Mild Cognitive ImpairmentPhase 4WATER-VETNCT04296565
Water-based Activity to Enhance Recall in Veterans: A Randomized Clinical Trial
A Phase 4 study testing WATER+CT in people with Mild Cognitive Impairment, run by VA Office of Research and Development at 1 site in United States.
Trial summary
This four-year study will evaluate the efficacy of an exercise training augmentation for cognitive training intervention to improve memory performance in Veterans with a diagnosis of amnestic Mild Cognitive Impairment (aMCI). This is a two-phased trial: 1) an exercise phase and 2) a cognitive training program. Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Mild Cognitive Impairment
- What is being tested?
- WATER+CT
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 121 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jan 2022to 30 Jun 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Veterans of any racial or ethnic group
- Diagnosis of single or multi-domain amnestic MCI using criteria per National Institute on Aging/Alzheimer's Association Guidelines
- Available informant for completion of the Clinical Dementia Rating Scale
- Visual and auditory acuity to allow neuropsychological testing
- Willingness to participate in clinical trial for 14 months (8-month treatment phase, 6-month no-contact follow-up phase)
- Musculoskeletal illness or injury (i.e., osteoporosis, degenerative disc or joint disease, arthritis, obesity)
- Approval by Primary Care Provider to participate in water-based physical exercise
Who cannot join
- Psychiatric Exclusions
- Current, uncontrolled severe psychiatric disorder, such as Bipolar I, Schizophrenia, or Major Depressive Disorder as determined by the Mini International Neuropsychiatric Interview (MINI)
- Diagnosis of dementia, Clinical Dementia Rating Scale (CDR) > 0.5; modified Hachinksi score 4; or delirium. Those Veterans with scores indicative of dementia (CDR > 0.5, modified Hachinksi 4) will be referred to the Memory Disorders Clinic at VAPAHCS for a full diagnostic work-up
- Medical Exclusions
- History of neurological (e.g., multiple sclerosis, seizure disorder, stroke,) or system illness affecting CNS function (e.g., liver failure, kidney failure, congestive heart failure, systemic cancer)
- Acute illness or unstable chronic illness, e.g., history of severe liver disease (cirrhosis, esophageal varices, ascites, portal hypertension, hepatic encephalopathy)
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- Current severe cardiac disease (e.g., uncontrolled atrial fibrillation, defined as mean 24 hour heart rate >85 beats/min, or 24 hour maximal ventricular rate >150 beats/min; uncontrolled ventricular arrhythmias, defined as recurrent ventricular tachycardia >3 beats in succession, or 24 hour PVC count >20%; active pericarditis or myocarditis; Class III/IV heart failure and / or ejection fraction < 20%; thrombophlebitis; pulmonary disease with a drop in O2 Sat with exercise to 90% without oxygen; embolism within past 6 months)
- Inability to participate in an exercise stress test
- Inability to read, verbalize understanding and voluntarily sign the Informed Consent
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Palo Alto Health Care System, Palo Alto, CA
Palo Alto, California, 94304-1207
About this study
This four-year study will evaluate the efficacy of an exercise training augmentation for cognitive training intervention to improve memory performance in Veterans with a diagnosis of amnestic Mild Cognitive Impairment (aMCI). This is a two-phased trial: 1) an exercise phase and 2) a cognitive training program. The exercise phase will be an aquatic based exercise program. A combination of exercise and cognitive training programs designed for persons without cognitive impairment have significantly improved memory more than other single intervention groups (exercise only, cognitive training only) and given the success of combination training programs with healthy older adults, it is important to adapt these programs for persons beginning to exhibit clinically significant memory problems, such as those with aMCI.
Read the detailed description
The primary research question of the proposed study is this: Is a water-based exercise plus cognitive training intervention efficacious in improving cognitive outcomes for Veterans with Mild Cognitive Impairment (MCI)? The investigators address the need to improve cognitive function in this vulnerable population through a novel multi-component training program that will combine two interventions: water-based exercise and cognitive training. The proposed four-year randomized controlled trial will compare water-based exercise + cognitive training (WATER+CT) to a Usual Care Control Condition (UC). The primary aim of the proposed research is to evaluate the efficacy of WATER+CT to improve cognitive function in Veterans with MCI. Secondary aims of the proposed research are: 1) to evaluate the efficacy of WATER+CT to improve peak oxygen consumption and 2) to evaluate the durability of the cognitive benefits derived from WATER+CT. Exploratory aims of the proposed research are to evaluate moderators and mediators of treatment response.
