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The promise of transcranial direct-current stimulation (tDCS) as a modulator of cognition has appealed to researchers, media, and the general public. Researchers have suggested that tDCS may increase effects of cognitive training. In this study of 123 older adults, we examined the interactive effects of 20 sessions of anodal tDCS over the left prefrontal cortex (vs. sham tDCS) and simultaneous working memory training (vs. control training) on change in cognitive abilities. Stimulation did not modulate gains from pre-to posttest on latent factors of either trained or untrained tasks in a statistically significant manner. A supporting meta-analysis (n = 266), including younger as well as older individuals, showed that, when combined with training, tDCS was not much more effective than sham tDCS at changing working memory performance (g = 0.07, 95% confidence interval, or CI = [-0.21, 0.34]) and global cognition performance (g = -0.01, 95% CI = [-0.29, 0.26]) assessed in the absence of stimulation. These results question the general usefulness of current tDCS protocols for enhancing the effects of cognitive training on cognitive ability.

Multidomain lifestyle interventions represents a promising strategy to counteract cognitive decline in older age. Brain-derived neurotrophic factor (BDNF) is essential for experience-dependent plasticity and increases following physical exercise, suggesting that physical exercise may facilitate subsequent learning. In a randomized-controlled trial, healthy older adults (65–75 years) completed a 12-week behavioral intervention that involved either physical exercise immediately before cognitive training ( n  = 25; 13 females), physical exercise immediately after cognitive training ( n  = 24; 11 females), physical exercise only ( n  = 27; 15 females), or cognitive training only ( n  = 21; 12 females). We hypothesized that cognition would benefit more from cognitive training when preceded as opposed to followed by physical exercise and that the relationship between exercise-induced increases in peripheral BDNF and cognitive training outcome would be greater when cognitive training is preceded by physical exercise. Greater increases of plasma BDNF were associated with greater cognitive training gains on trained task paradigms, but only when such increases preceded cognitive training (ß = 0.14, 95% CI [0.04, 0.25]). Average cognitive training outcome did not differ depending on intervention order (ß = 0.05, 95% CI [−0.10, 0.20]). The study provides the first empirical support for a time-critical but advantageous role for post-exercise increases in peripheral BDNF for learning at an interindividual level in older adults, with implications for future multidomain lifestyle interventions.

VO 2 max (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 VO 2 max were also tested. Exercise did not induce statistically significant changes in brain activity, grey matter volume, or cortical thickness. Cardiovascular fitness, measured by VO 2 max, 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.

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. Forty-nine older adults were randomized to a 30-min 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 labeling (pASL) magnetic resonance imaging (MRI) acquisition, and working memory performance, measured by figurative n-back tasks with increasing loads were assessed before and 7 min after exercising/resting. 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. 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.

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.

Adolescence is a crucial phase for the development of cognitive abilities linked to academic performance. Factors such as physical activity (PA) and fitness have been hypothesized to be linked to these outcomes, although the evidence is inconclusive. This study aimed to examine the associations between PA, fitness, academic, and cognitive performance in the same sample of adolescents. In this cross-sectional study, 1139 Swedish adolescents (mean age 13.4 years) participated. We assessed PA (accelerometry), cardiovascular fitness (submaximal ergometer test), cognitive performance (computer-based test assessing episodic and working memory with 3 tests per domain), and academic performance (grades in math and language, Swedish). We utilized multilevel mixed models to explore associations and structural equation modeling to perform mediation analyses. We found a weak positive association between cardiovascular fitness and math grades (b: 0.18, 95% CI: 0.09, 0.26 β: 0.18), language grades (b: 0.16, 95% CI: 0.07, 0.25 β: 0.13), and cognitive performance (b: 0.01, 95% CI: 0.00, 0.02 β: 0.11). Further, cognitive performance scores mediated 40% of the associations between fitness and math, and language grades. Adolescents with parents with short education (≤12 years of education) or foreign-born had lower fitness levels and grades in math and language (all p < 0.05). Fitness was the only significant factor associated with cognitive and academic performance, although the association was weak. Given our findings of low fitness and academic performance among adolescents with parents with short education or parents born abroad, future studies should tailor their interventions to ensure the inclusion of these groups.

Contemporary imaging measures of the human brain explain less than half of the differences in cognitive functioning and change among older adults. Researchers have advanced several theories and concepts to guide research that aims to better explain these individual differences in cognitive aging. Taking the fundamental measurement model in the empirical sciences as a starting point, we here scrutinize two such complementary theories, brain maintenance and cognitive reserve, in an attempt to clarify these theories, gauge their usefulness, and identify ways in which they can be further developed. We demonstrate that, although both theories are highly useful for spawning theorizing and empirical work, they can be further developed by detailing the theoretical and operational definitions of the concepts that they propose. We propose a few ways forward in these directions.

