Clinical trial NCT02737878: Reshaping the Path of Mild Cognitive Impairment by Refining Exercise Prescription
Official title: Reshaping the Path of Mild Cognitive Impairment by Refining Exercise Prescription: Understanding Training Type and Exploring Mechanisms
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Mild Cognitive Impairment
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2016-04-14
Enrollment: 216
Sex: ALL
Minimum age (years): 65
Maximum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: Dementia is one of the most pressing health care issues of the 21st century. Evidence suggests that exercise enhances cognitive function in healthy older adults. Most research has focused on aerobic training (AT). Therefore, investigators aim to assess the individual effects of AT and resistance training (RT), as well as the interaction effect of combining the two types of exercise training, on cognitive function in older adults with mild cognitive impairment.

Detailed description: Investigators will conduct a 6-month assessor-blinded randomized-controlled trial of 216 community-dwelling adults with mild cognitive impairment. Individuals will be randomized to one of four experimental groups, all which receive 6 months of exercise classes four times per week: 1) combined aerobic training and resistance training; 2) aerobic training; 3) resistance training; or 4) balance and toning exercise. There will be two measurement sessions: baseline and 6 months (end of intervention period). A 12-month followup (i.e., 18 months from baseline) measurement will be done for a sub-set of participants.

Eligibility criteria: Inclusion Criteria:

* Community-dwelling in Metro Vancouver
* Have subjective memory complaints, defined as the self-reported feeling of memory worsening with an onset within the last 5 years, as determined by interview and corroborated by an informant
* Have a baseline Montreal Cognitive Assessment (MoCA) score \< 26/30
* Mini-Mental State Examination (MMSE) score = or \> 22 at screening
* Read, write, and speak English
* Not expected to start or are stable on a fixed dose of anti-dementia medications (e.g., donepezil, galantamine, etc.) during the 6-month intervention period
* Able to walk independently
* Must be in sufficient health to participate in the exercise programs
* Able to comply with scheduled visits, treatment plan, and other trial procedures
* Provide a personally signed and dated informed consent document indicating that the individual (or a legally acceptable representative) has been informed of all pertinent aspects of the trial. In addition, an assent form will be provided at baseline and again at regular intervals

Exclusion Criteria:

* Engaged in moderate (e.g., brisk walking) physical activity \> 1 time per week, or \> 60 minutes per week, in the 3 months prior to study entry
* Diagnosed with dementia of any type
* Clinically suspected to have neurodegenerative disease as the cause of mild cognitive impairment (MCI) that is not Alzheimer's Disease (AD), vascular cognitive impairment (VCI), or both (e.g., multiple sclerosis, Parkinson's disease, Huntington's disease, frontotemporal dementia)
* At high risk for cardiac complications during exercise or unable to self-regulate activity or to understand recommended activity level; 5) have clinically important peripheral neuropathy or severe musculoskeletal or joint disease that impairs mobility, as determined by his/her family physician
* Taking medications that may negatively affect cognitive function, such as anticholinergics, including agents with pronounced anticholinergic properties (e.g., amitriptyline), major tranquilizers (i.e., typical and atypical antipsychotics), and anticonvulsants (e.g., gabapentin, valproic acid)
* On any hormone therapy (estrogen, progesterone, or testosterone) in the last 24 months
* Planning to participate, or already enrolled in, a concurrent clinical drug or exercise trial

