Cerebral Haemodynamic Changes During Cognitive Testing: A fTCD Study

NCT03134963 | Completed Results

• 1 other identifier: 0613
• Study Type: observational
• Target: 42
• Locations: 1 country
• Sites: 2

Brief Summary

850,000 people live with dementia in the UK, with that number expected to rise to more than 1 million within the next 5 years. The most common type of dementia (55%) is Alzheimer's dementia, and vascular dementia is the second commonest type (15%). Mild cognitive impairment (MCI) affects up to 20% of older adults and describes a set of symptoms rather than a specific medical condition or disease. A person with MCI has subtle problems with one or more of the following: day-to-day memory, concentrating, planning or organising, language (eg struggling to find the right word), and judging distances and seeing objects properly. Although MCI significantly increases the risk of developing dementia (by up to 5 times), at present it is not possible to accurately predict which patients with MCI will progress to dementia. In recent times there has been an increasing awareness that problems with brain blood flow may contribute to the development, or progression, of dementia. Tests of mental abilities, with standardised questions and pen-and-paper tests are a key component of the formal diagnosis of dementia, yet little is known of the effects of these tests on brain blood flow. Brain blood flow can be can be assessed non-invasively by the use of Trans Cranial Doppler (TCD). This means using ultrasound probes over both sides of the head to measure changes in blood flow in one of the main brain arteries (the middle cerebral artery). This proposed study will therefore use TCD to evaluate changes in brain blood flow during performance of the Addenbrooke's-III (ACE-III) cognitive assessment in four key groups of patients, specifically:

1. 1.Healthy older adults
2. 2.Patients with mild cognitive impairment (MCI)
3. 3.Patients with vascular dementia
4. 4.Patients with Alzheimer's dementia

Conditions

Mild Cognitive Impairment; Alzheimer Disease; Vascular Dementia; Healthy Controls

Outcome Measures

Primary Outcomes (1)

• Percentage of Recruited Subjects Able to Comply With the Protocol

  The percentage of recruited subjects (HC, MCI patients, VascD patients and AlzD patients) able to comply with the full measurement protocol.

  8 months

Secondary Outcomes (3)

• Number of Participants With Rejected Measurements

  8 months

• Number of Participants in Which Percentage Change in CBFv Can be Derived

  8 months

• Number of Participants in Which the Change in the Autoregulation Index (ARI) Can be Derived

  8 months

Study Arms (4)

Mild cognitive impairment

MCI Patient-specific Inclusion Criteria Clinical diagnosis of MCI made by a specialist\* in a patient who fulfils the established clinical consensus criteria for MCI \[NIA/AA 2011\] specifically: * Concern regarding a change in cognition compared to the person's previous level, by the patient and/or informant * Objective evidence of impairment of one or more cognitive domains, greater than expected for age, and educational background, over time if repeated measures are available. * Preserved independence of functional abilities and minimal to no impairment on complex instrumental functions * Not demented

Other: Transcranial doppler ultrasonography; Other: Blood pressure monitoring; Other: Heart rate monitoring; Other: End tidal CO2 monitoring; Other: Addenbrooke's cognitive examination

Alzheimer disease

NIA/AA criteria * Meets the criteria for dementia o The memory impairment and cognitive deficits cause significant impairment functioning, a significant decline from a previous level of functioning, Impairment of at least two cognitive domains * Insidious or gradual onset * Clear history of worsening cognition by report or observation * The initial and most prominent cognitive deficits are evident on history and examination in one of the following domains: * Amnestic: impaired learning and recall of recently learned information * Non amnestic: language/visuospatial/executive dysfunction

Other: Transcranial doppler ultrasonography; Other: Blood pressure monitoring; Other: Heart rate monitoring; Other: End tidal CO2 monitoring; Other: Addenbrooke's cognitive examination

Vascular dementia

NINDS-AIREN criteria for VascD, specifically: * Cerebrovascular disease defined by the presence of focal signs on neurological examination consistent with stroke and evidence of cerebrovascular disease on brain imaging. * One or more of: * Onset of dementia within 3 months of a diagnosed stroke * Abrupt deterioration in cognitive function * Fluctuating, stepwise progression of cognitive deficits

Other: Transcranial doppler ultrasonography; Other: Blood pressure monitoring; Other: Heart rate monitoring; Other: End tidal CO2 monitoring; Other: Addenbrooke's cognitive examination

Healthy controls

Healthy Controls-specific Inclusion Criteria 1. No evidence of subjective or objective memory impairment on cognitive testing 2. No major medical co-morbidity (outlined in detail in the exclusion criteria) or medication use that could adversely affect cognition

Other: Transcranial doppler ultrasonography; Other: Blood pressure monitoring; Other: Heart rate monitoring; Other: End tidal CO2 monitoring; Other: Addenbrooke's cognitive examination

Interventions

Transcranial doppler ultrasonography OTHER

Measurement of cerebral blood flow whilst undertaking cognitive tasks with TCD monitoring.

