Background and Aim. Intrinsic capacity (IC), defined by the World Health Organization as the composite of an individual’s physical and mental capacities, declines progressively with ageing and increases the risk of frailty and dependency. Resistance training (RT) is considered an effective strategy to counteract age-related functional decline; however, its association with specific IC domains remains insufficiently quantified. Therefore, this study aimed to compare overall intrinsic capacity and selected domains (locomotion and cognition) between resistance-trained and active control group. Methods. A randomised controlled trial was conducted among community-dwelling older adults aged 65 years and older. Participants were divided into two groups: a RT group consisting of individuals who had engaged in regular, structured resistance training for 12 weeks, and a control group who did static stretching exercise. IC was assessed using standardised domain-specific measures. Locomotion was evaluated using gait speed (m/s) and the 30-Second Chair Stand Test (repetitions). Cognitive function was assessed using a validated screening instrument (MoCA; total score /30). Group differences were analysed using independent samples t-tests, and multiple regression analysis was performed to identify predictors of overall intrinsic capacity. Statistical significance was set at p < 0.05. Results. Preliminary findings are expected to indicate that older adults participating in resistance training demonstrate higher overall IC compared with active control group. Improvements are anticipated in locomotion measures (gait speed and 30-second chair stand performance) as well as in cognitive scores. Conclusion. Understanding the relationship between resistance training and intrinsic capacity may provide important insights for developing exercise-based strategies aimed at promoting healthy ageing, maintaining functional independence, and improving quality of life among older adults. Keywords: Intrinsic capacity; resistance training; healthy ageing; locomotion; cognitive function; older adults

Sport and exercise science encompasses multiple disciplines (psychology, physiology, and motor behavior) and deals with human behavior issues that have multicausal explanations. Establishing causality in such complex topics is a challenging task as multiple underlying mechanisms typically contribute to a given outcome. The purpose of this theoretical article is to introduce Chamberlin’s method of multiple working hypotheses originally proposed in the late 19th century. We argue that researchers can enhance their understanding of their research topics by employing Chamberlin’s method. In this article, we describe this method, explain its relevance to sport and exercise science, provide two examples of its benefits, and outline practical implications for researchers seeking to incorporate this method into their study design workflow. Incorporating the method of multiple working hypotheses at the research design stage can improve the ability to show causation and account for multiple underlying mechanisms that explain a certain phenomenon.

Background: Intrinsic capacity (IC) is a novel concept for healthy ageing, introduced by the WHO less than 10 years ago. Although the theoretical framework of the IC consists of five fundamental domains: vitality, locomotion, cognition, sensory, and psychological, there is variance in the tests that are used to assess them. Purpose: To quantitatively assess the IC of older healthy adults, based on the WHO ICOPE recommendation, see: https://apps.who.int/iris/bitstream/handle/10665/326843/WHOFWC-ALC-19.1-eng.pdf?sequence=17&isAllowed=y. We aimed to establish a composite score that could identify the points of functional decline among the healthy older population and identify possible correlations between the five subdomains. Method: Participants: 50 community-dwelling, aged 65+, fluent in the Lithuanian language, with no symptomatic diseases, metabolic disorders, or orthopaedic issues. Tests: Vitality – Mini Nutritional Assessment, handgrip strength, Multidimensional Fatigue Inventory, body mass index, blood tests for haemoglobin, albumin, white blood cells, C-RP. Cognitive – Montreal Cognitive Assessment (MoCA). Locomotion – Short Physical Performance Battery (SPPB) – balance, gait speed, and chair rise tests. Psychological – Geriatric Depression Scale (GDS-15). Sensory – hearing and vision subjective reports. Scoring: The score for each domain was calculated as the points obtained were divided by the maximum possible scores. The global IC score is the sum of all sub-domains and is expected to range between 0 (declining capacity in all sub-domains) and 5 (no impairments in any of the sub-domains). Results: Thirty-nine participants completed all measures (23 women, mean age 72.08 ± 4.54 years). Mean composite score of IC is 3.964 ± 0.408 (range 2.695–4.617) with a proportional distribution. Subdomains Scores: Vitality = 0.795 ± 0.122 (0.455–1.00), Cognitive = 0.692 ± 0.121 (0.250–0.750), Locomotion = 0.902 ± 0.103 (0.667–1.00), Psychological = 0.936 ± 0.159 (0.250–1.00), Sensory = 0.639 ± 0.142 (0.333–1.00). Significant correlations were detected between Vitaliy and Locomotion (r = 0.590, p < 0.001), Vitality and Cognitive (r = 0.492, p < 0.001), and Locomotion and Cognitive (r = 0.325, p < 0.05). The balance test and the nutrition questionnaire had a ceiling effect, and all participants received the maximal score. Conclusion: A lower composite IC score may reflect declining reserves even among healthy older adults. A more sensitive balance test and comprehensive nutritional assessment would enhance diagnostic accuracy and evaluation capabilities. This method should also be tested with less healthy cohorts.

