Clinical trial NCT03656107: The Cognition and Flow Study
Official title: The Effects of Brain Training on Brain Blood Flow: The Cognition and Flow Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Dementia
Alzheimer Disease
Mild Cognitive Impairment
Aging
Cognitive Impairment
Lead sponsor: University of Leicester
Sponsor class: OTHER
Collaborators: name: The Dunhill Medical Trust
name: University Hospitals, Leicester
name: Leicestershire Partnership NHS Trust
name: University of Nottingham
name: Lumosity
First posted: 2018-09-04
Enrollment: 56
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: About the research

There are currently 850,000 people living with dementia in the United Kingdom. It is now understand that Alzheimer's disease (AzD) can result from damaged blood vessels in the brain. Brain blood flow can be measured using ultrasound, known as transcranial Doppler ultrasonography (or TCD).

Brain training (BT) uses exercises or brain-teasers to try to make the brain work faster and more accurately. In recent years, BT has been used to try to improve memory, mood, learning, quality of life, and ability to carry out every-day activities in people with dementia.

Aims

1. To find out how acceptable and manageable this BT program is for people with dementia to undertake larger studies of BT in the future.
2. To look for any benefits for people with dementia, such as, improvements in quality of life, ability to carry out everyday tasks, mood, and brain blood flow.

How will the research be carried out?

* Forty patients with AzD, or mild cognitive impairment (MCI), and twenty healthy older adults will be recruited from memory and geriatric clinics, Join Dementia Research, general practice surgeries and community groups.
* Participants will be randomly assigned to brain training or control. The control group will be offered the program at the end of the study.
* First visit: Participants will complete questionnaires on quality of life, mood, everyday abilities, memory and an assessment of brain blood flow
* Brain training program: Participants will complete 15-30 minute sessions, 3-5 times per week
* Follow-up: participants will repeat the questionnaires and assessment of brain blood flow
* Interviews and feedback: to discuss how participants felt the program went, and find out if there are any ways it could be improved.

Detailed description: Study design, recruitment

This will be a randomised clinical trial, undertaken at the University of Leicester, University Hospitals of Leicester (UHL) and Leicestershire Partnership National Health Service (NHS) Trusts (LPT). Following successful ethical approval, sponsorship, regulatory approvals, 40 participants with a diagnosis of MCI, or AzD, and 20 healthy volunteers will be recruited from memory clinics, general geriatric clinics, Join Dementia Research, community groups. Patients with a diagnosis of mild MCI, or mild to moderate AzD that are not under follow-up with the memory service will also be invited to participate in the study by letter invitation through their GP surgery.

Summary of the intervention

Lumosity© is a commercially available software, developed by a group of neuropsychologists, which has been used across several studies of brain training and disciplines. The brain training software targets multiple brain areas, is based online, and is relatively easy to use and administer. It has been designed to adapt to the individual's memory performance to personalise the training program to their needs. Brain exercises will be selected with the support of Lumosity© to target the following brain areas; attention, memory, visuospatial, verbal fluency, and language.

First Visit

Participants who meet the inclusion criteria, will undergo formal written consent with a member of the research team, or research delivery officer, either at home, designated LPT research space, memory service, or invited to attend the Leicester Cerebral Haemodynamics in Ageing and Stroke Medicine (CHiASM) research laboratory. Baseline assessments will be performed at this first visit including; background information on age, sex, ethnicity, medical conditions, and medication use, the Edinburgh handedness inventory (to determine left or right hand dominance), and questionnaires on mood, quality of life, and ability to carry out everyday activities. Participants who have had their baseline assessment at home will then be referred to the researcher to undertake a baseline assessment of brain blood flow at the CHiASM research space. This will be undertaken by performing selected questions from a memory test covering five major brain areas(attention, fluency, language, visuospatial and memory) with continuous TCD (ultrasound), heart rate (ECG), blood pressure (finger blood pressure monitor), and waste gases (CO2 - nasal tubes).

Randomisation

Following the collection of baseline information, participants will be chosen at random to either complete a brain training program or control. Randomisation will be performed using Sealed Envelope©. This is an online based randomisation tool which uses random permuted blocks to allocate participants to waiting list control or intervention. Participants will be enrolled and assigned a participant identification number (PIN) consecutively, and randomised to a treatment arm corresponding to the PIN. Given the nature of the trial, it is not possible to blind participants to the intervention. The Investigator will be providing weekly telephone support with the intervention, in addition to undertaking baseline and follow-up measurements, and therefore blinding of the investigator is also not possible. However, data analysis will be blinded by generating a batch anonymised data set. Randomisation will be undertaken at the initial visit. As this is an un-blinded trial, code breaking will not be required.

Intervention

Control participants will be waiting listed to receive the brain training program at the end of the study. Participants selected to brain training will be given instructions on how to access and use the program at home for 15-30minutes, 3-5 times per week for 8-12 weeks. Adherence to the program can be monitored through Lumosity©. During the 8-12 weeks participants will be provided with technical support by the investigator to minimise adherence issues and will be offered a weekly telephone call to assist with any issues that have arisen.

