Background: In this randomized controlled trial, we assessed the neuroprotective effect of a 12-week resistance training (RT) program on executive control and cortical thickness of the prefrontal, temporal, parietal, and central cortex, regions prone to structural decline in individuals with mild cognitive impairment (MCI). Methods: Seventy older adults (aged 60-85 y old, 38 females and 32 males) were randomly allocated to a 12-week lower limb RT program or a waiting list control group. The Montreal Cognitive Assessment (MoCA) was used to stratify participants screened for high (< 26) or low (>= 26) MCI risk. Cognitive measurements consisted of the two-choice reaction time, Go/No-go, mathematical processing, and memory search tests. Cortical thickness was estimated from 3D T1-weighted MR images. Results: Complete randomized controlled trial data was obtained from 50 individuals (24 with high MCI risk). Significant Group x Time interactions were found for response on the Go/No-go task and cortical thickness of the right parahippocampal gyrus [F >= 5.3, p <= 0.03; eta(2)(p) >= 0.12]. An inspection of these observations revealed an increase in cortical thickness (+1.18 %) and a decrease in response time (-4.35 %) in individuals with high MCI risk allocated to the exercise group (both uncorrected p = 0.08). Decreased response time on the Go/No-go task was associated with increased cortical thickness in the right entorhinal gyrus (uncorrected p = 0.01). Conclusions: Our study demonstrated that 12 weeks of RT intervention may effectively improve cognitive performance and slow neuronal loss in the hippocampal complex of older adults at high MCI risk. Findings support evidence for the neuroprotective effects of resistance training and its potential role in cognitive health.

In this study we aimed to test if acute strength exercise would induce cognitive improvements. Secondarily, we examined the relationship between exercise-induced changes in cognitive function and postural dual-task control. Thirty-seven cognitively intact, non-faller older adults (>= 60 years) were nonrandomly allocated to strength exercise or control. Strength exercise consisted of Smith machine squats (one session, 3 x 3reps at 90%, 95%, and 100% one-repetition maximum). Control participants held seated rest for 45 min. Cognitive functions, recognition (memory search), working memory (mathematical processing), processing speed (2-choice reaction time), and postural dual-task control were tested before and immediately after exercise or control using the Automated Neuropsychological Assessment Metrics-4 (ANAM4) battery and a mathematical counting task while maintaining a tandem Romberg stance with eyes open on a force plate. Outcome measures were response time and performance index (100 x [accuracy/response time]) on the ANAM4 tests and sway activity and entropy during the postural dual-task. We found a non-significant improvement with moderate effect size in performance index on the mathematical processing task of experimental participants compared to control participants (p = 0.145, eta(2)(p) = 0.060). Improvements in the mathematical processing task over time in the control group were associated with increased sway activity during the postural dual-task. No significant associations were found between changes in cognitive function and changes in postural control in the experimental group. Ultimately, our results may direct researchers and healthcare professionals in designing the optimal exercise treatment to improve cognitive function and postural control in older adults.

Introduction Individuals with spinal cord injury (SCI) can experience accelerated cognitive aging. Myokines (factors released from muscle cells during contractions), such as brain-derived neurotrophic factor (BDNF), are thought to have beneficial effects on cognition. Neuromuscular electrical stimulation (NMES) was shown to elicit a large release of myokines. However, the effects of NMES on cognitive function have not been studied. Objective To present the study protocol for a clinical trial evaluating the effects of NMES aimed at improving cognition and BDNF. Methods A replicated randomized three-phases single-case experimental design (SCED) with sequential multiple baseline time series and a single-armed prospective trial will be conducted with 15 adults with chronic SCI (> 12 months after injury) above L1 neurological level undergoing 30-min quadriceps NMES, 3 days per week for 12 weeks. Main study endpoints Primary endpoint is cognitive performance (assessed by a smartphone test) conducted three times per week during the baseline phase with random duration of 3 to 8 weeks, the intervention phase of 12 weeks, and the follow-up phase of 3 weeks after a no measurement rest period of 12 weeks. Secondary endpoints are changes in BDNF levels and cognitive performance measured before the baseline period, before and after intervention and after a 12 weeks follow-up. Conclusion This will be the first study investigating the effects of 12 weeks NMES on both cognition and BDNF levels in individuals with SCI. The SCED results provide information on individual treatment effect courses which may direct future research. Trial registration ClinicalTrials.gov (NCT05822297, 12/01/2023).