Blood-based biomarkers of neurodegeneration demonstrate great promise for the diagnosis and prognosis of Alzheimer’s disease. Ultra-sensitive plasma assays now allow for quantification of the lower concentrations in cognitively unimpaired older adults, making it possible to investigate whether these markers can provide insight also into the early neurodegenerative processes that affect cognitive function and whether the markers are influenced by modifiable risk factors. Adopting an exploratory approach in 93 healthy older adults (65–75 years), we used structural equation modelling to investigate cross-sectional associations between multiple latent cognitive abilities (working memory, episodic memory, spatial and verbal reasoning) and plasma amyloid beta (Aβ42/Aβ40 ratio), phosphorylated-tau 181 (ptau-181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL), as well as the influence of device-measured habitual physical activity on these associations. The results showed that NfL was negatively associated with working memory, and that NfL interacted with moderate-to-vigorous physical activity in its association with episodic memory. The study has thereby demonstrated the potential of neurodegenerative plasma markers for improving understanding of normative cognitive aging and encourages future research to test the hypothesis that high levels of NfL, indicative of white matter pathology, limit the beneficial effect of physical activity on episodic memory in healthy aging.

Background We have previously reported on the design and efficacy of two cluster-randomized multi-level workplace interventions, attempting to decrease sedentary behavior (SED) or increase moderate to vigorous physical activity (MVPA) among office workers to improve mental health outcomes. The aim of this study was to investigate intervention effects on mental health outcomes, i.e., mental wellbeing, depression or anxiety symptoms, and stress immediately after the 6-month intervention period. Methods Teams of 263 office workers were cluster-randomized to one of two interventions or a waitlist control group. The PA intervention (iPA) focused on increasing MVPA and the SED intervention (iSED) on reducing SED. Both multi-level interventions targeted individual office workers and their social, physical, and organizational work environment, incorporating counseling based on cognitive behavioral therapy and motivational interviewing. Mental health outcomes were assessed using validated questionnaires before and immediately after the intervention. Intervention effects were analyzed using linear mixed effects models. Results Participants were mostly female and highly educated, with a mean age of 42 years and had favorable levels of mental health at baseline. Mental wellbeing improved for the iSED group (β = 8, 95% CI 1 to 15, p  = 0.030) but not for the iPA group (β = 6, 95% CI -1 to 12, p  = 0.072) compared to the control group. No effects were found for depression or anxiety symptoms or stress. Conclusions The multi-level interventions improved mental wellbeing among this population of office workers, reaching statistical significance in the iSED group. The size of the effect can be regarded meaningful, considering favorable mental health and high PA level at baseline. Thus, workplace interventions that provide support on multiple levels appear to have potential for improving mental wellbeing, but not reducing ill-health variables, among healthy office workers. More research is needed to understand the mechanisms through which such improvements can be achieved and to identify the most effective intervention components. Trial registration ISRCTN92968402 (27 February 2018).

Older adults show relatively minor age-related decline in memory for single items, while their memory for associations is markedly reduced. Inter-individual differences in memory function in older adults are substantial but the neurobiological underpinnings of such differences are not well understood. In particular, the relative importance of inter-individual differences in the medio-temporal lobe (MTL) and the lateral prefrontal cortex (PFC) for associative and item recognition in older adults is still ambiguous. We therefore aimed to first establish the distinction between inter-individual differences in associative memory (recollection-based) performance and item memory (familiarity-based) performance in older adults and subsequently link these two constructs to differences in cortical thickness in the MTL and lateral PFC regions, in a latent structural equation modelling framework. To this end, a sample of 160 older adults (65–75 years old) performed three intentional item-associative memory tasks, of which a subsample (n ​= ​72) additionally had cortical thickness measures in MTL and PFC regions of interest available. The results provided support for a distinction between familiarity-based item memory and recollection-based associative memory performance in older adults. Cortical thickness in the ventro-medial prefrontal cortex was positively correlated with associative recognition performance, above and beyond any relationship between item recognition performance and cortical thickness in the same region and between associative recognition performance and brain structure in the MTL (parahippocampus). The findings highlight the relative importance of the ventromedial prefrontal cortex in allowing for intentional recollection-based associative memory functioning in older adults. •Latent structural equation modeling supports dual-process theories of recognition.•Cortical thickness in the ventro-lateral PFC is linked to associative recognition.•No link between ventro-lateral PFC thickness and item recognition.•Medial-temporal lobe and associative recognition not linked in healthy older adults.