Physical Fitness and Risk of Mental Disorders in Children and Adolescents.

Importance: With the rising prevalence of mental disorders among children and adolescents, identifying modifiable associations is critical. Objective: To examine the association between physical fitness and mental disorder risks. Design, Setting, and Participants: This nationwide cohort study used data from the Taiwan National Student Fitness Tests and National Health Insurance Research Databases from January 1, 2009 to December 31, 2019. Participants were divided into 2 cohorts targeting anxiety and depression (1 996 633 participants) and attention-deficit/hyperactivity disorder (ADHD; 1 920 596 participants). Participants were aged 10 to 11 years at study entry and followed up for at least 3 years, had a nearly equal gender distribution, and an average follow-up of 6 years. Data were analyzed from October 2022 to February 2024. Exposures: Assessments of physical fitness included cardiorespiratory fitness (CF), muscular endurance (ME), muscular power (MP), and flexibility, measured through an 800-m run time, bent-leg curl-ups, standing broad jump, and sit-and-reach test, respectively. Main Outcomes and Measures: Kaplan-Meier method calculated the cumulative incidence of anxiety, depression, and ADHD across fitness quartiles. Additionally, multivariable Cox proportional hazards models were used that included all 4 fitness components and explored sex and income as modifiers. Results: The anxiety and depression cohort had 1 996 633 participants (1 035 411 participants were male [51.9%], and the median [IQR] age was 10.6 [10.3-11.0] years), while the ADHD cohort had 1 920 596 (975 568 participants were male [51.9%], and the median [IQR] age was 10.6 [10.3-11.0] years). Cumulative incidence of mental disorders was lower among participants in better-performing fitness quartiles, suggesting a dose-dependent association. Gender-specific analyses, controlling for confounders, revealed that improved CF, indicated by a 30-second decrease in run times, was associated with reduced risks of anxiety, depression, and ADHD in female participants, and lower risks of anxiety and ADHD in male participants (adjusted hazard ratio [aHR] for ADHD risk for female participants, 0.92; 95% CI, 0.90-0.94; P < .001; for male participants, 0.93; 95% CI, 0.92-0.94; P < .001). Enhanced ME, marked by an increase of 5 curl-ups per minute, was associated with decreased risks of depression and ADHD in female participants, and lower anxiety and ADHD risks in male participants (aHR for ADHD risk for female participants, 0.94; 95% CI, 0.92-0.97; P < .001; for male participants, 0.96; 95% CI, 0.95-0.97; P < .001). Improved MP, reflected by a 20-cm increase in jump distance, was associated with reduced risks of anxiety and ADHD in female participants and reduced anxiety, depression, and ADHD in male participants (aHR for ADHD risk for female participants, 0.95; 95% CI, 0.91-1.00; P = .04; for male participants, 0.96; 95% CI, 0.94-0.99; P = .001). Conclusions and Relevance: This study highlights the potential protective role of cardiorespiratory fitness, muscular endurance, and muscular power in preventing the onset of mental disorders. It warrants further investigation of the effectiveness of physical fitness programs as a preventive measure for mental disorders among children and adolescents.

Foxp2 Is Required for Nucleus Accumbens-mediated Multifaceted Limbic Function.

The forkhead box protein P2 (Foxp2), initially identified for its role in speech and language development, plays an important role in neural development. Previous studies investigated the function of the Foxp2 gene by deleting or mutating Foxp2 from developmental stages. Little is known about its physiological function in adult brains. Although Foxp2 has been well studied in the dorsal striatum, its function in the nucleus accumbens (NAc) of the ventral striatum remains elusive. Here, we examine the physiological function of Foxp2 in NAc of mouse brains. We conditionally knocked out Foxp2 by microinjections of AAV-EGFP-Cre viruses into the medial shell of NAc of Foxp2 floxed (cKO) mice. Immunostaining showed increased c-Fos positive cells in cKO NAc at basal levels, suggesting an abnormality in Foxp2-deficient NAc cells. Unbiased behavioral profiling of Foxp2 cKO mice showed abnormalities in limbic-associated function. Foxp2 cKO mice exhibited abnormal social novelty without preference for interaction with strangers and familiar mice. In appetitive reward learning, Foxp2 cKO mice failed to learn the time expectancy of food delivery. In fear learning, Foxp2 cKO mice exhibited abnormal increases in freezing levels in response to tone paired with foot shock during fear conditioning. The extinction of the fear response was also altered in Foxp2 cKO mice. In contrast, conditional knockout of Foxp2 in NAc did not affect locomotion, motor coordination, thermal pain sensation, anxiety- and depression-like behaviors. Collectively, our study suggests that Foxp2 has a multifaceted physiological role in NAc in the regulation of limbic function in the adult brain.