Follow-up

Participants will then be invited to follow up assessment at 8-12 weeks, where the TCD (ultrasound) assessment of brain blood flow will be repeated, in addition to memory testing, mood, quality of life, and ability to carry out daily activities. All travel and parking expenses to and from the study for assessments will be refunded to participants, and refreshments will be provided. No financial incentive will be offered for participating in this study. Participants will be provided with a lay summary of the results at the end of the study.

Qualitative sub-study

A qualitative study will be undertaken following the training program, which will take the form of interviews and a focus group to determine barriers and facilitators (benefits) to the brain training program. A sample of the participants who completed the brain training program and who are willing to return for interview will be included in this study. Participants will be recruited until thematic saturation is achieved (i.e. where no further themes arise from interviews or focus group). The maximum number of participants recruited to this arm would be twenty (only patient participants who have completed the intervention arm will be recruited). Where possible, the investigators will interview participants jointly with their carers in order to obtain a broader view of the impact of brain training on patients and their support network. This would allow the investigators to explore the potential wider impacts of these interventions on patients, and benefits not measured by the outcomes described above.

Eligibility criteria: Inclusion Criteria:

One of:

1. Healthy controls will be free of any medical co-morbidity or medication that could adversely affect cognition. Volunteers with well-controlled co-morbidities (i.e. hypertension, diabetes, will be considered for inclusion)
2. MCI as defined by National Institute on Aging and Alzheimer's Association (NIA-AA) 2011 and Petersen criteria
3. AzD as defined by the NIA-AA 2011 criteria

   And:
4. Deficits will be mild to moderate as defined by Montreal Cognitive Assessment (MoCA) score of 19-26 for MCI, and 9-18 for AzD (32-34).
5. Willing to participate
6. Capacity to consent to the study/personal consultee
7. Patients on and off anti-dementia medications will be included (acetylcholinesterase inhibitors, glutamate receptor antagonists)
8. Good understanding of written and spoken English
9. Age \>50 years
10. Access to the internet and a computer/laptop or tablet device.

Exclusion Criteria:

1. Healthy controls with any medical co-morbidity or medication that could adversely affect cognition, or poorly controlled medical co-morbidities (i.e. hypertension, diabetes)
2. Unwilling to take part
3. Unable to consent/no personal consultee
4. Major medical co-morbidity; severe heart failure (ejection fraction \<20%), carotid artery stenosis, severe respiratory disease, major stroke
5. Pregnancy, planning pregnancy, or lactating
6. Inadequate bilateral TCD windows
7. Participants already enrolled into other interventional studies
8. Insufficient understanding of written and spoken English
9. Age \<50 years
10. No access to the internet and a computer/laptop or tablet device

Primary outcomes:
measure: Percentage of Participants Successfully Recruited
timeFrame: 15 months
measure: Percentage of Participants Able to Successfully Complete the Minimum (15 Mins, 3x Per Week, for 8 Weeks) and Maximum (30 Mins, 5x Per Week, for 12 Weeks) Criteria CT Program and Complete All Assessments
timeFrame: 17 months
measure: Percentage of Participants With Full Bilateral Data for Cerebral Blood Flow Velocity (CBFv)
timeFrame: 17 months
measure: Percentage of Control Participants Willing to be Randomised to Waiting List Control
timeFrame: 17 months
Secondary outcomes:
measure: Change in Cognition Score as Detected by the Addenbrooke's Cognitive Examination (ACE-III) From Baseline to Follow-up at 12 Weeks
timeFrame: 12 weeks
measure: Change in Functional Status - Lawton Instrumental Activities of Daily Living (IADL) From Baseline to Follow-up at 12 Weeks
timeFrame: 12 weeks
measure: Change in Mood - Geriatric Depression Scale (GDS-15) From Baseline to Follow-up at 12 Weeks
timeFrame: 12 weeks
measure: Change in Quality of Life Measure - Dementia Quality of Life Measure (DEMQOL) From Baseline to Follow-up at 12 Weeks
timeFrame: 12 weeks
measure: Percentage Increase in Cerebral Blood Flow Velocity (CBFv) From Baseline to Follow-up at 12 Weeks
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
state: Leicestershire
city: Leicester
country: United Kingdom
facility: Leicestershire Partnership Trust
state: Leicestershire
Study officials:
References:
citation: Beishon L, Evley R, Panerai RB, Subramaniam H, Mukaetova-Ladinska E, Robinson T, Haunton V. Effects of brain training on brain blood flow (The Cognition and Flow Study-CogFlowS): protocol for a feasibility randomised controlled trial of cognitive training in dementia. BMJ Open. 2019 May 22;9(5):e027817. doi: 10.1136/bmjopen-2018-027817.