Gymnastik- och idrottshögskolan, GIH

The interplay between biomarkers of relevance to neuroplasticity and its association with learning and cognitive ability in old age remains poorly understood. The present study investigated acute changes in plasma concentrations of mature brain-derived neurotrophic factor (mBDNF), its precursor protein (pro-BDNF), and cortisol, in response to acute physical exercise and cognitive training interventions, their covariation and role in predicting cognitive performance. Confirmatory results provided no support for mBDNF, pro-BDNF and cortisol co-varying over time, as the acute interventions unfolded, but did confirm a positive association between mBDNF and pro-BDNF at rest. The confirmatory results did not support the hypothesis that mBDNF change following physical exercise were counteracted by temporally coupled changes in cortisol or pro-BDNF, or by cortisol at rest, in its previously demonstrated faciliatory effect on cognitive training outcome. Exploratory results instead provided indications of a general and trait-like cognitive benefit of exhibiting greater mBDNF responsiveness to acute interventions when coupled with lesser cortisol responsiveness, greater pro-BDNF responsiveness, and lower cortisol at rest. As such, the results call for future work to test whether certain biomarker profiles are associated with preserved cognition in old age.

It has been demonstrated that physical activity has a small but positive effect on cognition in old age, which suggests that it may be possible to alter the trajectory of age-related cognitive decline. However, our understanding of which aspects of physical activity that are important for modifying cognition remains incomplete. Adopting an exploratory approach in a sample of 115 healthy older adults (65–75 years), the present cross-sectional study used structural equation modelling to investigate the dissociable associations of physical activity (moderate-to-vigorous activity, derived from 7-day accelerometry) and cardiorespiratory fitness (VO2 max, derived from maximal treadmill ergometer test) with multiple latent cognitive abilities (working memory, episodic memory, spatial and verbal reasoning). The results showed a significant positive association between fitness and working memory, when physical activity was statistically controlled for, and a positive association of similar point magnitude between physical activity and episodic memory, when fitness was statistically controlled for, although the latter association did not reach statistical significance. The results add to the foundation for a more careful investigation of the dissociable associations of moderate-to-vigorous physical activity and fitness with cognition in old age, and encourages future research to test the hypothesis that cardiorespiratory fitness benefits working memory via general cerebrovascular effects on grey matter volume, whilst moderate-to-vigorous physical activity benefits episodic memory via effects on neuroplastic processes.

BACKGROUND: We previously reported the effects of two cluster-randomized 6-month multi-component workplace interventions, targeting reducing sedentary behavior or increasing physical activity among office workers, on movement behaviors and cardiorespiratory fitness. The primary aim of this study was to investigate the effects of these interventions on cognitive functions compared to a wait-list control group. The secondary aims were to examine if changes in cognition were related to change in cardiorespiratory fitness or movement behaviors and if age, sex, or cardiorespiratory fitness moderated these associations.

METHODS: Both interventions encompassed multi-components acting on the individual, environmental, and organizational levels and aimed to change physical activity patterns to improve mental health and cognitive function. Out of 263 included participants, 139 (mean age 43 years, 76% females) completed a neuropsychological test battery and wore accelerometers at baseline and 6-month follow-up. The intervention effect (aim 1) on cognitive composite scores (i.e., Executive Functions, Episodic Memory, Processing Speed, and Global Cognition) was investigated. Additionally, associations between changes in movement behaviors and cardiorespiratory fitness, and changes in cognition were examined (aim 2). Moreover, age, sex, and cardiorespiratory fitness level were investigated as possible moderators of change associations (aim 3).

RESULTS: Overall, cognitive performance improved from baseline to follow-up, but the change did not differ between the intervention groups and the control group. Changes in cardiorespiratory fitness or any movement behavior category did not predict changes in cognitive functions. The association between changes in time in bed and changes in both Executive Function and Global Cognition were moderated by age, such that a more positive relation was seen with increasing age. A less positive association was seen between changes in sedentary behavior and Processing Speed for men vs. women, whereas higher cardiorespiratory fitness was related to a more positive association between changes in moderate-intensity physical activity and Global Cognition.