Shared genetic architectures of educational attainment in East Asian and European populations.

Educational attainment (EduYears), a heritable trait often used as a proxy for cognitive ability, is associated with various health and social outcomes. Previous genome-wide association studies (GWASs) on EduYears have been focused on samples of European (EUR) genetic ancestries. Here we present the first large-scale GWAS of EduYears in people of East Asian (EAS) ancestry (n = 176,400) and conduct a cross-ancestry meta-analysis with EduYears GWAS in people of EUR ancestry (n = 766,345). EduYears showed a high genetic correlation and power-adjusted transferability ratio between EAS and EUR. We also found similar functional enrichment, gene expression enrichment and cross-trait genetic correlations between two populations. Cross-ancestry fine-mapping identified refined credible sets with a higher posterior inclusion probability than single population fine-mapping. Polygenic prediction analysis in four independent EAS and EUR cohorts demonstrated transferability between populations. Our study supports the need for further research on diverse ancestries to increase our understanding of the genetic basis of educational attainment.

Cancer survivorship and risk of pregnancy complications, adverse obstetric outcomes, and maternal morbidities in female adolescents and young adults: a nationwide population-based study from Taiwan.

BACKGROUND: Cancer treatment in female adolescent and young adult (AYA) cancer survivors (i.e., those diagnosed between 15 and 39 years of age) may adversely affect multiple bodily functions, including the reproductive system. METHODS: We initially assembled a retrospective, nationwide population-based cohort study by linking data from two nationwide Taiwanese data sets. We subsequently identified first pregnancies and singleton births to AYA cancer survivors (2004-2018) and select AYA without a previous cancer diagnosis matched to AYA cancer survivors for maternal age and infant birth year. RESULTS: The study cohort consisted of 5151 and 51,503 births to AYA cancer survivors and matched AYA without a previous cancer diagnosis, respectively. The odds for overall pregnancy complications (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.01-1.18) and overall adverse obstetric outcomes (OR, 1.07; 95% CI, 1.01-1.13) were significantly increased in survivors compared with matched AYA without a previous cancer diagnosis. Specifically, cancer survivorship was associated with an increased risk of preterm labour, labour induction, and threatened abortion or threatened labour requiring hospitalisation. CONCLUSIONS: AYA cancer survivors are at increased risk for pregnancy complications and adverse obstetric outcomes. Efforts to integrate individualised care into clinical guidelines for preconception and prenatal care should be thoroughly explored.

Altered gut microbiota in older adults with mild cognitive impairment: a case-control study.

Introduction: The microbiota-gut-brain axis is implicated in Alzheimer's disease. Gut microbiota alterations in mild cognitive impairment (MCI) are inconsistent and remain to be understood. This study aims to investigate the gut microbial composition associated with MCI, cognitive functions, and structural brain differences. Methods: A nested case-control study was conducted in a community-based prospective cohort where detailed cognitive functions and structural brain images were collected. Thirty-one individuals with MCI were matched to sixty-five cognitively normal controls by age strata, gender, and urban/rural area. Fecal samples were examined using 16S ribosomal RNA (rRNA) V3-V4 sequencing. Compositional differences between the two groups were identified and correlated with the cognitive functions and volumes/thickness of brain structures. Results: There was no significant difference in alpha and beta diversity between MCIs and cognitively normal older adults. However, the abundance of the genus Ruminococcus, Butyricimonas, and Oxalobacter decreased in MCI patients, while an increased abundance of nine other genera, such as Flavonifractor, were found in MCIs. Altered genera discriminated MCI patients well from controls (AUC = 84.0%) and were associated with attention and executive function. Conclusion: This study provides insights into the role of gut microbiota in the neurodegenerative process.

Physical Fitness and Inflammatory Bowel Disease Risk Among Children and Adolescents in Taiwan.

Importance: The incidence of inflammatory bowel disease (IBD) is increasing in newly industrialized countries but disease etiologies remain unclear. Objective: To investigate the association between physical fitness and subsequent IBD risk among children and adolescents in Taiwan. Design, Setting, and Participants: This nationwide cohort study was conducted between January 1, 2010, and December 31, 2018. Data sources included the Taiwan National Health Insurance Research Database, the National Student Fitness Tests Database, and the Air Quality Monitoring System Database. This study included students who were aged 10 years, completed physical fitness tests between grades 4 and 13, and had at least 1 year of follow-up. Data analysis was last performed on January 15, 2023. Exposures: Physical fitness tests included cardiorespiratory endurance (CE; number of minutes to complete an 800-m run), musculoskeletal endurance (ME; number of bent-leg curl-ups in 1 minute), musculoskeletal power (MP; standing broad jump distance), and flexibility fitness (FF; 2-leg sit-and-reach distance). Main Outcomes and Measures: Subsequent risk of IBD was compared among students based on physical fitness test results. Six-year cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing mortality. Performance was reported in quantiles, ranging from 1 (best) to 4 (poorest). Results: There were 4 552 866 students who completed physical fitness tests between grades 4 and 13; among these students, 1 393 641 were aged 10 years and were included in the analysis. Six-year cumulative incidence of IBD risk was lowest among students in the best-performing quantile of CE (quantile 1, 0.74% [95% CI, 0.63%-0.86%]; P < .001), ME (0.77% [0.65%-0.90%]; P < .001), and MP (0.81% [0.68%-0.93%]; P = .005) compared with students in quantiles 2 through 4, respectively; however, no association was observed for quantiles of FF. After adjusting for competing HRs for mortality and other confounders, better CE was inversely associated with IBD risk (adjusted HR, 0.36 [95% CI, 0.17-0.75]; P = .007). Other measures of physical fitness were not independently associated with IBD risk. Conclusions and Relevance: The results of this study suggest that CE was inversely associated with IBD risk among children and adolescents, but ME, MP, and FF were not independently associated with IBD risk. Future studies that explore the mechanisms are needed.

White matter hyperintensities in cholinergic pathways are associated with dementia severity in e4 carriers but not in non-carriers.

Background and objectives: Among individuals with Alzheimer's disease (AD), APOE e4 carriers with increased white matter hyperintensities (WMHs) may selectively be at increased risk of cognitive impairment. Given that the cholinergic system plays a crucial role in cognitive impairment, this study aimed to identify how APOE status modulates the associations between dementia severity and white matter hyperintensities in cholinergic pathways. Methods: From 2018 to 2022, we recruited participants (APOE e4 carriers, n = 49; non-carriers, n = 117) from the memory clinic of Cardinal Tien Hospital, Taipei, Taiwan. Participants underwent brain MRI, neuropsychological testing, and APOE genotyping. In this study, we applied the visual rating scale of the Cholinergic Pathways Hyperintensities Scale (CHIPS) to evaluate WMHs in cholinergic pathways compared with the Fazekas scale. Multiple regression was used to assess the influence of CHIPS score and APOE carrier status on dementia severity based on Clinical Dementia Rating-Sum of Boxes (CDR-SB). Results: After adjusting for age, education and sex, higher CHIPS scores tended to be associated with higher CDR-SB in APOE e4 carriers but not in the non-carrier group. Conclusions: Carriers and non-carriers present distinct associations between dementia severity and WMHs in cholinergic pathways. In APOE e4 carriers, increased white matter in cholinergic pathways are associated with greater dementia severity. In non-carriers, WMHs exhibit less predictive roles for clinical dementia severity. WMHs on the cholinergic pathway may have a different impact on APOE e4 carriers vs. non-carriers.

Effects of losartan and exercise on muscle mass and exercise endurance of old mice.

This study evaluated the effects of angiotensin II type I receptor blocker (ARB) on muscle mass and exercise capacity in healthy older animals. The effects of combined ARB and exercise training were also determined. Eighty 18-month-old mice were randomized into the control group (C), exercise group (E), losartan group (L) and losartan plus exercise group (LE). Mice in the L and LE groups received losartan from drinking water every day. Mice in the E and LE groups trained on a treadmill 30 min per day, 3 days per week for 4 months. Exercise endurance and spontaneous physical activity of mice were measured at baseline and monthly for 4 months. After 4 months of intervention, serum interleukin-6 (IL-6) levels, muscle mass, and muscle fiber cross sectional area (CSA) were measured. Total antioxidant capacity (TAC), lipid peroxidation and IL-6 levels were determined in quadriceps. We found that exercise endurance only increased in the E and LE groups. Muscle TAC levels of E, L, and LE groups were greater than that in the C group. Serum IL-6 and lipid peroxidation levels were not different among groups. LE group, but not E and L groups, had greater muscle mass, larger muscle fiber CSA, and greater muscle IL-6 levels than that in the C group after 4 months of intervention. These results suggest that losartan promotes the adaptions of muscle mass with exercise training in healthy older animals.

Urban-rural differences in the prevalence and correlates of mild cognitive impairment in community-dwelling older adults in Taiwan: The EMCIT study.

BACKGROUND: Taiwan is a rapidly aging society. The elderly with mild cognitive impairment (MCI) have increased risk of dementia, and this is a population-based report using standard neuropsychological tests and expert consensus diagnosis to assess the MCI prevalence and its associated factors in Taiwan. METHOD: The Epidemiology of Mild Cognitive Impairment study in Taiwan (EMCIT) is a community-based, prospective cohort study. Independently-living individuals aged ≧60 years in a rural area (n = 122) and in an urban area (n = 348) of New Taipei City, Taiwan, completed detailed neuropsychological tests at the cohort baseline. Diagnosis of MCI was ascertained through expert consensus based on 2011 NIA-AA criteria. RESULTS: Of 470 participants recruited between 2017 and 2019 (mean age 71.2 ± 5.4 years), the prevalence of MCI was higher in the rural area than in the urban area (25.1% vs. 10.8%, p < 0.001) after standardized for age, gender, and level of education. Having lower education and having depression symptoms were consistently associated with increased risk of MCI in both urban and rural areas (p < 0.05). Being male and diabetes were additionally associated with MCI prevalence in urban areas. CONCLUSION: In this community-based prospective cohort study in Taiwan, the prevalence of MCI in the rural community was much higher than that in the urban community. Different strategies may be needed to targeted different types of communities.

Association between real-world home blood pressure measurement patterns and blood pressure variability among older individuals with hypertension: A community-based blood pressure variability study.

Home blood pressure (BP) monitoring is a useful tool for hypertension management. BP variability (BPV) has been associated with an increased risk of cardiovascular events. However, little is known about the correlation between BPV and different measurement patterns of long-term home BP monitoring. This longitudinal cohort study aimed to assess the associations between dynamic BP measurement patterns and BPV. A total of 1128 participants (mean age, 77.4 ± 9.3 years; male, 51%) with 23 269 behavior measuring units were included. We used sliding window sampling to classify the home BP data with a regular 6-month interval into units in a sliding manner until the data are not continuous. Three measurement patterns (stable frequent [SF], stable infrequent [SI], and unstable [US]) were assessed based on the home BP data obtained within the first 3 months of the study, and the data in the subsequent 3 months were used to assess the BPV of that unit. We used linear mixed-effects model to assess the association between BP measurement patterns and BPV with adjustment for possible confounding factors including average BP. Average real variability and coefficient variability were used as measures of the BPV. No significant differences were observed in average BP between the SF, SI, and US patterns. However, BPV in the SF group was significantly lower than that in the US and SI groups (all p-values < .05). The BPV in SI and US groups was not significantly different. A stable and frequent BP measuring pattern was independently associated with a lower BPV.

Emergence of T cell immunosenescence in diabetic chronic kidney disease.

