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

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).

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