SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through Multidomain interventions via facE-to-facE and video communication plaTforms in mild cognitive impairment (SUPERBRAIN-MEET): Protocol for a Multicenter Randomized Controlled Trial.

Background and Purpose: The SoUth Korea study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention (SUPERBRAIN) proved the feasibility of multidomain intervention for elderly people. One-quarter of the Korean population over 65 years of age has mild cognitive impairment (MCI). Digital health interventions may be cost-effective and have fewer spatial constraints. We aim to examine the efficacy of a multidomain intervention through both face-to-face interactions and video communication platforms using a tablet personal computer (PC) application in MCI. Methods: Three hundred participants aged 60-85 years, with MCI and at least one modifiable dementia risk factor, will be recruited from 17 centers and randomly assigned in a 1:1 ratio to the multidomain intervention and the waiting-list control groups. Participants will receive the 24-week intervention through the tablet PC SUPERBRAIN application, which encompasses the following five elements: managing metabolic and vascular risk factors, cognitive training, physical exercise, nutritional guidance, and boosting motivation. Participants will attend the interventions at a facility every 1-2 weeks. They will also engage in one or two self-administered cognitive training sessions utilizing the tablet PC application at home each week. They will participate in twice or thrice weekly online exercise sessions at home via the ZOOM platform. The primary outcome will be the change in the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to study end. Conclusions: This study will inform the effectiveness of a comprehensive multidomain intervention utilizing digital technologies in MCI. Trial Registration: ClinicalTrials.gov Identifier: NCT05023057.

Impact of a multidomain lifestyle intervention on white matter integrity: the SUPERBRAIN exploratory sub-study.

In the South Korean study to prevent cognitive impairment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), we evaluated the impact of a 24-week facility-based multidomain intervention (FMI) and home-based MI (HMI) on white matter integrity. Among 152 participants, aged 60-79 years without dementia but with ≥1 modifiable dementia risk factor, 19 FMI, 20 HMI, and 16 controls underwent brain MRI at baseline and 24 weeks. Between the intervention and control groups, we compared changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) at regions-of-interest (ROI) including the cingulum cingulate gyrus (CgC), cingulum hippocampus (CgH), superior longitudinal fasciculus (SLF), as well as the uncinate fasciculus (UF). In addition, correlations between total and standard scores cognitive domains of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) or serum brain-derived neurotrophic factor (BDNF) and changes in brain image measures were evaluated at a statistical significance level of p < 0.05 (uncorrected for multiple corrections). The FA, MD, AD, and RD at each ROI at the baseline were not different among groups after Bonferroni correction. In the statistical analysis using two-way repeated measures ANOVA, any significant difference in longitudinal changes in the FA, MD, AD, and RD was not revealed. The statistical analysis, among the significant regions in paired t-test of the intervention group, compared with the control group, the FMI, HMI, and intervention group yielded significantly more beneficial effects on the AD of the CgC. In addition, longitudinal AD changes of the left CgC correlated with the BDNF changes (r = 0.280, p = 0.048). In this study, enhanced cognitive reserve after the multidomain lifestyle intervention could be revealed by changes in brain imaging for white matter integrity.

Functional brain changes using electroencephalography after a 24-week multidomain intervention program to prevent dementia.

Quantitative electroencephalography (QEEG) has proven useful in predicting the response to various treatments, but, until now, no study has investigated changes in functional connectivity using QEEG following a lifestyle intervention program. We aimed to investigate neurophysiological changes in QEEG after a 24-week multidomain lifestyle intervention program in the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN). Participants without dementia and with at least one modifiable dementia risk factor, aged 60-79 years, were randomly assigned to the facility-based multidomain intervention (FMI) (n = 51), the home-based multidomain intervention (HMI) (n = 51), and the control group (n = 50). The analysis of this study included data from 44, 49, and 34 participants who underwent EEG at baseline and at the end of the study in the FMI, HMI, and control groups, respectively. The spectrum power and power ratio of EEG were calculated. Source cortical current density and functional connectivity were estimated by standardized low-resolution brain electromagnetic tomography. Participants who received the intervention showed increases in the power of the beta1 and beta3 bands and in the imaginary part of coherence of the alpha1 band compared to the control group. Decreases in the characteristic path lengths of the alpha1 band in the right supramarginal gyrus and right rostral middle frontal cortex were observed in those who received the intervention. This study showed positive biological changes, including increased functional connectivity and higher global efficiency in QEEG after a multidomain lifestyle intervention. Clinical trial registration: [https://clinicaltrials.gov/ct2/show/NCT03980392] identifier [NCT03980392].

Impact of a multidomain lifestyle intervention on regional spontaneous brain activity.

