Gymnastik- och idrottshögskolan, GIH

Foreign language learning in older age has been proposed as a promising avenue for combatting age-related cognitive decline. We tested this hypothesis in a randomized controlled study in a sample of 160 healthy older participants (aged 65-75 years) who were randomized to 11 weeks of either language learning or relaxation training. Participants in the language learning condition obtained some basic knowledge in the new language (Italian), but between-groups differences in improvements on latent factors of verbal intelligence, spatial intelligence, working memory, item memory, or associative memory were negligible. We argue that this is not due to either poor measurement, low course intensity, or low statistical power, but that basic studies in foreign languages in older age are likely to have no or trivially small effects on cognitive abilities. We place this in the context of the cognitive training and engagement literature and conclude that while foreign language learning may expand the behavioral repertoire, it does little to improve cognitive processing abilities. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Education is positively associated with level of cognitive function but the association between education and rate of cognitive decline remains unresolved, partly for methodological reasons. In this article, we address this issue using linear mixed models and Bayesian hypothesis testing, using data from the Betula cohort-sequential longitudinal study. Our results support the null hypothesis that education does not alter the rate of cognitive decline for visuospatial ability, semantic knowledge, and episodic memory. We propose that education is only a relevant variable for understanding cognitive performance in older age because of the association between performance and education that is formed in early development.

Paired associative stimulation (PAS) can induce plasticity in the motor cortex, as measured by changes in corticospinal excitability (CSE). This effect is attenuated in older and less active individuals. Although a single bout of exercise enhances PAS-induced plasticity in young, physically inactive adults, it is not yet known if physical activity interventions affect PAS-induced neuroplasticity in middle-aged inactive individuals. Sixteen inactive middle-aged office workers participated in a randomized cross-over design investigating how CSE and short-interval intracortical inhibition (SICI) were affected by PAS preceded by 3 h of sitting (SIT), 3 h of sitting interrupted every 30 min by 3 min of frequent short bouts of physical activity (FPA) and 2.5 h of sitting followed by 25 min of moderate-intensity exercise (EXE). Transcranial magnetic stimulation was applied over the primary motor cortex (M1) of the dominant abductor pollicis brevis to induce recruitment curves before and 5 min and 30 min post-PAS. Linear mixed models were used to compare changes in CSE using time and condition as fixed effects and subjects as random effects. There was a main effect of time on CSE and planned within-condition comparisons showed that CSE was significantly increased from baseline to 5 min and 30 min post-PAS, in the FPA condition, with no significant changes in the SIT or EXE conditions. SICI decreased from baseline to 5 min post-PAS, but this was not related to changes in CSE. Our findings suggest that in middle-aged inactive adults, FPAs may promote corticospinal neuroplasticity. Possible mechanisms are discussed.

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.

Episodic memory enables the detailed and vivid recall of past events, including target and wider contextual information. In this paper, we investigated whether/how encoding intentionality affects the retention of target and contextual episodic information from a novel experience. Healthy adults performed (1) a What-Where-When (WWW) episodic memory task involving the hiding and delayed recall of a number of items (what) in different locations (where) in temporally distinct sessions (when) and (2) unexpected tests probing memory for wider contextual information from the WWW task. Critically, some participants were informed that memory for WWW information would be subsequently probed (intentional group), while this came as a surprise for others (incidental group). The probing of contextual information came as a surprise for all participants. Participants also performed several measures of episodic and nonepisodic cognition from which common episodic and nonepisodic factors were extracted. Memory for target (WWW) and contextual information was superior in the intentional group compared with the incidental group. Memory for target and contextual information was unrelated to factors of nonepisodic cognition, irrespective of encoding intentionality. In addition, memory for target information was unrelated to factors of episodic cognition. However, memory for wider contextual information was related to some factors of episodic cognition, and these relationships differed between the intentional and incidental groups. Our results lead us to propose the hypothesis that intentional encoding of episodic information increases the coherence of the representation of the context in which the episode took place. This hypothesis remains to be tested.

BACKGROUND: Exercise training (ET) has beneficial effects on multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the intensity-dependent effects of ET on the systemic immune system in EAE remain undefined.

OBJECTIVE: (1) To compare the systemic immune modulatory effects of moderate versus high-intensity ET protocols in protecting against development of EAE; (2) To investigate whether ET affects autoimmunity selectively, or causes general immunosuppression.

METHODS: Healthy mice performed moderate or high-intensity treadmill running programs. Proteolipid protein (PLP)-induced transfer EAE was utilized to examine ET effects specifically on the systemic immune system. Lymph node (LN)-T cells from trained versus sedentary donor mice were transferred to naïve recipients and EAE severity was assessed, by clinical assessment and histopathological analysis. LN-T cells derived from donor trained versus sedentary PLP-immunized mice were analyzed in vitro for proliferation assays by flow cytometry analysis and cytokine and chemokine receptor gene expression using real-time PCR. T cell-dependent immune responses of trained versus sedentary mice to the nonautoantigen ovalbumin and susceptibility to Escherichia coli-induced acute peritonitis were examined.

RESULTS: High-intensity training in healthy donor mice induced significantly greater inhibition than moderate-intensity training on proliferation and generation of encephalitogenic T cells in response to PLP-immunization, and on EAE severity upon their transfer into recipient mice. High-intensity training also inhibited LN-T cell proliferation in response to ovalbumin immunization. E. coli bacterial counts and dissemination were not affected by training.

INTERPRETATION: High-intensity training induces superior effects in preventing autoimmunity in EAE, but does not alter immune responses to E. coli infection.

BACKGROUND: Hippocampal volume reductions in major depression have been frequently reported. However, evidence for functional abnormalities in the same region in depression has been less clear. We investigated hippocampal function in depression using functional magnetic resonance imaging (fMRI) and neuropsychological tasks tapping spatial memory function, with complementing measures of hippocampal volume and resting blood flow to aid interpretation.

METHOD: A total of 20 patients with major depressive disorder (MDD) and a matched group of 20 healthy individuals participated. Participants underwent multimodal magnetic resonance imaging (MRI): fMRI during a spatial memory task, and structural MRI and resting blood flow measurements of the hippocampal region using arterial spin labelling. An offline battery of neuropsychological tests, including several measures of spatial memory, was also completed.

RESULTS: The fMRI analysis showed significant group differences in bilateral anterior regions of the hippocampus. While control participants showed task-dependent differences in blood oxygen level-dependent (BOLD) signal, depressed patients did not. No group differences were detected with regard to hippocampal volume or resting blood flow. Patients showed reduced performance in several offline neuropsychological measures. All group differences were independent of differences in hippocampal volume and hippocampal blood flow.

CONCLUSIONS: Functional abnormalities of the hippocampus can be observed in patients with MDD even when the volume and resting perfusion in the same region appear normal. This suggests that changes in hippocampal function can be observed independently of structural abnormalities of the hippocampus in depression.

The purpose of this study was to quantify isolated coupling mechanisms of calcaneal adduction/abduction and calcaneal eversion/inversion to proximal bones in vitro. The in vitro approach is necessary because in vivo both movements appear together, making it impossible to determine the extent of their individual contribution to overall ankle joint coupling. Eight fresh frozen foot-leg specimens were tested. Data describing bone orientation and coupling mechanisms between segments were obtained using bone pin marker triads. The bone movement was described in a global coordinate system to examine the coupling between the calcaneus, talus and tibia. The strength of coupling was determined by means of the slope of a linear least squares fit to an angle-angle plot. The coupling coefficients in the present study indicate that not only calcaneal eversion/inversion (coupling coefficient: 0.68 ± 0.15) but to an even greater extent calcaneal adduction/abduction (coupling coefficient: 0.99 ± 0.10) was transferred into talus and tibial rotation, highlighting the relevance of calcaneal adduction for the overall ankle joint coupling. The results of this study present the possibility that controlling calcaneal adduction/abduction can affect talus and tibial rotation and therefore the possible genesis of overuse knee injuries.

The dorsolateral prefrontal cortex (DLPFC) is part of a network important for emotional regulation and the possibility of modulating activity in this region with transcranial direct current stimulation (TDCS) to change mood has gained great interest, particularly for application in clinical populations. Whilst results in major depressive disorder have been promising, less is known about the effects of TDCS on mood in non-clinical populations. We hypothesized that multiple sessions of anodal TDCS applied over the left DLPFC would enhance mood, primarily as measured by the Profile of Mood States questionnaire, in healthy older adults. In addition, in an exploratory analysis, we examined the potentially moderating role of working memory training. Working memory, just like emotional regulation, taxes the DLPFC, which suggests that engaging in a working memory task whilst receiving TDCS may have a different effect on activity in this region and consequently mood. A total of 123 participants between 65 and 75 years of age were randomly assigned to receive either 20 sessions of TDCS, with or without working memory training, or 20 sessions sham stimulation, with or without working memory training. We found no support for enhancement of mood due to TDCS in healthy older adults, with or without cognitive training and conclude that the TDCS protocol used is unlikely to improve mood in non-depressed older individuals.

