Back to resultsLifestyle, Exercise and Diet: The LEAD Study (LEAD)
Primary Purpose
Subjective Cognitive Decline, Age-Related Cognitive Decline
Status
Terminated
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Exercise plus nutrition
Exercise
Sponsored by
About this trial
This is an interventional prevention trial for Subjective Cognitive Decline focused on measuring diet, nutrition, aerobic exercise, cognition, grey matter, cerebral blood flow, neural activity, resting state connectivity
Eligibility Criteria
Inclusion Criteria:
meeting criteria for subjective cognitive impairment (1 through 5 below)
Answer Yes to both following questions:
- Do you feel like your memory or thinking is becoming worse?
- Does this concern you?
Have a delayed recall score on 1 paragraph of the Logical Memory test (Wechsler Memory Scale, maximum score 25) above the education-adjusted cut-offs:
- ≥9 for 16+ years of education;
- ≥5 for 8-15 years of education;
- ≥3 for 0-7 years of education.
- Have a Montreal Cognitive Assessment (MoCA) total score of 20 and over (≥20/30).
- Have a delayed recall score on the CERAD word list of 5 and over (≥5).
- Have a global Clinical Dementia Rating score (CDR) equal to 0.5 or less (≤0.5).
- ≥2 vascular risk factors (overweight (BMI>25), T2DM, hypercholesterolemia or hypertension),
- Consuming a poor quality diet (at least median or below on number of servings of vegetable, fruit, fish and nuts based on Canadian consumption patterns in older adults)
- Reasonably sedentary (less than 75min per week of moderate - vigorous intensity physical activity)
- Be available for the whole intervention (6 months) and a 12- month follow-up visit
- English speaking
Exclusion Criteria:
- The presence of significant known chronic brain disease such as: moderate to severe chronic static leukoencephalopathy (including previous traumatic injury), multiple sclerosis, a serious developmental handicap, malignant tumors, Parkinson's disease, and other rarer brain illnesses.
- Ongoing alcohol or drug abuse that in the opinion of the investigator may interfere with the subject's ability to comply with the study procedures.
- Subject does not have a study partner who can provide corroborative information.
- Symptomatic stroke within the previous year.
- Unable to undergo MRI scan due to medical contraindications or inability to tolerate the procedure.
- Major surgery within last 2 months.
- History of intracranial surgery
- Serious comorbid condition that, in the opinion of the study investigator, is likely to result in death within a year.
- High performance athletes
Sites / Locations
- Toronto Rehabilitation Institute Rumsey Centre
- Sunnybrook Health Sciences Centre
- Rotman Research Institute
- Centre for Community, Clinical Applied Research Excellence (CCCARE) at the University of Waterloo
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Exercise plus Nutrition
Exercise
Arm Description
6 months of supervised group exercise plus education and strategy training to alter diet to be consistent with recommendations outlined in our brain health food guide (BHFG).
Identical exercise to the experimental plus education and passive discussion about brain health and healthy lifestyle to control for experimental group nutrition sessions.
Outcomes
Primary Outcome Measures
Changes from baseline brain structure at 6 months and 12 months.
Cortical and subcortical grey matter density using MRI three-dimensional T1 weighted structural scan (MPRAGE)
Secondary Outcome Measures
Changes from baseline cerebral blood flow at 6 months and 12 months.
Pseudo-continuous arterial spin labeling MRI (pcASL) to quantify cerebral blood flow
Changes from baseline cognition at 6 months and 12 months
pen and paper and computerized tasks, monitoring memory, executive function, and speed of processing. The results will be presented as a composite score of total neuro-psychological performance aggregating scores from the above cognitive domains.
