Clinical trial NCT02913053: The Effects of an Extensive Exercise Program on the Progression of Mild Cognitive Impairment
Official title: The Effects of an Extensive Exercise Program on the Progression of Mild Cognitive Impairment (MCI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mild Cognitive Impairment
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: German Sport University, Cologne
name: University of Dublin, Trinity College
name: University of Bonn
name: University Hospital, Bonn
First posted: 2016-09-23
Enrollment: 183
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

Eligibility criteria: 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

Primary outcomes:
measure: Cognitive performance
timeFrame: One year
Secondary outcomes:
measure: Global cognitive function
timeFrame: One year
measure: Cardiovascular fitness
timeFrame: One year
measure: Physical activity
timeFrame: One year
measure: Health related Quality of Life
timeFrame: One year
measure: Depressive symptoms
timeFrame: One year
measure: Neuroticism-Extraversion-Openness-Five Factor Inventory (NEO-FFI)
timeFrame: One year
measure: Timed up and Go (TUG)
timeFrame: One year
measure: Hand grip strength
timeFrame: One year
measure: 30 second chair stand
timeFrame: One year
measure: Epigenetics
timeFrame: One year
measure: Brain imaging
timeFrame: 6 months
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: German Sport University
city: Dublin
country: Ireland
facility: Trinity College Dublin
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
Study officials:
affiliation: German Sport University, Germany
name: Stefan Schneider, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Trinity College Dublin, Ireland
name: Brian Lawlor, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University, Netherlands
name: Marcel Olde Rikkert, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stuckenschneider T, Sanders ML, Devenney KE, Aaronson JA, Abeln V, Claassen JAHR, Guinan E, Lawlor B, Meeusen R, Montag C, Olde Rikkert MGM, Polidori MC, Reuter M, Schulz RJ, Vogt T, Weber B, Kessels RPC, Schneider S. NeuroExercise: The Effect of a 12-Month Exercise Intervention on Cognition in Mild Cognitive Impairment-A Multicenter Randomized Controlled Trial. Front Aging Neurosci. 2021 Jan 14;12:621947. doi: 10.3389/fnagi.2020.621947. eCollection 2020.
citation: Devenney KE, Sanders ML, Lawlor B, Olde Rikkert MGM, Schneider S; NeuroExercise Study Group. The effects of an extensive exercise programme on the progression of Mild Cognitive Impairment (MCI): study protocol for a randomised controlled trial. BMC Geriatr. 2017 Mar 22;17(1):75. doi: 10.1186/s12877-017-0457-9.