Circadian rhythm of brain-derived neurotrophic factor in serum and plasma.

The neurotrophic growth factor brain-derived neurotrophic factor (BDNF) plays a crucial role in various neurodegenerative and psychiatric diseases, such as Alzheimer's disease, schizophrenia and depression. BDNF has been proposed as a potential biomarker for diagnosis, prognosis and monitoring therapy. Understanding the factors influencing BDNF levels and whether they follow a circadian rhythm is essential for interpreting fluctuations in BDNF measurements. We aimed to investigate the circadian rhythm of BDNF by collecting multiple peripheral venous blood samples from young, healthy male participants at 12 different time points over 24 h. In addition, vital parameters, cortisol and insulin like growth factor 1 (IGF1) were measured to explore potential regulatory mechanisms, interfering variables and their correlations with BDNF concentration. The findings revealed that plasma BDNF did not exhibit any significant fluctuations over 24 h, suggesting the absence of a circadian rhythm. However, serum BDNF levels decreased during sleep. Furthermore, serum BDNF showed a positive correlation with heart rate but a negative correlation with IGF1. No significant correlation was observed between cortisol and BDNF or IGF1. Although plasma BDNF suggests steady-state conditions, the decline of serum BDNF during the nocturnal period could be attributed to physical inactivity and associated with reduced haemodynamic blood flow (heart rate reduction during sleep). The type of sample collection (peripheral venous cannula vs. blood sampling using a butterfly system) does not significantly affect the measured BDNF levels. The sample collection during the day did not significantly affect BDNF analysis, emphasizing the importance of considering activity levels rather than timing when designing standardized protocols for BDNF assessments.

Controlled Hypoxia Acutely Prevents Physical Inactivity-Induced Peripheral BDNF Decline.

Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. A total of 25 healthy adults (25.8 ± 3.3 years, 15 female) were analyzed in a randomized controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO2] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO2 were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. NH decreased SpO2 (p < 0.001, ηp2 = 0.747) and increased heart rate (p = 0.006, ηp2 = 0.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p < 0.001, ηp2 = 0.581) and plasma (p < 0.001, ηp2 = 0.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p = 0.018) in serum and after 30 min (p = 0.040) and 90 min (p = 0.005) in plasma. There was no significant BDNF decline under NH. A 24 h follow-up examination showed a significant decline in serum BDNF, both after NH and NOR. Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

Neuromuscular Aging: A Case for the Neuroprotective Effects of Dancing.

AIM: We planned a cross-sectional investigation (study 1) and a longitudinal training intervention (study 2) to investigate whether recreational dancing affords greater neuroprotective effects against age-related neuromuscular junction (NMJ) degeneration compared to general fitness exercise training. METHODS: In study 1, we recruited 19 older volunteers regularly practising dancing (older dancers [OD]) and 15 recreationally physically active older individuals (OA) and physical performance, muscle morphology, muscle function, and NMJ stability (from serum C-terminal agrin fragment [CAF] concentration) were assessed. In study 2, employing a longitudinal study design in a different cohort (composed of 37 older adults), we aimed to study whether a 6-month dancing intervention decreased CAF concentration compared to general fitness exercise training in older adults. RESULTS: Our findings show that OD had a lower CAF concentration (suggesting an increased NMJ stability) compared to OA. This result was accompanied by superior functional performance despite no differences in muscle size. In study 2, we observed a reduction in CAF concentration only in the dancing group. CONCLUSION: Overall, these findings suggest that dancing is an effective training modality to promote neuroprotection and increase muscle function in healthy older individuals.

[Motoric cognitive risk syndrome-Setting the course for dementia prevention?] / Motor-kognitives Risikosyndrom ­ Weichenstellung für die Demenzprävention?

BACKGROUND: The predicted increase in adults with dementia will pose a major challenge for the German healthcare system. To mitigate this challenge, the early detection of adults with an increased risk of dementia is crucial. In this context, the concept of motoric cognitive risk (MCR) syndrome has been introduced into the English literature but is currently relatively unknown in German-speaking countries. OBJECTIVE: What are the characteristics and diagnostic criteria of MCR? What is the impact of MCR on health-related parameters? What is the current state of evidence regarding the risk factors and prevention of the MCR? MATERIAL AND METHODS: We reviewed the English language literature concerning MCR, the associated risk factors, and protective factors, similarities or differences with the concept of mild cognitive impairment (MCI), and its influence on the central nervous system. RESULTS: The MCR syndrome is characterized by subjective cognitive impairment and a slower gait speed. Compared to healthy adults, adults with the MCR have a higher risk of dementia, falls, and mortality. Modifiable risk factors provide a starting point for specific multimodal lifestyle-related preventive interventions. CONCLUSION: As MCR can be easily diagnosed in practical settings, it could become an important concept for the early detection of adults with an increased risk of dementia in German-speaking countries, although further research is necessary to empirically confirm this assumption.