Physical exercise is suggested to promote hippocampal neuroplasticity by increasing circulating neurotrophic and anti-inflammatory factors. Our aim was to explore the interplay between the effect of progressive resistance exercise on blood biomarker levels, hippocampal neurometabolite levels and hippocampal volume in older adults with a low compared to a high risk of mild cognitive impairment (MCI). Seventy apparently healthy male/female older adults (aged 60–85 years old) were randomly allocated to a 12 week lower limb progressive resistance or no intervention, stratified for low (< 26/30) or high (≥ 26/30) Montreal Cognitive Assessment (MoCA) score, indicating MCI risk. Outcome measures were blood levels of insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6) or kynurenine (KYN); hippocampal total and subfield volumes of the cornu ammonis 1 (CA1) and 4 (CA4), subiculum, presubiculum, and dentate gyrus measured with magnetic resonance imaging (MRI); and hippocampus neurometabolites including total N-acetylaspartate (NAA), myo-inositol (mIns), and total creatine (Cr) measured with proton magnetic resonance spectroscopy (1H-MRS). We evaluated the intervention effect, cognitive status effect, their interaction and the bivariate relationship between exercise-induced changes between the outcome measures. Higher kynurenine levels (p = 0.015) and lower subiculum volumes (p = 0.043) were found in older adults with high MCI risk compared to older adults with low MCI risk. Exercise-induced CA1 volume changes were negatively correlated with hippocampal tNAA/mIns level changes (r = -0.605, p = 0.006). This study provides valuable insight in the multifactorial processes related to resistance training in older adults with low or high MCI risk.

BACKGROUND:Neurological complications of the COVID-19 infection may be caused in part by local neurochemical and structural abnormalities that could not be detected during routine medical examinations. We examined within subject neurometabolic and structural brain alterations from pre-to post-COVID-19 in the hippocampal region of three elderly individuals (aged 63-68 years) who had a COVID-19 infection with mild symptoms. Patients were participating in an interventional study in which they were closely monitored at the time they were diagnosed with COVID-19. Patients 1 and 2 just completed 18-20 resistance training sessions prior to their diagnosis. Patient 3 was assigned to a non-training condition in the same study. METHODS:Whole brain magnetic resonance imaging (MRI) images and proton magnetic resonance spectroscopy (1H-MRS) of the left hippocampus were collected before and after infection. Structural and spectroscopic imaging measures post-COVID-19 were contrasted to the pre-COVID-19 measures and were compared with values for Minimal Detectable Change at 95% (MDC95) and 90% (MDC90) confidence from a group of six elderly (aged 60-79 years) without COVID-19 that participated in the same study. RESULTS:After SARS-COV-2 infection, we observed a reduction of glutamate-glutamine (Glx) in Patients 1 and 2 (≥ 42.0%) and elevation of myo-inositol (mIns) and N-acetyl-aspartate (NAA) in Patient 3 (≥ 36.4%); all > MDC90. MRI findings showed increased (Patients 1 and 2) or unchanged (Patient 3) hippocampal volume. CONCLUSIONS:Overall, findings from this exploratory study suggest that mild COVID-19 infection could be associated with development of local neuroinflammation and reduced glutamate levels in the hippocampus. Our 1H-MRS findings may have clinical value for explaining chronic neurological and psychological complaints in COVID-19 long-haulers.