Changes from baseline brain activity related to attention at 6 months and 12 months
BOLD functional MRI while participants performing an attention task
Changes from baseline resting state connectivity at 6 months and 12 months
BOLD functional MRI while participants at rest
Changes from baseline diet quality at 6 months and 12 months
Principle component analyses based on Canadian Diet History Questionnaire II (C-DHQII)
Changes from baseline adherence to diet recommendations at 6 months and 12 months
Principle component analyses based on the Eating Pattern Self-Assessment
Changes from baseline grip strength at 6 months and 12 months
Grip strength using a hand held dynamometer
Changes from baseline gait performance at 6 months and 12 months
Gait velocity, stride length/width, and associated variability assessed using a GAITRite pressure sensor mat.
Changes from baseline balance performance at 6 months and 12 months
Posturography assessment on balance platform
Changes from baseline maximal oxygen uptake at 6 months and 12 months
VO2max determined during cardiopulmonary assessment
Changes from baseline blood moderators at 6 months and 12 months
e.g. BDNF, pro-BDNF, ApoE,
Changes from baseline HbA1C at 6 months and 12 months
HbA1C
Changes from baseline fasting glucose at 6 months and 12 months
fasting glucose
Changes from baseline insulin levels at 6 months and 12 months
insulin
Changes from baseline lipid levels at 6 months and 12 months
lipid profile
Changes from baseline homocysteine levels at 6 months and 12 months
homocysteine
Changes from baseline C reactive protein levels at 6 months and 12 months
CRP
Changes from baseline TNF-alpha levels at 6 months and 12 months
TNF-alpha
Changes from baseline IL6 levels at 6 months and 12 months
IL6
Changes from baseline vitamin K levels at 6 months and 12 months
Vitamin K
Full Information
NCT ID
NCT03056508
First Posted
February 9, 2017
Last Updated
October 9, 2020
Sponsor
Rotman Research Institute at Baycrest
Collaborators
Sunnybrook Health Sciences Centre, Toronto Rehabilitation Institute, The Centre for Memory and Aging, University of Waterloo
1. Study Identification
Unique Protocol Identification Number
NCT03056508
Brief Title
Lifestyle, Exercise and Diet: The LEAD Study
Acronym
LEAD
Official Title
Nutrition, Exercise and Lifestyle: Team 6 of the Canadian Consortium on Neurodegeneration in Aging (CCNA)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Terminated
Why Stopped
Due to COVID-19, recruitment and enrollment was suspended and never resumed. COVID-related changes have been made to the clinical program which houses our intervention, and we could not compare new participants with our previous cohort.
Study Start Date
July 1, 2018 (Actual)
Primary Completion Date
October 8, 2020 (Actual)
Study Completion Date
October 8, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rotman Research Institute at Baycrest
Collaborators
Sunnybrook Health Sciences Centre, Toronto Rehabilitation Institute, The Centre for Memory and Aging, University of Waterloo
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will explore the impact of an exercise and nutrition (EX+NUTR) , relative to exercise alone (EX) intervention, on brain structure and function as well as blood biomarkers in older adults with subjective cognitive decline (SCD) and vascular risk factors. The overall hypotheses are that a combined EX+NUTR, relative to EX, intervention will evoke more positive changes in brain structure (e.g. hippocampal volume), neural activity (e.g. task associated functional activations monitored through fMRI), and cognitive performance. These changes will be associated with an improved metabolic profile, reductions in inflammatory cytokines and oxidative burden, and greater intervention compliance.
