The Effects of an Extensive Exercise Program on the Progression of Mild Cognitive Impairment

Study Overview
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Brief Summary
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Exercise interventions to prevent dementia and delay cognitive decline have gained considerable attention in recent years. Human and animal studies have demonstrated that regular physical activity targets brain function by increasing cognitive reserve. Although initial studies indicate enhanced cognitive performance in patients with mild cognitive impairment (MCI) following an exercise intervention, little is known about the effect of an extensive, controlled and regular exercise regimen on the neuropathology of patients with MCI. The aim of this study is to compare a 12- month aerobic exercise programme versus a stretching and toning (non-aerobic) programme versus a control group on the progression of cognitive decline in MCI. It is hypothesized that MCI-related decreases in cognitive and psychomotor functioning will show less progression or even be improved after a one-year aerobic exercise intervention compared to a group of patients undergoing stretching and toning exercise as well as to a control group provided with no intervention.

Detailed Description
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This randomised controlled clinical intervention study will take place across three European sites; the German Sport University Cologne, Germany, University of Nijmegen, The Netherlands and Trinity College Dublin, Ireland. Seventy-five previously sedentary patients with a clinical diagnosis of MCI will be recruited at each site. Participants will be randomised to one of three intervention arms. One group will receive a standardised one-year extensive aerobic exercise intervention (3 units of 45min / week). The second group will complete stretching and toning (non-aerobic) exercise (3 units of 45min / week) and the third group will receive usual care. Change in all outcomes will be measured at baseline (T0), after six months (T1) and after 12 months (T2).

Official Title
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The Effects of an Extensive Exercise Program on the Progression of Mild Cognitive Impairment (MCI)

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Behavioral: Aerobic exercise
* Behavioral: Non-aerobic exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease (AD) according to the Albert et al (2011) criteria Montreal Cognitive Assessment (MoCA) (Nasreddine et al. 2005) score 18-26 Stable medical condition for more than 6 months Stable medications for more than 3 months Adequate visual and auditory acuity to complete neuropsychological testin Electrocardiogram without significant abnormalities that might interfere with the study Physical ability sufficient to allow performance of endurance exercise training Capacity to provide written and dated informed consent form Medical clearance to undergo a symptom-limited cardiopulmonary exercise test and extensive aerobic exercise training Participants recruited from the community via newspaper articles and community advertisement will complete additional testing to determine MCI status. Participants must score ≤1.5 standard deviation (SD) of cut-off scores on episodic memory test Exclusion Criteria: Diagnosis of AD or other type of dementia History of familial early-onset dementia Enrollment onto any investigational drug study History in the past 2 years of epileptic seizures (Participants with epilepsy who have been stable off medication and seizure free for 2 years may be included) Any major psychiatric disorder (a clinical diagnosis of major depressive disorder, bipolar or schizophrenia) Past history or MRI evidence of brain damage, including significant trauma, stroke, hydrocephalus, mental retardation, or serious neurological disorder Carotid stent or severe stenosis History of myocardial infarction within previous year congestive heart failure (New York Heart Association Class II, III or IV) Uncontrolled hypertension or hypotension (systolic blood pressure >200 mm Hg and/or diastolic blood pressure >110 mm Hg at rest) Unstable cardiac, renal, lung, liver, or other severe chronic disease Type 2 diabetes mellitus with hypoglycemia in the last 3 months Significant history of alcoholism or drug abuse within last 10 years Significant obesity limiting active participation in the exercise program Engagement in moderate-intensity aerobic exercise training for more than 30 minutes, 3 times per week, during past 2 years History of vitamin B12 deficiency or hypothyroidism (stable treatment for at least 3 months is allowed) Serious or non-healing wound, ulcer, or bone fracture

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aerobic exercise<br> | Behavioral: Aerobic exercise<br>* Patients with mild cognitive impairment will undergo a one-year aerobic exercise program of 3 units of 45 min / week<br>|
| Active Comparator: Stretching and Toning<br> | Behavioral: Non-aerobic exercise<br>* Patients with mild cognitive impairment will undergo a one-year stretching and toning (non-aerobic) exercise program of 3 units of 45 min / week<br>|
| No Intervention: Usual care: Control Group<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive performance | Cognitive performance will be assessed by an extensive neuropsychological test battery | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global cognitive function | MoCA (Montreal Cognitive Assessment) | One year | 
| Cardiovascular fitness | (sub)maximal ergometer exercise test | One year | 
| Physical activity | Activity monitoring with accelerometers | One year | 
| Health related Quality of Life | Health Related Quality of Life for People with Dementia (DemQOL) | One year | 
| Depressive symptoms | Center for Epidemiologic Studies Depression (CES-D) | One year | 
| Neuroticism-Extraversion-Openness-Five Factor Inventory (NEO-FFI) | Personality traits assessment | One year | 
| Timed up and Go (TUG) | Frailty measurement | One year | 
| Hand grip strength | Frailty measurement | One year | 
| 30 second chair stand | Frailty measurement | One year | 
| Epigenetics | Genotyping of the Apolipoprotein E (APOE) 4 allele in venous blood. | One year | 
| Brain imaging | Magnetic Resonance Imaging (MRI) scan: brain structure | 6 months |