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Frederik Nørregaard Pedersen

Department of Ophthalmology

Diabetic retinopathy as a marker of cognitive dysfunction and depression: a clinical and epidemiological approach

In recent years, damage to the nerve fibers in the back of the eye (retina) has been experienced as an early sign of damage in type 2 diabetes. In addition, it is now known that people with type 2 diabetes are at increased risk of developing brain diseases, such as mild memory impairment and Alzheimer’s disease, as well as mental illness in the form of depression. Currently, it is time and cost consuming to asses changes in the brain, but recent research has shown that patient-friendly eye examinations can detect neurodegenerative diseases.

Recent studies have also shown that depression can have a physiological component, which can be measured by changes in structures in the retina of the eye. In this study, we explore the fact the eye is a protruding part of the brain, which means that the brain and the eye share common features. We will conduct a clinical study, to assess whether there is an association between changes in the retina of the eye (e.g. vascular structure, retinal thickness and oxygen saturation) and mild memory impairment and depression, respectively, in people with type 2 diabetes.

Furthermore, we will conduct a register-based study to test whether there is a connection between the severity of diabetic eye disease (diabetic retinopathy, DR) and Alzheimer’s disease and depression, respectively, in Danes who have been screened for DR. The research project thus consists of two parts: 1) a clinical cross-sectional study and 2) a register-based cohort study.

In the clinical study, 200 people with type 2 diabetes will be invited to participate in a clinical cross-sectional study. The Funen Diabetes Database will be used as recruitment tool. Participants will undergo a thorough eye examination as well as neuropsychological examinations for signs of mild memory impairment. They will also complete questionnaires regarding depressive symptoms.

The clinical study is being conducted in close collaboration with a large European multicenter research project, RECOGNISED, which will investigate whether the light-sensitivity of retina can predict the development of mild memory impairment and dementia in patients with type 2 diabetes. We are part of this international research project, which means that participants in the cross-sectional study will also, if they wish, have the opportunity to participate in RECOGNISED. The current PhD is an independent extension of the RECOGNISED study and the applicant will participate in RECOGNISED as local team manager.

The register-based cohort study will use national registers. DiaBase is a national register containing information about 200,000 people with diabetes including severity of DR. Individuals can be linked to the National Patient Register, which contains information about diagnoses. Hereafter, we can investigate the 5-year risk to develope Alzheimer’s disease or depression, and assess whether this is related to the severity of DR. Furthermore, we will look the other way around and test the importance of Alzheimer’s disease and depression have on the development of DR. To ensure optimal study design, each person from DiaBase will be linked to five control persons (same age and gender) without diabetes from the National Patient Register.

The study will, based on the total population of eye-screened Danish patients with diabetes, clarify the connection between the development of DR and, Alzheimer’s disease and depression. These studies will, by far, be the largest conducted worldwide on these topics.

Overall, the research project will help to create awareness in this area among both healthcare professionals and patients. Early risk detection could mean better diabetes care and fewer complications, which will have a major impact on quality of life and contribute to socio-economic gains. Any findings may contribute to the discussion of individualized screening and treatment, if some individuals within this group are at increased risk of developing memory impairment or depression.

Tasks to be solved during the study: 1) planning of examination procedure (performed), 2) obtain required permits (currently awaiting approvals), 3) invite participants (September 2020), 4) examine participants (Oktober to February 2020), 5) perform data analysis (initiated in the register-based study), 6) write and publish research results and present these at conferences (first results are expected to be submitted December 2020).