These aims will be tested in a single-blind randomized controlled trial that will compare the efficacy of WATER+CT to UC. This trial will include 130 Veterans meeting criteria for MCI age 50-90 with half randomized to WATER+CT and half randomized to UC. For the WATER+CT condition, the exercise training (i.e., WATER) consists of a six-month long individualized exercise program of water-based exercises. During this phase, Veterans will come to thrice-weekly group sessions at Aquatic Therapy Center at the VA Palo Alto Health Care System (VAPAHCS). After completion of the exercise program, Veterans will begin classroom-based cognitive training at the VAPAHCS for up to two months. The CT is based on an efficacious training program that is structured around two components, pre-training and mnemonic training, both of which have been used successfully in persons with MCI. Veterans randomized to the UC control condition will receive educational materials about brain health in addition to their usual care, which is the care they would typically receive in the VA. After completion of the active treatment phase, Veterans will transition to the six-month long follow-up phase. At the end of the six-month long follow-up phase, participants will return to the VA for a final follow-up visit.
Participants will complete a variety of neuropsychological measures taping into areas of cognition such as attention, executive functioning, and memory. Participants will also undergo physical fitness assessments including a 6-minute walk test and an exercise treadmill test. To study possible predictors of response to treatment, the investigators will also collect biological (cardiovascular functioning and BDNF plasma levels) and genetic data (APOE and BDNF genotypes) from these participants. The investigators hope to provide evidence of the efficacy of an exercise training augmentation for cognitive training thus laying the groundwork for future VA health care system wide deployment of a lifestyle intervention to prevent Alzheimer's disease.
- Conditions
- Mild Cognitive Impairment
- Being tested
- Usual Care, WATER+CT
- Keywords
- Mild Cognitive Impairment, Cognition, Alzheimer's Disease, Physical Exercise, Cognitive Training
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Usual CareBehavioural
Usual Care condition involves receipt of educational materials about brain health and healthy lifestyles as well as regular contact with study staff
WATER+CTBehavioural
This is an 8 month long two phase intervention. The first phase consists of 6 months of thrice weekly pool based physical activity occurring at the Palo Alto VA Health Care System. After completion of the 6 month long water based physical activity, participants transition to a ten session cognitive training program at the Palo Alto VA. The cognitive training classes are approximately two hours in length and will be spread over ten sessions across 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Usual Care | Other | Usual Care condition involves receipt of educational materials about brain health and healthy lifestyles as well as regular contact with study staff. Receives: Behavioral: Usual Care |
| WATER+CT | Experimental | This is an 8 month long two phase intervention. The first phase consists of 6 months of thrice weekly pool based physical activity occurring at the Palo Alto VA Health Care System. After completion of the 6 month long water based physical activity, participants transition to a ten session cognitive training program at the Palo Alto VA. The cognitive training classes are approximately two hours in length and will be spread over ten sessions across 4 weeks. Receives: Behavioral: WATER+CT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive Function Composite Score (ADAS-Cog-Exe)
The ADAS-Cog is a structured scale that evaluates multiple cognitive domains including: orientation, memory, reasoning, language, and praxis.
Measured: 8 months
Secondary outcomes (1)
Peak VO2
Peak VO2, or VO2Max, is defined as the minute volume of O2 utilization
Measured: 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2020
- Study start3 Jan 2022
- Primary completion31 Mar 2026
- Study completion30 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Jennifer Kaci Fairchild, PhD, Principal investigator, VA Palo Alto Health Care System, Palo Alto, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04296565
- Sponsor's protocol ID
- E3143-R
- Other IDs
- 1I01RX003143-01A2
- Acronym
- WATER-VET
- Status last verified
- Sep 2026
- First submitted
- 2 Mar 2020
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Water-based Activity to Enhance Recall in Veterans: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04296565
- Acronym / sponsor ID
- WATER-VET / E3143-R
- Conditions
- Mild Cognitive Impairment
- Keywords
- Mild Cognitive Impairment, Cognition, Alzheimer's Disease, Physical Exercise, Cognitive Training
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 3 Jan 2022 (actual)
- Primary completion
- 31 Mar 2026 (actual)
- Study completion
- 30 Jun 2026 (actual)
- First posted
- 5 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This four-year study will evaluate the efficacy of an exercise training augmentation for cognitive training intervention to improve memory performance in Veterans with a diagnosis of amnestic Mild Cognitive Impairment (aMCI). This is a two-phased trial: 1) an exercise phase and 2) a cognitive training program. The exercise phase will be an aquatic based exercise program. A combination of exercise and cognitive training programs designed for persons without cognitive impairment have significantly improved memory more than other single intervention groups (exercise only, cognitive training only) and given the success of combination training programs with healthy older adults, it is important to adapt these programs for persons beginning to exhibit clinically significant memory problems, such as those with aMCI.
Detailed description
The primary research question of the proposed study is this: Is a water-based exercise plus cognitive training intervention efficacious in improving cognitive outcomes for Veterans with Mild Cognitive Impairment (MCI)? The investigators address the need to improve cognitive function in this vulnerable population through a novel multi-component training program that will combine two interventions: water-based exercise and cognitive training. The proposed four-year randomized controlled trial will compare water-based exercise + cognitive training (WATER+CT) to a Usual Care Control Condition (UC). The primary aim of the proposed research is to evaluate the efficacy of WATER+CT to improve cognitive function in Veterans with MCI. Secondary aims of the proposed research are: 1) to evaluate the efficacy of WATER+CT to improve peak oxygen consumption and 2) to evaluate the durability of the cognitive benefits derived from WATER+CT. Exploratory aims of the proposed research are to evaluate moderators and mediators of treatment response.