In the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), we evaluated the impact of multidomain lifestyle intervention on regional homogeneity (ReHo) in resting-state functional brain magnetic resonance imaging (MRI) data. Of 152 participants aged 60-79 years without dementia assigned to either facility-based multidomain intervention (FMI), home-based MI, or controls, we analyzed 56 scanned MRIs at baseline and 24 weeks. ReHo values from regions with significant longitudinal changes were compared between the intervention and control groups and their correlations with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) or serum brain-derived neurotrophic factor (BDNF) were evaluated. ReHo values in the left medial orbitofrontal gyrus and right superior parietal lobule were increased [p = 0.021, correlated positively with serum BDNF changes (r = 0.504, p = 0.047)] and decreased [p = 0.021, correlated negatively with changes in the total (r = -0.509, p = 0.044) and attention (r = -0.562, p = 0.023). RBANS], respectively, in the participants assigned to the FMI group than those of the controls. Our results suggest that facility-based group preventive strategies may have cognitive benefits through neuroplastic changes in functional processing circuits in the brain areas which play a crucial role in the adaptive learning and internally directed cognition.

Effects of a High-Intensity Interval Physical Exercise Program on Cognition, Physical Performance, and Electroencephalogram Patterns in Korean Elderly People: A Pilot Study.

Background and Purpose: The effects of high-intensity interval training (HIIT) interventions on functional brain changes in older adults remain unclear. This preliminary study aimed to explore the effect of physical exercise intervention (PEI), including HIIT, on cognitive function, physical performance, and electroencephalogram patterns in Korean elderly people. Methods: We enrolled six non-dementia participants aged >65 years from a community health center. PEI was conducted at the community health center for 4 weeks, three times/week, and 50 min/day. PEI, including HIIT, involved aerobic exercise, resistance training (muscle strength), flexibility, and balance. Wilcoxon signed rank test was used for data analysis. Results: After the PEI, there was improvement in the 30-second sit-to-stand test result (16.2±7.0 times vs. 24.8±5.5 times, p=0.027), 2-minute stationary march result (98.3±27.2 times vs. 143.7±36.9 times, p=0.027), T-wall response time (104.2±55.8 seconds vs.71.0±19.4 seconds, p=0.028), memory score (89.6±21.6 vs. 111.0±19.1, p=0.028), executive function score (33.3±5.3 vs. 37.0±5.1, p=0.046), and total Literacy Independent Cognitive Assessment score (214.6±30.6 vs. 241.6±22.8, p=0.028). Electroencephalography demonstrated that the beta power in the frontal region was increased, while the theta power in the temporal region was decreased (all p<0.05). Conclusions: Our HIIT PEI program effectively improved cognitive function, physical fitness, and electroencephalographic markers in elderly individuals; thus, it could be beneficial for improving functional brain activity in this population.

Impact of Multidomain Lifestyle Intervention on Cerebral Cortical Thickness and Serum Brain-Derived Neurotrophic Factor: the SUPERBRAIN Exploratory Sub-study.

In the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), we evaluated the impact of a 24-week facility-based multidomain intervention (FMI) and home-based MI (HMI) on cortical thickness, brain volume, and the serum brain-derived neurotrophic factor (BDNF). Totally, 152 participants, aged 60-79 years without dementia but with ≥ 1 modifiable dementia risk factor, were randomly assigned to the FMI, HMI, or control groups. Among them, 55 participants (20 FMI, 19 HMI, and 16 controls) underwent brain MRI at baseline and 24 weeks. We compared changes in global/regional mean cortical thickness at the region-of-interest (ROI) between the intervention and control groups. The changes in the total cortical gray matter volume and global mean cortical thickness were compared using analysis of covariance with age, sex, and education as covariates. ComBat site harmonization was applied for cortical thickness values across the scanners. ROI-based analysis was controlled for multiple comparisons, with a false discovery rate threshold of p < 0.05. Serum BDNF levels were significantly higher in the FMI group than in the control group (p = 0.029). Compared with the control group, the mean global cortical thickness increased in the FMI group (0.033 ± 0.070 vs. - 0.003 ± 0.040, p = 0.013); particularly, cortical thickness of the bilateral frontotemporal lobes, cingulate gyri, and insula increased. The increase in cortical thickness and serum BDNF in the FMI group suggests that group preventive strategies at the facility may be beneficial through structural neuroplastic changes in brain areas, which facilitates learning and neurotrophic factors.

Facility-based and home-based multidomain interventions including cognitive training, exercise, diet, vascular risk management, and motivation for older adults: a randomized controlled feasibility trial.