Prolonged sitting is increasingly common and may possibly be unfavorable for cognitive function and mood. In this randomized crossover study, the effects of frequent, short physical activity breaks during prolonged sitting on cognitive task-related activation of the prefrontal cortex were investigated. The effects on working memory, psychological factors, and blood glucose were also examined, and whether arterial stiffness moderated prefrontal cortex activation. Thirteen subjects (mean age 50.5 years; eight men) underwent three 3-h sitting conditions, interrupted every 30-min by a different 3-min break on separate, randomized-ordered days: seated social interactions (SOCIAL), walking (WALK), or simple resistance activities (SRA). Arterial stiffness was assessed at baseline. Before and after each 3-h condition, psychological factors (stress, mood, sleepiness, and alertness) were assessed through questionnaires and functional near-infrared spectroscopy (fNIRS) was used to measure changes in prefrontal oxygenated hemoglobin (Oxy-Hb), indicative of cortical activation, while performing working memory tasks [1- (baseline), 2-, and 3-back]. Blood glucose levels were continuously measured throughout the conditions. Results revealed no significant changes in Oxy-Hb during the 2-back compared with the 1-back test in any condition, and no time-by-condition interactions. During the 3-back test, there was a significant decrease in Oxy-Hb compared with the 1-back after the WALK condition in the right prefrontal cortex, but there were no time-by-condition interactions, although 3-back reaction time improved only in the WALK condition. Mood and alertness improved after the WALK condition, which was significantly different from the SOCIAL condition. Arterial stiffness moderated the effects, such that changes in Oxy-Hb were significantly different between WALK and SOCIAL conditions only among those with low arterial stiffness. Blood glucose during the interventions did not differ between conditions. Thus, breaking up prolonged sitting with frequent, short physical activity breaks may reduce right prefrontal cortex activation, with improvements in some aspects of working memory, mood, and alertness. Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT04137211.

PURPOSE: Physical activity (PA) breaks during school lessons have been suggested as a promising strategy to improve working memory performance in children and adolescents. There is a lack of studies investigating the underlying physiological mechanisms of PA on cognition, especially among adolescents. This study aimed to investigate the effects of different types of short frequent PA on adolescents' cognitive task-related changes in cerebral blood flow in the prefrontal cortex (PFC) and working memory performance compared to prolonged sitting.

METHODS: In this randomized crossover study, adolescents visited the laboratory on three different occasions for 80-minute sessions of prolonged sitting interrupted by four breaks for three minutes of simple resistance training (SRA), step-up at a pre-determined pace (STEP), or remaining seated (SOCIAL). Before and after each session, cognitive task-related changes in cerebral blood flow (oxygenated-hemoglobin, Oxy-Hb) during working memory tasks (1-, 2-, 3-back tests) were measured using functional near-infrared spectroscopy in the PFC. Accuracy and reaction time were derived from the working memory tasks. Linear mixed-effect models were used to analyze the data.

RESULTS: A total of 17 students participated (mean age 13.6 years, 11 girls). Significant time x condition interactions were noted for Oxy-Hb in the most demanding working memory task (3-back), with a decrease following prolonged sitting in the SOCIAL condition compared to both the SRA (β 0.18, 95% CI 0.12, 0.24) and the STEP (β 0.11, 95% CI 0.05, 0.17). This was observed in parallel with improvements in reaction time following SRA (β -30.11, 95% CI -59.08, -1.13) and STEP (β -34.29, 95% CI -69.22, 0.63) although this was only significant for the SRA and no improvements in the SOCIAL condition.

CONCLUSION: We found that short frequent PA breaks during prolonged sitting among adolescents can prevent the decrease in cognitive task-related changes in cerebral blood flow that occur following prolonged sitting. This was observed simultaneously with improvements in working memory, indicating that changes in cerebral blood flow could be one factor explaining the effects on working memory. Future studies should investigate the efficacy of implementing these PA breaks in schools.

