Assessing Cognitive fUnction and MEasuring the Cerebral circulatioN on HaemoDialysis

Study Overview
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Brief Summary
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Stroke disease and cognitive impairment are common in patients established on haemodialysis (HD) for end-stage renal disease (ESRD). Further, initiation of HD appears to transiently increase the risk of stroke. The mechanism by which this occurs is not known. Using ultrasound, patient questionnaires and brain MRI our study will observe changes in cognition and cerebral blood flow whilst receiving HD compared to a non-dialysis day. Transient clinical and ultrasound alterations will be correlated to radiographic changes in cerebral perfusion and structure on MRI to determine the underlying mechanism for the increased stroke risk. The investigators will observe this effect in the immediate and longer term (12 months observation). A greater understanding will allow development of effective preventive strategies.

Detailed Description
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Stroke is common in the United Kingdom and a leading cause of adult disability. It has been reported that more than half of all stroke survivors remain dependent on carers for everyday activities. A greater understanding stroke disease has led to improvements in stroke care for the general population. Patients with ESRD are at increased risk of cerebrovascular disease with a risk approximately 5-10 times higher than the general population yet a relative paucity of data exploring the mechanisms and impact of stroke disease on patients on HD remains. Signs of cerebrovascular disease are common with evidence of early stroke disease (white matter hyperintensities on MRI) having been described in up to 50% of ESRD patients. In addition to this it is now estimated that up to 70% of patients on dialysis aged 55 years and older have moderate to severe cognitive impairment. Previous work has revealed that cognition declines during dialysis - specifically a decrease in executive function has been reported, without significant memory impairment. Such findings are in suggestive of vascular related injury. Mean cerebral blood flow assessed by transcranial Doppler ultrasound is reduced during dialysis, although whether this finding is associated with a clinical outcome is not clear. In order to generate appropriate preventive strategies for stroke in ESRD the mechanism by which injury occurs must be confirmed. In addition, although a decrease in executive function has been shown during HD it is unclear if long-term HD is associated with progressive decline or if this clinical finding correlates with neuroimaging. This study is being performed to determine: The impact of long term HD (including indices of cardiovascular instability) on changes on brain MRI and cognitive function. The relationship between intracerebral blood flow rate, brain MRI findings and neurocognitive function The relationship between intracranial blood flow measures (during and post haemodialysis (HD)) and brain perfusion and structure Following informed written consent patients will be observed over a 12 month period. On the first visit participants will undergo a transcranial ultrasound before and during HD to achieve baseline and intra-dialytic blood flow velocities. During the dialysis sessions a neurocognitive assessment (patient questionnaire) will be performed which will assess multiple cognitive domains. On completion of dialysis a subgroup will undergo a brain MRI. All patients will meet with the investigators within 2 weeks to repeat the neurocognitive assessment on a non-dialysis day. This will allow for comparison of cognitive changes, alterations in cerebral blood flow and (in some) correlation with MRI findings. All participants will repeat this process 12 months later.

Official Title
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Exploring the Natural History of Cerebrovascular Disease in Patients With End-stage Renal Disease on Haemodialysis

Conditions
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End-Stage Renal Disease, Stroke, Cognition Disorders

Intervention / Treatment
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* Other: Observing effect of routine HD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients treated with HD at the Glasgow Renal Unit and its satellite units Exclusion Criteria: Planned live donor transplant is planned during the next 6 months Predicted life expectancy <6 months Inability to give informed consent Contraindications to MRI imaging (pacemaker, extreme claustrophobia), Known clinical or radiological diagnoses of cerebrovascular disease Severe cognitive impairment (MOCA <17)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with ESRD on HD<br>Adult patients with ESRD on HD. Observing the effect of a single HD session on cerebral blood flow (assessed by transcranial doppler) and cognitive function (assessed by neurocognitive questionnaires). Subgroup to undergo brain MRI. | Other: Observing effect of routine HD<br>* Observing effect of routine HD via transcranial doppler, neurocognitive questionnaires and (in some) brain MRI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of white matter hyperintensities on MRI | Use of visual rating scales to quantify white matter burden at time 0 and 12 months | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between alterations in cerebral blood flow and cognition | Statistical correlation determined between a decreased in cerebral blood flow (as measured on transcranial doppler) and reduction in cognitive scores on assessment | Within 4 hour treatment period (of HD) | 
| Correlation between alterations in cerebral blood flow and white matter hyperintensity burden progression | Statistical correlation between reductions in cerebral bloe | 12 months | 
| Evidence of transient cognitive impairment during HD | Use of multi-domain neurocognitive battery to assess cognition during HD. Baseline cognition will be assessed on a non-dialysis day. | Within 2 weeks (direct comparison of cognition during dialysis and on non-dialysis day) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ESRD, Dialysis, Cerebrovascular disease