Cortical hemodynamics as a function of handgrip strength and cognitive performance: a cross-sectional fNIRS study in younger adults.

BACKGROUND: There is growing evidence for a positive correlation between measures of muscular strength and cognitive abilities. However, the neurophysiological correlates of this relationship are not well understood so far. The aim of this study was to investigate cortical hemodynamics [i.e., changes in concentrations of oxygenated (oxyHb) and deoxygenated hemoglobin (deoxyHb)] as a possible link between measures of muscular strength and cognitive performance. METHODS: In a cohort of younger adults (n = 39, 18-30 years), we assessed (i) handgrip strength by a handhold dynamometer, (ii) short-term working memory performance by using error rates and reaction times in the Sternberg task, and (iii) cortical hemodynamics of the prefrontal cortex (PFC) via functional near-infrared spectroscopy (fNIRS). RESULTS: We observed low to moderate negative correlations (rp = ~ - 0.38 to - 0.51; p < 0.05) between reaction time and levels of oxyHb in specific parts of the PFC. Furthermore, we noticed low to moderate positive correlations (rp = ~ 0.34 to 0.45; p < 0.05) between reaction times and levels of deoxyHb in distinct parts of the PFC. Additionally, higher levels of oxyHb (rp (35) = 0.401; p = 0.014) and lower levels of deoxyHb (rp (34) = - 0.338; p = 0.043) in specific parts of the PFC were linked to higher percentage of correct answers. We also found low to moderate correlations (p < 0.05) between measures of handgrip strength and levels of oxyHb (rp = ~ 0.35; p < 0.05) and levels of deoxyHb (rp = ~ - 0.25 to - 0.49; p < 0.05) in specific parts of the PFC. However, there was neither a correlation between cognitive performance and handgrip strength nor did cortical hemodynamics in the PFC mediate the relationship between handgrip strength and cognitive performance (p > 0.05). CONCLUSION: The present study provides evidence for a positive neurobehavioral relationship between cortical hemodynamics and cognitive performance. Our findings further imply that in younger adults higher levels of handgrip strength positively influence cortical hemodynamics although the latter did not necessarily culminate in better cognitive performance. Future research should examine whether the present findings can be generalized to other cohorts (e.g., older adults).

Sleep-dependent memory consolidation and its implications for psychiatry.

Both sleep disturbance and memory impairment are very common in psychiatric disorders. Since sleep has been shown to play a role in the process of transferring newly acquired information into long-term memory, i.e., consolidation, it is important to highlight this link in the context of psychiatric disorders. Along these lines, after providing a brief overview of healthy human sleep, current neurobiological models on sleep-dependent memory consolidation and resultant opportunities to manipulate the memory consolidation process, recent findings on sleep disturbances and sleep-dependent memory consolidation in patients with insomnia, major depression, schizophrenia, and post-traumatic stress disorder are systematically reviewed. Furthermore, possible underlying neuropathologies and their implications on therapeutic strategies are discussed. This review aims at sensitizing the reader for recognizing sleep disturbances as a potential contributor to cognitive deficits in several disorders, a fact which is often overlooked up to date.

Successful physical exercise-induced weight loss is modulated by habitual sleep duration in the elderly: results of a pilot study.

Although it is widely accepted that physical exercise promotes weight loss, physical exercise alone had been found to result in only marginal weight loss compared to no treatment. Interestingly, both subjective and objective sleep duration have been shown to be negatively correlated to the body mass index (BMI). Despite this growing evidence of a relation between sleep duration and body weight, the role of habitual sleep duration in physical exercise-induced weight loss has not been studied so far. Twenty-two healthy elderly good sleepers aged 61-76 years (mean 68.36 years, 55 % female, BMI mean 25.15 kg/m2) either took part in a 12-week aerobic endurance training (3 × 30 min/week) or in a relaxation control (2 × 45 min/week). The BMI was assessed prior to and after intervention. Subjects maintained sleep logs every morning/evening during the training period, allowing for calculation of habitual sleep duration. Besides a significant main effect of the type of training, a significant interaction of type of training and habitual sleep duration was observed: while after treadmill training subjects who slept less than 7.5 h/night during intervention reduced their BMI by nearly 4 %, a comparable decrease in the BMI was found neither in subjects who slept more than 7.5 h nor after relaxation training independent of sleep duration. Sleep duration itself did not change in any group. Although results should be interpreted with caution due to the small sample size, this is the first study to indicate that physical exercise might compensate for disturbed body weight regulation associated with short sleep duration.

