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Front. Neurol., 06 May 2011 |

Exercise-induced cognitive plasticity, implications for mild cognitive impairment and Alzheimer’s disease

Philip P. Foster1,2,3,4*, Kevin P. Rosenblatt5 and Rodrigo O. Kuljiš2,3,4
  • 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
  • 2 Division of Cognitive and Behavioral Neurology, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA
  • 3 Encephalogistics, Inc., Galveston, TX, USA
  • 4 Brain-Mind Project, Inc., Galveston, TX, USA
  • 5 Brown Foundation, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA

Lifestyle factors such as intellectual stimulation, cognitive and social engagement, nutrition, and various types of exercise appear to reduce the risk for common age-associated disorders such as Alzheimer’s disease (AD) and vascular dementia. In fact, many studies have suggested that promoting physical activity can have a protective effect against cognitive deterioration later in life. Slowing or a deterioration of walking speed is associated with a poor performance in tests assessing psychomotor speed and verbal fluency in elderly individuals. Fitness training influences a wide range of cognitive processes, and the largest positive impact observed is for executive (a.k.a. frontal lobe) functions. Studies show that exercise improves additional cognitive functions such as tasks mediated by the hippocampus, and result in major changes in plasticity in the hippocampus. Interestingly, this exercise-induced plasticity is also pronounced in APOE ε4 carriers who express a risk factor for late-onset AD that may modulate the effect of treatments. Based on AD staging by Braak and Braak (1991) and Braak et al. (1993) we propose that the effects of exercise occur in two temporo-spatial continua of events. The “inward” continuum from isocortex (neocortex) to entorhinal cortex/hippocampus for amyloidosis and a reciprocal “outward” continuum for neurofibrillary alterations. The exercise-induced hypertrophy of the hippocampus at the core of these continua is evaluated in terms of potential for prevention to stave off neuronal degeneration. Exercise-induced production of growth factors such as the brain-derived neurotrophic factor (BDNF) has been shown to enhance neurogenesis and to play a key role in positive cognitive effects. Insulin-like growth factor (IGF-1) may mediate the exercise-induced response to exercise on BDNF, neurogenesis, and cognitive performance. It is also postulated to regulate brain amyloid β (Aβ) levels by increased clearance via the choroid plexus. Growth factors, specifically fibroblast growth factor and IGF-1 receptors and/or their downstream signaling pathways may interact with the Klotho gene which functions as an aging suppressor gene. Neurons may not be the only cells affected by exercise. Glia (astrocytes and microglia), neurovascular units and the Fourth Element may also be affected in a differential fashion by the AD process. Analyses of these factors, as suggested by the multi-dimensional matrix approach, are needed to improve our understanding of this complex multi-factorial process, which is increasingly relevant to conquering the escalating and intersecting world-wide epidemics of dementia, diabetes, and sarcopenia that threaten the global healthcare system. Physical activity and interventions aimed at enhancing and/or mimicking the effects of exercise are likely to play a significant role in mitigating these epidemics, together with the embryonic efforts to develop cognitive rehabilitation for neurodegenerative disorders.

Keywords: hippocampus, entorhinal cortex, insulin-like growth factor, reduction of systemic inflammation, p38 effector of Aβ-induced neurodegeneration, virtual reality environment, exponentially decreasing risk of cell death, loss of cognitive performance

Citation: Foster PP, Rosenblatt KP and Kuljiš RO (2011) Exercise-induced cognitive plasticity, implications for mild cognitive impairment and Alzheimer’s disease. Front. Neur. 2:28. doi: 10.3389/fneur.2011.00028

Received: 11 April 2011; Accepted: 18 April 2011;
Published online: 06 May 2011.

Edited by:

Cristian Lasagna Reeves, University of Texas Medical Branch, USA

Reviewed by:

Craig Atwood, University of Wisconsin, USA
Cristian Lasagna Reeves, University of Texas Medical Branch, USA
Diana Laura Castillo-Carranza, University of Texas Medical Branch, USA
Marcos Jair Guerrero-Munoz, University of Texas Medical Branch, USA

Copyright: © 2011 Foster, Rosenblatt and Kuljiš. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Philip P. Foster, Department of Internal Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0561, USA. e-mail: