Young, Depressed, and Diabetic?

The burden of chronic illness (eg, diabetes, obesity, hypertension) and mental illnesses (eg, depression) are steadily rising in the US and globally. Depression worsens the outcomes of other chronic comorbidities, such as diabetes.¹ As people live longer, we need to consider ways to support healthy aging to better address both mental and physical chronic illnesses.²

In a collaborative effort between Aarhus University and the University of Copenhagen (Denmark), and the University of Washington (US), Katon and colleagues³ demonstrate that depression or diabetes independently increase the risk for dementia, and depression and diabetes together magnify the risk for dementia,³ especially in persons under aged 65 years.

In their introduction, the authors succinctly describe suspected reasons that depression and diabetes co-occur and how these illnesses are associated with poor health behaviors important to controlling diabetes. While they acknowledge that previous studies have demonstrated how each of these illnesses increase the risk for dementia, they note that no studies have investigated the interactive effect between depression and diabetes in heightening the risk for dementia, and whether age makes a difference.

This study used data from the Danish Civil Registration System, to assess a population cohort of nearly 2.5 million people-a huge sample size! They chose that cohort by starting with people above aged 50 years, who had no diagnosis of dementia at the beginning of 2007. Within that pool of selected people, they then assessed for how many had diabetes (9.1%), depression (19.4%), or both (3.9%)-numbers that roughly reflect averages in the US and developed countries, telling us that this study cohort is a fair representation of the general population as far as these illnesses being represented.

Researchers tracked this selected cohort over 7 years’ worth of data through the end of 2013. At that point, they measured how many had been diagnosed as new cases of dementia (2.4% incidence) during those 7 years. They also of course gathered data on how many in the cohort were men versus women, age, and marital status. Although the methods of determining diagnoses of depression and dementia might have introduced some selection bias, a prospective nationwide cohort database effectively eliminated nonresponse and recall biases.

Using Cox proportional hazards regression models, the researchers estimated how much increased risk for dementia a person would have over time, if he had diabetes, depression, or both. These estimation models were adjusted for factors that could otherwise hide or falsely increase that calculated risk amount.

Interestingly, the researchers present 4 different risk models, adjusted for different factors ranging from basic demographics like sex, to additional comorbidities and complications of diabetes. This allows the clinician to evaluate what model risk estimate makes most population-based and clinical sense, without overadjusting for factors that might actually mediate part of the causal pathway between a condition such as diabetes and the incidence of dementia.

Overall, having these illnesses carries a stepwise progression of increased risk of dementia-persons with diabetes had a 20% increased risk of dementia, followed by an 80% higher risk in persons with depression. Those with a combination of depression and diabetes had 117% more risk of dementia than those without either illness. The risk of Alzheimer disease or vascular dementia specifically was also similarly high.

The magnified amount of risk for dementia for those with comorbid depression and diabetes was not simply from adding the risk from having each illness individually. The 2 illnesses interacted with each other in some way, multiplying the risk of dementia.

Six percent of diagnosed dementia came from this interactive effect in the cohort. More worrisome is that those younger than aged 65 years living with both depression and diabetes, had a 384% increased risk of being diagnosed with dementia. Twenty five percent of those occurred from this interactive effect. This interactive effect could be from overlapping pathological effects on risk factors for dementia, such as more inflammation and autonomic nervous system dysfunction.⁴

Depression doubled the risk of dementia within approximately 2 to 4 years. Persons with diabetes saw a similar, smaller trend. Of note, a diabetes diagnosis at an early age carried a 50% higher risk of dementia than at a later age, all else being equal. Given that earlier studies have found that comorbid depression and diabetes occur more frequently in younger groups,⁵ these findings of that same group then being at much higher risk for dementia is concerning.

Does it also mean that younger age groups with comorbid depression and diabetes could have an earlier onset of dementia, affecting their cognitive functional abilities during their latter working years? That remains to be seen. While we need to better understand the pathways of how depression and diabetes might interact toward dementia developing, we do know that collaborative care models based in primary care settings help to reduce both depressive symptoms and improve diabetic glycemic control, when both are targeted for treatment together.⁶

However, at a population and policy-making level, what do we need to consider targeting as a society both to treat these diseases and promote health in their prevention? Shoud we focus on food insecurity, harmful health behaviors, limited access to health care and education, or deprived positive social connection? What is our responsibility as psychiatrists in promoting overall health and well-being? In the era of accountable care organizations and blossoming medical homes, the time is now to move that discussion forward.

Disclosures:

Dr D’Silva is a Psychiatry in Primary Care Fellow, MPH candidate; in the department of psychiatry and behavioral sciences, University of Washington, Seattle.

References:

1. Lin EH, Katon W, Von Korff M, et al. Relationship of depression and diabetes self-care, medication adherence, and preventive care. Diabetes Care. 2004;27:2154-2160.
2. Reynolds CF 3rd. Promoting healthy brain aging. JAMA Psychiatry. 2015;72:619-620.
3. Katon W, Pedersen HS, Ribe AR, et al. Effect of depression and diabetes mellitus on the risk for dementia: a national population-based cohort study. JAMA Psychiatry. 2015;72:612-619.
4. Ismail K, Winkley K, Stahl D, Chalder T, Edmonds M. A cohort study of people with diabetes and their first foot ulcer: the role of depression on mortality. Diabetes Care. 2007;30:1473-1479.
5. Katon W, von Korff M, Ciechanowski P, et al. Behavioral and clinical factors associated with depression among individuals with diabetes. Diabetes Care. 2004;27:914-20.
6. Katon WJ, Lin EH, Von Korff M, et al. Collaborative care for patients with depression and chronic illnesses. N Engl J Med. 2010;363:2611-2620.