The Association Between Cognitive Function and Neuropathy in Individuals With Type 2 Diabetes

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.

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