Disentangling the Effect of Brain Insulin Resistance on Brain Health

Summary

People with diabetes are at increased risk of developing dementia, including Alzheimer's disease and vascular dementia. In addition, persons with diabetes have more pronounced age-related brain atrophy and cognitive difficulties compared to people without diabetes. The mechanisms behind the effects on the brain of diabetes are still unclear. New research suggests that the brains of some people with diabetes do not respond normally to insulin signals, a condition known as brain insulin resistance (BIR). To date, there have been no large clinical studies investigating BIR and its impact on brain health, but several smaller studies suggest that BIR may be a cause of cognitive decline and impaired brain health in people with diabetes. Another mechanism that may contribute to impaired brain health in people with diabetes is damage to the blood vessels in the brain. Damage to blood vessels is a well-known complication of diabetes, but how it affects the brain is not fully described. In this project, we will investigate the relationship between BIR and brain blood vessel dysfunction and its relationship to cognition and brain function. This is done by examining patients with type 1 diabetes (T1D), type 2 diabetes (T2D) and healthy controls. The participants will undergo MRI brain scans to assess the impact of BIR on the brain physiology and to evaluate brain blood vessel health. Participants will undergo comprehensive assessments of their cognitive abilities and thorough health examination.

Eligibility

Inclusion Criteria (all):

* age 50-80 years

Inclusion Criteria (diabetes only):

* Diagnosis of either type 1 diabetes or type 2 diabetes
* Diabetes duration of ≥10 years for individuals with type 1 diabetes and ≥5 years for individuals with type 2 diabetes

Exclusion Criteria:

* HbA1c \>100 mmol/mol
* Other type of diabetes
* Weight \>140 Kg
* Treatment with drugs that cannot be paused for 12 hours
* Diagnosis of dementia
* Active and recent (1year) malignant disease
* History of major stroke
* Major depression and/or treatment with antipsychotics
* History of traumatic brain injury
* Other medical condition or disorder (e.g., epilepsy, recent concussion) that in the opinion of the investigator precludes compliance with the protocol, evaluation of the results or represent an unacceptable risk for the participant's safety.
* Inability to perform neuropsychological tests (e.g., severe vision and hearing impairment that cannot be improved with aids such as glasses and hearing aids, or language barrier.)
* Severe claustrophobia
* Foreign bodies of metal in the body which prohibits brain MRI scans (e.g. pacemaker or screws/plates from surgery in the head or neck region)
* Participants who do not wish to be informed about accidental findings by MRI
* eGFR measurement \<45 within 3 months of study visit

Conditions3

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