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Cerebral Haemodynamic Changes During Cognitive Testing: A fTCD Study

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ClinicalTrials.gov Identifier: NCT03134963
Recruitment Status : Completed
First Posted : May 1, 2017
Results First Posted : November 25, 2020
Last Update Posted : April 22, 2021
Sponsor:
Information provided by (Responsible Party):
University of Leicester

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

Condition or disease Intervention/treatment
Mild Cognitive Impairment Alzheimer Disease Vascular Dementia Healthy Controls Other: Transcranial doppler ultrasonography Other: Blood pressure monitoring Other: Heart rate monitoring Other: End tidal CO2 monitoring Other: Addenbrooke's cognitive examination

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Study Type : Observational
Actual Enrollment : 42 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Cerebral Haemodynamic Changes During Cognitive Testing: a Functional Transcranial Doppler (fTCD) Study
Actual Study Start Date : May 5, 2017
Actual Primary Completion Date : December 1, 2017
Actual Study Completion Date : December 1, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dementia

Group/Cohort Intervention/treatment
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
Measurement of cerebral blood flow whilst undertaking cognitive tasks with TCD monitoring.
Other Name: TCD

Other: Blood pressure monitoring
Continuous blood pressure recording
Other Name: Finometer

Other: Heart rate monitoring
Continuous heart rate monitoring
Other Name: Electrocardiogram

Other: End tidal CO2 monitoring
Continuous ETCO2 monitoring
Other Name: Capnography

Other: Addenbrooke's cognitive examination
Performance of a memory test
Other Name: ACE III

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

Other: Blood pressure monitoring
Continuous blood pressure recording
Other Name: Finometer

Other: Heart rate monitoring
Continuous heart rate monitoring
Other Name: Electrocardiogram

Other: End tidal CO2 monitoring
Continuous ETCO2 monitoring
Other Name: Capnography

Other: Addenbrooke's cognitive examination
Performance of a memory test
Other Name: ACE III

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

Other: Blood pressure monitoring
Continuous blood pressure recording
Other Name: Finometer

Other: Heart rate monitoring
Continuous heart rate monitoring
Other Name: Electrocardiogram

Other: End tidal CO2 monitoring
Continuous ETCO2 monitoring
Other Name: Capnography

Other: Addenbrooke's cognitive examination
Performance of a memory test
Other Name: ACE III

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

Other: Blood pressure monitoring
Continuous blood pressure recording
Other Name: Finometer

Other: Heart rate monitoring
Continuous heart rate monitoring
Other Name: Electrocardiogram

Other: End tidal CO2 monitoring
Continuous ETCO2 monitoring
Other Name: Capnography

Other: Addenbrooke's cognitive examination
Performance of a memory test
Other Name: ACE III




Primary Outcome Measures :
  1. Percentage of Recruited Subjects Able to Comply With the Protocol [ Time Frame: 8 months ]
    The percentage of recruited subjects (HC, MCI patients, VascD patients and AlzD patients) able to comply with the full measurement protocol.


Secondary Outcome Measures :
  1. Number of Participants With Rejected Measurements [ Time Frame: 8 months ]
    The percentage of measurements rejected because of aspects related to data quality during the analysis protocol, with recorded reasons

  2. Number of Participants in Which Percentage Change in CBFv Can be Derived [ Time Frame: 8 months ]

    Overall, the percentage of recruited subjects (healthy controls, MCI patients, VascD patients and AlzD patients) in whom values for the following parameters can be derived:

    • % change of CBFv at baseline in response to performance of the ACE-III Cognitive Examination


  3. Number of Participants in Which the Change in the Autoregulation Index (ARI) Can be Derived [ Time Frame: 8 months ]

    Overall, the percentage of recruited subjects (healthy controls, MCI patients, VascD patients and AlzD patients) in whom values for the following parameters can be derived:

    • Autoregulation index (using the Tiecks model and from the phase, gain and coherence).




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
Criteria

Inclusion Criteria:

  • 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

Healthy Controls-specific Inclusion Criteria

  • No evidence of subjective or objective memory impairment on cognitive testing
  • No major medical co-morbidity (outlined in detail in the exclusion criteria) or medication use that could adversely affect cognition

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

Vascular Dementia Specific Inclusion Criteria

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

Alzheimer's Dementia Specific Inclusion Criteria

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
  • 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
  • No evidence of substantial cerebrovascular disease, core features of dementia with lewy bodies, features of frontotemporal dementia, prominent features of semantic variant primary progressive aphasia, evidence of active neurological disease, a non-neurological co-morbidity or medication that could affect cognition

    • A specialist being defined as a psychiatrist or a geriatrician, or a specialist mental health nurse with a specific interest or expertise in cognitive disorders.

Exclusion Criteria:

Exclusion Criteria

  • Male or Female, aged under 18 years
  • Unable (in the Investigator's opinion) or unwilling to comply with any study requirements
  • Female participants who are pregnant, lactating or planning pregnancy during the course of the study
  • Major co-morbidity likely to affect cerebral autoregulation; severe respiratory disease, carotid artery stenosis, atrial fibrillation, severe cardiac failure (left ventricular ejection fraction <20%), extreme frailty or multi-morbidity.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03134963


Locations
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United Kingdom
University Hospitals of Leicester NHS Trust
Leicester, Leicestershire, United Kingdom, LE1 5WW
Leicestershire Partnership Trust
Leicester, Leicestershire, United Kingdom
Sponsors and Collaborators
University of Leicester
Investigators
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Principal Investigator: Thompson G Robinson, MD University of Leicester
  Study Documents (Full-Text)

Documents provided by University of Leicester:
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Responsible Party: University of Leicester
ClinicalTrials.gov Identifier: NCT03134963    
Other Study ID Numbers: 0613
First Posted: May 1, 2017    Key Record Dates
Results First Posted: November 25, 2020
Last Update Posted: April 22, 2021
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia, Vascular
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Cerebrovascular Disorders
Intracranial Arteriosclerosis
Intracranial Arterial Diseases
Leukoencephalopathies
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases