Enrichment and MALDI-TOF MS Analysis of Phosphoinositides in Brain Tissue.

Triazolium cyclodextrin click cluster (+CCC) is an ideal scaffold to specifically bind phosphoinositides (PIPs) via multivalent electrostatic interaction. A new enrichment material, triazolium cyclodextrin click cluster-magnetic agarose bead conjugate (+CCC-MAB), was synthesized and applied to the PIP enrichment of brain tissue. The enriched sample was analyzed using MALDI-TOF MS in negative ion mode without any derivatization. The PIP extract of brain tissue is known to contain abundant lipid interferences. By employing magnetic pull-down separation using +CCC-MAB, we effectively removed the weak-binding interferences in the PIP extract, thereby improving the signal-to-noise ratio (S/N) of the PIPs. Our +CCC-MAB-based PIP enrichment enabled us to analyze 16 PIP species in brain tissue. Six species with high S/N were assigned by MS/MS, while the remaining 10 species with low S/N were characterized by an empirical selection guide based on the biological relevance of PIPs. We conclude that +CCC-MAB-based PIP enrichment is a promising MALDI sample preparation method for specific PIP analysis in brain tissue.

Detecting DNA hydroxymethylation: exploring its role in genome regulation.

DNA methylation is one of the most extensively studied epigenetic regulatory mechanisms, known to play crucial roles in various organisms. It has been implicated in the regulation of gene expression and chromatin changes, ranging from global alterations during cell state transitions to locus-specific modifications. 5-hydroxymethylcytosine (5hmC) is produced by a major oxidation, from 5-methylcytosine (5mC), catalyzed by the ten-eleven translocation (TET) enzymes, and is gradually being recognized for its significant role in genome regulation. With the development of state-of-the-art experimental techniques, it has become possible to detect and distinguish 5mC and 5hmC at base resolution. Various techniques have evolved, encompassing chemical and enzymatic approaches, as well as thirdgeneration sequencing techniques. These advancements have paved the way for a thorough exploration of the role of 5hmC across a diverse array of cell types, from embryonic stem cells (ESCs) to various differentiated cells. This review aims to comprehensively report on recent techniques and discuss the emerging roles of 5hmC. [BMB Reports 2024; 57(3): 135-142].

RFX4 is an intrinsic factor for neuronal differentiation through induction of proneural genes POU3F2 and NEUROD1.

Proneural genes play a crucial role in neuronal differentiation. However, our understanding of the regulatory mechanisms governing proneural genes during neuronal differentiation remains limited. RFX4, identified as a candidate regulator of proneural genes, has been reported to be associated with the development of neuropsychiatric disorders. To uncover the regulatory relationship, we utilized a combination of multi-omics data, including ATAC-seq, ChIP-seq, Hi-C, and RNA-seq, to identify RFX4 as an upstream regulator of proneural genes. We further validated the role of RFX4 using an in vitro model of neuronal differentiation with RFX4 knock-in and a CRISPR-Cas9 knock-out system. As a result, we found that RFX4 directly interacts with the promoters of POU3F2 and NEUROD1. Transcriptomic analysis revealed a set of genes associated with neuronal development, which are highly implicated in the development of neuropsychiatric disorders, including schizophrenia. Notably, ectopic expression of RFX4 can drive human embryonic stem cells toward a neuronal fate. Our results strongly indicate that RFX4 serves as a direct upstream regulator of proneural genes, a role that is essential for normal neuronal development. Impairments in RFX4 function could potentially be related to the development of various neuropsychiatric disorders. However, understanding the precise mechanisms by which the RFX4 gene influences the onset of neuropsychiatric disorders requires further investigation through human genetic studies.

The Usefulness of 18F-FDG PET to Differentiate Subtypes of Dementia: The Systematic Review and Meta-Analysis.

Background and Purpose: Dementia subtypes, including Alzheimer's dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review examines the effectiveness of 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) in differentiating these subtypes for precise treatment and management. Methods: A systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted using databases like PubMed and Embase to identify studies on the diagnostic utility of 18F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the gold-standard clinical diagnosis for dementia subtypes. Results: From 12,815 articles, 14 were selected for final analysis. For AD versus FTD, the sensitivity was 0.96 (95% confidence interval [CI], 0.88-0.98) and specificity was 0.84 (95% CI, 0.70-0.92). In the case of AD versus DLB, 18F-FDG PET showed a sensitivity of 0.93 (95% CI 0.88-0.98) and specificity of 0.92 (95% CI, 0.70-0.92). Lastly, when differentiating AD from non-AD dementias, the sensitivity was 0.86 (95% CI, 0.80-0.91) and the specificity was 0.88 (95% CI, 0.80-0.91). The studies mostly used case-control designs with visual and quantitative assessments. Conclusions: 18F-FDG PET exhibits high sensitivity and specificity in differentiating dementia subtypes, particularly AD, FTD, and DLB. This method, while not a standalone diagnostic tool, significantly enhances diagnostic accuracy in uncertain cases, complementing clinical assessments and structural imaging.

The Possible Preventative Role of Lactate- and Butyrate-Producing Bacteria in Colorectal Carcinogenesis.

Background/Aims: : The gut microbiome has emerged as a key player that mechanistically links various risk factors to colorectal cancer (CRC) etiology. However, the role of the gut microbiome in CRC pathogenesis remains unclear. This study aimed to characterize the gut microbiota in healthy controls (HCs) and patients with colorectal adenoma (AD) and CRC in subgroups based on sex and age. Methods: : Study participants who visited the hospital for surveillance of CRC or gastrointestinal symptoms were prospectively enrolled, and the gut microbiome was analyzed based on fecal samples. Results: : In terms of HC-AD-CRC sequence, commensal bacteria, including lactate-producing (Streptococcus salivarius) and butyrate-producing (Faecalibacterium prausnitzii, Anaerostipes hadrus, and Eubacterium hallii) bacteria, were more abundant in the HC group than in the AD and CRC groups. In the sex comparison, the female HC group had more lactate-producing bacteria (Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Lactobacillus ruminis) than the male HC group. In age comparison, younger subjects had more butyrate-producing bacteria (Agathobaculum butyriciproducens and Blautia faecis) than the older subjects in the HC group. Interestingly, lactate-producing bacteria (B. catenulatum) were more abundant in females than males among younger HC group subjects. However, these sex- and age-dependent differences were not observed in the AD and CRC groups. Conclusions: : The gut microbiome, specifically lactate- and butyrate-producing bacteria, which were found to be abundant in the HC group, may play a role in preventing the progression of CRC. In particular, lactate-producing bacteria, which were found to be less abundant in healthy male controls may contribute to the higher incidence of CRC in males.

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.

DMRT1 regulates human germline commitment.

Germline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for gametogenesis. Here we follow the progression of nascent PGC-like cells derived from human embryonic stem cells in vitro. We show that switching from BMP signalling for PGC specification to Activin A and retinoic acid resulted in DMRT1 and CDH5 expression, the indicators of migratory PGCs in vivo. Moreover, the induction of DMRT1 and SOX17 in PGC-like cells promoted epigenetic resetting with striking global enrichment of 5-hydroxymethylcytosine and locus-specific loss of 5-methylcytosine at DMRT1 binding sites and the expression of DAZL representing DNA methylation-sensitive genes, a hallmark of the germline commitment programme. We provide insight into the unique role of DMRT1 in germline development for advances in human germ cell biology and in vitro gametogenesis.

Pearls & Oy-sters: Familial Verbal Auditory Agnosia Due to C9orf72 Repeat Expansion.

Chromosome 9 open reading frame 72 (C9orf72) gene pathogenic variants have been typically associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), but recent studies suggest their involvement in other disorders. This report describes a family with an autosomal dominant pattern of inheritance of progressive verbal auditory agnosia due to GGGGCC repeat expansion in C9orf72. A 60-year-old right-handed male truck driver presented with slowly progressive poor speech perception for 8 years, which became most troublesome when receiving verbal orders over the phone. He had difficulty recognizing single-syllable spoken words beyond his hearing loss but had no problem understanding complex written language. He had a heterozygous pathogenic variant carrying 160 hexanucleotide repeats in the C9orf72 gene. His family history included his deceased mother with similar symptoms that had progressed over 30 years, as well as his older brother and youngest sister who experienced speech perception difficulty beginning in their early fifties. His asymptomatic younger brother had a heterozygous 2 repeat in the C9orf72 gene, while his symptomatic youngest sister had a heterozygous 159 repeat. The patient and his sister exhibited more pronounced cortical thinning in the frontotemporoparietal areas. The discrepancy observed between the distribution of atrophy and the presentation of symptoms in patients with C9orf72 pathogenic repeat expansion may be attributable to the slow progression of their clinical course over time. The variable symptom presentation of C9orf72 pathogenic repeat expansion highlights the importance of considering this pathogenic variant as a potential cause of autosomal dominant degenerative brain diseases beyond FTD and ALS.

Comparison of automated quantification of amyloid deposition between PMOD and Heuron.