This study investigated the effects of combined concentric–eccentric high-intensity resistance training (HIRT) and low-load blood flow restriction training (BFRT) on tendon properties and function in older men. This parallel three-group controlled trial with constrained allocation included two exercise interventions (i.e., HIRT and BFRT) and a non-exercise control (CON). Participants in the exercise groups trained twice weekly for 12 weeks, and the total relative training volume was matched between groups. Assessments before and after the intervention included patellar tendon stiffness as the primary outcome, followed by tendon morpho-mechanical characteristics (cross-sectional area and tangent modulus) and knee extensor strength. Leg extension one-repetition maximum (1RM) increased in both HIRT (+ 40.4

BACKGROUND:Handgrip strength asymmetry (HGS-A) has emerged as a potential non-invasive biomarker reflecting cognitive and neural vulnerability in older adults, yet the neural mechanisms linking asymmetry with cognitive decline remain incompletely characterized. This study aimed to determine the relationships between HGS-A, cognitive function, and regional cortical thickness in healthy older adults and individuals with mild cognitive impairment (MCI). METHODS:Sixty-eight community-dwelling adults aged 60-85 (42 cognitively healthy, 26 MCI) underwent bilateral handgrip strength assessment using Jamar dynamometry. Cognitive evaluations included global cognition (MoCA) and domain-specific functions (ANAM4 battery). Structural MRI was performed, and cortical thickness was quantified from T1-weighted images within regions affected in MCI and Alzheimer's disease. Associations between HGS-A, cognitive performance, and cortical thickness were examined using partial correlation analyses adjusted for age and sex. RESULTS:In cognitively healthy participants, greater handgrip strength asymmetry within normal limits (<15%) significantly correlated with higher global cognitive scores (MoCA; r = 0.32, p = 0.043) and increased cortical thickness in the left postcentral gyrus (r = 0.52, p < 0.001; FDR-corrected). Conversely, these relationships were absent in participants with MCI and in those exhibiting high asymmetry levels (≥15%). Domain-specific cognitive tasks showed no significant associations with HGS-A in either group. Exploratory analyses suggested an inverted U-shaped relationship, where both minimal and excessive asymmetry reflect worse cognitive function. CONCLUSIONS:Handgrip strength asymmetry within normal limits (<15%) is linked to better cognition and cortical integrity, whereas both minimal and excessive asymmetry may reflect reduced cognitive function in older adults.

Objectives: While longitudinal studies have linked parietal lobe structure and muscle mass, no resistance exercise studies have evaluated whether interventions can have a positive impact on parietal lobe structure. Therefore, we investigated the effects of high-intensity resistance training (HIRT) and blood-flow restriction training (BFRT) on cortical thickness and white matter integrity in the parietal region, as well as in other regions, in an exploratory manner. Methods: A total of 63 older men were assigned to BFRT, HIRT or control groups for 12 weeks of intervention. A total of 48 participants completed brain and thigh magnetic resonance imaging before and after intervention. Cortical thickness was assessed using FreeSurfer, fractional anisotropy (FA) values were calculated using ExploreDTI, thigh muscle anatomical cross-sectional area was measured from MRI. Results: A significant difference in cortical thickness was observed only in HIRT group in the left parietal cortex-inferior parietal, supramarginal and posterior cingulate. Exploratory analyses revealed cortical thickness changes in other left-hemisphere regions, including the temporal (bankssts, inferior temporal), frontal (medial orbitofrontal, precentral, rostral middle frontal), and occipital (lateral occipital) cortices. In contrast, the BFRT group showed significant FA value change in parietal region - in left inferior parietal, left precuneus and right superior parietal. Exploratory analyses showed FA value change in additional regions in the BFRT group, including the left frontal (caudal middle frontal and superior frontal), left temporal (fusiform), right occipital (lateral occipital), and in the HIRT group, in the left frontal region (pars opercularis). Conclusions: HIRT and BFRT were associated with beneficial brain structural changes, although through distinct neurobiological mechanisms, with HIRT primarily influencing cortical thickness and BFRT predominantly affecting white matter microstructure.

