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

Not Applicable

Completed

Interventions: Behavioral: Non-aerobic exercise
Behavioral: Aerobic exercise

Brief Summary: 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: 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).

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Stretching and Toning	Non-aerobic exercise	-
Aerobic exercise	Aerobic exercise	-

Primary Outcome Measures

Name	Time	Method
Cognitive performance	One year	Cognitive performance will be assessed by an extensive neuropsychological test battery

Secondary Outcome Measures

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

Locations (3): Radboud University Medical Center
🇳🇱
Nijmegen, Netherlands
Trinity College Dublin
🇮🇪
Dublin, Ireland
German Sport University
🇩🇪
Cologne, Germany