Several programs are widely used for clinical and research purposes to automatically quantify the degree of amyloid deposition in the brain using positron emission tomography (PET) images. Given that very few studies have investigated the use of Heuron, a PET image quantification software approved for clinical use, this study aimed to compare amyloid deposition values quantified from 18F-flutemetamol PET images using PMOD and Heuron. Amyloid PET data obtained from 408 patients were analysed using each quantitative program; moreover, the standardized uptake value ratios (SUVRs) of target areas were obtained by dividing the standardized uptake value (SUV) of the target region by the SUV of cerebellar grey matter as a reference. Compared with PMOD, Heuron yielded significantly higher SUVRs for all target areas (paired sample t-test, p < 0.001), except for the PC/PCC (p = 0.986). However, the Bland-Altman plot analysis indicated that the two quantitative methods may be used interchangeably. Moreover, receiver operating characteristic curve analysis revealed no significant between-method difference in the performance of the SUVRs in evaluating the visual positivity of amyloid deposits (p = 0.948). In conclusion, Heuron and PMOD have comparable performance in quantifying the degree of amyloid deposits in PET images.

Case report: Cerebrotendinous xanthomatosis with a novel mutation in the CYP27A1 gene mimicking behavioral variant frontotemporal dementia.

Background: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disease caused by a mutation in the CYP27A1 gene. Due to the disruption of bile acid synthesis leading to cholesterol and cholestanol accumulation, CTX manifests as premature cataracts, chronic diarrhea, and intellectual disability in childhood and adolescence. This report presents a case of CTX with an unusual phenotype of behavioral variant frontotemporal dementia (bvFTD) in middle age. Case presentation: A 60-year-old woman presented with behavioral and personality changes. She showed disinhibition, such as hoarding and becoming aggressive over trifles; compulsive behavior, such as closing doors; apathy; and dietary change. The patient showed a progressive cognitive decline and relatively sparing memory and visuospatial function. She had hyperlipidemia but no family history of neurodegenerative disorders. Initial fluid-attenuated inversion recovery (FLAIR) images showed a high signal in the periventricular area, and brain spectroscopy showed hypoperfusion in the frontal and temporal lobes, mimicking bvFTD. However, on physical examination, xanthomas were found on both the dorsum of the hands and the Achilles tendons. Hyperactive deep tendon reflexes in the bilateral biceps, brachioradialis, and knee and positive Chaddock signs on both sides were observed. Four years later, FLAIR images showed symmetrical high signals in the bilateral dentate nuclei of the cerebellum. Her serum cholestanol (12.4 mg/L; normal value ≤6.0) and 7α,12α-dihydroxycholest-4-en-3-one (0.485 nmol/mL; normal value ≤0.100) levels were elevated. A novel likely pathogenic variant (c.1001T>A, p.Met334Lys) and a known pathogenic variant (c.1420C>T, p.Arg474Trp) of the CYP27A1 gene were found in trans-location. The patient was diagnosed with CTX and prescribed chenodeoxycholic acid (750 mg/day). Conclusions: This report discusses the case of a middle-aged CTX patient with an unusual phenotype of bvFTD. A novel likely pathogenic variant (c.1001T>A, p.Met334Lys) was identified in the CYP27A1 gene. Early diagnosis is important because supplying chenodeoxycholic acid can prevent CTX progression.

Distinct effect of exercise modes on mood-related behavior in mice.

Exercise can afford several benefits to combat mood disorders in both rodents and humans. Engagement in various physical activities upregulates levels of neurotrophic factors in several brain regions and improves mental health. However, the type of exercise that regulates mood and the underlying mechanisms in the brain remain elusive. Herein, we performed two distinct types of exercise and RNA sequencing analyses to investigate the effect of exercise on mood-related behaviors and explain the distinct patterns of gene expression. Specifically, resistance exercise exhibited reduced immobility time in the forced swim test when compared with both no exercise and treadmill exercise (in the aerobic training [AT] group). Interestingly, anxiety-like behaviors in the open field and nest-building tests were ameliorated in the AT group when compared with those in the control group; however, this was not observed in the RT group. To elucidate the mechanism underlying these different behavioral changes caused by distinct exercise types, we examined the shift in the gene expression pattern in the hippocampus, a brain region that plays a critical role in regulating mood. We discovered that 38 and 40 genes were altered in the AT and RT groups, respectively, compared with the control group. Both exercises regulated 16 common genes. Compared with the control group, mitogen-activated protein kinase (MAPK) was enriched in the AT group and phosphatidylinositol-3-kinase (PI3K)/AKT and neurotrophin signaling pathways were enriched in the RT group, as determined by bioinformatics pathway analysis. PCR results revealed that Cebpß expression was increased in AT group, and Dcx expression was upregulated in both groups. Our findings indicate that different exercise types may exert substantially distinct effects on mood-like behaviors. Accordingly, appropriate types of exercise can be undertaken based on the mood disorder to be regulated.