[Preventive strategies for dementia]. / Präventionsstrategien gegen Demenz.

In the context of the demographically induced increase in the prevalence of dementia and the simultaneous lack of causal pharmacological therapies, preventive approaches are gaining in importance. By reducing risk factors and with measures which induce neuroplasticity successful aging can be supported. This article summarizes the current developments in preventing dementia by modification of life style factors. The main focus lies on the impact of cognitive and physical activity on neuroprotection. A promising approach combines both activities within a dance training program. Further studies that meet the demanding criteria of a randomized clinical trial are urgently needed.

Training of Attentional Filtering, but Not of Memory Storage, Enhances Working Memory Efficiency by Strengthening the Neuronal Gatekeeper Network.

Memory training (MT) in older adults with memory deficits often leads to frustration and, therefore, is usually not recommended. Here, we pursued an alternative approach and looked for transfer effects of 1-week attentional filter training (FT) on working memory performance and its neuronal correlates in young healthy humans. The FT effects were compared with pure MT, which lacked the necessity to filter out irrelevant information. Before and after training, all participants performed an fMRI experiment that included a combined task in which stimuli had to be both filtered based on color and stored in memory. We found that training induced processing changes by biasing either filtering or storage. FT induced larger transfer effects on the untrained cognitive function than MT. FT increased neuronal activity in frontal parts of the neuronal gatekeeper network, which is proposed to hinder irrelevant information from being unnecessarily stored in memory. MT decreased neuronal activity in the BG part of the gatekeeper network but enhanced activity in the parietal storage node. We take these findings as evidence that FT renders working memory more efficient by strengthening the BG-prefrontal gatekeeper network. MT, on the other hand, simply stimulates storage of any kind of information. These findings illustrate a tight connection between working memory and attention, and they may open up new avenues for ameliorating memory deficits in patients with cognitive impairments.

Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults.

Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here.

What part of the cerebellum contributes to a visuospatial working memory task?

Although there is evidence that the cerebellum is involved in working memory (WM), it remains unclear which functions within WM the cerebellum supports and which structures are involved in WM. We tested whether the cerebellum is involved in the filtering of incoming information or in its storage. Using a statistical brain mapping approach in 29 patients with cerebellar ischemic stroke, we found that the cerebellum plays a gatekeeper role, as lesions of the tonsil, the lobus semilunaris inferior, and parts of the vermal pyramid rendered WM susceptible to irrelevant information. We conclude that the cerebellum controls incoming WM information.

Repetition suppression versus enhancement--it's quantity that matters.

Upon repetition, certain stimuli induce reduced neural responses (i.e., repetition suppression), whereas others evoke stronger signals (i.e., repetition enhancement). It has been hypothesized that stimulus properties (e.g., visibility) determine the direction of the repetition effect. Here, we show that the very same stimuli can induce both repetition suppression and enhancement, whereby the only determining factor is the number of repetitions. Repeating the same, initially novel low-visible pictures of scenes for up to 5 times enhanced the blood oxygen level-dependent (BOLD) response in scene-selective areas, that is, the parahippocampal place area (PPA) and the transverse occipital sulcus (TOS), presumably reflecting the strengthening of the internal representation. Additional repetitions (6-9) resulted in progressively attenuated neural responses indicating a more efficient representation of the now familiar stimulus. Behaviorally, repetition led to increasingly faster responses and higher visibility ratings. Novel scenes induced the largest BOLD response in the PPA and also higher activity in yet another scene-selective region, the retrospenial cortex (RSC). We propose that 2 separable processes modulate activity in the PPA: one process optimizes the internal stimulus representation and involves TOS and the other differentiates between familiar and novel scenes and involves RSC.

Alexa, let's train now! - A systematic review and classification approach to digital and home-based physical training interventions aiming to support healthy cognitive aging.