BACKGROUND: Type 2 diabetes is an important challenge given the worldwide epidemic and is the most important cause of end-stage renal disease (ESRD) in developed countries. It is known that patients with ESRD and advanced renal failure suffer from immunosenescence and premature T cell aging, but whether such changes develop in patients with less severe chronic kidney disease (CKD) is unclear. METHOD: 523 adult patients with type 2 diabetes were recruited for this study. Demographic data and clinical information were obtained from medical chart review. Immunosenescence, or aging of the immune system was assessed by staining freshly-obtained peripheral blood with immunophenotyping panels and analyzing cells using multicolor flow cytometry. RESULT: Consistent with previously observed in the general population, both T and monocyte immunosenescence in diabetic patients positively correlate with age. When compared to diabetic patients with preserved renal function (estimated glomerular filtration rate > 60 ml/min), patients with impaired renal function exhibit a significant decrease of total CD3+ and CD4+ T cells, but not CD8+ T cell and monocyte numbers. Immunosenescence was observed in patients with CKD stage 3 and in patients with more severe renal failure, especially of CD8+ T cells. However, immunosenescence was not associated with level of proteinuria level or glucose control. In age, sex and glucose level-adjusted regression models, stage 3 CKD patients exhibited significantly elevated percentages of CD28-, CD127-, and CD57+ cells among CD8+ T cells when compared to patients with preserved renal function. In contrast, no change was detected in monocyte subpopulations as renal function declined. In addition, higher body mass index (BMI) is associated with enhanced immunosenescence irrespective of CKD status. CONCLUSION: The extent of immunosenescence is not significantly associated with proteinuria or glucose control in type 2 diabetic patients. T cells, especially the CD8+ subsets, exhibit aggravated characteristics of immunosenescence during renal function decline as early as stage 3 CKD. In addition, inflammation increases since stage 3 CKD and higher BMI drives the accumulation of CD8+CD57+ T cells. Our study indicates that therapeutic approaches such as weight loss may be used to prevent the emergence of immunosenescence in diabetes before stage 3 CKD.

Angiotensin II Blood Levels Are Associated with Smaller Hippocampal and Cortical Volumes in Cognitively Normal Older Adults.

BACKGROUND: There is emerging evidence about possible involvement of the renin-angiotensin system (RAS) in the pathogenesis of Alzheimer's disease (AD) and decline of cognitive function. However, little is known about associations with brain biomarkers. OBJECTIVE: Our study aimed to examine associations between blood ACE-1 and ANG II levels and brain MRI based volumes in non-demented participants, and whether these associations were mediated by blood pressure. METHODS: This cross-sectional study was conducted in 34 older participants from the Baltimore Experience Corps Trial (BECT) Brain Health Sub-study (BHS). Blood ANGII and ACE-1 levels were measured by ELISA and brain MRI volumes were generated using FreeSurfer 6.0. Multiple linear regression analysis, adjusting for intracranial volume and confounders, was used to determine associations between log transformed ANGII and ACE-1 levels and MRI volumes (mm3). RESULTS: Participants were predominantly female (76%), African-American (94%), with mean age of 66.9 and education of 14.4 years. In the fully adjusted model we observed significant inverse associations between log ANGII levels and total grey matter (ß=Angiotensin II associated with smaller hippocampus14,935.50, ±7,444.83, p = 0.05), total hippocampus (ß=-129.97, ±105.27, p = 0.03), rostral middle frontal (ß= -1580.40, ±584.74, p = 0.02), and supramarginal parietal (ß= -978.90, ±365.54, p = 0.02) volumes. There were no associations between ANGII levels and total white matter or entorhinal cortex volumes, or ACE-1 levels and any brain volumes. CONCLUSION: We observed that increased blood ANGII levels were associated with lower total grey matter, hippocampal, rostral middle frontal, and supramarginal parietal volumes, which are associated with cognitive domains that decline in preclinical AD.

Plasma Leucine-Rich α-2-Glycoprotein 1 Predicts Cardiovascular Disease Risk in End-Stage Renal Disease.

Plasma leucine-Rich α-2-glycoprotein 1 (LRG1) is an innovative biomarker for inflammation and angiogenesis. Many adverse pathophysiological changes including inflammation, atherosclerosis, and premature mortality is associated with End-stage renal disease (ESRD). However, whether levels of plasma LRG1 correlate with the co-morbidities of ESRD patients is unknown. Plasma LRG1 and high-sensitivity C-reactive protein (hsCRP) were analyzed by ELISA in 169 hemodialysis patients from the Immunity in ESRD (iESRD) study. Patient demographics and comorbidities at the time of enrollment were recorded. Peripheral blood monocyte and T cell subsets were assessed by multicolor flow cytometry. In the univariate analysis, a higher level of LRG1 was associated with the presence of cardiovascular disease (CVD) and peripheral arterial occlusive disease (PAOD). In multivariate logistic regression models, higher LRG1 tertile was significantly associated with PAOD (odds ratio = 3.49) and CVD (odds ratio = 1.65), but not with coronary artery disease, history of myocardial infarction, or stroke after adjusting for gender, diabetes, hemoglobin, albumin, calcium-phosphate product, and level of hsCRP. In addition, the level of LRG1 had a positive correlation with IL-6, hsCRP, and also more advanced T cell differentiation. The association suggests that LRG1 participates in the progression of atherosclerosis by inducing inflammation. Therefore, the role of LRG1 in coexisting inflammatory response should be further investigated in the pathogenesis of cardiovascular morbidity and mortality in patients with ESRD.

