Train the sedentary brain: move smart to reduce the risk of dementia;Sub study: Alternating aerobic and strength exercise in APOEe4 carriers and non-carriers in early stage dementia: effects and dose-response relation

There is no cure for dementia. Physical activity could be an alternative to
medications in an effort to slow the dementia-related cognitive decline. In
healthy older subjects physical activity leads to improved cognition. In people
with dementia the results are mixed, although a recent study revealed
beneficial cognitive effects of alternating aerobic and strength exercise in
people with moderate to moderate-severe dementia. Whether these effects hold in
an earlier stage of the disease is unknown. In addition, a dose-response is not
established yet and it is unknown whether effects are moderated by APOEe4
status, the most important biological risk factor of dementia. Furthermore, the
underlying mechanisms through which exercise influences cognition are
understudied in patients with dementia.

Main objectives are to investigate the cognitive effects of alternating
endurance-strength training in APOEe4 carriers and non-carriers in early stage
dementia and to identify a dose-response relationship of the cognitive effects
of exercise.
Secondary objective is to investigate the physical effects of this training
regimen.
We expect that alternating endurance and strength training is feasible and
leads dose-dependently to improved cognition and physical fitness. We expect
stronger effects in APOEe4 carriers than in non-carriers. In addition, we
expect IGF1 to mediate the association between exercise and cognition.

The design is a single blinded RCT with a cross-over element (low intensity
versus higher intensity).

The experimental group receives alternating aerobic-strength exercise, 3
sessions per week for 30 minutes, 12 weeks with low intensity and 12 weeks with
high intensity. The control group receives stretching exercises and
recreational activities with matched attention with the same duration and
frequency.

The burden consists of participation in the intervention (36 hours),
measurements (approximately 5.5 hours) and venapunction (approximately 40
minutes) over a period of 24 weeks. The exercises and tests are safe and
feasible for older people with dementia. All activities in this study are
within the range of normal activities of daily life. Participants are guided
individually and they stay in their own familiar environment. However, minor
muscle pain or tiredness may occur occasionally. For the experimental group
anticipated benefits are improvements in cognition, physical functioning, ADLs,
mood and quality of life. For the control group we anticipate benefits in
muscle flexibility, specific ADLs, mood and quality of life. Both groups
receive a lot of attention, which is generally experienced as pleasant.