Clinical trial NCT03056508: Lifestyle, Exercise and Diet: The LEAD Study
Official title: Nutrition, Exercise and Lifestyle: Team 6 of the Canadian Consortium on Neurodegeneration in Aging (CCNA)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Subjective Cognitive Decline
Age-Related Cognitive Decline
Keywords: diet
nutrition
aerobic exercise
cognition
grey matter
cerebral blood flow
neural activity
resting state connectivity
Lead sponsor: Rotman Research Institute at Baycrest
Sponsor class: OTHER
Collaborators: name: Sunnybrook Health Sciences Centre
name: Toronto Rehabilitation Institute
name: The Centre for Memory and Aging
name: University of Waterloo
First posted: 2017-02-17
Enrollment: 14
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

* meeting criteria for subjective cognitive impairment (1 through 5 below)

  1. Answer Yes to both following questions:

     1. Do you feel like your memory or thinking is becoming worse?
     2. Does this concern you?
  2. 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.
  3. Have a Montreal Cognitive Assessment (MoCA) total score of 20 and over (≥20/30).
  4. Have a delayed recall score on the CERAD word list of 5 and over (≥5).
  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

Primary outcomes:
measure: Changes from baseline brain structure at 6 months and 12 months.
timeFrame: 6 months plus 6 month follow-up
Secondary outcomes:
measure: Changes from baseline cerebral blood flow at 6 months and 12 months.
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline cognition at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline brain activity related to attention at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline resting state connectivity at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline diet quality at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline adherence to diet recommendations at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline grip strength at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline gait performance at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline balance performance at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline maximal oxygen uptake at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline blood moderators at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline HbA1C at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline fasting glucose at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline insulin levels at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline lipid levels at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline homocysteine levels at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline C reactive protein levels at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline TNF-alpha levels at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline IL6 levels at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
measure: Changes from baseline vitamin K levels at 6 months and 12 months
timeFrame: 6 months plus 6 month follow-up
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto Rehabilitation Institute Rumsey Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Rotman Research Institute
state: Ontario
city: Waterloo
country: Canada
facility: Centre for Community, Clinical Applied Research Excellence (CCCARE) at the University of Waterloo
state: Ontario
Study officials:
affiliation: Rotman Research Institute Baycrest Health Sciences
name: Carol E Greenwood, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rotman Research Institute Baycrest Health Sciences
name: Nicole D Anderson, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.