Interaction between Apolipoprotein E and Butyrylcholinesterase Genes on Risk of Alzheimer's Disease in a Prospective Cohort Study.

BACKGROUND: An epistatic interaction between the ɛ4 allele of apolipoprotein E (APOEɛ4) gene and the K-variant of butyrylcholinesterase (BCHE-K) genes has been previously reported to increase risk of Alzheimer's disease (AD). However, these observations were largely from case-control studies with small sample sizes. OBJECTIVE: To examine the interaction between APOEɛ4 and BCHE-K on: 1) the risk of incident AD and 2) rates of change in brain volumes and cognitive performance during the preclinical stages of AD in a prospective cohort study. METHODS: The study sample for survival analysis included 691 Caucasian participants (age at baseline, 58.4±9.9 years; follow-up time,16.9±9.7 years) from the Baltimore Longitudinal Study of Aging. The neuroimaging sample included 302 participants with 1,388 magnetic resonance imaging (MRI) scans. Cognitive performance was assessed in 703 participants over 4,908 visits. RESULTS: A total of 122 diagnoses (79 AD, 43 mild cognitive impairment [MCI]) were identified. Participants with both APOEɛ4 and BCHE-K variants had a 3.7-fold greater risk of AD (Hazard ratio [HR] 95% CI=1.99-6.89, p < 0.001) compared to non-carriers of both genes (APOE ɛ4 x BCHE-K interaction p = 0.025). There was no APOE ɛ4-BCHE-K interaction effect on rate of cognitive decline and brain atrophy. CONCLUSION: The APOE and BCHE genes interact to influence risk of incident AD/MCI but not rates of brain atrophy and decline in cognitive performance before onset of cognitive impairment. This may suggest the epistatic interaction between APOE ɛ4 and BCHE-K on AD risk is disease stage-dependent.

Adverse birth outcomes in adolescent and young adult female cancer survivors: a nationwide population-based study.

BACKGROUND: For female adolescent and young adult (AYA), cancer with treatments may affect their children's health. Our aim was to determine reliable risk estimates of adverse birth outcomes in AYA cancer survivors and the differential effects of treatments. METHODS: The study population of 4547 births in the AYA cancer survivor group and 45,463 in the comparison group were identified from two national databases between 2004 and 2014. Detailed maternal health conditions, such as maternal comorbidities, medication use during pregnancy and lifestyles, were adjusted in the statistical analyses. The outcomes included low birth weight, preterm labour, stillbirth, small or large for gestational age, a 5-min Apgar score <7, congenital malformation and foetal distress. RESULTS: The AYA cancer survivor group had a 9% higher risk of overall adverse birth outcomes (adjusted odds ratio, 1.09; 95% confidence interval, 1.02-1.16), especially low birth weight and preterm labour than the comparison group. The radiotherapy-only group additionally had a higher risk of foetal distress, and a 5-min Apgar score <7. CONCLUSION: AYA cancer survivors, especially those who have received radiotherapy, still have higher risks of adverse birth outcomes after adjusting for detailed maternal health conditions. Preconception counselling and additional surveillance may be warranted in this population.

Engagement in Enriching Early-Life Activities Is Associated With Larger Hippocampal and Amygdala Volumes in Community-Dwelling Older Adults.

OBJECTIVES: Numerous studies show benefits of mid- and late-life activity on neurocognitive health. Yet, few studies have examined how engagement in enriching activities during childhood, when the brain is most plastic, may confer long-term neurocognitive benefits that may be especially important to individuals raised in low-income settings. We examined associations between enriching early-life activities (EELAs) and hippocampal and amygdala volumes in a sample of predominantly African-American, community-dwelling older adults. We further assessed whether these associations were independent of current activity engagement. METHODS: Ninety participants from the baseline Brain Health Substudy of the Baltimore Experience Corps Trial (mean age: 67.4) completed retrospective activity inventories and an magnetic resonance imaging scan. Volumes were segmented using FreeSurfer. RESULTS: Each additional EELA was associated with a 2.3% (66.6 mm3) greater amygdala volume after adjusting for covariates. For men, each additional EELA was associated with a 4.1% (278.9 mm3) greater hippocampal volume. Associations were specific to these regions when compared with the thalamus, used as a control region. DISCUSSION: Enriching lifestyle activities during an important window of childhood brain development may be a modifiable factor that impacts lifelong brain reserve, and results highlight the importance of providing access to such activities in historically underserved populations.