Detailed Description
All participants will engage in group supervised exercise sessions once per week as well as engage in additional exercise sessions at home 4 days/week. The exercise program will be run out of two sites (Toronto Rehabilitation Institute (TRI) - Rumsey Centre in Toronto, and the Centre for Community, Clinical Applied Research Excellence (CCCARE) at the University of Waterloo). The supervised exercise sessions modeled after the standard TRI Cardiovascular Prevention and Rehabilitation program, including aerobic training, resistance training and education/counseling. The active group will receive strategy training to simultaneously improve their diet in conjunction with our newly developed Brain Health Food Guide (EX+BHFG); the placebo control group (EX+BHEd) will receive brain health education to control for time and social participation. [NOTE All participants must also be enrolled in the SCD cohort of the CCNA and undergo the CCNA's COMPASS-ND assessment at the beginning of the trial.] The study is 6 months in duration and requires participants to attend 2.5 hr weekly sessions (1 hr supervised exercise, 0.5 hr exercise/stress education and 1 hr nutrition or brain health education) and to exercise on their own an additional 3-4 times per week. Participants are assessed on measures of cognition, brain health (MRI), functional status at baseline, post intervention and 6 month follow-up.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Subjective Cognitive Decline, Age-Related Cognitive Decline
Keywords
diet, nutrition, aerobic exercise, cognition, grey matter, cerebral blood flow, neural activity, resting state connectivity
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Exercise plus Nutrition
Arm Type
Experimental
Arm Description
6 months of supervised group exercise plus education and strategy training to alter diet to be consistent with recommendations outlined in our brain health food guide (BHFG).
Arm Title
Exercise
Arm Type
Active Comparator
Arm Description
Identical exercise to the experimental plus education and passive discussion about brain health and healthy lifestyle to control for experimental group nutrition sessions.
Intervention Type
Behavioral
Intervention Name(s)
Exercise plus nutrition
Intervention Description
On the same day as the exercise class, participants will also receive nutrition support. Participants will alter their overall diet to be consistent with recommendations outlined in our brain health food guide (BHFG) and receive diet counseling and strategy training to promote retention and enable this dietary change. For the first two months, diet group sessions will be held on a weekly basis. For the remaining four months, sessions will be divided between group sessions and individual meetings with study dietitians, on a predefined schedule. Participants will submit weekly logs outlining diet goals, plans, successes and obstacles to help direct identification of sequential goals.
Intervention Type
Behavioral
Intervention Name(s)
Exercise
Intervention Description
Supervised group exercise will be performed once per week (60 minutes) and self-directed exercise (4 additional aerobic and 2-3 resistance training sessions per week) will be monitored by an exercise diary. The initial walking prescription will be set at ~1.6 km and an intensity equivalent to the anaerobic threshold and/or 60% VO2-peak. Progressions will be made every 2 weeks, increasing distance to a maximum of 6.4 km and then increasing to a max intensity of 80% of VO2-peak and/or max duration of 60 minutes. Heart rate and perceived exertion will be monitored. The program will last 6 months.
Primary Outcome Measure Information:
Title
Changes from baseline brain structure at 6 months and 12 months.
Description
Cortical and subcortical grey matter density using MRI three-dimensional T1 weighted structural scan (MPRAGE)
Time Frame
6 months plus 6 month follow-up
Secondary Outcome Measure Information:
Title
Changes from baseline cerebral blood flow at 6 months and 12 months.
Description
Pseudo-continuous arterial spin labeling MRI (pcASL) to quantify cerebral blood flow
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline cognition at 6 months and 12 months
Description
pen and paper and computerized tasks, monitoring memory, executive function, and speed of processing. The results will be presented as a composite score of total neuro-psychological performance aggregating scores from the above cognitive domains.
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline brain activity related to attention at 6 months and 12 months
Description
BOLD functional MRI while participants performing an attention task
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline resting state connectivity at 6 months and 12 months
Description
BOLD functional MRI while participants at rest
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline diet quality at 6 months and 12 months
Description
Principle component analyses based on Canadian Diet History Questionnaire II (C-DHQII)
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline adherence to diet recommendations at 6 months and 12 months
Description
Principle component analyses based on the Eating Pattern Self-Assessment
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline grip strength at 6 months and 12 months
Description
Grip strength using a hand held dynamometer
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline gait performance at 6 months and 12 months
Description
Gait velocity, stride length/width, and associated variability assessed using a GAITRite pressure sensor mat.