Abstract Background The aging brain exhibits a neuroinflammatory state, driven partly by peripheral pro-inflammatory stimuli, that accelerates cognitive deterioration. A growing body of evidence clearly indicates that physical exercise partly alleviates neuroinflammation and positively affects the aging process and cognition. In this randomized controlled trial, we aimed to observe the effect of 12 weeks of resistance training (RT) on peripheral biomarker levels, cognitive function changes and their interrelationship, and explore differences in those exercise-induced changes in older adults with high risk of mild cognitive impairment (MCI) compared to older adults with low risk of MCI. Methods Fifty-two participants (aged 60–85 years old, 28 female) were randomly allocated to a 12 week lower limb RT program consisting of two training sessions per week or waiting list control group. The Montreal Cognitive Assessment (MoCA) was used to stratify participants screened as high (< 26/30) or low risk (≥ 26/30) of MCI. We assessed serum Interleukin 6 (IL-6), Insulin-like Growth Factor-1 (IGF-1), and Kynurenine (KYN) levels. Cognitive measurement consisted of and four subtests of Automated Neuropsychological Assessment Metrics (ANAM), the two-choice reaction time, go/no-go, mathematical processing, and memory search test. Results Twelve weeks of RT improved Go/No-go test results in older adults with high MCI risk. RT did not significantly affect blood biomarkers. However, IGF-1 level increases were associated with improvements in response time on the mathematical processing test in the exercise group, and IL-6 level increases were associated with improvements in response time on the memory search test in the total group of participants. Finally, KYN levels significantly differed between older adults with low and high MCI risk but no significant associations with performance were found. Conclusion Our study results suggest a different effect of RT on inhibitory control between older adults with low compared to high MCI risk. IGF-1 may play a role in the mechanism behind the cognitive benefit of RT and KYN may be a surrogate biomarker for neurodegeneration and cognitive decline.

OBJECTIVE:Aging is a natural process associated with a decline in cognition. However, the mediating effect of physical function and circulating myokines on this relationship has yet to be fully clarified. This study investigated how muscle strength and circulating insulin-like growth factor-1 (IGF-1) levels mediate the relationship between age and cognitive functions. SUBJECTS AND METHODS:A total of 1255 participants aged 25-74 years included in the Midlife in the United States II study were retrospectively analyzed. In this cross-sectional analysis, we applied a serial mediation model to explore the mediating effects of muscle strength and circulating IGF-1 levels on the relationship between age and cognitive functions. We included potential confounding factors related to sociodemographics, lifestyle, and health status as covariates in the model. RESULTS:The results showed that aging had both direct and indirect effects on cognition. As predicted, muscle strength and IGF-1 levels mediated the relationship between age and specific cognitive functions. In addition, mediation analyses indicated that the association between aging and cognitive flexibility, immediate and delayed memory, and inductive reasoning were partially mediated by muscle strength and IGF-1 levels in a serial manner. CONCLUSIONS:Our study demonstrated the serial multiple mediation roles of muscle strength and IGF-1 levels on the relationship between age and specific cognitive functions. Further longitudinal research should be performed to confirm the serial mediation results.

Proton magnetic resonance spectroscopy (1H-MRS) holds promise for revealing and understanding neurodegenerative processes associated with cognitive and functional impairments in aging. In the present study, we examined the neurometabolic correlates of balance performance in 42 cognitively intact older adults (healthy controls - HC) and 26 older individuals that were diagnosed with mild cognitive impairment (MCI). Neurometabolite ratios of total N-acetyl aspartate (tNAA), glutamate-glutamine complex (Glx), total choline (tCho) and myo-inositol (mIns) relative to total creatine (tCr) were assessed using single voxel 1H-MRS in four different brain regions. Regions of interest were the left hippocampus (HPC), dorsal posterior cingulate cortex (dPCC), left sensorimotor cortex (SM1), and right dorsolateral prefrontal cortex (dlPFC). Center-of-pressure velocity (Vcop) and dual task effect (DTE) were used as measures of balance performance. Results indicated no significant group differences in neurometabolite ratios and balance performance measures. However, our observations revealed that higher tCho/tCr and mIns/tCr in hippocampus and dPCC were generic predictors of worse balance performance, suggesting that neuroinflammatory processes in these regions might be a driving factor for impaired balance performance in aging. Further, we found that higher tNAA/tCr and mIns/tCr and lower Glx/tCr in left SM1 were predictors of better balance performance in MCI but not in HC. The latter observation hints at the possibility that individuals with MCI may upregulate balance control through recruitment of sensorimotor pathways.

