Cardiovascular Autonomic Neuropathy, Cognitive Impairment, Diabetes Type 2, Peripheral Diabetic Neuropathy
Conditions
Brief summary
The goal of this observational study is to evaluate whether individuals with different types of diabetic neuropathy (peripheral and cardiovascular autonomic neuropathy) are at an increased risk of cognitive impairment and to investigate the potential reasons for this association. The primary research question is: Is diabetic peripheral and cariovascular autonomic neuropathy in type 2 diabetes associated with cognitive decline? To address this question, the study will include individuals with and without type 2 diabetes. All participants will undergo comprehensive neuropathy assessments, neuropsychological evaluations and blood biomarker analysis. In addition, some individuals will undergo structural and functional brain MRI.
Detailed description
Type 2 diabetes (T2D) is a chronic disease with complications that affect various organs over time. While certain complications have been well- established for decades, recent research points to the brain as an important site of diabetes-associated damage. This aligns with the growing awareness of the cognitive impact of diabetes. Diabetes is associated with mild to moderate alterations in cognitive functions across diverse age groups and an increased risk of developing dementia. The precise mechanism underlying these associations remains elusive, but some studies suggest that impaired peripheral nerve function correlates with negative cognitive outcomes and may be associated with structural and functional brain changes. Since diabetic neuropathy is one of the most common complications of diabetes, it might contribute to an increased dementia risk. ASCEND is a clinical descriptive study that aims to evaluate the association between diabetic neuropathy and cognitive function in individuals with type 2 diabetes (compared to controls without diabetes). The study comprises the following visits: * Screening visit * Neuropathy assessment and neuropsychological testing visit * Structural and functional MRI (only a subset of participants) The neuropathy assessment will include the following measures: * Peripheral vibration sensation (biothesiometer) * Cardiovascular autonomic neuropathy (Vagus device) both resting heart rate variability and cardiovascular reflex tests * Nerve conduction velocity and amplitude of the Sural nerves by DPN-check * Light touch and pain sensation (10 g monofilament and 40g needle) * Peripheral small-fiber sympathetic function (Sudoscan device) * Cold and warm sensation of foot and lower leg The neuropsychological test will include 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 (letters S and D) * Grooved Pegboard * Rapid Visual Processing (RVP) test from the Cambridge Neuropsychological Test Automated Battery (CANTAB) using A' (RVP-A) and mean latency for correct responses
Interventions
None listed
Sponsors
Steno Diabetes Center Copenhagen
Rigshospitalet, Denmark
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Since the study includes both individuals with and without diabetes, there are two sets of inclusion criteria.
Exclusion criteria
apply to both indivdiuals with and without diabetes. Inclusion Criteria: For individuals with type 2 diabetes: * Age \>= 65 years * Type 2 Diabetes diagnosis (defined according to the criteria from World Health Organization) for more than 5 years * BMI \<= 35 * Stable diabetes treatment for at least 8 weeks (adjustments of already prescribed insulin doses are accepted) * Plasma hemoglobin ≥ 8.00 mmol/L (male) or ≥ 6.4 mmol/L (female) * Speaks and understands Danish (required for the cognitive tests) * Informed and written consent For individuals without type 2 diabetes: * Age ≥ 65 years * Not diagnosed with T2D diagnosis (defined according to criteria from World Health Organization (WHO)) * Speaks and understands Danish (required for the cognitive tests) * Informed and written consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive composite score (global score) | Baseline (only measured once) | The global score is based on the scores the neuropsychological test battery. The tests are grouped based on cognitive domains and the global cognitive score is assessed by the mean of individual component z-scores. The neuropsychological test battery will include 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 (letters S and D) * Grooved Pegboard * Rapid Visual Processing (RVP) test from the Cambridge Neuropsychological Test Automated Battery (CANTAB) using A' (RVP-A) and mean latency for correct responses |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive domain scores | Baseline (only measured once) | The cognitive domain scores are based on the scores from the neuropsychological test battery. The cognitive domain score is assessed by the mean of individual component z-scores. The neuropsychological test battery will include 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 (letters S and D) * Grooved Pegboard * Rapid Visual Processing (RVP) test from the Cambridge Neuropsychological Test Automated Battery (CANTAB) using A' (RVP-A) and mean latency for correct responses |
| The reduction in gray matter volume in primary somatosensory cortex (S1), primary motor cortex (M1) and hippocampus | Baseline (only measured once) | Structural brain MRI |
| Differences in whiter matter hyperintensities and microbleeds | Baseline (only measured once) | Structural brain MRI |
| Differences in resting state BOLD (Blood oxygenation level dependent) signal | Baseline (only measured once) | Functional brain MRI |
| Differences in BOLD (Blood oxygenation level dependent) signal during n-back memory task | Baseline (only measured once) | Functional MRI |
Countries
Denmark
Outcome results
None listed