Effective treatment for cognitive dysfunction is the Holy Grail in research for most brain diseases. With the exception of stimulants for attention deficit hyperactivity disorder (ADHD), there is little evidence for any pharmacological intervention to restore cognitive dysfunction once a brain disease is diagnosed. Although future success of new drugs should not be ruled out yet, the many negative results so far suggest that drug interventions may be better to prevent cognitive dysfunction in brain diseases than to treat them once present.
In sharp contrast to the disappointing findings of pharmacological interventions, are the promising results of studies assessing the potential of physical exercise to improve cognition.
- Malchow et al included 3 groups: patients with schizophrenia who were offered endurance training for 3 months, augmented in the last 6 weeks with cognitive remediation, a similar group of patients who were provided table soccer for 3 months, again augmented with cognitive remediation in the last 6 weeks and a healthy control group, given the same interventions as the first patient group. They showed superior effects of endurance training over table soccer on symptom severity, depression, and some (but not all) cognitive tasks.
- Svatkova et al assessed the effect of biking for 6 months on the integrity of white matter connections in patients and controls, as compared with life as usual. In both groups, exercise improved fiber integrity, especially in the motor circuit, while the patients in the control group showed deterioration of fiber integrity over the 6 months of the study.
- Kimhy et al demonstrated a 15% improvement in cognition as assessed with the Matrix Consensus Cognitive Battery in the exercise group as compared with 2% decline in the control group. They further showed that increases in the serum levels of BDNF could explain only a small percentage of the improvement in cognition.
“Since the beneficial effects of exercise are observed in many different brain disorders, the neurobiological mechanisms underlying these effects are expected to involve general aspects of brain function that are affected in all diseases. This indeed seems to be the case. Firstly, increased cardiac output improves cerebral circulation and optimizes oxygen extraction and glucose uptake of neurons and glia cells. Secondly, neurogenesis is improved, most pronounced in the hippocampal dentate gyrus, which may be secondary to increased neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor. Further, moderate exercise reduces the inflammatory status of the brain, by increasing levels of the anti-inflammatory cytokine interleukin-10, among others, although stringent exercise can have a negative impact on the immune system. Recently, the route to explain the association between cognition and exercise was further elucidated. Expression of peroxisome proliferator-activated receptor-gamma coactivator-1α1 is increased when skeletal muscles become active. This substance enhances the conversion of the tryptophan metabolite kynurenine to kynurenic acid, thereby lowering kynurenine levels in the blood. Through this mechanism, muscle activity restores the immune balance in the brain.”