Primary outcomes:
measure: Cognitive function as measured by Alzheimer's Disease Assessment Scale Cognitive Subscale Plus (ADAS-Plus)
timeFrame: Baseline to 6 months
Secondary outcomes:
measure: Executive functions as measured by standard neuropsychological and computerized tests
timeFrame: Baseline and 6 months and 18 months
measure: Cardiometabolic risk factors as measured by blood panel
timeFrame: Baseline and 6 months
measure: Health related quality of life as measured by the EuroQol five dimensions questionnaire (EQ-5D-5L)
timeFrame: Baseline, 3 months, 6 months, 12 months, and 18 months
measure: Health related quality of life as measured by the ICE-CAP
timeFrame: Baseline, 3 months, 6 months, 12 months, and 18 months
measure: Mood as measured by the Center for Epidemiologic Studies Depression Scale (CES-D)
timeFrame: Baseline and 6 months
measure: Brain function as measured by functional magnetic resonance imaging (fMRI)
timeFrame: Baseline and 6 months
measure: Brain structure as measured by structural magnetic resonance imaging
timeFrame: Baseline and 6 months
measure: White matter lesion volume as measured by magnetic resonance imaging
timeFrame: Baseline and 6 months
measure: Diffusion tensor imaging as measured by magnetic resonance imaging
timeFrame: Baseline and 6 months
measure: Memory as measured by standard neuropsychological and computerized tests
timeFrame: Baseline and 6 months and 18 months
measure: Visualspatial ability as measured by standard neuropsychological and computerized tests
timeFrame: Baseline and 6 months
measure: Cardiorespiratory capacity as measured by treadmill test
timeFrame: Baseline and 6 months
measure: Mobility as measured by 400-m walk
timeFrame: Baseline and 6 months and 18 months
measure: Cardiometabolic risk as measured by waist to hip ratio
timeFrame: Baseline and 6 months and 18 months
measure: Cardiometabolic risk as measured by body mass index
timeFrame: Baseline and 6 months and 18 months.
measure: Cardiometabolic risk as measured by pulse wave velocity (arterial stiffness)
timeFrame: Baseline and 6 months
measure: Cortisol levels through saliva samples (subset)
timeFrame: 5 times from baseline to 6 months
measure: Lower body strength as measured by the 30 sec sit-to-stand (subset)
timeFrame: Baseline and 6 months and 18 months
measure: Lower body strength as measured by Biodex
timeFrame: Baseline and 6 months
measure: Upper body strength as measured by grip strength
timeFrame: Baseline and 6 months
measure: Sleep quality as measured by Motion Watch actigraphy
timeFrame: Baseline and 6 months
measure: Neurotrophic factors as measured by blood
timeFrame: Baseline and 6 months
measure: Mobility as measured by Short Physical Performance Battery
timeFrame: Baseline and 6 months and 18 months
measure: Community mobility as measured by the Life Space Questionnaire
timeFrame: Baseline, 3 months, 6 months, 12 months, and 18 months
measure: Body composition as measured by DXA
timeFrame: Baseline and 6 months
measure: Loneliness as measured by the UCLA Loneliness Scale
timeFrame: Baseline and 6 months
measure: Cognitive function as measured by Alzheimer's Disease Assessment Scale Cognitive Subscale - 13 items
timeFrame: Baseline and 6 months and 18 months
measure: Sedentary behaviour as measure by the Sedentary Behaviour Questionnaire
timeFrame: Baseline, 3 months, 6 months, 12 months, and 18 months
measure: Risk of sleep apnea as measured by the STOP Bang Questionnaire
timeFrame: Baseline and 6 months
measure: Prospective falls via Monthly Calendars
timeFrame: Baseline and 3 months and 6 months and monthly
measure: Social support as measured by Social Provision Scale
timeFrame: Baseline and 6 months
measure: Mindfulness as measured by the Mindfulness Attention Awareness Scale
timeFrame: Baseline and 6 months
measure: Memory as measured by the Everyday Memory Questionnaire
timeFrame: Baseline and 6 months
measure: Sleep as measured by the Pittsburgh Sleep Quality Index
timeFrame: Baseline, 6 months, 12 months, and 18 months
measure: Functional ability as measured by the Lawson IADL
timeFrame: Baseline and 6 months
measure: Comorbidities as measured by the Function Comorbidity Index
timeFrame: Baseline, 6 months, 12 months, and 18 months
measure: Mood as measured by the State and Trait Anxiety Inventory
timeFrame: Baseline and 6 months and 18 months
measure: Social network as measured by Lubben Social Network Scale
timeFrame: Baseline and 6 months
measure: Physical activity as measured by the CHAMP Questionnaire
timeFrame: Baseline and 3 months and 6 months and monthly
measure: ADAS-Cog Plus
timeFrame: 18 months
measure: Verbal memory and learning using the Rey Auditory Verbal Learning Test
timeFrame: Baseline, 6 months, and 18 months
measure: Verbal fluency (categorial of animals and semantic using F,A,S)
timeFrame: Baseline, 6 months, and 18 months
measure: Cytokines - proteins involved in immune response, as measured by blood
timeFrame: Baseline and 6 months
measure: Dual-task gait using Gaitrite
timeFrame: Baseline and 6 months
measure: Health resource utilization (e.g., access health system services/resources)
timeFrame: Baseline, 3 months, and 6 months
measure: Physical activity level (i.e., amount of light, moderate, and vigorous) measured by Motion Watch actigraphy
timeFrame: Baseline and 6 months
measure: Sedentary behaviour (i.e., less than = or less than1.5 mets of activity) measured by Motion Watch actigraphy
timeFrame: Baseline and 6 months
measure: Quality of life measured by EQ-5D-5L
timeFrame: Baseline, 3 months, 6 months, and 18 months
measure: Wellbeing measured by ICE-CAP
timeFrame: Baseline, 3 months, 6 months, and 18 months
measure: Telemere length
timeFrame: Baseline and 6 months
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Teresa Liu-Ambrose, PhD, PT
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: John Best, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Jennifer Davis, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Lara Boyd, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Liisa Galea, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Simon Fraser University
name: Charlie Goldsmith, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Ging-Yuek Robin Hsiung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Alexander MacKay, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Western University
name: Lindsay Nagamatsu, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pacific University
name: Claudia Jacova, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northeastern University
name: Arthur Kramer, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Iowa
name: Michelle Voss, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Cindy Barha, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Joel Singer, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barha CK, Falck RS, Best JR, Nagamatsu LS, Hsiung GR, Sheel AW, Hsu CL, Kramer AF, Voss MW, Erickson KI, Davis JC, Shoemaker JK, Boyd L, Crockett RA, Ten Brinke L, Bherer L, Singer J, Galea LAM, Jacova C, Bullock A, Grant S, Liu-Ambrose T. Reshaping the path of mild cognitive impairment by refining exercise prescription: a study protocol of a randomized controlled trial to understand the "what," "for whom," and "how" of exercise to promote cognitive function. Trials. 2022 Sep 9;23(1):766. doi: 10.1186/s13063-022-06699-7.