Protocol for a randomized controlled trial evaluating the effect of physical activity on delaying the progression of white matter changes on MRI in older adults with memory complaints and mild cognitive impairment: The AIBL Active trial

This single-blind randomized controlled trial (RCT) is offered to 156 participants, aged 60 and older, in the Melbourne arm of the Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL). Participants must have SMC with or without MCI and at least one VRF. The PA intervention is a modification of the intervention previously trialed in older adults with SMC and MCI (Fitness for the Ageing Brain Study). It comprises 24 months of moderate, home-based PA (150 minutes per week) and a behavioral intervention package. The primary outcome measure will be change in WMH after 24 months on MRI. Cognition, quality of life, functional fitness, level of physical activity, plasma biomarkers for cerebrovascular disease and amyloid positron emission tomography (PET) imaging comprise secondary measures.Currently, there is no effective pharmacological treatment available to delay cognitive decline and dementia in older adults at risk. Should our findings show that physical activity can slow down the progression of WMH, this RCT would provide an important proof of concept. Since imbedded in AIBL this RCT will also be able to investigate the interaction between vascular and Alzheimer's disease pathologies.Australia New Zealand Clinical Trials Registry ACTRN12611000612910The proportion of the global population aged over 60 years is expected to increase from 11% in 2009 to 22% by 2050 [1]. With increased longevity comes a greater risk of developing age-related diseases, including cognitive impairment and dementia. In 2010, the estimated number of people with dementia worldwide was 35.6 million with a projected increase to 115.4 million people by 2050 [2].Older adults at risk of cognitive decline are those free of dementia but with subjective memory complaints (SMC) and mild cognitive impairment (MCI). SMC is defined as complaining about a deterioration of cognitive function without showing objective impairment on cognitive testing [3] and MCI additionally requires objec