BACKGROUND:Exercise training has attracted increasing attention as a non-pharmacological intervention approach to counteract age-related deterioration of brain and muscle function, yet objective biomarkers are needed to understand mechanisms and optimize interventions. Magnetic resonance spectroscopy (MRS) provides non-invasive, in vivo assessment of metabolic profiles altered by aging and exercise. However, MRS-based exercise research in older populations remains limited. This scoping review aims to identify brain and muscle metabolites detectable by MRS that can serve as markers of exercise training effects in aging. METHODS:We conducted a literature search from inception to October 2024 in PubMed, Embase, Web of Science, and Scopus. Inclusion criteria comprised randomized control trials (RCT) and observational studies including older adults (≥60 years) who underwent exercise training interventions which were preceded/followed by brain/muscle MRS scanning. RESULTS:Fourteen studies were included. Exercise intervention characteristics varied from low or moderate aerobic type of exercise to high intensity training, with the interventions placing variable emphasis on the strength-endurance continuum. Scanning methods were 1H brain MRS (n = 6), 31P brain MRS (n = 1), 31P muscle MRS (n = 8) and 1H muscle MRS (n = 1). Main 1H-MRS brain neurometabolic outcomes were the ratios to creatine of total N-acetyl-aspartate (tNAA/tCr) and total choline (tCho/tCr) in the right/left hippocampus. However, findings regarding the effect of exercise training interventions on these neurometabolic outcomes were inconclusive. 31P muscle MRS demonstrated an increase in phosphocreatine (PCr) recovery rate from pre-to-post exercise suggesting an improvement of mitochondrial function following exercise when applying exercise interventions with an emphasis on improving cardiometabolic functions. CONCLUSIONS:Despite limited guidance on methods and biomarkers, this scoping review supports MRS as a promising tool for monitoring exercise-induced metabolic changes in muscle and brain of older adults. However, standardized methodologies and larger number of studies are required to determine which metabolites reliably reflect exercise benefits in aging brain and muscle.

OBJECTIVE:Neurofibromatosis type 1 (NF1) is a genetic disorder associated with cognitive and behavioral deficits. In NF1, decreased neurofibromin levels attenuate hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) activity, thereby increasing inhibitory interneuron activity and decreasing synaptic plasticity. Lamotrigine, an HCN1-agonist, rescued this electrophysiological phenotype in an NF1 mouse model. We investigated whether lamotrigine can alter cortical inhibition and plasticity in adolescents with NF1 using transcranial magnetic stimulation (TMS). METHODS:We performed an explorative analysis of secondary outcomes in the NF1-EXCEL trial (Clinicaltrials.gov identifier NCT02256124). Thirty-one adolescents with NF1 were randomized to either receive lamotrigine or a placebo. Using TMS, cortical inhibition was assessed with short-interval intracortical inhibition (SICI) and cortical plasticity with paired associative stimulation (PAS) at baseline and after 10 weeks of intervention. RESULTS:Lamotrigine did not affect baseline cortical excitability. Additionally, no significant effects on either SICI or PAS responses were found after lamotrigine treatment in adolescents with NF1. Finally, lamotrigine did not affect pre-PAS single-pulse cortical excitability measures. CONCLUSION:10-week lamotrigine treatment does not alter cortical inhibition and plasticity in adolescents with NF1. SIGNIFICANCE:While limited by a small sample size, our study indicates that lamotrigine cannot consistently modulate SICI or PAS in adolescents with NF1, suggesting limited potential for treating the underlying pathophysiological mechanisms.