BACKGROUND: There is mounting evidence that regular physical activity is an important prerequisite for healthy cognitive aging. Consequently, the finding that almost one-third of the adult population does not reach the recommended level of regular physical activity calls for further public health actions. In this context, digital and home-based physical training interventions might be a promising alternative to center-based intervention programs. Thus, this systematic review aimed to summarize the current state of the literature on the effects of digital and home-based physical training interventions on adult cognitive performance. METHODS: In this pre-registered systematic review (PROSPERO; ID: CRD42022320031), 5 electronic databases (PubMed, Web of Science, PsycInfo, SPORTDiscus, and Cochrane Library) were searched by 2 independent researchers (FH and PT) to identify eligible studies investigating the effects of digital and home-based physical training interventions on cognitive performance in adults. The systematic literature search yielded 8258 records (extra 17 records from other sources), of which 27 controlled trials were considered relevant. Two reviewers (FH and PT) independently extracted data and assessed the risk of bias using a modified version of the Tool for the assEssment of Study qualiTy and reporting in EXercise (TESTEX scale). RESULTS: Of the 27 reviewed studies, 15 reported positive effects on cognitive and motor-cognitive outcomes (i.e., performance improvements in measures of executive functions, working memory, and choice stepping reaction test), and a considerable heterogeneity concerning study-related, population-related, and intervention-related characteristics was noticed. A more detailed analysis suggests that, in particular, interventions using online classes and technology-based exercise devices (i.e., step-based exergames) can improve cognitive performance in healthy older adults. Approximately one-half of the reviewed studies were rated as having a high risk of bias with respect to completion adherence (≤85%) and monitoring of the level of regular physical activity in the control group. CONCLUSION: The current state of evidence concerning the effectiveness of digital and home-based physical training interventions is mixed overall, though there is limited evidence that specific types of digital and home-based physical training interventions (e.g., online classes and step-based exergames) can be an effective strategy for improving cognitive performance in older adults. However, due to the limited number of available studies, future high-quality studies are needed to buttress this assumption empirically and to allow for more solid and nuanced conclusions.

The Best of Two Worlds to Promote Healthy Cognitive Aging: Definition and Classification Approach of Hybrid Physical Training Interventions.

A healthy lifestyle can be an important prerequisite to prevent or at least delay the onset of dementia. However, the large number of physically inactive adults underscores the need for developing and evaluating intervention approaches aimed at improving adherence to a physically active lifestyle. In this regard, hybrid physical training, which usually combines center- and home-based physical exercise sessions and has proven successful in rehabilitative settings, could offer a promising approach to preserving cognitive health in the aging population. Despite its potential, research in this area is limited as hybrid physical training interventions have been underused in promoting healthy cognitive aging. Furthermore, the absence of a universally accepted definition or a classification framework for hybrid physical training interventions poses a challenge to future progress in this direction. To address this gap, this article informs the reader about hybrid physical training by providing a definition and classification approach of different types, discussing their specific advantages and disadvantages, and offering recommendations for future research. Specifically, we focus on applying digital technologies to deliver home-based exercises, as their use holds significant potential for reaching underserved and marginalized groups, such as older adults with mobility impairments living in rural areas.

Sedentary behavior and lifespan brain health.

Higher levels of physical activity are known to benefit aspects of brain health across the lifespan. However, the role of sedentary behavior (SB) is less well understood. In this review we summarize and discuss evidence on the role of SB on brain health (including cognitive performance, structural or functional brain measures, and dementia risk) for different age groups, critically compare assessment approaches to capture SB, and offer insights into emerging opportunities to assess SB via digital technologies. Across the lifespan, specific characteristics of SB (particularly whether they are cognitively active or cognitively passive) potentially act as moderators influencing the associations between SB and specific brain health outcomes. We outline challenges and opportunities for future research aiming to provide more robust empirical evidence on these observations.

Imaging body-mind crosstalk in young adults.

