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 (WM) degeneration occurs with increasing age and is associated with declining cognitive function. Research has shown that cardiorespiratory 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 WM integrity in the context of a one-year exercise intervention. Further, we examined the pattern of diffusivity changes to better understand the underlying biological mechanisms. Finally, we assessed whether training-induced changes in WM integrity would be associated with improvements in cognitive performance independent of aerobic fitness gains. Results showed that aerobic fitness training did not affect group-level change in WM integrity, executive function, or short-term memory, but that greater aerobic fitness derived from the walking program was associated with greater change in WM integrity in the frontal and temporal lobes, and greater improvement in short-term memory. Increases in WM integrity, however, were not associated with short-term memory improvement, independent of fitness improvements. Therefore, while not all findings are consistent with previous research, we provide novel evidence for correlated change in training-induced aerobic fitness, WM integrity, and cognition among healthy older adults.

Age-related differences in cortical recruitment and suppression: implications for cognitive performance.

The discovery of a coherent set of cortical regions showing activation during rest and deactivation during task performance has reignited an old debate in the field of neuroscience, one that questions the reflexivity of the human brain and provides evidence towards a more intrinsic functional architecture. The default-mode network (DMN) comprising of such consistent cortical regions has become a topic of increasing interest in both healthy and diseased populations. In this study, using a well-examined version of the verbal n-back task, interleaved with periods of rest blocks, we investigated whether the deactivation of the cortical regions comprising the DMN moderates individual differences in behavioral performance in a group of older adults. We recruited 25 young and 25 older adults for our study and presented them with blocks of the n-back task, with varying levels of load, interleaved with periods of fixation. A direct comparison of the young and older participants revealed both a reduction in the up-regulation of the prefrontal and parietal regions in response to increasing task demands, along with a reduction in the down-regulation of DMN regions with increasing cognitive load in the elderly. Better performance in the young adults was associated with the capability to modulate the regions of the working memory network with increasing task difficulty, however enhanced performance in the older cohort was associated with greater load-induced deactivation of the posterior cingulate cortex. This study adds to the existing gamut of aging literature, providing evidence that DMN function is critical to cognitive functioning in older adults.

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.

Plasticity of brain networks in a randomized intervention trial of exercise training in older adults.

Research has shown the human brain is organized into separable functional networks during rest and varied states of cognition, and that aging is associated with specific network dysfunctions. The present study used functional magnetic resonance imaging (fMRI) to examine low-frequency (0.008 < f < 0.08 Hz) coherence of cognitively relevant and sensory brain networks in older adults who participated in a 1-year intervention trial, comparing the effects of aerobic and non-aerobic fitness training on brain function and cognition. Results showed that aerobic training improved the aging brain's resting functional efficiency in higher-level cognitive networks. One year of walking increased functional connectivity between aspects of the frontal, posterior, and temporal cortices within the Default Mode Network and a Frontal Executive Network, two brain networks central to brain dysfunction in aging. Length of training was also an important factor. Effects in favor of the walking group were observed only after 12 months of training, compared to non-significant trends after 6 months. A non-aerobic stretching and toning group also showed increased functional connectivity in the DMN after 6 months and in a Frontal Parietal Network after 12 months, possibly reflecting experience-dependent plasticity. Finally, we found that changes in functional connectivity were behaviorally relevant. Increased functional connectivity was associated with greater improvement in executive function. Therefore the study provides the first evidence for exercise-induced functional plasticity in large-scale brain systems in the aging brain, using functional connectivity techniques, and offers new insight into the role of aerobic fitness in attenuating age-related brain dysfunction.

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.

Resting hippocampal blood flow, spatial memory and aging.

Aging is accompanied by a general deterioration of fluid cognitive processes and a reduction in resting cerebral blood flow (CBF). While the two phenomena have been observed independently, it is uncertain whether individual differences in cerebral blood flow are reliably associated with cognitive functioning in older adults. Furthermore, previous studies have concentrated primarily on gross measures of cognition and global gray matter CBF, leaving open the possibility that perfusion of specific brain regions may relate differentially to distinct cognitive domains. The present study sought to provide a more focused treatment of CBF and cognitive function in the context of aging by investigating the relationships among aging, spatial memory and resting hippocampal blood flow, both between and within younger and older adult groups. Blood flow was quantified using a novel Flow-Enhanced Signal Intensity (FENSI) technique which provides a localized, functionally relevant measure of volumetric flow across a given unit area. As expected, we found that aging was associated with poorer spatial memory and reduced resting CBF. Moreover, hippocampal blood flow was positively correlated with spatial memory performance in the older adult group, suggesting that increased blood flow to the hippocampus is associated with superior memory performance in older adults. These results demonstrate a region-specific CBF-cognition relationship and thereby offer new insight into the complex connection between the aging brain and behavior.