CONCLUSION: The lack of an intervention effect on cognitive functions was expected since the intervention did not change movement behavior or fitness. Age, sex, and cardiorespiratory fitness level might moderate the relationships between movement behaviors and cognitive functions changes.

TRIAL REGISTRATION: ISRCTN92968402 . Registered 09/04/2018.

VO₂max (maximal oxygen consumption), a validated measure of aerobic fitness, has been associated with better cerebral artery compliance and measures of brain morphology, such as higher cortical thickness (CT) in frontal, temporal and cingular cortices, and larger grey matter volume (GMV) of the middle temporal gyrus, hippocampus, orbitofrontal cortex and cingulate cortex. Single sessions of physical exercise can promptly enhance cognitive performance and brain activity during executive tasks. However, the immediate effects of exercise on macro-scale properties of the brain's grey matter remain unclear. We investigated the impact of one session of moderate-intensity physical exercise, compared with rest, on grey matter volume, cortical thickness, working memory performance, and task-related brain activity in older adults. Cross-sectional associations between brain measures and VO₂max were also tested. Exercise did not induce statistically significant changes in brain activity, grey matter volume, or cortical thickness. Cardiovascular fitness, measured by VO₂max, was associated with lower grey matter blood flow in the left hippocampus and thicker cortex in the left superior temporal gyrus. Cortical thickness was reduced at post-test independent of exercise/rest. Our findings support that (1) fitter individuals may need lower grey matter blood flow to meet metabolic oxygen demand, and (2) have thicker cortex.

Background

Regular physical activity is beneficial for cognitive performance in older age. A single bout of aerobic physical exercise can transiently improve cognitive performance. Researchers have advanced improvements in cerebral circulation as a mediator of long-term effects of aerobic physical exercise on cognition, but the immediate effects of exercise on cognition and cerebral perfusion are not well characterized and the effects in older adults are largely unknown.

Methods

Forty-nine older adults were randomized to a 30-minutes aerobic exercise at moderate intensity or relaxation. Groups were matched on age and cardiovascular fitness (VO2 max). Average Grey Matter Blood Flow (GMBF), measured by a pulsed arterial-spin labelling (pASL) magnetic resonance imaging (MRI) acquisition, and working memory performance, measured by figurative n-back tasks with increasing loads were assessed before and 7 minutes after exercising/resting.

Results

Accuracy on the n-back task increased from before to after exercising/resting regardless of the type of activity. GMBF decreased after exercise, relative to the control (resting) group. In the exercise group, higher n-back performance after exercise was associated with lower GMBF in the right hippocampus, left medial frontal cortex and right orbitofrontal cortex, and higher cardiovascular fitness was associated with lower GMBF.

Conclusion

The decrease of GMBF reported in younger adults shortly after exercise also occurs in older adults and relates to cardiovascular fitness, potentially supporting the link between cardiovascular fitness and cerebrovascular reactivity in older age.

It has previously been demonstrated that short-term foreign language learning can lead to structural brain changes in younger adults. Experience-dependent brain plasticity is known to be possible also in older age, but the specific effect of foreign language learning on brain structure in language-and memory-relevant regions in the old brain remains unknown. In the present study, 160 older Swedish adults (65-75 years) were randomized to complete either an entry-level Italian course or a relaxation course, both with a total duration of 11 weeks. Structural MRI scans were conducted before and after the intervention in a subset of participants to test for differential change in gray matter in the two groups in the inferior frontal gyrus, the superior temporal gyrus, and the hippocampus, and in white matter microstructure in the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), fronto-occipital fasciculus, and the hippocampal (HC) section of the cingulum. The study found no evidence for differential structural change following language training, independent of achieved vocabulary proficiency. However, hippocampal volume and associative memory ability before the intervention were found to be robust predictors of vocabulary proficiency at the end of the language course. The results suggest that having greater hippocampal volume and better associative memory ability benefits vocabulary learning in old age but that the very initial stage of foreign language learning does not trigger detectable changes in brain morphometry in old age.