BackgroundThe world’s population is aging, but life expectancy has risen more than healthy life expectancy (HALE). With respect to brain and cognition, the prevalence of neurodegenerative disorders increases with age, affecting health and quality of life, and imposing significant healthcare costs. Although the effects of physical exercise on cognition in advanced age have been widely explored, in-depth fundamental knowledge of the underlying mechanisms of the exercise-induced cognitive improvements is lacking. Recent research suggests that myokines, factors released into the blood circulation by contracting skeletal muscle, may play a role in mediating the beneficial effect of exercise on cognition. Our goal in this ongoing (living) review is to continuously map the rapidly accumulating knowledge on pathways between acute or chronic exercise-induced myokines and cognitive domains enhanced by exercise.MethodRandomized controlled studies will be systematically collected at baseline and every 6 months for at least 5 years. Literature search will be performed online in PubMed, EMBASE, PsycINFO, Web of Science, SportDiscus, LILACS, IBECS, CINAHL, SCOPUS, ICTRP, and ClinicalTrials.gov. Risk of bias will be assessed using the Revised Cochrane Risk of Bias tool (ROB 2). A random effects meta-analysis with mediation analysis using meta-analytic structural equation modeling (MASEM) will be performed. The primary research question is to what extent exercise-induced myokines serve as mediators of cognitive function. Secondarily, the pooled effect size of specific exercise characteristics (e.g., mode of exercise) or specific older adults’ populations (e.g., cognitively impaired) on the relationship between exercise, myokines, and cognition will be assessed. The review protocol was registered in PROSPERO (CRD42023416996).DiscussionUnderstanding the triad relationship between exercise, myokines and cognition will expand the knowledge on multiple integrated network systems communicating between skeletal muscles and other organs such as the brain, thus mediating the beneficial effects of exercise on health and performance. It may also have practical implications, e.g., if a certain myokine is found to be a mediator between exercise and cognition, the optimal exercise characteristics for inducing this myokine can be prescribed. The living review is expected to improve our state of knowledge and refine exercise regimes for enhancing cognitive functioning in diverse older adults’ populations.RegistrationSystematic review and meta-analysis protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on the 24th of April 2023 (registration number CRD42023416996).

Obesity and sarcopenia are associated with cognitive impairments at older age. Current research suggests that blood biomarkers may mediate this body-brain crosstalk, altering neurometabolism and brain structure eventually resulting in cognitive performance changes. Seventy-four older adults (60-85 years old) underwent bio-impedance body composition analysis, handgrip strength measurements, 8-Foot Up-and-Go (8UG) test, Montreal Cognitive Assessment (MoCA), blood analysis of interleukin-6 (IL-6), kynurenine, and insulin-like growth factor-1 (IGF-1), as well as brain magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (H-1-MRS), estimating neurodegeneration and neuroinflammation. Normal fat% or overweight was associated with larger total gray matter volume compared to underweight or obesity in older adults and obesity was associated with higher N-acetylaspartate/Creatine levels in the sensorimotor and dorsolateral prefrontal cortex. Muscle strength, not muscle mass/physical performance, corresponded to lower kynurenine and higher N-acetylaspartate/Creatine levels in the dorsal posterior cingulate and dorsolateral prefrontal cortex. The inflammatory and neurotrophic blood biomarkers did not significantly mediate these body-brain associations. This study used a multimodal approach to comprehensively assess the proposed mechanism of body-brain crosstalk. (c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license

