Findings from transgenic
Alzheimer dogs and mice studies propose some potential mechanisms through which
exercise may reduce or stop progression of dementia. In Alzheimer mice brain
derived neurotrophic factor (BDNF) is stimulated by exercise, resulting in higher
concentrations within several areas of the brain, including the hippocampus, thought
to have a role in mediating the symptoms of dementia. In animal dementia
models, effects of BDNF are consistently
observed 3 months after initiation of exercise, and result in improvements
in spatial memory which last for some period of time but begin to decline in the absence of ongoing exercise. Other
effects of exercise relevant to dementia patients include increased blood flow
and neurogenesis, improved synaptic function, reduction of damaging beta
amyloid effects, stimulation of anabolic metabolism and improved mitochondrial
ROS production. Recent studies of autopsied human brain have encouragingly
shown a positive correlation between the amount of physical activity and volume
of the hippocampus and other areas of the central nervous system which are
prone to pathological change in dementia.

These studies provide optimistic
evidence, and some guidance to the duration and dose of physical activity
required to benefit people with dementia. Interventional studies in humans are rare,
but a few, mainly of MCI and memory impairment, guide the development of an
exercise programme by providing important data. The most relevant Cochrane
Review (Forbes et al. 2008) of the topic drew no conclusions about the effectiveness
of interventions due to the low quality
of 3 out of the 4 included studies. The
fourth study tested high intensity aerobic training (>75% of heart rate
max, 4 times a week, 1hr sessions for 6 months) in people with MCI, and
demonstrated improvements in biomarkers related to Alzheimer’s as well as in
tests of cognitive function. Also what was interesting was some evidence of a
differential effect between men and women although no follow up data has been
published and so sustainability is undetermined. Activity of moderate
intensity, defined as exercise 3 times a week, has been investigated in most
trials as it is most acceptable to participants.

Thus most of the
current evidence that suggests improved
cognition is derived from animal studies, studies of healthy subjects or people
with subjective memory impairment or MCI. Very
few have trialled exercise interventions in actual dementia patients. As no high quality randomised controlled
trial exists to provide evidence for this, this trial aims to fill the gap in
the literature and provide guidance to guideline and policy makers and resource
allocators regarding the role physical activity can play in the management of
dementia. It was
decided to conduct the trial in a community setting as 2/3 of people living
with dementia reside in the community5 so results can be generalised
more reliably to a larger number of dementia patients. The intervention was
restricted to those with mild to moderate dementia as those with severe
dementia would struggle to undertake the exercises amongst other issues.