Pediatric humoral immune responses and infection risk after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and two-dose vaccination during SARS-CoV-2 omicron BA.5 and BN.1 variants predominance in South Korea.

Background: Humoral immune responses and infection risk after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination during the Omicron BA.5 and BN.1 variants predominant period remains unexplored in pediatric population. Methods: We examined anti-spike (anti-S) immunoglobulin G (IgG) responses in a total of 986 children aged 4-18 years who visited outpatient clinics between June 2022 and January 2023, with a history of SARS-CoV-2 infection alone, completed two doses of COVID-19 vaccination alone, vaccine-breakthrough infection (i.e., infection after the single dose of vaccination), and no antigenic exposure. Furthermore, to determine SARS-CoV-2 infection risk, the incidence of newly developed SARS-CoV-2 infection was investigated up to March 2023. Results: The anti-S IgG levels in the 'vaccine-breakthrough infection' group exceeded those in the 'infection alone' and 'vaccination alone' groups (both P <0.01). Furthermore, the 'vaccination alone' group experienced more rapid anti-S IgG waning than the 'infection alone' and 'vaccine-breakthrough infection' groups (both P <0.01). We could not identify newly developed SARS-CoV-2 infection in the 'vaccine-breakthrough infection' group. Conclusion: Our findings suggest that hybrid immunity, acquired from SARS-CoV-2 infection and COVID-19 vaccination, was a potentially higher and longer-lasting humoral immune response and protected against SARS-CoV-2 infection in pediatric population during Omicron BA.5 and BN.1 variants predominant.

In planta Production and Validation of Neuraminidase Derived from Genotype 4 Reassortant Eurasian Avian-like H1N1 Virus as a Vaccine Candidate.

Influenza viruses are a major public health threat that causes repetitive outbreaks. In recent years, genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 (G4 EA H1N1) has garnered attention as a potential novel pandemic strain. The necessity of developing vaccines against G4 EA H1N1 is growing because of the increasing cases of human infection and the low cross-reactivity of the strain with current immunity. In this study, we produced a G4 EA H1N1-derived neuraminidase (G4NA) as a vaccine candidate in Nicotiana benthamiana. The expressed G4NA was designed to be accumulated in the endoplasmic reticulum (ER). The M-domain of the human receptor-type tyrosine-protein phosphatase C was incorporated into the expression cassette to enhance the translation of G4NA. In addition, the family 3 cellulose-binding module and Brachypodium distachyon small ubiquitin-like modifier sequences were used to enable the cost-effective purification and removal of unnecessary domains after purification, respectively. The G4NA produced in plants displayed high solubility and assembled as a tetramer, which is required for the efficacy of an NA-based vaccine. In a mouse immunization model, the G4NA produced in plants could induce significant humoral immune responses. The plant-produced G4NA also stimulated antigen-specific CD4 T cell activation. These G4NA vaccine-induced immune responses were intensified by the administration of the antigen with a vaccine adjuvant. These results suggest that G4NA produced in plants has great potential as a vaccine candidate against G4 EA H1N1.

Immunogenicity and Durability of Antibody Responses to Homologous and Heterologous Vaccinations with BNT162b2 and ChAdOx1 Vaccines for COVID-19.

During the COVID-19 pandemic, vaccines were developed based on various platform technologies and were approved for emergency use. However, the comparative analysis of immunogenicity and durability of vaccine-induced antibody responses depending on vaccine platforms or vaccination regimens has not been thoroughly examined for mRNA- or viral vector-based vaccines. In this study, we assessed spike-binding IgG levels and neutralizing capacity in 66 vaccinated individuals prime-boost immunized either by homologous (BNT162b2-BNT162b2 or ChAdOx1-ChAdOx1) or heterologous (ChAdOx1-BNT162b2) vaccination for six months after the first vaccination. Despite the discrepancy in intervals for the prime-boost vaccination regimen of different COVID-19 vaccines, we found stronger induction and relatively rapid waning of antibody responses by homologous vaccination of the mRNA vaccine, while weaker boost effect and stable maintenance of humoral immune responses were observed in the viral vector vaccine group over 6 months. Heterologous vaccination with ChAdOx1 and BNT162b2 resulted in an effective boost effect with the highest remaining antibody responses at six months post-primary vaccination.

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].

Semantic variant primary progressive aphasia with a pathogenic variant p.Asp40Gly in the ANXA11 gene.

We report a patient with right-predominant semantic variant primary progressive aphsia linked with p.Asp40Gly variant of ANXA11, which is the first description of frontotemporal dementia without clinical and electrophysiological evidences of amyotrophic lateral sclerosis associated with a known pathogenic variant of ANXA11.

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.