Background: Promoting healthy ageing is a major public health challenge, especially with increasing mild cognitive impairment (MCI) prevalence and associated dementia risk in older adults. Exercise training may improve cognitive function, yet studies on its effects in MCI populations remain limited and inconsistent in design and outcomes. This study investigated the impact of a 12-week structured lower limb resistance training (RT) programme on cognitive performance, specifically memory and executive function in older adults at low and high risk of MCI. Methods: Fifty-three older adults (aged 60–80) completed the study and were categorised into low risk (lrMCI, n = 28) and high risk (hrMCI, n = 25) MCI groups. Participants were assigned to a 12-week RT programme (2 sessions/week, 4 lower-limb exercises, 3 sets of 6–10 reps at 70–85% 1RM) or a passive control group. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) and ANAM4™ neurocognitive battery before and after the intervention. Results: At week 12, participants with high risk MCI in the resistance training group showed a significant improvement in MoCA total scores, particularly in executive function and delayed recall domains. An increase in MoCA scores was also observed in the control group, suggesting a potential learning effect. Performance across ANAM4 cognitive tasks did not show statistically significant changes following the intervention. Conclusion: A twice-weekly RT programme over 12 weeks did not produce robust improvements across all cognitive domains, but trends suggested potential benefits in executive function and inhibitory control among older adults at higher risk of MCI. The cognitive response to RT appears to vary by MCI risk level and baseline cognitive status. Keywords: older adults, MoCA (Montreal Cognitive Assessment), executive function, memory, ANAM4 neurocognitive battery

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.

Resistance Training (RT) is considered a promising intervention to counteract inflammation and cognitive decline. However, the relationship between RT dose (training duration, frequency, intensity, volume, rest period) and RT-induced changes in circulating biomarkers of inflammation and neuroplasticity remains unclear. The aim of this systematic review and meta-analysis was to determine the overall and dose-response effects of RT on circulating biomarkers of inflammation and neuroplasticity in older adults. Electronic databases (PubMed, Web of Science and Scopus) were systematically screened for relevant studies. The search identified 8306 articles, of which 36 randomized controlled trials (RCTs) were included. Effect sizes (ES) were calculated, and a meta-analysis (RT-effects) and meta-regression (dose-response) were performed when possible. Risk of bias was assessed using the Cochrane Risk of Bias (ROB) 2.0 tool. Meta-analysis showed that RT significantly increased neuroplasticity biomarkers including IGF-1, BDNF, and FGF-21 (ES=0.51, 95 %CI [0.19, 0.84], p = 0.002). Greater improvements were observed with longer training periods (≥20 weeks), a higher number of exercises (≥8), higher weekly training volume and total training program volume, and shorter rest in between exercises (90-120 s). Additionally, RT significantly reduced pro-inflammatory biomarkers including TNF-α, CAF, IL-6, IL-1β, KYN and CRP (ES=-0.66, 95 %CI [-0.80, -0.52], p < 0.001)), with more pronounced effects seen with a higher frequency (at least 3 times per week) and a higher intensity (≥70 % 1RM). Although RT also increased anti-inflammatory biomarkers (IL-10, IL-13, and IL-4, ES=0.75 95 %CI [0.45, 1.04], p < 0.001) the limited number of studies prevented a meta-regression analysis to determine a significant dose-response relationship. These findings demonstrate that RT can significantly improve circulating biomarkers of neuroplasticity and inflammation and highlight key dose-response relationships critical for optimizing RT programs.

INTRODUCTION:Individuals with spinal cord injuries (SCI) exhibit an accelerated age-related cognitive decline compared to healthy individuals, even after adjusting for mood factors and concomitant traumatic brain injury. We hypothesized that neuromuscular electrical stimulation (NMES) on hamstring and gluteal muscles may induce a dose-dependent increase in lactate and insulin-like growth factor-1 (IGF-1) which is hypothesized to be associated with a temporary enhancement of cognitive performance. METHODS:Twenty-two individuals with chronic SCI participated in a randomized cross-over study, receiving NMES on one of both visits. Participants randomly underwent a single session of 30 or 60-minute NMES. Lactate, IGF-1 levels and processing speed on the Symbol Digit Modalities test (SDMT) were tested before, immediately after and 30 minutes after intervention or 60 minutes rest. RESULTS:Lactate levels increased significantly immediately after NMES conditions compared to control (p = 0.004). Lactate increases were larger in the 30-minute NMES group compared to the 60-minute NMES group, consistent with the higher current amplitude applied in the former (100 mA compared to 40 mA). IGF-1 increases did not significantly differ between groups (p = 0.262), and there were no significant differences in SDMT performance changes over time between groups (p = 0.892). CONCLUSION:Acute NMES did not induce changes in IGF-1 levels or cognitive performance in individuals with SCI. However, 30 min of 100 mA of NMES significantly increased lactate levels, and could be used as a marker of NMES intensity in this population. Further research is required to explore various NMES protocols and their impact on cognitive domains in individuals with SCI.

