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Studies have shown that aerobic exercise has the potential to improve cognition and reduce brain atrophy in older adults. However, the literature is equivocal with regards to the specificity or generality of these effects. To this end, we report results on cognitive function and brain structure from a 6-month training intervention with 60 sedentary adults (64–78 years) randomized to either aerobic training or stretching and toning control training. Cognitive functions were assessed with a neuropsychological test battery in which cognitive constructs were measured using several different tests. Freesurfer was used to estimate cortical thickness in frontal regions and hippocampus volume. Results showed that aerobic exercisers, compared to controls, exhibited a broad, rather than specific, improvement in cognition as indexed by a higher “Cognitive score,” a composite including episodic memory, processing speed, updating, and executive function tasks (p = 0.01). There were no group differences in cortical thickness, but additional analyses revealed that aerobic fitness at baseline was specifically related to larger thickness in dorsolateral prefrontal cortex (dlPFC), and hippocampus volume was positively associated with increased aerobic fitness over time. Moreover, “Cognitive score” was related to dlPFC thickness at baseline, but changes in “Cognitive score” and dlPFC thickness were associated over time in the aerobic group only. However, aerobic fitness did not predict dlPFC change, despite the improvement in “Cognitive score” in aerobic exercisers. Our interpretation of these observations is that potential exercise-induced changes in thickness are slow, and may be undetectable within 6-months, in contrast to change in hippocampus volume which in fact was predicted by the change in aerobic fitness. To conclude, our results add to a growing literature suggesting that aerobic exercise has a broad influence on cognitive functioning, which may aid in explaining why studies focusing on a narrower range of functions have sometimes reported mixed results.

In longitudinal positron emission tomography (PET), the presence of volumetric changes over time can lead to an overestimation or underestimation of the true changes in the quantified PET signal due to the partial volume effect (PVE) introduced by the limited spatial resolution of existing PET cameras and reconstruction algorithms. Here, a 3D-printed anthropomorphic brain phantom with attachable striata in three sizes was designed to enable controlled volumetric changes. Using a method to eliminate the non-radioactive plastic wall, and manipulating BP levels by adding different number of events from list-mode acquisitions, we investigated the artificial volume dependence of BP due to PVE, and potential bias arising from varying BP. Comparing multiple reconstruction algorithms we found that a high-resolution ordered- subsets maximization algorithm with spatially variant point-spread function resolution modeling provided the most accurate data. For striatum, the BP changed by 0.08% for every 1% volume change, but for smaller volumes such as the posterior caudate the artificial change in BP was as high as 0.7% per 1% volume change. A simple gross correction for striatal volume is unsatisfactory, as the amplitude of the PVE on the BP differs depending on where in the striatum the change occurred. Therefore, to correctly interpret age-related longitudinal changes in the BP, we must account for volumetric changes also within a structure, rather than across the whole volume. The present 3D-printing technology, combined with the wall removal method, can be implemented to gain knowledge about the predictable bias introduced by the PVE differences in uptake regions of varying shape.

There is much evidence that dopamine is vital for cognitive functioning in aging. Here we tested the hypothesis that aerobic exercise and fitness influences dopaminergic neurotransmission in the striatum as measured by positron emission tomography (PET) and the non-displacable binding potential (BPND ) of [11C]raclopride, and in turn performance on offline working-memory updating tasks. In a sample of 58 older sedentary adults undergoing a six-months exercise intervention, aerobic exercise compared to stretching, toning, and resistance training did not have a differential effect on BPND . At baseline, higher aerobic fitness levels (VO2peak ) were associated with higher BPND  in the striatum. Following the intervention, for both forms of training, we found reduced BPND , indicating increased dopamine (DA), in a cluster in the anterior striatum in individuals with larger improvements in VO2peak . This reduction in BPND  mediated a positive indirect effect of VO2peak  on working-memory updating performance. Collectively these findings implicate DA as a neurocognitive mechanism explaining the positive effects of staying physically active at an old age for working memory.