PURPOSE: The aim of this study was to validate the submaximal Ekblom-Bak test (EB-test) and the Åstrand test (Å-test) for an elderly population.

METHODS: Participants (n = 104), aged 65-75 years, completed a submaximal aerobic test on a cycle ergometer followed by an individually adjusted indirect calorimetry VO₂max test on a treadmill. The HR from the submaximal test was used to estimate VO₂max using both the EB-test and Å-test equations.

RESULTS: The correlation between measured and estimated VO₂max using the EB method and Å method in women was r = 0.64 and r = 0.58, respectively and in men r = 0.44 and r = 0.44, respectively. In women, the mean difference between estimated and measured VO₂max was - 0.02 L min^-1 (95% CI - 0.08 to 0.04) for the EB method and - 0.12 L min^-1 (95% CI - 0.22 to - 0.02) for the Å method. Corresponding values for men were 0.05 L min^-1 (95% CI - 0.04 to 0.14) and - 0.28 L min^-1 (95% CI - 0.42 to - 0.14), respectively. However, the EB method was found to overestimate VO₂max in men with low fitness and the Å method was found to underestimate VO₂max in both women and men. For women, the coefficient of variance was 11.1%, when using the EB method and 19.8% when using the Å method. Corresponding values for men were 11.6% and 18.9%, respectively.

CONCLUSION: The submaximal EB-test is valid for estimating VO₂max in elderly women, but not in all elderly men. The Å-test is not valid for estimating VO₂max in the elderly.

Physical exercise (PE) has been shown to improve brain function via multiple neurobiological mechanisms promoting neuroplasticity. Cognitive exercise (CE) combined with PE may show an even greater effect on cognitive function. Brain-derived neurotrophic factor (BDNF) is important for neuroplastic signaling, may reduce with increasing age, and is confounded by fitness. The source and physiological role of human peripheral blood BDNF in plasma (pBDNF) is thought to differ from that in serum (sBDNF), and it is not yet known how pBDNF and sBDNF respond to PE and CE. A training intervention study in healthy older adults investigated the effects of acute (35 min) and prolonged (12 weeks, 30 sessions) CE and PE, both alone and in combination, on pBDNF and sBDNF. Cross-sectional associations between baseline pBDNF, sBDNF and cardiorespiratory fitness (CRF) were also investigated. Participants (65-75 years) were randomly assigned to four groups and prescribed either CE plus 35 min of rest (n = 21, 52% female); PE [performed on a cycle ergometer at moderate intensity (65-75% of individual maximal heart rate)] plus 35 min of rest (n = 27, 56% female); CE plus PE (n = 24, 46% female), or PE plus CE (n = 25, 52% female). Groups were tested for CRF using a maximal treadmill ergometer test (VO2peak); BDNF levels (collected 48 h after CRF) during baseline, after first exercise (PE or CE) and after second exercise (PE, CE or rest); and cognitive ability pre and post 12-week training. At both pre and post, pBDNF increased after CE and PE (up to 222%), and rest (∼67%), whereas sBDNF increased only after PE (up to 18%) and returned to baseline after rest. Acute but not prolonged PE increased both pBDNF and sBDNF. CE induced acute changes in pBDNF only. Baseline pBDNF was positively associated with baseline sBDNF (n = 93, r = 0.407, p < 0.001). No changes in CRF were found in any of the groups. Baseline CRF did not correlate with baseline BDNF. Even though baseline pBDNF and sBDNF were associated, patterns of changes in pBDNF and sBDNF in response to exercise were explicitly different. Further experimental scrutiny is needed to clarify the biological mechanisms of these results.