Resistance training's impact on blood biomarkers and cognitive function in older adults with low and high risk of mild cognitive impairment: a randomized controlled trial.

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.

Resistance exercise effects on hippocampus subfield volumes and biomarkers of neuroplasticity and neuroinflammation in older adults with low and high risk of mild cognitive impairment: a randomized controlled trial.

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.

Hippocampal neurometabolic and structural changes from pre-to post-COVID-19: A case-series study.

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.

Body fat and components of sarcopenia relate to inflammation, brain volume, and neurometabolism in older adults.

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 (1H-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.

N-acetyl-aspartate and Myo-inositol as Markers of White Matter Microstructural Organization in Mild Cognitive Impairment: Evidence from a DTI-1H-MRS Pilot Study.

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.

Strength gains after 12 weeks of resistance training correlate with neurochemical markers of brain health in older adults: a randomized control 1H-MRS study.

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% of 1 repetition maximum (n = 20) or served as the passive control group (n = 21). The study used proton magnetic resonance spectroscopy to quantify the ratio of total N-acetyl aspartate, total choline, glutamate-glutamine complex, and myo-inositol relative to total creatine (tNAA/tCr, tCho/tCr, Glx/tCr, and mIns/tCr respectively) in the hippocampus (HPC), sensorimotor (SM1), and prefrontal (dlPFC) cortices. The peak torque (PT at 60°/s) of knee extension and flexion was assessed using an isokinetic dynamometer. We used repeated measures time × group ANOVA to assess time and group differences and correlation coefficient analyses to examine the pre-to-post change (∆) associations between PT and neurometabolite variables. The control group showed significant declines in tNAA/tCr and Glx/tCr of SM1, and tNAA/tCr of dlPFC after 12 weeks, which were not seen in the experimental group. A significant positive correlation was found between ∆PT knee extension and ∆SM1 Glx/tCr, ∆dlPFC Glx/tCr and between ∆PT knee flexion and ∆dlPFC mIns/tCr in the experimental group. Overall, findings suggest that resistance training seems to elicit alterations in various neurometabolites that correspond to exercise-induced "preservation" of brain health, while simultaneously having its beneficial effect on augmenting muscle functional characteristics in older adults.

Neurometabolic correlates of posturography in normal aging and older adults with mild cognitive impairment: Evidence from a 1H-MRS study.

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.

Inflammatory Blood Biomarker Kynurenine Is Linked With Elevated Neuroinflammation and Neurodegeneration in Older Adults: Evidence From Two 1H-MRS Post-Processing Analysis Methods.

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.

Reasons and Barriers for University Students' Leisure-Time Physical Activity: Moderating Effect of Health Education.

This study aimed to investigate the relationship between health education and motives and barriers for university students' engagement in leisure-time physical activity (PA). The research sample included 709 students (312 females and 397 males) in different years of study, ranging in age between 18-25 years. A questionnaire survey method revealed a significant positive relationship between fitness and health motives and students' leisure-time PA. External barriers were negative predictors of students' leisure-time PA, while more health education-related courses per week were positively associated with students' leisure-time PA. Finally, we found that the number of health education-related courses per week moderated the relationship between fitness and health motives and students' leisure-time PA. These findings suggest that university students' fitness and health motives and external barriers to be physically active outweigh other motives and barriers in determining their leisure-time PA. In addition, health education in university studies can effectively increase students' health-related motivation for PA.

Do parents' exercise habits predict 13-18-year-old adolescents' involvement in sport?

This study examined links between parents' exercise habits and adolescents' participation in sports activities, considering the aspects of gender and age. It was hypothesized that regular exercise by both parents would be related to children's involvement in sport regardless of their gender and age. Moreover, it was hypothesized that children's sports activities would be more strongly related to their father's exercise activities. The study also examined the links between parents' exercise habits and children's motivation for sports. It was hypothesized that competition motives would be more important for children whose parents exercised regularly. The research sample included 2335 students from the seventh (n = 857), ninth (n = 960) and eleventh (n = 518) grades of various Lithuanian schools. The study used a questionnaire survey method, which revealed the links between parents' exercise habits and their children's participation in sport. Assessment of data for girls and boys showed that daughters' participation in sport could be predicted by both their fathers' and mothers' exercise habits, but sons' sports activities could be predicted only by the regular physical activities of their fathers. The assessment of children's sporting activities according to age revealed links between parental exercising and the engagement of older (15-16 years old), but not younger adolescents (13-14 years old). Analysis of sports motivation showed that competition motives were more important for boys than for girls. Fitness, well-being and appearance motives were more important for older adolescents (15-18 years old), while competition motives were more important for younger adolescents (13-14 years old). Research revealed the relationship between children's sport motives and fathers' exercise habits, while examination of mothers' exercise revealed no difference. Key pointsParental exercising significantly predicts adolescents' engagement in sport. Daughter's engagement in sport is related to both parents whereas son's involvement in sport is related only to father's exercise habits.Regular exercising of both mother and father predicts 13 - 14-year-old adolescents' engagement in sport. However, mother exercising is not related to older adolescents' involvement in sport.Research revealed the relation of adolescents' sport motives and father's exercising, and no differences were established depending on mother's exercise habits.