Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX Trial): Rationale and Design

Abstract

Background: Exercise is hypothesized to improve cognition, physical performance, functional ability and quality of life, but evidence is scarce. Previous studies were of short duration, often underpowered and involving home-based light exercise programs in patients with undefined dementia. The aim of the ADEX (‘Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: the Effect of Physical Exercise') trial is to establish whether aerobic exercise is effective in improving cognition as well as in reducing the prevalence of psychiatric symptoms among patients with Alzheimer's disease (AD). Methods: The ADEX study is a multicenter, single-blind, randomized trial with two arms: an intervention group attending 16 weeks of continuously supervised moderate-to-high intensity aerobic exercise and a control group receiving usual care. We plan to recruit 192 patients with mild AD. The primary outcome measure is change from baseline in cognitive performance at 16 weeks (as measured by the Symbol Digit Modalities test). Conclusions: To our knowledge this is the first large-scale controlled study to investigate the effects of supervised moderate aerobic exercise on cognition in patients with AD. Recruitment began in January 2012 and results are expected to be available in 2014. We summarize the methodological challenges we and other studies have faced in this type of complex multicenter intervention with unique challenges to study design.

Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer’s Disease: A Randomized Controlled Trial

“…An uncontrolled pilot study was carried out in 2011 [13] to ensure the acceptability, safety, and feasibility of the intervention, as recommended in the Medical Research Council's guidelines for complex interventions [14]. A detailed description of the methods of the study has previously been published [15].…”

Effect of aerobic exercise on physical performance in patients with Alzheimer's disease

“…The rationale, design, and the results regarding the effects of the physical exercise intervention on cognition, health-related quality of life, activities of daily living, behavioral, and psychological symptoms have been published previously [15,16].…”

“…Participants were recruited consecutively from 8 memory clinics in Denmark [16]. Eligibility for inclusion was (1) a diagnosis of AD according to the NINCDS-ADRDA criteria [19], (2) an MMSE score of 20, (3) age between 50-90 years, (4) a caregiver who was willing to participate in the study and who were in contact with the participant more than once monthly, and (5) if receiving anti-dementia or mood stabilizing medication, the dose should be stable for at least 3 months before inclusion.…”

“…Exclusion criteria were (1) co-morbidity that prevented exercising including musculoskeletal, joint, neurological, and cardiac diseases and (2) performing regular moderate-to-high-intensity exercise twice or more weekly before the study entry. A detailed description of the inclusion and exclusion criteria has been published previously [16]. At each memory clinic, participants were subsequently randomized in blocks of 4-10 participants to an intervention group or a control group using a computerized random-number generator in favor of the exercise program if an odd number of participants were included.…”

Cerebrospinal Fluid Amyloid Beta and Tau Concentrations Are Not Modulated by 16 Weeks of Moderate- to High-Intensity Physical Exercise in Patients with Alzheimer Disease

“…All subjects donated a blood sample before and after the intervention, and were tested at baseline and at the 16-week follow-up with a comprehensive battery of tests of cognitive function, activities of daily function, quality of life, physical activity and neuropsychiatric symptoms. For details of inclusion and exclusion criteria and methods, see Hoffmann et al [25]. From the 200 participating subjects, a subgroup of 56 subjects, recruited from three out of eight centres, had a lumbar puncture performed to collect CSF samples before and after the intervention.…”