Cognitive Impairment and Cerebral Haemodynamics in Individuals With Symptomatic Peripheral Arterial Disease (CInCH PAD)

Background:

Arterial disease of the legs causes symptoms such as pain when walking and may ultimately lead to a leg amputation. Many older people with arterial disease of the legs also have problems with their thinking and memory. Blood flow in the brain may be altered in these people and may be a cause for memory and thinking problems.

Aim:

The aim of this project is to investigate whether people with arterial disease of the legs have altered blood flow in the brain causing problems with memory and thinking.

Research plan:

Twenty people with arterial disease of the legs causing pain while walking and twenty healthy people will have a series of non-invasive assessments. Arterial disease in the legs will be measured using ankle blood pressures before and after walking. Blood flow in the brain will be measured using ultrasound whilst performing memory and thinking tests. Results will be compared between the people with arterial disease in the legs and the healthy people to see if there are any differences in blood flow to the brain and memory and thinking.

Benefits to society:

This project will help determine if there is a link between arterial disease of the legs and memory and thinking problems caused by altered blood flow in the brain. It will enable future research in people with cognitive impairment caused by altered blood supply to the brain and to prevent confusion and further memory and thinking problems in people undergoing surgery for arterial disease of the legs.

Study Overview

• Status: Not yet recruiting
• Conditions: Peripheral Arterial Disease; Cognitive Impairment
• Intervention / Treatment: Diagnostic test: Cerebral haemodynamic testing using transcranial Doppler; Diagnostic test: Ankle-brachial pressure index; Diagnostic test: Six-minute walk test

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: John SM Houghton; Phone Number: +44 (0)116 2502645; Email: jsmh2@le.ac.uk
• Study Contact Backup: Name: Tanya J Payne; Phone Number: +44 (0)116 2502645; Email: tjp28@le.ac.uk

Study Locations

• United Kingdom
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE3 9QP
      • Glenfield Hospital Leicester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

A cohort of individuals with symptomatic peripheral arterial disease (intermittent claudication) with an age- and sex-matched healthy control cohort.

Description

Inclusion Criteria:

• Capacity to provide Informed volunteer/patient consent
• Male or female, aged ≥50 years of age
• Able (in the Investigator's opinion) and willing to comply with all study requirements
• Good understanding of written and verbal English

Peripheral arterial disease specific inclusion criteria:

• Clinical diagnosis of symptomatic PAD (intermittent claudication) confirmed by positive haemodynamic tests (ABPI <0.90 in the symptomatic leg; and/or,
• Post-exercise [walk test] reduction in ABPI of >20% or post-exercise [walk test] reduction in absolute ankle pressure of >30mmHg)

Exclusion Criteria:

• Male or Female, aged under 50 years
• Pregnant
• Unable (in the Investigator's opinion) or unwilling to comply with any study requirements
• Major co-morbidity likely to affect cerebral autoregulation; severe respiratory disease, unilateral carotid artery stenosis (≥50%), atrial fibrillation, severe cardiac failure (left ventricular ejection fraction <20%), or extreme frailty
• History of significant diagnosed psychiatric disorder, learning disability (e.g. dyslexia) or neurological disorder (head injury, epilepsy, stroke and/or transient ischaemic attack [TIA])
• Diagnosis of dementia
• Uncorrected hearing impairment and/or significant visual impairment

Healthy control specific exclusion criteria

• Symptoms of intermittent claudication; and/or,
• Clinical diagnosis or history of PAD

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Individuals with symptomatic peripheral arterial disease; Individuals with intermittent claudication caused by confirmed peripheral arterial disease defined as a resting ankle-brachial pressure index of <0.9 and/or a post-exercise reduction in either ankle-brachial pressure index of >20% or absolute ankle pressure of >30mmHg.	Diagnostic test: Cerebral haemodynamic testing using transcranial Doppler; Measurement of cerebral haemodynamics using transcranial Doppler to insonate the middle cerebral arteries bilaterally testing neurovascular coupling with selected domains from the Addenbrooks cognitive examination III and the digit span forward and backwards.; Diagnostic test: Ankle-brachial pressure index; Ratio of ankle to brachial blood pressure measured using handheld Doppler at rest and after exercise (six-minute walk test).; Diagnostic test: Six-minute walk test; Supervised brisk walk for six minutes. Time and distance to onset of claudication pain and total distance walked (and total time walked if did not complete the full six minutes).
Healthy controls; Age- and sex-matched cohort of individuals without peripheral arterial disease.	Diagnostic test: Cerebral haemodynamic testing using transcranial Doppler; Measurement of cerebral haemodynamics using transcranial Doppler to insonate the middle cerebral arteries bilaterally testing neurovascular coupling with selected domains from the Addenbrooks cognitive examination III and the digit span forward and backwards.; Diagnostic test: Ankle-brachial pressure index; Ratio of ankle to brachial blood pressure measured using handheld Doppler at rest and after exercise (six-minute walk test).; Diagnostic test: Six-minute walk test; Supervised brisk walk for six minutes. Time and distance to onset of claudication pain and total distance walked (and total time walked if did not complete the full six minutes).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak % change of CBv from baseline	Change in response to performance of the ACE-III Cognitive Examination and Digit Span forward and backward.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Autoregulation index (Tieck's model)	Change in response to performance of the ACE-III Cognitive Examination and Digit Span forward and backward.	Baseline
Digit span forward and backward scores	Maximum list length correctly recalled and response consistency (total correct trials)	Baseline
Absolute score achieved on the Addenboook's cognitive examination (III)	Minimum score 0; Maximum score 100 (High scores indicate better cognitive performance)	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Claudication distance	Distance to onset of pain in the six minute walk test	Baseline
Maximal walking distance	Total distance walked during the six minute walk test	Baseline
Ankle-brachial pressure index	Ratio of ankle blood pressure to the brachial blood pressure measured using handheld Doppler	Baseline

Collaborators and Investigators

• Sponsor: University of Leicester
• Collaborators: University Hospitals, Leicester
• Investigators: Principal Investigator: Rob D Sayers, MD, University of Leicester

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: April 12, 2024
• First Submitted That Met QC Criteria: April 12, 2024
• First Posted (Actual): April 17, 2024

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Neurocognitive Disorders; Atherosclerosis; Cognition Disorders; Peripheral Arterial Disease; Peripheral Vascular Diseases; Cognitive Dysfunction
• Other Study ID Numbers: 0963

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Fully-anonymised electronic data will be stored in the Cerebral Haemodynamics in ageing and Stroke Medicine research database for 25 years and will be made available via the University of Leicester data repository (https://leicester.figshare.com/) for a minimum of 10 years.
• IPD Sharing Access Criteria: Access upon request to the study Chief Investigator (Prof R Sayers).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No