Persons with spinal cord injury (SCI) can suffer accelerated cognitive aging, even when correcting for mood and concomitant traumatic brain injury. Studies in healthy older adults have shown that myokines (i.e. factors released from muscle tissue during exercise) may improve brain health and cognitive function. Myokines may target chronic neuroinflammation, which is considered part of the mechanism of cognitive decline both in healthy older adults and SCI. An empty systematic review, registered in PROSPERO (CRD42022335873), was conducted as proof of the lack of current research on this topic in people with SCI. Pubmed, Embase, Cochrane and Web of Science were searched, resulting in 387 articles. None were considered eligible for full text screening. Hence, the effect of myokines on cognitive function following SCI warrants further investigation. An in-depth narrative review on the mechanism of SCI-related cognitive aging and the myokine-cognition link was added to substantiate our hypothetical framework. Readers are fully updated on the potential role of exercise as a treatment strategy against cognitive aging in persons with SCI.

Physical exercise is considered a potent countermeasure against various age-associated physiological deterioration processes. We therefore assessed the effect of 12 weeks of resistance training on brain metabolism in older adults (age range: 60–80 years). Participants either underwent two times weekly resistance training program which consisted of four lower body exercises performed for 3 sets of 6–10 repetitions at 70–85

We implemented a multimodal approach to examine associations between structural and neurochemical changes that could signify neurodegenerative processes related to mild cognitive impairment (MCI). Fifty-nine older adults (60–85 years; 22 MCI) underwent whole-brain structural 3T MRI (T1W, T2W, DTI) and proton magnetic resonance spectroscopy (1H-MRS). The regions of interest (ROIs) for 1H-MRS measurements were the dorsal posterior cingulate cortex, left hippocampal cortex, left medial temporal cortex, left primary sensorimotor cortex, and right dorsolateral prefrontal cortex. The findings revealed that subjects in the MCI group showed moderate to strong positive associations between the total N-acetylaspartate to total creatine and the total N-acetylaspartate to myo-inositol ratios in the hippocampus and dorsal posterior cingulate cortex and fractional anisotropy (FA) of WM tracts crossing these regions—specifically, the left temporal tapetum, right corona radiata, and right posterior cingulate gyri. In addition, negative associations between the myo-inositol to total creatine ratio and FA of the left temporal tapetum and right posterior cingulate gyri were observed. These observations suggest that the biochemical integrity of the hippocampus and cingulate cortex is associated with a microstructural organization of ipsilateral WM tracts originating in the hippocampus. Specifically, elevated myo-inositol might be an underlying mechanism for decreased connectivity between the hippocampus and the prefrontal/cingulate cortex in MCI.

Rationale and Objectives Pro-inflammatory processes have been argued to play a role in conditions associated with cognitive decline and neurodegeneration, like aging and obesity. Only a limited number of studies have tried to measure both peripheral and central biomarkers of inflammation and examined their interrelationship. The primary aim of this study was to examine the hypothesis that chronic peripheral inflammation would be associated with neurometabolic changes that indicate neuroinflammation (the combined elevation of myoinositol and choline), brain gray matter volume decrease, and lower cognitive functioning in older adults. Materials and Methods Seventy-four older adults underwent bio-impedance body composition analysis, cognitive testing with the Montreal Cognitive Assessment (MoCA), blood serum analysis of inflammatory markers interleukin-6 (IL-6) and kynurenine, magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopy (1H-MRS) of the brain. Neurometabolic findings from both Tarquin and LCModel 1H-MRS post-processing software packages were compared. The regions of interest for MRI and 1H-MRS measurements were dorsal posterior cingulate cortex (DPCC), left hippocampal cortex (HPC), left medial temporal cortex (MTC), left primary sensorimotor cortex (SM1), and right dorsolateral prefrontal cortex (DLPFC). Results Elevated serum kynurenine levels were associated with signs of neuroinflammation, specifically in the DPCC, left SM1 and right DLPFC, and signs of neurodegeneration, specifically in the left HPC, left MTC and left SM1, after adjusting for age, sex and fat percentage (fat%). Elevated serum IL-6 levels were associated with increased Glx levels in left HPC, left MTC, and right DLPFC, after processing the 1H-MRS data with Tarquin. Overall, the agreement between Tarquin and LCModel results was moderate-to-strong for tNAA, tCho, mIns, and tCr, but weak to very weak for Glx. Peripheral inflammatory markers (IL-6 and kynurenine) were not associated with older age, higher fat%, decreased brain gray matter volume loss or decreased cognitive functioning within a cohort of older adults. Conclusion Our results suggest that serum kynurenine may be used as a peripheral inflammatory marker that is associated with neuroinflammation and neurodegeneration, although not linked to cognition. Future studies should consider longitudinal analysis to assess the causal inferences between chronic peripheral and neuroinflammation, brain structural and neurometabolic changes, and cognitive decline in aging.

