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
Sex
ALL
Min age
50 Years
Max age
80 Years
Healthy volunteers
Accepted
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
Primary outcome measure(s)
Correlation between brain insulin response and cognitive measures — Baseline (only measured once) Brain insulin response is assessed by measuring changes in cerebral blood flow following intranasal insulin administration, using arterial spin labelling (ASL) MRI.
The neuropsychological test battery includes the following:
* Rey Auditory Verbal Learning Test (RAVLT)
* Trail Making Test (TMT) part A and B
* Symbol Digit Modalities Test (SDMT)
* RBANS Digit Span forward (Version A)
* Wechsler Adult Intelligence Scale III Letter-Number Sequencing test (WAIS-LNS)
* Verbal Fluency test (phonetic and semantic)
* Rapid Visual Processing (RVP) test from the Cambridge Neuropsychological Test Automated Battery (CANTAB) using A' (RVP-A) and mean latency for correct responses
Motor function (Grooved Pegboard)
Montreal Cognitive Assessment (MoCA)
Correlation between cerebrovascular reactivity and cognitive measures — Baseline (only measured once) Cerebrovascular reactivity is assessed by measuring changes in cerebral blood flow responses to inhalation of hypercapnic air (air enriched with 5% CO2). Cerebral blood flow is measured using combined blood-oxygen-level-dependent (BOLD) MRI, ASL MRI, and phase contrast mapping (PCM) MRI.
The neuropsychological test battery includes the following:
* Rey Auditory Verbal Learning Test (RAVLT)
* Trail Making Test (TMT) part A and B
* Symbol Digit Modalities Test (SDMT)
* RBANS Digit Span forward (Version A)
* Wechsler Adult Intelligence Scale III Letter-Number Sequencing test (WAIS-LNS)
* Verbal Fluency test (phonetic and semantic)
* Rapid Visual Processing (RVP) test from the Cambridge Neuropsychological Test Automated Battery (CANTAB) using A' (RVP-A) and mean latency for correct responses
Motor function (Grooved Pegboard)
Montreal Cognitive Assessment (MoCA)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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