The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: results of a one-year exercise intervention

Cerebral white matter degeneration occurs with increasing age and is associated with declining cognitive function. Given the expected rise in the number and proportion of older adults in the United States, it is imperative to identify lifestyle factors that can counteract the deleterious effects of aging. Research has shown that cardiovascular fitness and exercise are effective as protective, even restorative, agents against cognitive and neurobiological impairments in older adults. In this study, we investigated whether the beneficial impact of aerobic fitness would extend to white matter integrity in the context of a one-year exercise intervention. Further, we examined the pattern of diffusivity changes to better understand the biological mechanisms underlying the observed differences. Finally, we tested whether white matter integrity mediated the fitness-associated improvements in cognitive performance. Using a region-of-interest approach on diffusion tensor images in 70 older adults, we examined longitudinal differences in fractional anisotropy, radial diffusivity and axial diffusivity within the prefrontal, parietal, occipital and temporal lobes. Our results indicate that improved cardiovascular fitness is associated with superior white matter integrity particularly in prefrontal and parietal brain regions, and that fractional anisotropy and radial diffusivity exhibit an overlapping pattern of distribution. In addition, we found a trend towards increased parietal white matter integrity partially mediating the relationship between improved aerobic fitness and enhanced short-term memory performance. We provide the first evidence for cerebral white matter integrity as one neurobiological mechanism explaining the beneficial influence of aerobic fitness on cognitive performance in older adults

Flexible, Transparent, and Noncytotoxic Graphene Electric Field Stimulator for Effective Cerebral Blood Volume Enhancement

Enhancing cerebral blood volume (CBV) of a targeted area without causing side effects is a primary strategy for treating cerebral hypoperfusion. Here, we report a new nonpharmaceutical and nonvascular surgical method to increase CBV. A flexible, transparent, and skin-like biocompatible graphene electrical field stimulator was placed directly onto the cortical brain, and a noncontact electric field was applied at a specific local blood vessel. Effective CBV increases in the blood vessels of mouse brains were directly observed from <i>in vivo</i> optical recordings of intrinsic signal imaging. The CBV was significantly increased in arteries of the stimulated area, but neither tissue damage nor unnecessary neuronal activation was observed. No transient hypoxia was observed. This technique provides a new method to treat cerebral blood circulation deficiencies at local vessels and can be applied to brain regeneration and rehabilitation

Exercise training increases size of hippocampus and improves memory

The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia. Hippocampal and medial temporal lobe volumes are larger in higher-fit adults, and physical activity training increases hippocampal perfusion, but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown. Here we show, in a randomized controlled trial with 120 older adults, that aerobic exercise training increases the size of the anterior hippocampus, leading to improvements in spatial memory. Exercise training increased hippocampal volume by 2%, effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF, a mediator of neurogenesis in the dentate gyrus. Hippocampal volume declined in the control group, but higher preintervention fitness partially attenuated the decline, suggesting that fitness protects against volume loss. Caudate nucleus and thalamus volumes were unaffected by the intervention. These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood, which is accompanied by improved memory function

Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume

Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain-derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age, and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age. In this study, we tested whether age-related reductions in serum levels of BDNF would be related to shrinkage of the hippocampus and memory deficits in older adults. Hippocampal volume was acquired by automated segmentation of magnetic resonance images in 142 older adults without dementia. The caudate nucleus was also segmented and examined in relation to levels of serum BDNF. Spatial memory was tested using a paradigm in which memory load was parametrically increased. We found that increasing age was associated with smaller hippocampal volumes, reduced levels of serum BDNF, and poorer memory performance. Lower levels of BDNF were associated with smaller hippocampi and poorer memory, even when controlling for the variation related to age. In an exploratory mediation analysis, hippocampal volume mediated the age-related decline in spatial memory and BDNF mediated the age-related decline in hippocampal volume. Caudate nucleus volume was unrelated to BDNF levels or spatial memory performance. Our results identify serum BDNF as a significant factor related to hippocampal shrinkage and memory decline in late adulthood. Copyright © 2010 the authors