Physical as well as cognitive training interventions improve specific cognitive functions but effects barely generalize on global cognition. Combined physical and cognitive training may overcome this shortcoming as physical training may facilitate the neuroplastic potential which, in turn, may be guided by cognitive training. This study aimed at investigating the benefits of combined training on global cognition while assessing the effect of training dosage and exploring the role of several potential effect modifiers. In this multi-center study, 322 older adults with or without neurocognitive disorders (NCDs) were allocated to a computerized, game-based, combined physical and cognitive training group (n = 237) or a passive control group (n = 85). Training group participants were allocated to different training dosages ranging from 24 to 110 potential sessions. In a pre-post-test design, global cognition was assessed by averaging standardized performance in working memory, episodic memory and executive function tests. The intervention group increased in global cognition compared to the control group, p = 0.002, Cohen’s d = 0.31. Exploratory analysis revealed a trend for less benefits in participants with more severe NCD, p = 0.08 (cognitively healthy: d = 0.54; mild cognitive impairment: d = 0.19; dementia: d = 0.04). In participants without dementia, we found a dose-response effect of the potential number and of the completed number of training sessions on global cognition, p = 0.008 and p = 0.04, respectively. The results indicate that combined physical and cognitive training improves global cognition in a dose-responsive manner but these benefits may be less pronounced in older adults with more severe NCD. The long-lasting impact of combined training on the incidence and trajectory of NCDs in relation to its severity should be assessed in future long-term trials.

Psychosocial stress and physical, cognitive, and social activity predict the risk of cognitive decline and dementia. The aim of this study was to elucidate brain-derived neurotrophic factor (BDNF), irisin, and the kynurenine pathway (KP) as potential underlying biological correlates. We evaluated associations of irisin and the KP with BDNF in serum and with cognition, stress, and activities. Furthermore, changes in serum concentrations of BDNF, irisin, and KP metabolites were investigated after physical or cognitive training. Forty-seven older adults at risk of dementia were assigned to 10 weeks of physical training, cognitive training, or a wait-list control condition. Previous physical, cognitive, and social activities and stressful life events were recorded; global cognition, episodic memory, and executive functions were assessed. Serum levels of L-kynurenine, kynurenic acid, 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN) were determined by validated assays based on liquid chromatography coupled to tandem mass spectrometry. BDNF and irisin serum levels were determined with enzyme-linked immunosorbent assays. BDNF and irisin correlated positively with global cognition and episodic memory, while the neurotoxic metabolite QUIN correlated negatively with executive functions. Stressful life events were associated with reduced BDNF and increased 3-HK. 3-HK decreased after cognitive training, while BDNF tended to increase after physical training. This suggests that psychosocial stress as well as cognitive and physical training may impact BDNF serum levels and the KP. Irisin and QUIN may constitute novel serum biomarkers of cognitive impairment, in addition to BDNF. Larger scale trials are needed to replicate and extend these novel findings.

Prevention of neurocognitive disorders is currently one of the greatest unmet medical challenges. The cognitive effects of solving jigsaw puzzles (JPs) have not been studied so far, despite its frequent use as a leisure activity in all age cohorts worldwide. This study aimed at closing this gap between a lack of science and a frequent real-world use by investigating the cognitive abilities recruited by JP as well as the cognitive benefits of lifetime and 30-day JP experience. A total of 100 cognitively healthy adults (≥50 years of age) were randomized to either a 30-day home-based JP intervention (≥1 h/day) plus four sessions of cognitive health counseling (JP group) or four sessions of cognitive health counseling only (counseling group). We measured global visuospatial cognition by averaging the scores of eight z-standardized visuospatial cognitive abilities (perception, constructional praxis, mental rotation, speed, flexibility, working memory, reasoning, and episodic memory). JP skill was assessed with an untrained 40 piece JP and lifetime JP experience with retrospective self-report. JP skill was associated with all assessed cognitive abilities (rs ≥ 0.45, ps < 0.001), and global visuospatial cognition (r = 0.80 [95% CI: 0.72–0.86], p < 0.001). Lifetime JP experience was associated with global visuospatial cognition, even after accounting for other risk and protective factors (β = 0.34 [95% CI: 0.18–0.50], p < 0.001). The JP group connected on average 3589 pieces in 49 h. Compared to the counseling group, they improved in JP skill (Cohen’s d = 0.38 [95% CI: 0.21–0.54], p < 0.001), but not in global visuospatial cognition (Cohen’s d = -0.08, [CI: -0.27 to 0.10], p = 0.39). The amount of jigsaw puzzling was related to changes in global visuospatial cognition within the JP group, only after accounting for baseline performance (β = 0.33 [95% CI: 0.02–0.63], p = 0.03). In sum, our results indicate that jigsaw puzzling strongly engages multiple cognitive abilities and long-term, but not short-term JP experiences could relevantly benefit cognition. Trial Registration: ClinicalTrials.gov Identifier: NCT02667314