Physical exercise may improve cognitive function by modulating molecular and cellular mechanisms within the brain. We propose that the facilitation of long-term synaptic potentiation (LTP)-related pathways, by products induced by physical exercise (i.e., exerkines), is a crucial aspect of the exercise-effect on the brain. This review summarizes synaptic pathways that are activated by exerkines and may potentiate LTP. For a total of 16 exerkines, we indicated how blood and brain exerkine levels are altered depending on the type of physical exercise (i.e., cardiovascular or resistance exercise) and how they respond to a single bout (i.e., acute exercise) or multiple bouts of physical exercise (i.e., chronic exercise). This information may be used for designing individualized physical exercise programs. Finally, this review may serve to direct future research towards fundamental gaps in our current knowledge regarding the biophysical interactions between muscle activity and the brain at both cellular and system levels.

Tot aan moment van schrijven van dit artikel aan het begin van de tweede golf, zijn er in Nederland 3483 patiënten met COVID-19 op de IC opgenomen geweest. 11De gemiddelde behandelduur was 18.8 (SD 18.3) dagen.Van deze patiënten zijn er 849 (24%) op de IC overleden. 11Uit studies, die rapporteren over de IC-periode van patiënten met COVID-19 blijkt dat 71-75% van de patiënten mechanische ventilatie kreeg, waarvan 42-75% invasief.Extracorporele membraanoxygenatie (ECMO) werd in verband met ernstig hart-of longfalen toegepast bij 0-11.5% en continue nierdialyse in 17%. 4,12Daarnaast werden trombo-embolische events gezien in 49-59% van de IC-patiënten met COVID-19.Revalidatiecentrum Adelante in Hoensbroek biedt opname en revalidatie van onder andere post-IC-patiënten.

OBJECTIVE:To describe clinical characteristics of patients after intensive care unit (ICU) treatment for coronavirus disease 2019 (COVID-19) who were admitted for inpatient rehabilitation.DESIGN:A cross-sectional design.SETTING:Inpatient rehabilitation care in the Netherlands.PARTICIPANTS:All post-ICU patients with COVID-19 admitted to the rehabilitation center between April 2 and May 13, 2020, were invited to participate in the study. Included were patients older than 18 years needing inpatient rehabilitation after ICU treatment for COVID-19 (N=60; mean age, 59.9y; 75% male).INTERVENTIONS:Not applicable.MAIN OUTCOME MEASURES:The following information was collected in the first week of inpatient rehabilitation care: (1) demographics; (2) ICU stay parameters; (3) medical, physical, and functional characteristics; and (4) self-reported symptoms.RESULTS:The most important findings for rehabilitation were the following: in the first week after discharge to the rehabilitation center, 38.3% of all patients experienced exercise-induced oxygen desaturation, in 72.7% muscle weakness was present in all major muscle groups, and 21.7% had a reduced mobility in 1 or both shoulders. Furthermore 40% had dysphagia, and 39.2% reported symptoms of anxiety.CONCLUSION:Post-ICU patients with COVID-19 display physical and anxiety symptoms as reported in other post-ICU patient groups. However, this study showed some remarkable clinical characteristics of post-ICU patients with COVID-19. Rehabilitation programs need to anticipate on this. Long-term follow-up studies are necessary.