TRIAL REGISTRATION: Retrospectively registered on 21/09/2020, ClinicalTrial (NCT04552626).

Personality is known to be relatively stable throughout adulthood. Nevertheless, it has been shown that major life events with high personal significance, including experiences engendered by psychedelic drugs, can have an enduring impact on some core facets of personality. In the present, balanced-order, placebo-controlled study, we investigated biological predictors of post-lysergic acid diethylamide (LSD) changes in personality. Nineteen healthy adults underwent resting state functional MRI scans under LSD (75µg, I.V.) and placebo (saline I.V.). The Revised NEO Personality Inventory (NEO-PI-R) was completed at screening and 2 weeks after LSD/placebo. Scanning sessions consisted of three 7.5-min eyes-closed resting-state scans, one of which involved music listening. A standardized preprocessing pipeline was used to extract measures of sample entropy, which characterizes the predictability of an fMRI time-series. Mixed-effects models were used to evaluate drug-induced shifts in brain entropy and their relationship with the observed increases in the personality trait openness at the 2-week follow-up. Overall, LSD had a pronounced global effect on brain entropy, increasing it in both sensory and hierarchically higher networks across multiple time scales. These shifts predicted enduring increases in trait openness. Moreover, the predictive power of the entropy increases was greatest for the music-listening scans and when "ego-dissolution" was reported during the acute experience. These results shed new light on how LSD-induced shifts in brain dynamics and concomitant subjective experience can be predictive of lasting changes in personality. Hum Brain Mapp 37:3203-3213, 2016. © 2016 Wiley Periodicals, Inc.

Cognitive aging creates major individual and societal burden, motivating search for treatment and preventive care strategies. Behavioural interventions can improve cognitive performance in older age, but effects are small. Basic research has implicated dopaminergic signalling in plasticity. We investigated whether supplementation with the dopamine-precursor L-dopa improves effects of cognitive training on performance. Sixty-three participants for this randomised, parallel-group, double-blind, placebo-controlled trial were recruited via newspaper advertisements. Inclusion criteria were: age of 65-75 years, Mini-Mental State Examination score >25, absence of serious medical conditions. Eligible subjects were randomly allocated to either receive 100/25 mg L-dopa/benserazide (n = 32) or placebo (n = 31) prior to each of twenty cognitive training sessions administered during a four-week period. Participants and staff were blinded to group assignment. Primary outcomes were latent variables of spatial and verbal fluid intelligence. Compared to the placebo group, subjects receiving L-dopa improved less in spatial intelligence (-0.267 SDs; 95%CI [-0.498, -0.036]; p = 0.024). Change in verbal intelligence did not significantly differ between the groups (-0.081 SDs, 95%CI [-0.242, 0.080]; p = 0.323). Subjects receiving L-dopa also progressed slower through the training and the groups displayed differential volumetric changes in the midbrain. No statistically significant differences were found for the secondary cognitive outcomes. Adverse events occurred for 10 (31%) and 7 (23%) participants in the active and control groups, correspondingly. The results speak against early pharmacological interventions in older healthy adults to improve broader cognitive functions by targeting the dopaminergic system and provide no support for learning-enhancing properties of L-dopa supplements in the healthy elderly. The findings warrant closer investigation about the cognitive effects of early dopamine-replacement therapy in neurological disorders. This trial was preregistered at the European Clinical Trial Registry, EudraCT#2016-000891-54 (2016-10-05).

Researchers have proposed that solving complex reasoning problems, a key indicator of fluid intelligence, involves the same cognitive processes as solving working memory tasks. This proposal is supported by an overlap of the functional brain activations associated with the two types of tasks and by high correlations between interindividual differences in performance. We replicated these findings in 53 older participants but also showed that solving reasoning and working memory problems benefits from different configurations of the functional connectome and that this dissimilarity increases with a higher difficulty load. Specifically, superior performance in a typical working memory paradigm ( n-back) was associated with upregulation of modularity (increased between-network segregation), whereas performance in the reasoning task was associated with effective downregulation of modularity. We also showed that working memory training promotes task-invariant increases in modularity. Because superior reasoning performance is associated with downregulation of modular dynamics, training may thus have fostered an inefficient way of solving the reasoning tasks. This could help explain why working memory training does little to promote complex reasoning performance. The study concludes that complex reasoning abilities cannot be reduced to working memory and suggests the need to reconsider the feasibility of using working memory training interventions to attempt to achieve effects that transfer to broader cognition.