Also known as: TCD

Alzheimer disease; Healthy controls; Mild cognitive impairment; Vascular dementia

Blood pressure monitoring OTHER

Continuous blood pressure recording

Also known as: Finometer

Alzheimer disease; Healthy controls; Mild cognitive impairment; Vascular dementia

Heart rate monitoring OTHER

Continuous heart rate monitoring

Also known as: Electrocardiogram

Alzheimer disease; Healthy controls; Mild cognitive impairment; Vascular dementia

End tidal CO2 monitoring OTHER

Continuous ETCO2 monitoring

Also known as: Capnography

Alzheimer disease; Healthy controls; Mild cognitive impairment; Vascular dementia

Addenbrooke's cognitive examination OTHER

Performance of a memory test

Also known as: ACE III

Alzheimer disease; Healthy controls; Mild cognitive impairment; Vascular dementia

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy controls - age, sex and co-morbidity matched. Patients with Alzheimer's dementia, vascular dementia, and mild cognitive impairment

You may qualify if:

• Informed volunteer consent, patient consent
• Male or female, aged between 18 and 100 years of age
• Able (in the Investigator's opinion) and willing to comply with all study requirements
• Willing to allow his or her General Practitioner (GP) to be notified of participation in the study
• Good understanding of written and verbal English
• No evidence of subjective or objective memory impairment on cognitive testing

You may not qualify if:

• Clinical diagnosis of MCI made by a specialist\* in a patient who fulfils the established clinical consensus criteria for MCI \[NIA/AA 2011\] specifically:
• Concern regarding a change in cognition compared to the person's previous level, by the patient and/or informant
• Objective evidence of impairment of one or more cognitive domains, greater than expected for age, and educational background, over time if repeated measures are available.
• Preserved independence of functional abilities and minimal to no impairment on complex instrumental functions
• Not demented
• Clinical diagnosis of VascD made by a specialist\* in a patient who fulfils the NINDS-AIREN criteria for VascD, specifically:
• Cerebrovascular disease defined by the presence of focal signs on neurological examination consistent with stroke and evidence of cerebrovascular disease on brain imaging.
• One or more of:
• Onset of dementia within 3 months of a diagnosed stroke
• Abrupt deterioration in cognitive function
• Fluctuating, stepwise progression of cognitive deficits
• Clinical Diagnosis of AlzD made by a specialist\* in a patient who fulfils the NIA/AA criteria for Probable AlzD, specifically:
• Meets the criteria for dementia
• The memory impairment and cognitive deficits cause significant impairment in social or occupational functioning, and represent a significant decline from a previous level of functioning, not explained by a delirium or a major psychiatric disorder
• Impairment of at least two cognitive domains

Sponsors & Collaborators

• University of Leicester: lead

Study Sites (2)

University Hospitals of Leicester NHS Trust

Leicester, Leicestershire, LE1 5WW, United Kingdom

Location

Leicestershire Partnership Trust

Leicester, Leicestershire, United Kingdom

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease; Dementia, Vascular

Interventions

Ultrasonography, Doppler, Transcranial; Blood Pressure Monitors

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Cerebrovascular Disorders; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Leukoencephalopathies; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Echoencephalography; Neuroradiography; Neuroimaging; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Radiography; Ultrasonography; Ultrasonography, Doppler; Diagnostic Techniques, Neurological; Investigative Techniques; Sphygmomanometers; Diagnostic Equipment; Equipment and Supplies

Results Point of Contact

• Title: Dr Lucy Beishon
• Organization: University of Leicester

lb330@le.ac.uk

0116252

Study Officials

• Thompson G Robinson, MD

  University of Leicester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2017
• First Posted: May 1, 2017
• Study Start: May 5, 2017
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: October 5, 2021
• Results First Posted: November 25, 2020

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)