We aimed to evaluate the feasibility of multidomain intervention (MI) tailored to the Korean context. In an outcome assessor-blinded, randomized controlled trial, participants without dementia and with one or more modifiable dementia risk factors, aged 60-79 years, were randomly assigned to the facility-based MI (FMI; n=51), the home-based MI (HMI; n=51), or the control group receiving general health advice (n=50). The 24-week intervention comprised vascular risk management, cognitive training, social activity, physical exercise, nutrition guidance, and motivational enhancement. The FMI participants performed all intervention programs at a facility three times a week. The HMI participants performed some programs at a facility once every 1-2 weeks and performed others at home. The primary outcome was feasibility measured through retention, adherence, and at least no differences from the control group in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). In the FMI and HMI groups, the retention rates were 88.2% and 96.1%, and adherence to the intervention was 94.5% and 96.8%, respectively. The RBANS total scale index score improved significantly in the FMI (5.46 ± 7.50, P = 0.004) and HMI (5.50 ± 8.14, P = 0.004) groups compared to the control group (-0.74 ± 11.51). The FMI and HMI are feasible and there are indicators of efficacy.

Treadmill Exercise Alleviates Brain Iron Dyshomeostasis Accelerating Neuronal Amyloid-ß Production, Neuronal Cell Death, and Cognitive Impairment in Transgenic Mice Model of Alzheimer's Disease.

Brain iron increases with age and abnormal brain iron metabolism is proving increasingly likely to be involved in the pathology of Alzheimer's disease (AD). The iron-regulatory effect of furin, a ubiquitously expressed proconvertase, might play an important role in AD. Therefore, there is an urgent need to study the effect of furin on iron regulation in AD. For that purpose, we aimed to determine the role of physical exercise in AD associated with brain iron dyshomeostasis. Treadmill exercise attenuated the AD-related abnormal brain iron regulation by furin in vivo, as demonstrated via experiments in aged APP-C105 mice. Next, we examined whether treadmill exercise decreases excessive iron, directly affecting amyloid-ß (Aß) production through the regulation of α-secretase-dependent processing of amyloid protein precursor (APP) involved in the modulation of furin activity. We first observed that cognitive decline and Aß-induced neuronal cell death were induced by disruption of APP processing via excess iron-induced disruption of furin activity in aged APP-C105 mice. The induced cognitive decline and cell death were attenuated by treadmill exercise. This result suggests that treadmill exercise alleviated cognitive decline and Aß-induced neuronal cell death by promoting α-secretase-dependent processing of APP through low iron-induced enhancement of furin activity. This is concomitant with decreasing levels of lipid peroxidation products and promoting antioxidant defense enzyme capacities. Therefore, iron-targeted therapeutic strategies involving treadmill exercise might be useful for patients with AD.

Feasibility of a 12 Week Physical Intervention to Prevent Cognitive Decline and Disability in the At-Risk Elderly Population in Korea.

There is a need for measures that can prevent the onset of dementia in the rapidly aging population. Reportedly, sustained physical exercise can prevent cognitive decline and disability. This study aimed to assess the feasibility of a 12-week physical exercise intervention (PEI) for delay of cognitive decline and disability in the at-risk elderly population in Korea. Twenty-six participants (aged 67.9 ± 3.6 years, 84.6% female) at risk of dementia were assigned to facility-based PEI (n = 15) or home-based PEI (n = 11). The PEI program consisted of muscle strength training, aerobic exercise, balance, and stretching using portable aids. Feasibility was assessed by retention and adherence rates. Physical fitness/cognitive function were compared before and after the PEI. Retention and adherence rates were 86.7% and 88.3%, respectively, for facility-based PEI and 81.8% and 62.3% for home-based PEI. No intervention-related adverse events were reported. Leg strength/endurance and cardiopulmonary endurance were improved in both groups: 30 s sit-to-stand test (facility-based, p = 0.002; home-based, p = 0.002) and 2 -min stationary march (facility-based, p = 0.001; home-based, p = 0.022). Cognitive function was improved only after facility-based PEI (Alzheimer's Disease Assessment Scale-cognitive total score, p = 0.009; story memory test on Literacy Independent Cognitive Assessment, p = 0.026). We found that, whereas our PEI is feasible, the home-based program needs supplementation to improve adherence.

South Korean Study to Prevent Cognitive Impairment and Protect Brain Health Through Lifestyle Intervention in At-Risk Elderly People: Protocol of a Multicenter, Randomized Controlled Feasibility Trial.