These aims will be tested in a single-blind randomized controlled trial that will compare the efficacy of WATER+CT to UC. This trial will include 130 Veterans meeting criteria for MCI age 50-90 with half randomized to WATER+CT and half randomized to UC. For the WATER+CT condition, the exercise training (i.e., WATER) consists of a six-month long individualized exercise program of water-based exercises. During this phase, Veterans will come to thrice-weekly group sessions at Aquatic Therapy Center at the VA Palo Alto Health Care System (VAPAHCS). After completion of the exercise program, Veterans will begin classroom-based cognitive training at the VAPAHCS for up to two months. The CT is based on an efficacious training program that is structured around two components, pre-training and mnemonic training, both of which have been used successfully in persons with MCI. Veterans randomized to the UC control condition will receive educational materials about brain health in addition to their usual care, which is the care they would typically receive in the VA. After completion of the active treatment phase, Veterans will transition to the six-month long follow-up phase. At the end of the six-month long follow-up phase, participants will return to the VA for a final follow-up visit.
Participants will complete a variety of neuropsychological measures taping into areas of cognition such as attention, executive functioning, and memory. Participants will also undergo physical fitness assessments including a 6-minute walk test and an exercise treadmill test. To study possible predictors of response to treatment, the investigators will also collect biological (cardiovascular functioning and BDNF plasma levels) and genetic data (APOE and BDNF genotypes) from these participants. The investigators hope to provide evidence of the efficacy of an exercise training augmentation for cognitive training thus laying the groundwork for future VA health care system wide deployment of a lifestyle intervention to prevent Alzheimer's disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Usual Care | Other | Behavioral: Usual CareUsual Care condition involves receipt of educational materials about brain health and healthy lifestyles as well as regular contact with study staff. |
| WATER+CT | Experimental | Behavioral: WATER+CTThis is an 8 month long two phase intervention. The first phase consists of 6 months of thrice weekly pool based physical activity occurring at the Palo Alto VA Health Care System. After completion of the 6 month long water based physical activity, participants transition to a ten session cognitive training program at the Palo Alto VA. The cognitive training classes are approximately two hours in length and will be spread over ten sessions across 4 weeks. |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Veterans of any racial or ethnic group
- Diagnosis of single or multi-domain amnestic MCI using criteria per National Institute on Aging/Alzheimer's Association Guidelines
- Available informant for completion of the Clinical Dementia Rating Scale
- Visual and auditory acuity to allow neuropsychological testing
- Willingness to participate in clinical trial for 14 months (8-month treatment phase, 6-month no-contact follow-up phase)
Key exclusion criteria (9 listed)
- Psychiatric Exclusions
- Current, uncontrolled severe psychiatric disorder, such as Bipolar I, Schizophrenia, or Major Depressive Disorder as determined by the Mini International Neuropsychiatric Interview (MINI)
- Diagnosis of dementia, Clinical Dementia Rating Scale (CDR) > 0.5; modified Hachinksi score 4; or delirium. Those Veterans with scores indicative of dementia (CDR > 0.5, modified Hachinksi 4) will be referred to the Memory Disorders Clinic at VAPAHCS for a full diagnostic work-up
- Medical Exclusions
- History of neurological (e.g., multiple sclerosis, seizure disorder, stroke,) or system illness affecting CNS function (e.g., liver failure, kidney failure, congestive heart failure, systemic cancer)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Usual CareUsual Care condition involves receipt of educational materials about brain health and healthy lifestyles as well as regular contact with study staff | Behavioural | Usual Care |
| WATER+CTThis is an 8 month long two phase intervention. The first phase consists of 6 months of thrice weekly pool based physical activity occurring at the Palo Alto VA Health Care System. After completion of the 6 month long water based physical activity, participants transition to a ten session cognitive training program at the Palo Alto VA. The cognitive training classes are approximately two hours in length and will be spread over ten sessions across 4 weeks. | Behavioural | WATER+CT |
Primary outcome
Cognitive Function Composite Score (ADAS-Cog-Exe)
Time frame: 8 months
The ADAS-Cog is a structured scale that evaluates multiple cognitive domains including: orientation, memory, reasoning, language, and praxis.
1 secondary outcome
Peak VO2
Time frame: 8 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer Kaci Fairchild, PhD principal investigator
VA Palo Alto Health Care System, Palo Alto, CA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing WATER+CT in people with Mild Cognitive Impairment, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive Function Composite Score (ADAS-Cog-Exe) (time frame: 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.