Background: Multimodal lifestyle interventions can benefit overall health, including cognition, in populations at-risk for dementia. However, little is known about the effect of lifestyle interventions in patients with prodromal Alzheimer's disease (AD). Even less is known about dietary intake and adherence to dietary recommendations within this population making it difficult to design tailored interventions for them.

Method: A 6-month MIND-ADmini pilot randomized controlled trial (RCT) was conducted among 93 participants with prodromal AD in Sweden, Finland, Germany, and France. Three arms were included in the RCT: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management, and social stimulation); 2) multimodal lifestyle intervention + medical food product; and 3) regular health advice (control group). Adherence to dietary advice was assessed with a brief food intake questionnaire by using the Healthy Diet Index (HDI) and Mediterranean Diet Adherence Screener (MEDAS). The intake of macro- and micronutrients were analyzed on a subsample using 3-day food records.

Results: The dietary quality in the intervention groups, pooled together, improved compared to that of the control group at the end of the study, as measured with by HDI (p = 0.026) and MEDAS (p = 0.008). The lifestyle-only group improved significantly more in MEDAS (p = 0.046) and almost significantly in HDI (p = 0.052) compared to the control group, while the lifestyle + medical food group improved in both HDI (p = 0.042) and MEDAS (p = 0.007) during the study. There were no changes in macro- or micronutrient intake for the intervention groups at follow-up; however, the intakes in the control group declined in several vitamins and minerals when adjusted for energy intake.

Conclusion: These results suggest that dietary intervention as part of multimodal lifestyle interventions is feasible and results in improved dietary quality in a population with prodromal AD. Nutrient intakes remained unchanged in the intervention groups while the control group showed a decreasing nutrient density.

Stem cells, believed to be the cellular origin of glioma, are able to generate gliomas, according to experimental studies. Here we investigated the potential and circumstances of more differentiated cells to generate glioma development. We and others have shown that oligodendrocyte precursor cells (OPCs) can also be the cell of origin for experimental oligodendroglial tumors. However, the question of whether OPCs have the capacity to initiate astrocytic gliomas remains unanswered. Astrocytic and oligodendroglial tumors represent the two most common groups of glioma and have been considered as distinct disease groups with putatively different origins. Here we show that mouse OPCs can give rise to both types of glioma given the right circumstances. We analyzed tumors induced by K-RAS and AKT and compared them to oligodendroglial platelet-derived growth factor B-induced tumors in Ctv-a mice with targeted deletions of Cdkn2a (p16(Ink4a-/-), p19(Arf-/-), Cdkn2a(-/-)). Our results showed that glioma can originate from OPCs through overexpression of K-RAS and AKT when combined with p19(Arf) loss, and these tumors displayed an astrocytic histology and high expression of astrocytic markers. We argue that OPC shave the potential to develop both astrocytic and oligodendroglial tumors given loss of p19(Arf), and that oncogenic signaling is dominant to cell of origin in determining glioma phenotype. Our mouse data are supported by the fact that human astrocytoma and oligodendroglioma display a high degree of overlap in global gene expression with no clear distinctions between the two diagnoses.

Glioblastoma (GBM) is the most frequent and deadly primary malignant brain tumor. Hallmarks are extensive intra-tumor and inter-tumor heterogeneity and highly invasive growth, which provide great challenges for treatment. Efficient therapy is lacking and the majority of patients survive less than 1 year from diagnosis. GBM progression and recurrence is caused by treatment-resistant glioblastoma stem cells (GSCs). GSC cultures are considered important models in target identification and drug screening studies. The current state-of-the-art method, to isolate and maintain GSC cultures that faithfully mimic the primary tumor, is to use serum-free (SF) media conditions developed for neural stem cells (NSCs). Here we have investigated the outcome of explanting 218 consecutively collected GBM patient samples under both SF and standard, serum-containing media conditions. The frequency of maintainable SF cultures (SFCs) was most successful, but for a subgroup of GBM specimens, a viable culture could only be established in serum-containing media, called exclusive serum culture (ESC). ESCs expressed nestin and SOX2, and displayed all functional characteristics of a GSC, that is, extended proliferation, sustained self-renewal and orthotopic tumor initiation. Once adapted to the in vitro milieu they were also sustainable in SF media. Molecular analyses showed that ESCs formed a discrete group that was most related to the mesenchymal GBM subtype. This distinct subgroup of GBM that would have evaded modeling in SF conditions only provide unique cell models of GBM inter-tumor heterogeneity.

Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion imaging technique, which can detect more distinct microstructural features compared to conventional Diffusion Tensor Imaging (DTI). NODDI allows the signal to be divided into multiple water compartments and derive measures for orientation dispersion index (ODI), neurite density index (NDI) and volume fraction of isotropic diffusion compartment (FISO). This study aimed to investigate which diffusion metric—fractional anisotropy (FA), mean diffusivity (MD), NDI, ODI, or FISO—is most influenced by aging and reflects cognitive function in a population of healthy older adults at risk for Alzheimer’s disease (AD). Age was significantly associated with all but one diffusion parameters and regions of interest. NDI and MD in the cingulate region adjacent to the cingulate cortex showed a significant association with a composite measure of Executive Function and was proven to partially mediate the relationship between aging and Executive Function decline. These results suggest that both DTI and NODDI parameters are sensitive to age-related differences in white matter regions vulnerable to aging, particularly among older adults at risk for AD.

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.

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.

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.

A parieto-medial temporal pathway is thought to underlie spatial navigation in humans. fMRI was used to assess the role of this pathway, including the hippocampus, in the cognitive processes likely to underlie navigation based on environmental cues. Participants completed a short-term spatial memory task in virtual space, which required no navigation but involved the recognition of a target location from a foil location based on environmental landmarks. The results showed that spatial memory retrieval based on environmental landmarks was indeed associated with increased signal in regions of the parieto-medial temporal pathway, including the superior parietal cortex, the retrosplenial cortex, and the lingual gyrus. However, the hippocampus demonstrated a signal decrease below the fixation baseline during landmark-based retrieval, whereas there was no signal change from baseline during retrieval based on viewer position. In a discussion of the origins of such negative BOLD response in the hippocampus, we consider both a suppression of default activity and an increase in activity without a corresponding boost in CBF as possible mechanisms.

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.

Transcranial direct current stimulation (tDCS) has been put forward as a non-pharmacological alternative for alleviating cognitive decline in old age. Although results have shown some promise, little is known about the optimal stimulation parameters for modulation in the cognitive domain. In this study, the effects of tDCS over the dorsolateral prefrontal cortex (dlPFC) on working memory performance were investigated in thirty older adults. An N-back task assessed working memory before, during and after anodal tDCS at a current strength of 1 mA and 2 mA, in addition to sham stimulation. The study used a single-blind, cross-over design. The results revealed no significant effect of tDCS on accuracy or response times during or after stimulation, for any of the current strengths. These results suggest that a single session of tDCS over the dlPFC is unlikely to improve working memory, as assessed by an N-back task, in old age.

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.

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.

White matter (WM) change plays an important role in age-related cognitive decline. In this review, we consider methodological advances with particular relevance to the role of WM in age-related changes in processing speed. In this context, intra-individual variability in processing speed performance has emerged as a sensitive proxy of cognitive and neurological decline while neuroimaging techniques used to assess WM change have become increasingly more sensitive. Together with a carefully designed task protocol, we emphasize that the combined implementation of intra-individual variability and neuroimaging techniques hold promise for specifying the WM-processing speed relationship with implications for normative and clinical samples.

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.

Abstract

Aim

The aim of this study was to investigate whether or not EMG-feedback from quadriceps and hamstrings has any acute effects on muscle activation and strength during a voluntary maximal isokinetic knee extensor action (eccentric and concentric) (20^o.s^-1).

Method

Nineteen healthy subjects, 9 female and 10 male, participated in the study. They reported no previous knee injuries and were not involved in strength training for the leg muscles. Subjects performed two sets of maximal voluntary unilateral knee extensor actions at a velocity of 20^o.s^-1 through a 60^o range of motion of the knee joint 120^o to 180^o, with 180^o representing a fully extended knee. EMG-feedback from the knee muscles was only given for the right leg during the second set. Knee extensor strength, level of activation and electromyographic activity of quadriceps and hamstrings were recorded during the whole range of motion (60^o).