Objective: There is evidence that complex relationships exist between motor functions, brain structure, and cognitive functions, particularly in the aging population. However, whether such relationships observed in older adults could extend to other age groups (e.g., younger adults) remains to be elucidated. Thus, the current study addressed this gap in the literature by investigating potential associations between motor functions, brain structure, and cognitive functions in a large cohort of young adults. Methods: In the current study, data from 910 participants (22-35 yr) were retrieved from the Human Connectome Project. Interactions between motor functions (i.e., cardiorespiratory fitness, gait speed, hand dexterity, and handgrip strength), brain structure (i.e., cortical thickness, surface area, and subcortical volumes), and cognitive functions were examined using linear mixed-effects models and mediation analyses. The performance of different machine-learning classifiers to discriminate young adults at three different levels (related to each motor function) was compared. Results: Cardiorespiratory fitness and hand dexterity were positively associated with fluid and crystallized intelligence in young adults, whereas gait speed and handgrip strength were correlated with specific measures of fluid intelligence (e.g., inhibitory control, flexibility, sustained attention, and spatial orientation; false discovery rate [FDR] corrected, p < 0.05). The relationships between cardiorespiratory fitness and domains of cognitive function were mediated by surface area and cortical volume in regions involved in the default mode, sensorimotor, and limbic networks (FDR corrected, p < 0.05). Associations between handgrip strength and fluid intelligence were mediated by surface area and volume in regions involved in the salience and limbic networks (FDR corrected, p < 0.05). Four machine-learning classifiers with feature importance ranking were built to discriminate young adults with different levels of cardiorespiratory fitness (random forest), gait speed, hand dexterity (support vector machine with the radial kernel), and handgrip strength (artificial neural network). Conclusions: In summary, similar to observations in older adults, the current study provides empirical evidence (i) that motor functions in young adults are positively related to specific measures of cognitive functions, and (ii) that such relationships are at least partially mediated by distinct brain structures. Furthermore, our analyses suggest that machine-learning classifier has a promising potential to be used as a classification tool and decision support for identifying populations with below-average motor and cognitive functions.

Interaction between bottom-up saliency and top-down control: how saliency maps are created in the human brain.

Whether an object captures our attention depends on its bottom-up salience, that is, how different it is compared with its neighbors, and top-down control, that is, our current inner goals. At which neuronal stage they interact to guide behavior is still unknown. In a functional magnetic resonance imaging study, we found evidence for a hierarchy of saliency maps in human early visual cortex (V1 to hV4) and identified where bottom-up saliency interacts with top-down control: V1 represented pure bottom-up signals, V2 was only responsive to top-down modulations, and in hV4 bottom-up saliency and top-down control converged. Two distinct cerebral networks exerted top-down control: distractor suppression engaged the left intraparietal sulcus, while target enhancement involved the frontal eye field and lateral occipital cortex. Hence, attentional selection is implemented in integrated maps in visual cortex, which provide precise topographic information about target-distractor locations thus allowing for successful visual search.

A Comparison of Immersive vs. Non-Immersive Virtual Reality Exercises for the Upper Limb: A Functional Near-Infrared Spectroscopy Pilot Study with Healthy Participants.

Functional near-infrared spectroscopy (fNIRS) allows for a reliable assessment of oxygenated blood flow in relevant brain regions. Recent advancements in immersive virtual reality (VR)-based technology have generated many new possibilities for its application, such as in stroke rehabilitation. In this study, we asked whether there is a difference in oxygenated hemoglobin (HbO2) within brain motor areas during hand/arm movements between immersive and non-immersive VR settings. Ten healthy young participants (24.3 ± 3.7, three females) were tested using a specially developed VR paradigm, called "bus riding", whereby participants used their hand to steer a moving bus. Both immersive and non-immersive conditions stimulated brain regions controlling hand movements, namely motor cortex, but no significant differences in HbO2 could be found between the two conditions in any of the relevant brain regions. These results are to be interpreted with caution, as only ten participants were included in the study.

The Potential Role of Gustatory Function as an Early Diagnostic Marker for the Risk of Alzheimer's Disease in Subjective Cognitive Decline.

Background: Patients with subjective cognitive decline (SCD) report memory deterioration and are at an increased risk of converting to Alzheimer's disease (AD) although psychophysical testing does not reveal any cognitive deficit. Objective: Here, gustatory function is investigated as a potential predictor for an increased risk of progressive cognitive decline indicating higher AD risk in SCD. Methods: Measures of smell and taste perception as well as neuropsychological data were assessed in patients with subjective cognitive decline (SCD): Subgroups with an increased likelihood of the progression to preclinical AD (SCD+) and those with a lower likelihood (SCD-) were compared to healthy controls (HC), patients with mild cognitive impairment and AD patients. The Sniffin' Sticks test contained 12 items with different qualities and taste was measured with 32 taste stripes (sweet, salty, bitter, sour) of different concentration. Results: Only taste was able to distinguish between HC/SCD- and SCD+ patients. Conclusion: This study provides a first hint of taste as a more sensitive marker than smell for detecting preclinical AD in SCD. Longitudinal observation of cognition and pathology are necessary to further evaluate taste perception as a predictor of pathological objective decline in cognition.