BACKGROUND AND PURPOSE: The prevalence of dementia is increasing in South Korea. Multidomain interventions may be useful for preventing dementia. Such programs need to be disseminated to elderly Koreans throughout the country. We have developed programs of the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), which consists of a facility-based multidomain intervention (FMI) program and a home-based multidomain intervention (HMI) program suitable for elderly Koreans. We aim to determine the feasibility of the SUPERBRAIN programs before a large-scale randomized controlled trial. METHODS: We will recruit 150 participants among those without dementia aged 60-79 years with at least 1 modifiable dementia risk factor. They will be randomly assigned in a 1:1:1 ratio to the FMI, HMI, and the waiting-list control arm. The 6-month multidomain intervention consists of management of metabolic and vascular risk factors, cognitive training and social activity, physical exercise, nutritional guidance, and motivational enhancement programs. The primary outcomes are adherence and retention rates and changes in the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to the study end. The main secondary outcomes are disability, depressive symptoms, quality of life, vascular risk factors, physical performance, nutritional assessment, and motivation questionnaire. There will be an exploratory evaluation of neurotrophic, neurodegeneration, and neuroinflammation factors, microbiome, telomere length, electroencephalography, and neuroimaging measures. CONCLUSIONS: The results obtained will provide information on the applicability of these multidomain intervention programs to at-risk elderly people.

Percent Body Fat Cut-Off Points for Diagnosing Metabolic Syndrome in Korean Adolescents.

BACKGROUND: This study aimed to identify percent body fat cut-off points related to metabolic syndrome in a large sample of Korean adolescents. METHODS: The subjects (n=2120; boys=1107, girls=1013) were middle and high school students aged 12-17 yr who participated in the Korean National Fitness Award Project in 2013. Percent body fat was estimated via eight-polar bioelectrical impedance analysis. Metabolic syndrome was classified using established standards based on the National Cholesterol Education Program with the definition modified for age. Age- and sex-specific percent body fat z-scores were calculated for every adolescent using skewness, median, and coefficient of variation curves to account for growth and development. Receiver operating characteristic curve analysis was used to identify the percent body fat cut-off points using percent body fat z-scores from skewness, median, and coefficient of variation curves as the test and metabolic syndrome as the criterion. RESULTS: Based on the modified National Cholesterol Education Program criteria for metabolic syndrome, the areas under the receiver operating characteristic curve for percent body fat were 0.882 and 0.893 for boys and girls, respectively. The percent body fat percentiles were 82.2 and 87.3 for boys and girls, respectively. According to the skewness, median, and coefficient of variation curves, the percent body fat cut-off points based on the modified National Cholesterol Education Program criteria were 23.6%-25.7% for boys and 32.8%-37.3% for girls, both aged 12-17 yr. Age- and sex-specific percent body fat cut-off points were identified in relation to the metabolic syndrome status of Korean adolescents. CONCLUSION: These percent body fat cut-offs might be useful for identifying metabolic abnormality due to obesity in Korean adolescents.

The effects of 10 weeks of ß-alanine supplementation on peak power, power drop, and lactate response in Korean national team boxers.

This study was designed to investigate the effects of ß-alanine (BA) supplementation on peak power, power drop, and lactate response in elite male amateur boxers. Nineteen male Korean national team boxers were divided into groups with either BA (n=9) or placebo (PL, n=10) supplementation. BA consumed 4.9-5.4 g/day of BA with training for 10 weeks and PL took PL in a similar manner. Physical fitness and lactate changes in sparring were measured before and after the 10-week intervention. Significant interactions (P<0.05) were shown for lower body peak power (P=0.049) and upper body power drop (P=0.042). Positive effects for the BA group were shown for lower body peak power (Cohen d=0.72; 95% confidence interval [CI], 0.09-1.35) and the maintenance of upper body power output (d=-0.91; 95% CI, -1.61 to -0.17). These findings suggest that Korean national amateur boxers who consumed BA demonstrated differential responses following a training intervention in specific physical fitness when compared to boxing athletes who consumed a PL.

Effects of 16-week functional movement screen training program on strength and flexibility of elite high school baseball players.

Functional Movement Screen (FMS) is a way to pretest functional movement. This study examined the effects of the FMS training program on the strength and flexibility of 62 elite male high school baseball players (31 in the training group, 31 in the control group). All players who received less than two points on each FMS test item had to join the 16-week, three times weekly FMS training program. To analyze results among the FMS participants, measures including intraclass correlation coefficient (ICC) and repeated measure ANOVA were utilized. The Kappa coefficient was 0.805 when the intraclass correlation coefficient of the three participants was inspected. Strength showed a significant interaction depending on time and group (hand grip strength: P=0.011, bench press and squat both for one-repetition maximum (1RM): P=0.001 and P=0.008, respectively). Back muscle strength did not show a significant difference (P=0.660). Trunk forward flexion showed no interaction depending on time and groups (P=0.983) but trunk extension backward showed significant differences depending on groups (P=0.004) and time (P=0.001). Splits showed a significant difference depending on time and groups (P=0.004). The FMS training program improved the strength and flexibility of elite high school baseball players.