Project 463345

Alzheimer's disease (AD) is a type of dementia that causes problems with memory, thinking, and behaviour. Currently, drugs called cholinesterase inhibitors are used in AD, however benefits are modest and side-effects such as loss of appetite, nausea, vomiting, and diarrhea are common. Disease modifying drugs such as aducanumab are emerging but costly, and modest improvements in memory and important side effects will limit use. As a result, there remains a critical need for treatments, particularly those focused on mild AD when quality of life is still better. Transcranial direct current stimulation (tDCS) is a method of non-invasive electrical brain stimulation. It has been shown to improve memory in mild AD with minimal side-effects, but only in some people. As tDCS needs active brain circuits, we believe exercise, which improves blood flow and brain activity, may help it work in more people. This study will assess whether adding exercise to tDCS can help improve memory in mild AD, and whether this combination improves memory better than either exercise or tDCS alone. Participants will be randomly assigned to 1) exercise and tDCS, 2) exercise and sham (non-active) tDCS, 3) tDCS alone (with exercise education rather than exercise) or 4) neither (double sham) for two weeks. Before and after the 2-week intervention, memory, thinking and behaviour will be assessed and blood samples will be collected to identify biomarkers related to memory response. Brain scans will also be looked at before and immediately after the 2-week treatment. We think that physical exercise with tDCS, compared to the other treatments, will show the greatest improvements in memory, and that improvements will be linked with positive changes in brain and blood markers. This study may identify a safe, non-invasive treatment approach that preserves memory in early AD, and therefore will have major health implications.