibility that depression was a prodrome of dementia, dementia diagnoses were only based on ICD-9-CM diagnoses identified in years 3 to 5 postbaseline. The risk of dementia for patients with depression and diabetes relative to patients with diabetes alone was estimated using Cox proportional hazard regression models that adjusted for sociodemographic, clinical, and health risk factors and health use.

Results  During the 3- to 5-year period, 80 of 3766 patients (2.1%) with comorbid depression and diabetes (incidence rate of 5.5 per 1000 person-years) vs 158 of 15 473 patients (1.0%) with diabetes alone (incidence rate of 2.6 per 1000 person-years) had 1 or more ICD-9-CM diagnoses of dementia. Patients with comorbid depression had a 100% increased risk of dementia during the 3 to 5 years postbaseline (adjusted hazard ratio, 2.02; 95% confidence interval, 1.73-2.35).

Conclusion  Depression in patients with diabetes was associated with a substantively increased risk for development of dementia compared with those with diabetes alone.

Author Affiliations: Department of Psychiatry and Behavioral Sciences, School of Medicine (Dr Katon), and Department of Health Services, School of Public Health (Drs Lyles and Karter), University of Washington, Seattle; Kaiser Permanente Division of Research, Oakland, California (Ms Parker and Drs Karter and Whitmer); and University of Chicago, Chicago, Illinois (Dr Huang).