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline balance performance at 6 months and 12 months
Description
Posturography assessment on balance platform
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline maximal oxygen uptake at 6 months and 12 months
Description
VO2max determined during cardiopulmonary assessment
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline blood moderators at 6 months and 12 months
Description
e.g. BDNF, pro-BDNF, ApoE,
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline HbA1C at 6 months and 12 months
Description
HbA1C
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline fasting glucose at 6 months and 12 months
Description
fasting glucose
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline insulin levels at 6 months and 12 months
Description
insulin
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline lipid levels at 6 months and 12 months
Description
lipid profile
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline homocysteine levels at 6 months and 12 months
Description
homocysteine
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline C reactive protein levels at 6 months and 12 months
Description
CRP
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline TNF-alpha levels at 6 months and 12 months
Description
TNF-alpha
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline IL6 levels at 6 months and 12 months
Description
IL6
Time Frame
6 months plus 6 month follow-up
Title
Changes from baseline vitamin K levels at 6 months and 12 months
Description
Vitamin K
Time Frame
6 months plus 6 month follow-up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
meeting criteria for subjective cognitive impairment (1 through 5 below)
Answer Yes to both following questions:
Do you feel like your memory or thinking is becoming worse?
Does this concern you?
Have a delayed recall score on 1 paragraph of the Logical Memory test (Wechsler Memory Scale, maximum score 25) above the education-adjusted cut-offs:
≥9 for 16+ years of education;
≥5 for 8-15 years of education;
≥3 for 0-7 years of education.
Have a Montreal Cognitive Assessment (MoCA) total score of 20 and over (≥20/30).
Have a delayed recall score on the CERAD word list of 5 and over (≥5).
Have a global Clinical Dementia Rating score (CDR) equal to 0.5 or less (≤0.5).
≥2 vascular risk factors (overweight (BMI>25), T2DM, hypercholesterolemia or hypertension),
Consuming a poor quality diet (at least median or below on number of servings of vegetable, fruit, fish and nuts based on Canadian consumption patterns in older adults)
Reasonably sedentary (less than 75min per week of moderate - vigorous intensity physical activity)
Be available for the whole intervention (6 months) and a 12- month follow-up visit
English speaking
Exclusion Criteria:
The presence of significant known chronic brain disease such as: moderate to severe chronic static leukoencephalopathy (including previous traumatic injury), multiple sclerosis, a serious developmental handicap, malignant tumors, Parkinson's disease, and other rarer brain illnesses.
Ongoing alcohol or drug abuse that in the opinion of the investigator may interfere with the subject's ability to comply with the study procedures.
Subject does not have a study partner who can provide corroborative information.
Symptomatic stroke within the previous year.
Unable to undergo MRI scan due to medical contraindications or inability to tolerate the procedure.
Major surgery within last 2 months.
History of intracranial surgery
Serious comorbid condition that, in the opinion of the study investigator, is likely to result in death within a year.
High performance athletes
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carol E Greenwood, PhD
Organizational Affiliation
Rotman Research Institute Baycrest Health Sciences
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nicole D Anderson, PhD
Organizational Affiliation
Rotman Research Institute Baycrest Health Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Toronto Rehabilitation Institute Rumsey Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4G 2V6
Country
Canada
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Rotman Research Institute
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6A 2E1
Country
Canada
Facility Name
Centre for Community, Clinical Applied Research Excellence (CCCARE) at the University of Waterloo
City
Waterloo
State/Province
Ontario
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
data will be uploaded to shared CCNA database - LORIS
Citations:
PubMed Identifier
35139918
Citation
Koblinsky ND, Anderson ND, Ajwani F, Parrott MD, Dawson D, Marzolini S, Oh P, MacIntosh B, Middleton L, Ferland G, Greenwood CE. Feasibility and preliminary efficacy of the LEAD trial: a cluster randomized controlled lifestyle intervention to improve hippocampal volume in older adults at-risk for dementia. Pilot Feasibility Stud. 2022 Feb 9;8(1):37. doi: 10.1186/s40814-022-00977-6.
Results Reference
derived
Learn more about this trial
Lifestyle, Exercise and Diet: The LEAD Study
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