Despite strong evidence linking exercise training to cognitive benefits, uncertainty remains regarding the underlying biological mechanisms, with some studies highlighting the need for greater consensus. Muscle-derived exerkines (myokines) are proposed mediators of exercise-induced effects with potential implications for mitigating age-related cognitive decline. This living systematic review and meta-analysis examined randomized controlled trials investigating the effects of exercise on both cognition and any of 1126 potential myokines in individuals aged 50 and older. From 17,177 screened records, 43 studies met inclusion criteria, reporting data on 7 neurotrophic, 11 pro-inflammatory, and 2 anti-inflammatory factors. A three-level meta-analysis revealed significantly improved cognitive performance post-exercise (SMD = 0.579) and elevated neurotrophic factor levels (SMD = 0.427) in exercise groups compared to controls, but no significant changes in pro-inflammatory or anti-inflammatory factor levels. Mediation analysis using meta-analytic structural equation modeling (MASEM) did not detect significant indirect effects of myokines on cognition, with only limited data (9 studies) reporting direct post-test correlations between myokine levels and cognitive outcomes. Exercise improved several cognitive domains and increased certain myokines, particularly BDNF, in older adults. However, current evidence is insufficient to determine whether myokines mediate these benefits, as mediation analyses were limited by small samples, incomplete reporting, and methodological constraints. Future well-powered trials with standardized protocols and comprehensive biomarker reporting are needed to clarify this mechanistic pathway. As a living review, this work will be continuously updated to refine our understanding of whether myokines mediate exercise-induced cognitive benefits in aging populations.

Background : Age-related decline can impair older adults’ ability to perform tasks involving a mix of motor and cognitive goals in a dual-task (DT) paradigm. The amount of DT interference effects has typically been associated with the availability of attentional resources and the degree of balance automaticity. Older adults with mild cognitive impairment may lack sufficient sensorimotor capacity for “automatic” regulation of posture under demanding balance conditions, resulting in larger DT interference effects due to increasing attentional control. Research question : Does the degree of automaticity affect balance stability in older adults with mild cognitive impairment during dual tasking, and does this relationship vary with the difficulty of the balance task? Methods : Sixty-seven older adults, aged 60–80 years (23 mild cognitive impairmentss), were positioned barefoot on a single piezoelectric force plate in a double-support and tandem stance with eyes open. Each stance condition was tested as single task during performance of a mathematical counting task (i.e., DT). DT cost (DTC) scores of center-of-pressure sway velocity (DTCVcop) were calculated, and regression analyses were conducted to assess the unique contribution of baseline center-of-pressure sway entropy under single-task conditions to DTCVcop, with age, Montreal Cognitive Assessment scores, gender, and cognitive status included as covariates. Results : Baseline sway entropy accounted for only 0.25%–4% of the variance in DTC of Vcop. Gender and cognitive status accounted for 12%–20% of the variance under double-support but not in tandem stance. Significance : Our findings suggest that sway entropy has only minimal impact on DT interference while gender and cognitive status play a more substantial role, highlighting the importance of these factors in balance control of older adults.

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.

Differences in expectations between experimental and control groups can influence the outcomes of exercise interventions, emphasizing the need to match expectations across study groups. This online study examined whether the expectations to improve the performance of different cognitive tasks differ between various activities commonly used in research on the effects of exercise and cognitive function. Two hundred and five middle-aged adults performed two reaction-time tasks and one memory task. They were then asked to rate, on a 1-5 Likert scale, their expectations to improve performance in those tasks should they engage in six types of activities for three months: brisk walking, resistance exercise, stretching and balance exercises, watching videos with lectures on art, history, and science, a program of relaxation techniques, and yoga/tai chi/meditation. Results revealed that the highest expectations for improvement were associated with relaxation techniques and yoga/tai chi/meditation. Some activities, such as brisk walking and stretch and balance exercises, shared similar expectations. Previous knowledge of the possible beneficial effects of exercise on cognitive performance also led to higher expectations. To establish causal relationships, researchers should strive to use activities that share similar expectations to improve performance for the experimental and control groups. The findings of this study provide such activity pairs. Finally, researchers should also try to match participants with and without prior knowledge of the benefits of exercise to cognitive function between experimental and control groups.