Mobilizing reserves: why does physical activity appear to be not beneficial, or even detrimental, in advanced stages of neurodegeneration?
Lamb et al. report potentially negative results of exercise interventions on cognition in patients with mild to moderate dementia. This appears counterintuitive, considering the beneficial effects of physical activity in a broad range of diseases, including various chronic diseases and neurodegenerative diseases. To better understand the risks and benefits of physical activity, more systematic studies are necessary. These studies should assess the impact of different types of exercises and take into account the heterogeneity of dementia and the individuals’ tolerance to exercise interventions.
Physical exercise benefits health and brain function, by processes at least partially mediated via preconditioning tissues, organs or organisms to later insults. In preconditioning, a stimulus below the threshold of damage induces a tolerance against subsequent similar or different harmful stimuli.
This concept however, implies the necessity of a certain reserve capacity. The smaller this reserve, the more likely the preconditioning stimulus exceeds the threshold, resulting in direct damage rather than increasing tolerance. We propose that such buffering reserves may be reduced in the brain of patients suffering from neurodegenerative diseases, like Alzheimer’s disease, and should be considered when designing exercise-based intervention strategies.
Interestingly, several physiological parameters that are positively affected by regular physical activity are compromised in neurodegenerative diseases: e.g. mitochondrial function, the antioxidative defense systems, neuroinflammation and neuronal proteostasis[4 5]. We argue that loss of buffering capacities in dementia patients (such as tolerance to oxidative stress, a well-documented event in early dementia and importantly affected by exercise) might have been responsible for the negative effects on cognition after an intense exercise challenge as applied by Lamb et al.
The study by Lamb et al. highlights important limitations of exercise interventions in patients already affected by dementia and contributes valuable information on the effects of physical activity on dementia patients. But the approach is lacking stratification on the basis of parameters linked to tolerance to physical exercise or consideration of individual threshold levels. Given the small, albeit statistically significant, difference observed in this study, we believe it is crucial to systematically assess to what extent the intensity and type of exercise regimen and individual reserve capacity influence the effect of physical exercise on brain function at different stages of disease progression. Accordingly, submaximal (below the reserve threshold) personalized exercising routines should not be excluded as useful interventions for neurodegeneration patients, in particular if combined with other novel approaches to enhance reserve capacities in controlled ways, for instance by intermittent hypoxic-hyperoxic training.
Please find a supporting figure here: https://imgur.com/a/jFdA3AE
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Competing interests: No competing interests