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Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure.
Fluid intelligence (fluid IQ), defined as the capacity for rapid problem solving and behavioral adaptation, is known to be modulated by learning and experience. Both stressful life events (SLES) and neural correlates of learning [specifically, a key mediator of adaptive learning in the brain, namely the ventral striatal representation of prediction errors (PE)] have been shown to be associated with individual differences in fluid IQ. Here, we examine the interaction between adaptive learning signals (using a well-characterized probabilistic reversal learning task in combination with fMRI) and SLES on fluid IQ measures. We find that the correlation between ventral striatal BOLD PE and fluid IQ, which we have previously reported, is quantitatively modulated by the amount of reported SLES. Thus, after experiencing adversity, basic neuronal learning signatures appear to align more closely with a general measure of flexible learning (fluid IQ), a finding complementing studies on the effects of acute stress on learning. The results suggest that an understanding of the neurobiological correlates of trait variables like fluid IQ needs to take socioemotional influences such as chronic stress into account.
The concurrent performance of cognitive and postural tasks is particularly impaired in old adults and associated with an increased risk of falls. Biological aging of the cognitive and postural control system appears to be responsible for increased cognitive-motor interference effects. We examined neural and behavioral markers of motor-cognitive dual-task performance in young and old adults performing spatial one-back working memory single and dual tasks during semitandem stance. On the neural level, we used EEG to test for age-related modulations in the frequency domain related to cognitive-postural task load. Twenty-eight healthy young and 30 old adults participated in this study. The tasks included a postural single task, a cognitive-postural dual task, and a cognitive-postural triple task (cognitive dual-task with postural demands). Postural sway (i.e., total center of pressure displacements) was recorded in semistance position on an unstable surface that was placed on top of a force plate while performing cognitive tasks. Neural activation was recorded using a 64-channel mobile EEG system. EEG frequencies were attenuated by the baseline postural single-task condition and demarcated in nine Regions-of-Interest (ROIs), i.e., anterior, central, posterior, over the cortical midline, and both hemispheres. Our findings revealed impaired cognitive dual-task performance in old compared to young participants in the form of significantly lower cognitive performance in the triple-task condition. Furthermore, old adults compared with young adults showed significantly larger postural sway, especially in cognitive-postural task conditions. With respect to EEG frequencies, young compared to old participants showed significantly lower alpha-band activity in cognitive-cognitive-postural triple-task conditions compared with cognitive-postural dual tasks. In addition, with increasing task difficulty, we observed synchronized theta and delta frequencies, irrespective of age. Taskdependent alterations of the alpha frequency band were most pronounced over frontal and central ROIs, while alterations of the theta and delta frequency bands were found in frontal, central, and posterior ROIs. Theta and delta synchronization exhibited a decrease from anterior to posterior regions. For old adults, task difficulty was reflected by theta synchronization in the posterior ROI. For young adults, it was reflected by alpha desynchronization in bilateral anterior ROIs. In addition, we could not identify any effects of task difficulty and age on the beta frequency band. Our results shed light on age-related cognitive and postural declines and how they interact. Modulated alpha frequencies during high cognitive-postural task demands in young but not old adults might be reflective of a constrained neural adaptive potential in old adults. Future studies are needed to elucidate associations between the identified age-related performance decrements with task difficulty and changes in brain activity.
The concurrent performance of cognitive and postural tasks is particularly impaired in old adults and associated with an increased risk of falls. Biological aging of the cognitive and postural control system appears to be responsible for increased cognitive-motor interference effects. We examined neural and behavioral markers of motor-cognitive dual-task performance in young and old adults performing spatial one-back working memory single and dual tasks during semitandem stance. On the neural level, we used EEG to test for age-related modulations in the frequency domain related to cognitive-postural task load. Twenty-eight healthy young and 30 old adults participated in this study. The tasks included a postural single task, a cognitive-postural dual task, and a cognitive-postural triple task (cognitive dual-task with postural demands). Postural sway (i.e., total center of pressure displacements) was recorded in semistance position on an unstable surface that was placed on top of a force plate while performing cognitive tasks. Neural activation was recorded using a 64-channel mobile EEG system. EEG frequencies were attenuated by the baseline postural single-task condition and demarcated in nine Regions-of-Interest (ROIs), i.e., anterior, central, posterior, over the cortical midline, and both hemispheres. Our findings revealed impaired cognitive dual-task performance in old compared to young participants in the form of significantly lower cognitive performance in the triple-task condition. Furthermore, old adults compared with young adults showed significantly larger postural sway, especially in cognitive-postural task conditions. With respect to EEG frequencies, young compared to old participants showed significantly lower alpha-band activity in cognitive-cognitive-postural triple-task conditions compared with cognitive-postural dual tasks. In addition, with increasing task difficulty, we observed synchronized theta and delta frequencies, irrespective of age. Taskdependent alterations of the alpha frequency band were most pronounced over frontal and central ROIs, while alterations of the theta and delta frequency bands were found in frontal, central, and posterior ROIs. Theta and delta synchronization exhibited a decrease from anterior to posterior regions. For old adults, task difficulty was reflected by theta synchronization in the posterior ROI. For young adults, it was reflected by alpha desynchronization in bilateral anterior ROIs. In addition, we could not identify any effects of task difficulty and age on the beta frequency band. Our results shed light on age-related cognitive and postural declines and how they interact. Modulated alpha frequencies during high cognitive-postural task demands in young but not old adults might be reflective of a constrained neural adaptive potential in old adults. Future studies are needed to elucidate associations between the identified age-related performance decrements with task difficulty and changes in brain activity.
