None listed
Conditions
Brief summary
To date, almost all large neurocognitive studies of type 1 diabetes (T1D) have focused on paediatric groups, as compared to most type 2 diabetes (T2D) studies which focus on old age. Early onset diabetes has severe impacts on the neurocognitive development of children and adolescents with T1D, particularly in learning and memory skills. This deficit is accompanied by atrophic changes in the medial prefrontal regions that are known to be rapidly developing in children. While there is a plethora of literature linking T2D with greater risk of dementia, little is known about the role of metabolic and vascular factors on the ageing brain in adults with T1D. One retrospective study has shown that elderly adults with T1D are 83% more likely to get dementia compared to a 50% greater risk in T2D than in non-diabetic adults. However, the frequent presence of comorbidities in older diabetic adults further complicates the underlying mechanism of accelerated brain ageing in T1D. A postulated underlying mechanism of T1D-related cognitive decline is endothelial dysfunction in the cerebral microvasculature caused by pro-inflammatory cytokines associated with the disease and advanced glycation end-products (AGE) due to hyperglycaemia. We have shown significant cerebral arterial stiffness (20%) in elderly T2D adults compared to non-diabetics, which is linked to poorer perfusion and performance during cognitive testing. Structural and functional changes of the cerebral vasculature is already evident in young T1D adults (mean age of 32 years) where a significant 20% reduction in cerebral vasodilator responsiveness to a hypercapnic challenge was seen compared to non-diabetic controls. The authors also reported significant stiffening of the carotid arteries that is independent of the presence of hyperlipidaemia. It seems that despite the arduous therapy of multiple insulin injections daily, this does not prevent the occurrence of serious late-arising complications including kidney failure, blindness and widespread cardiovascular disease in T1D. Given that diabetes is a systemic disease, it is plausible that multiple organs including the auditory system are also affected; yet little attention has been given to preserving auditory function in diabetes. Age-related neurodegeneration of different cortical areas and/or cognitive impairment may also affect central auditory function. Central auditory dysfunction is hypothesised to occur before objective cognitive tests become abnormal. There is no study evaluating the link between cerebrovascular dysfunction and cognitive impairment and central auditory dysfunction in T1D. We hypothesise that T1D adults have cerebrovascular dysfunction and elevated inflammation, mediated by glycation of the endothelium, which will negatively impact their cognitive and auditory function.
Interventions
A pilot cross-sectional study involving Type 1 Diabetic (T1D) adults and age-matched non-diabetic controls will be conducted over two visits scheduled up to seven days apart.
Anthropometric measurements of height, weight and waist circumference will then be obtained prior to clinic Blood Pressure (BP) and arterial compliance (AC) measurements. We will obtain a finger-prick glucose reading from T1D to ensure that their blood glucose levels are at least 6.5mmol/L before proceeding with the rest o
A pilot cross-sectional study involving Type 1 Diabetic (T1D) adults and age-matched non-diabetic controls will be conducted over two visits scheduled up to seven days apart. Anthropometric measurements of height, weight and waist circumference will then be obtained prior to clinic Blood Pressure (BP) and arterial compliance (AC) measurements. We will obtain a finger-prick glucose reading from T1D to ensure that their blood glucose levels are at least 6.5mmol/L before proceeding with the rest of the assessments. Participants will then be fitted with a headpiece with two ultrasound probes on both sides of the temporal region. This transcranial doppler (TCD) device will monitor the blood flow velocity in either the middle cerebral artery or the anterior cerebral artery. Participants will have their cerebral blood flow velocity recorded at rest. Participants will then perform a series of cognitive tasks continuously for approximately 70 mins, whilst the TCD device records changes in blood flow velocities. The neuropsychological test battery will consist of the Trail Making Task, the N-back task, Rey-Osterrieth complex figure, and the NIH Toolbox Battery of cognitive function. Volunteers will arrive for the second visit and a blood sample will be obtained. They will complete paper-based questionnaires that will measure various subjective perceptions of their current mood states using the Profile of Mood States (POMS) Questionnaire and the Center for Epidemiological Studies Depression Scale (CES-D) and diabetes self-care. Volunteers will then proceed to do a 10-min auditory function test, the NIH Toolbox 9-hole Pegboard Dexterity test, and the Addenbrooke’s Cognitive Examination-III (a measure of global cognitive status) (ACE-III).
Sponsors
University of Newcastle
Eligibility
Sex/Gender
All
Age
30 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria for T1D: Age 30 – 80 years old T1D diagnosed before 18 years of age No advanced diabetes complications such as blindness or deafness Not hospitalised for severe glycemic events in the last 3 months Inclusion criteria for control group: No T1D or T2D diagnosis and HbA1c <6.5% Not taking medication for hypertension and cholesterol
Exclusion criteria
Not fluent in reading and writing in English No detectable transcranial Doppler (TCD) ultrasound signal in the middle cerebral artery on either side. Liver or kidney disease Malignant cancer Excessive alcohol intake (>15 drinks per week) Pregnancy Neurological conditions including stroke, TIA, major depression, multiple sclerosis, Parkinson’s disease or dementia or mild cognitive impairment. Unwilling to provide a blood sample
Outcome results
None listed