Results

The results of this study showed that the knee extensor strength increased significantly (by 10 %) from 144 ± 48 with no feedback to 158 ± 53 Nm with feedback. With regard to the level of activation of the knee extensors it increased significantly (by 9%) from 75 ±15 % with no feedback to 81 ± 15 % with feedback. However, biofeedback did not contribute to decreased levels of hamstrings activity.

Conclusions

The main findings of the study were that the EMG-rms feedback acutely increased the strength and voluntary activation of quadriceps during a maximal voluntary isokinetic knee extensor action. However, the study showed no reduction in hamstring activation when feedback was given during the knee extensor actions. Therefore, the increased strength output was likely related to the enhanced activation of quadriceps and not a result of decreased hamstrings activation.

Background: Modifiable vascular risk factors have been associated with late-life cognitive impairment. The Life Simple 7 (LS7) score comprises seven cardiovascular health metrics: smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure. Objective: To investigate the association between individual and composite LS7 metrics and rate of cognitive decline, and potential differences in these associations between young-old and old-old individuals. Methods: This cohort study included 1,950 participants aged >= 60 years (M= 70.7 years) from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), who underwent repeated neuropsychological testing (episodic and semantic memory, verbal fluency, processing speed, global cognition) across 12 years. The LS7 score was assessed at baseline and categorized as poor, intermediate, or optimal. Level and change in cognitive performance as a function of LS7 categories were estimated using linear mixed-effects models. Results: Having an optimal LS7 total score was associated with better performance (expressed in standard deviation units) at baseline for perceptual speed (beta=0.21, 95% CI 0.12-0.29), verbal fluency (beta=0.08, 0.00-0.16), and global cognition (beta = 0.06, 0.00-0.12) compared to the poor group. Age-stratified analyses revealed associations for cognitive level and change only in the young-old (< 78 years) group. For the specific metrics, diverging patterns were observed for young-old and old-old individuals. Conclusion: Meeting the LS7 criteria for ideal cardiovascular health in younger old age is associated with slower rate of cognitive decline. However, the LS7 criteria may have a different meaning for cognitive function in very old adults.

The concept of reserve has been developed to account for the discontinuity between the extent of brain damage at its clinical manifestation in the form of cognitive decline or dementia. In this chapter, we discuss contributors to cognitive reserve from various stages of the life-course, including childhood, early adulthood, middle age, and late life. Evidence from observational studies as well as intervention trials is presented and assessed. We conclude by arguing that reserve formation in dementia risk is a life-course process whereby baseline cognitive abilities are subjected to modulation by subsequent experiences at diverse stages over the entire life-course. Variations among individuals in their ability to withstand age-related brain changes are ultimately dependent on their life-time accumulation of mental, physical, and lifestyle inputs into cognitive reserve.

Cerebral hypoperfusion is thought to contribute to cognitive decline in Alzheimer's disease, but the natural trajectory of cerebral perfusion in cognitively healthy adults has not been well-studied. This longitudinal study is consisted of 950 participants (40-89 years), who were cognitively unimpaired at their first visit. We investigated the age-related changes in cerebral perfusion, and their associations with APOE-genotype, biological sex, and cardiometabolic measurements. During the follow-up period (range 0.13-8.24 years), increasing age was significantly associated with decreasing cerebral perfusion, in total gray-matter (β=-1.43), hippocampus (-1.25), superior frontal gyrus (-1.70), middle frontal gyrus (-1.99), posterior cingulate (-2.46), and precuneus (-2.14), with all P-values < 0.01. Compared with male-ɛ4 carriers, female-ɛ4 carriers showed a faster decline in global and regional cerebral perfusion with increasing age, whereas the age-related decline in cerebral perfusion was similar between male- and female-ɛ4 non-carriers. Worse cardiometabolic profile (i.e., increased blood pressure, body mass index, total cholesterol, and blood glucose) was associated with lower cerebral perfusion at all the visits. When time-varying cardiometabolic measurements were adjusted in the model, the synergistic effect of sex and APOE-ɛ4 on age-related cerebral perfusion-trajectories became largely attenuated. Our findings demonstrate that APOE-genotype and sex interactively impact cerebral perfusion-trajectories in mid- to late-life. This effect may be partially explained by cardiometabolic alterations.