Background
Postoperative delirium is a common disorder in older adults that is associated with higher morbidity and mortality, prolonged cognitive impairment, development of dementia, higher institutionalization rates, and rising healthcare costs. The probability of delirium after surgery increases with patients’ age, with pre-existing cognitive impairment, and with comorbidities, and its diagnosis and treatment is dependent on the knowledge of diagnostic criteria, risk factors, and treatment options of the medical staff. In this study, we will investigate whether a cross-sectoral and multimodal intervention for preventing delirium can reduce the prevalence of delirium and postoperative cognitive decline (POCD) in patients older than 70 years undergoing elective surgery. Additionally, we will analyze whether the intervention is cost-effective.
Methods
The study will be conducted at five medical centers (with two or three surgical departments each) in the southwest of Germany. The study employs a stepped-wedge design with cluster randomization of the medical centers. Measurements are performed at six consecutive points: preadmission, preoperative, and postoperative with daily delirium screening up to day 7 and POCD evaluations at 2, 6, and 12 months after surgery. Recruitment goals are to enroll 1500 patients older than 70 years undergoing elective operative procedures (cardiac, thoracic, vascular, proximal big joints and spine, genitourinary, gastrointestinal, and general elective surgery procedures.
Discussion
Results of the trial should form the basis of future standards for preventing delirium and POCD in surgical wards. Key aims are the improvement of patient safety and quality of life, as well as the reduction of the long-term risk of conversion to dementia. Furthermore, from an economic perspective, we expect benefits and decreased costs for hospitals, patients, and healthcare insurances.
Trial registration
German Clinical Trials Register, DRKS00013311. Registered on 10 November 2017.
Background
Postoperative delirium is a common disorder in older adults that is associated with higher morbidity and mortality, prolonged cognitive impairment, development of dementia, higher institutionalization rates, and rising healthcare costs. The probability of delirium after surgery increases with patients’ age, with pre-existing cognitive impairment, and with comorbidities, and its diagnosis and treatment is dependent on the knowledge of diagnostic criteria, risk factors, and treatment options of the medical staff. In this study, we will investigate whether a cross-sectoral and multimodal intervention for preventing delirium can reduce the prevalence of delirium and postoperative cognitive decline (POCD) in patients older than 70 years undergoing elective surgery. Additionally, we will analyze whether the intervention is cost-effective.
Methods
The study will be conducted at five medical centers (with two or three surgical departments each) in the southwest of Germany. The study employs a stepped-wedge design with cluster randomization of the medical centers. Measurements are performed at six consecutive points: preadmission, preoperative, and postoperative with daily delirium screening up to day 7 and POCD evaluations at 2, 6, and 12 months after surgery. Recruitment goals are to enroll 1500 patients older than 70 years undergoing elective operative procedures (cardiac, thoracic, vascular, proximal big joints and spine, genitourinary, gastrointestinal, and general elective surgery procedures.
Discussion
Results of the trial should form the basis of future standards for preventing delirium and POCD in surgical wards. Key aims are the improvement of patient safety and quality of life, as well as the reduction of the long-term risk of conversion to dementia. Furthermore, from an economic perspective, we expect benefits and decreased costs for hospitals, patients, and healthcare insurances.
Trial registration
German Clinical Trials Register, DRKS00013311. Registered on 10 November 2017.
Background: Continuous treatment is an important indicator of medication adherence in dementia. However, long-term studies in larger clinical settings are lacking, and little is known about moderating effects of patient and service characteristics.
Methods: Data from 12,910 outpatients with dementia (mean age 79.2 years; SD = 7.6 years) treated between January 2003 and December 2013 in Germany were included. Continuous treatment was analysed using Kaplan-Meier curves and log-rank tests. In addition, multivariate Cox regression models were fitted with continuous treatment as dependent variable and the predictors antidementia agent, age, gender, medical comorbidities, physician specialty, and health insurance status.
Results: After one year of follow-up, nearly 60% of patients continued drug treatment. Donezepil (HR: 0.88; 95% CI: 0.82-0.95) and memantine (HR: 0.85; 0.79-0.91) patients were less likely to be discontinued treatment as compared to rivastigmine users. Patients were less likely to be discontinued if they were treated by specialist physicians as compared to general practitioners (HR: 0.44; 0.41-0.48). Younger male patients and patients who had private health insurance had a lower discontinuation risk. Regarding comorbidity, patients were more likely to be continuously treated with the index substance if a diagnosis of heart failure or hypertension had been diagnosed at baseline.
Conclusions: Our results imply that besides type of antidementia agent, involvement of a specialist in the complex process of prescribing antidementia drugs can provide meaningful benefits to patients, in terms of more disease-specific and continuous treatment.
There is evidence for cortical contribution to the regulation of human postural control. Interference from concurrently performed cognitive tasks supports this notion, and the lateral prefrontal cortex (lPFC) has been suggested to play a prominent role in the processing of purely cognitive as well as cognitive-postural dual tasks. The degree of cognitive-motor interference varies greatly between individuals, but it is unresolved whether individual differences in the recruitment of specific lPFC regions during cognitive dual tasking are associated with individual differences in cognitive-motor interference. Here, we investigated inter-individual variability in a cognitive-postural multitasking situation in healthy young adults (n = 29) in order to relate these to inter-individual variability in lPFC recruitment during cognitive multitasking. For this purpose, a oneback working memory task was performed either as single task or as dual task in order to vary cognitive load. Participants performed these cognitive single and dual tasks either during upright stance on a balance pad that was placed on top of a force plate or during fMRI measurement with little to no postural demands. We hypothesized dual one-back task performance to be associated with lPFC recruitment when compared to single one-back task performance. In addition, we expected individual variability in lPFC recruitment to be associated with postural performance costs during concurrent dual one-back performance. As expected, behavioral performance costs in postural sway during dual-one back performance largely varied between individuals and so did lPFC recruitment during dual one-back performance. Most importantly, individuals who recruited the right mid-lPFC to a larger degree during dual one-back performance also showed greater postural sway as measured by larger performance costs in total center of pressure displacements. This effect was selective to the high-load dual one-back task and suggests a crucial role of the right lPFC in allocating resources during cognitivemotor interference. Our study provides further insight into the mechanisms underlying cognitive-motor multitasking and its impairments.
There is evidence for cortical contribution to the regulation of human postural control. Interference from concurrently performed cognitive tasks supports this notion, and the lateral prefrontal cortex (lPFC) has been suggested to play a prominent role in the processing of purely cognitive as well as cognitive-postural dual tasks. The degree of cognitive-motor interference varies greatly between individuals, but it is unresolved whether individual differences in the recruitment of specific lPFC regions during cognitive dual tasking are associated with individual differences in cognitive-motor interference. Here, we investigated inter-individual variability in a cognitive-postural multitasking situation in healthy young adults (n = 29) in order to relate these to inter-individual variability in lPFC recruitment during cognitive multitasking. For this purpose, a oneback working memory task was performed either as single task or as dual task in order to vary cognitive load. Participants performed these cognitive single and dual tasks either during upright stance on a balance pad that was placed on top of a force plate or during fMRI measurement with little to no postural demands. We hypothesized dual one-back task performance to be associated with lPFC recruitment when compared to single one-back task performance. In addition, we expected individual variability in lPFC recruitment to be associated with postural performance costs during concurrent dual one-back performance. As expected, behavioral performance costs in postural sway during dual-one back performance largely varied between individuals and so did lPFC recruitment during dual one-back performance. Most importantly, individuals who recruited the right mid-lPFC to a larger degree during dual one-back performance also showed greater postural sway as measured by larger performance costs in total center of pressure displacements. This effect was selective to the high-load dual one-back task and suggests a crucial role of the right lPFC in allocating resources during cognitivemotor interference. Our study provides further insight into the mechanisms underlying cognitive-motor multitasking and its impairments.
Background: Infection with human immunodeficiency virus (HIV) affects muscle mass, altering independent activities of people living with HIV (PLWH). Resistance training alone (RT) or combined with aerobic exercise (AE) is linked to improved muscle mass and strength maintenance in PLWH. These exercise benefits have been the focus of different meta-analyses, although only a limited number of studies have been identified up to the year 2013/4. An up-to-date systematic review and meta-analysis concerning the effect of RT alone or combined with AE on strength parameters and hormones is of high value, since more and recent studies dealing with these types of exercise in PLWH have been published.
Methods: Randomized controlled trials evaluating the effects of RT alone, AE alone or the combination of both (AERT) on PLWH was performed through five web-databases up to December 2017. Risk of bias and study quality was attained using the PEDro scale. Weighted mean difference (WMD) from baseline to post-intervention changes was calculated. The I2 statistics for heterogeneity was calculated.
Results: Thirteen studies reported strength outcomes. Eight studies presented a low risk of bias. The overall change in upper body strength was 19.3 Kg (95% CI: 9.8±28.8, p< 0.001) after AERT and 17.5 Kg (95% CI: 16±19.1, p< 0.001) for RT. Lower body change was 29.4 Kg (95% CI: 18.1±40.8, p< 0.001) after RT and 10.2 Kg (95% CI: 6.7±13.8, p< 0.001) for AERT. Changes were higher after controlling for the risk of bias in upper and lower body strength and for supervised exercise in lower body strength. A significant change towards lower levels of IL-6 was found (-2.4 ng/dl (95% CI: -2.6, -2.1, p< 0.001).
Conclusion: Both resistance training alone and combined with aerobic exercise showed a positive change when studies with low risk of bias and professional supervision were analyzed, improving upper and, more critically, lower body muscle strength. Also, this study found that exercise had a lowering effect on IL-6 levels in PLWH.