While observational studies show that an active lifestyle including cognitive, physical, and social activities is associated with a reduced risk of cognitive decline and dementia, experimental evidence from corresponding training interventions is more inconsistent with less pronounced effects. The aim of this study was to evaluate and compare training- and lifestyle-related changes in cognition. This is the first study investigating these associations within the same time period and sample. Fifty-four older adults at risk of dementia were assigned to 10 weeks of physical training, cognitive training, or a matched wait-list control condition. Lifestyle was operationalized as the variety of self-reported cognitive, physical, and social activities before study participation. Cognitive performance was assessed with an extensive test battery prior to and after the intervention period as well as at a 3-month follow-up. Composite cognition measures were obtained by means of a principal component analysis. Training- and lifestyle-related changes in cognition were analyzed using linear mixed effects models. The strength of their association was compared with paired t-tests. Neither training intervention improved global cognition in comparison to the control group (p = .08). In contrast, self-reported lifestyle was positively associated with benefits in global cognition (p < .001) and specifically in memory (p < .001). Moreover, the association of an active lifestyle with cognitive change was significantly stronger than the benefits of the training interventions with respect to global cognition (ps < .001) and memory (ps < .001). The associations of an active lifestyle with cognitive change over time in a dementia risk group were stronger than the effects of short-term, specific training interventions. An active lifestyle may differ from training interventions in dosage and variety of activities as well as intrinsic motivation and enjoyment. These factors might be crucial for designing novel interventions, which are more efficient than currently available training interventions. ClinicalTrials.gov Identifier NCT01061489 . Registered February 2, 2010.

Cognitive and physical activities can benefit cognition. However, knowledge about the neurobiological mechanisms underlying these activity-induced cognitive benefits is still limited, especially with regard to the role of white matter integrity (WMI), which is affected in cognitive aging and Alzheimer’s disease. To address this knowledge gap, we investigated the immediate and long-term effects of cognitive or physical training on WMI, as well as the association between cognitive and physical lifestyles and changes in WMI over a 6-month period. Additionally, we explored whether changes in WMI underlie activity-related cognitive changes, and estimated the potential of both trainings to improve WMI by correlating training outcomes with WMI. In an observational and interventional pretest, posttest, 3-month follow-up design, we assigned 47 community-dwelling older adults at risk of dementia to 50 sessions of auditory processing and working memory training (n=13), 50 sessions of cardiovascular, strength, coordination, balance and flexibility exercises (n=14), or a control group (n=20). We measured lifestyles trough self-reports, cognitive training skills through training performance, functional physical fitness through the Senior Fitness Test, and global cognition through a cognitive test battery. WMI was assessed via a composite score of diffusion tensor imaging-based fractional anisotropy (FA) of three regions of interest shown to be affected in aging and Alzheimer’s disease: the genu of corpus callosum, the fornix, and the hippocampal cingulum. Effects for training interventions on FA outcomes, as well as associations between lifestyles and changes in FA outcomes were not significant. Additional analyses did show associations between cognitive lifestyle and global cognitive changes at the posttest and the 3-month follow-up (β≥0.40, p≤0.02) and accounting for changes in WMI did not affect these relationships. The targeted training outcomes were related to FA scores at baseline (cognitive training skills and FA composite score, rs=0.68, p=0.05; functional physical fitness and fornix FA, r=0.35, p=0.03). Overall, we found no evidence of a link between short-term physical or cognitive activities and WMI changes, despite activity-related cognitive changes in older adults at risk of dementia. However, we found positive associations between the two targeted training outcomes and WMI hinting at a potential of long-term activities to affect WMI.