Synergistic Benefits of Combined Aerobic and Cognitive Training on Fluid Intelligence and the Role of IGF-1 in Chronic Stroke

Abstract

Background. Paired exercise and cognitive training have the potential to enhance cognition by "priming" the brain and upregulating neurotrophins. Methods. Two-site randomized controlled trial. Fifty-two patients >6 months poststroke with concerns about cognitive impairment trained 50 to 70 minutes, 3× week for 10 weeks with 12-week follow-up. Participants were randomized to 1 of 2 physical interventions: Aerobic (>60% VO 2peak using <10% body weight-supported treadmill) or Activity (range of movement and functional tasks). Exercise was paired with 1 of 2 cognitive interventions (computerized dual working memory training [COG] or control computer games [Games]). The primary outcome for the 4 groups (Aerobic + COG, Aerobic + Games, Activity + COG, and Activity + Games) was fluid intelligence measured using Raven's Progressive Matrices Test administered at baseline, posttraining, and 3-month follow-up. Serum neurotrophins collected at one site (N = 30) included brain-derived neurotrophic factor (BDNF) at rest (BDNF resting) and after a graded exercise test (BDNF response) and insulin-like growth factor-1 at the same timepoints (IGF-1 rest , IGF-1 response). Results. At follow-up, fluid intelligence scores significantly improved compared to baseline in the Aerobic + COG and Activity + COG groups; however, only the Aerobic + COG group was significantly different (+47.8%) from control (Activity + Games −8.5%). Greater IGF-1 response at baseline predicted 40% of the variance in cognitive improvement. There was no effect of the interventions on BDNF resting or BDNF response ; nor was BDNF predictive of the outcome. Conclusions. Aerobic exercise combined with cognitive training improved fluid intelligence by almost 50% in patients >6 months poststroke. Participants with more robust improvements in cognition were able to upregulate higher levels of serum IGF-1 suggesting that this neurotrophin may be involved in behaviorally induced plasticity.

Cognitive Reserve as an Emerging Concept in Stroke Recovery

“…Future research should explore the benefits of combining aerobic exercise and/or strength training with a cognitive reserve "boosting" intervention on outcomes and recovery following stroke. Aerobic exercise and/or strength training in conjunction with a cognitive reserve "boosting" intervention might demonstrate synergistic or complementary treatment effects above and beyond standalone physical or cognitive interventions (eg, Bo et al 75 and Ploughman et al 76 ). However, the amount, sustainability, and maintenance of a brain and/or cognitive reserve "boosting" intervention, and which cognitive reserve factors would facilitate the greatest protection against impairment or decline remains unknown.…”

Role of Regular Physical Activity in Neuroprotection against Acute Ischemia

“…IGF-1 might participate in behaviorally induced plasticity [93,94] whereas BDNF, whose effects and mechanism of action will be discussed in more detail below, is thought to be one potential element linking PA with memory, neurogenesis and synaptogenesis.…”

“…Induced by circulating growth hormone (GH), IGF-1 is primarily produced by the liver before being released into the circulatory system. Various reports indicate that IGF-1 is released by other tissues including the skeletal muscle [93,[179][180][181] playing an active role in mediating the recovery of neuronal function through the PA together with BDNF, despite an excessive release of IGF-1 is reported to have opposite effects, inducing an increased level of neuroinflammation and the worst outcome [182]. The attempt to assess if acute exercise effects peripheral IGF-1 levels in humans lead to conflicting results [183,184], although Rojas Vega et al reported a plasmatic increase of IGF-1 (but not of BDNF) levels after a single bout of resistance training [185], Sillanpaa et al [186] report an 8% (p = 0.097) increase after 21 weeks of endurance training in healthy old women and Cappon et al [187] showed that 10-min above-lactate threshold cycle ergometer exercise led to a brief and small increases in circulating IGF-I that were independent of circulating GH, other authors failed to obtain similar results [152,169,170,188].…”

Cognition in Stroke Rehabilitation and Recovery Research: Consensus-Based Core Recommendations From the Second Stroke Recovery and Rehabilitation Roundtable

“…Similarly, Brain Derived Neurotrophic Factor (BDNF) has been implicated as mediating improved spatial memory in a trial of aerobic exercise training in older adults, where training increased hippocampal volume, effectively reversing age-related loss by 1 to 2 years 30 . A recent phase II clinical trial in patients with post-stroke cognitive impairment, showed that exercise paired with cognitive training did improve fluid intelligence, but the relationship to BDNF was less clear 31 . It is here that animal models provide a much more fine-grained approach to understanding the intricacies of the cellular and genetic substrates that underpin human cognition 32 .…”