Correction to: T-cell aging in end-stage renal disease: an evolving story with CMV.

Unfortunately in the original article the first author name incorrectly published as TienYu Yang. The correct name is TienYu Owen Yang.

T-cell aging in end-stage renal disease: an evolving story with CMV.

Established evidence from the last decade has suggested that chronic cytomegalovirus infection has strong impact on the human immune system, resulting in aggravated aging-associated T-cell changes that are associated with poorer vaccination responses, cardiovascular disease and shortened survival. Patients with end-stage renal disease (ESRD), the most severe form of chronic kidney disease, exhibit premature aging phenotypes in almost all organ systems, including the immune system. Longitudinal studies of T-cell aging in healthy humans have been scanty because it requires a large number of study subjects and a study duration for decades. In recent years, it became clear that ESRD patients with cytomegalovirus (CMV) infection exhibit enhanced aging-related immune changes than CMV-seropositive individuals without renal disease, including chronic inflammation, decreased numbers of naïve CD4+ and CD8+ T cells, increased clonality of memory T cells with skewed repertoire and shortened telomeres. These findings lead to the hypothesis that the uremic milieu and treatment for renal failure can lead to premature aging of T cells independent from CMV infection and suggest that ESRD can be an important disease model for studying human aging. Future studies deciphering the underlying mechanisms of accelerated T cell aging in ESRD patients may eventually reveal additional insights into T-cell persistence and function during aging in CMV-seropositive, non-ESRD individuals.

Cognitive impairment in patients with end-stage renal disease: Accelerated brain aging?

BACKGROUND: Chronic kidney disease exhibits a prominent premature aging phenotype in many different organ systems, including the brain. Nevertheless, a comprehensive characterization of brain aging in non-demented patients with end-stage renal disease (ESRD) is lacking and it remains unclear if the collective changes of cognitive functions and brain structures in ESRD is compatible with aging. METHODS: We compared 56 non-demented, independently living dialysis patients (mean age 59.4 ± 11.0 years; mean dialysis vintage of 5.9 years) and 60 non-dialysis controls on a battery of neuropsychological tests, brain MRI T1 imaging and diffusion tensor imaging. Participants with diagnosis of dementia, Mini-Mental State Examination <24, medical history of stroke, or recent hospitalization within 1 month were excluded. RESULTS: Dialysis patients showed significantly worse performance in attention/information processing speed and executive function adjusted for age, sex, education, diabetes and depression. Reduced total brain volume and subcortical volume including hippocampus were found in dialysis patients. Vertex-wise analysis showed cortical thinning in middle frontal, lateral occipital and precuneus region. Furthermore, decreased white matter integrity was found primarily in bilateral anterior thalamic tract, fronto-occipital fasciculus, forceps minor and uncinate tract after correction for multiple comparisons. CONCLUSION: Overall, differences in cognitive functions, cortical volumes/thickness and white matter integrity associated with dialysis are also cognitive domains and brain structure changes associated with normal aging. In other words, non-demented, independently living dialysis patients present an accelerated brain aging phenotype even after taking into account effects of age, diabetes and depression.

A comprehensive characterization of aggravated aging-related changes in T lymphocytes and monocytes in end-stage renal disease: the iESRD study.

BACKGROUND: Patients with end-stage renal disease (ESRD) exhibit a premature aging phenotype of the immune system. Nevertheless, the etiology and impact of these changes in ESRD patients remain unknown. RESULTS: Compared to healthy individuals, ESRD patients exhibit accelerated immunosenescence in both T cell and monocyte compartments, characterized by a dramatic reduction in naïve CD4+ and CD8+ T cell numbers but increase in CD8+ TEMRA cell and proinflammatory monocyte numbers. Notably, within ESRD patients, aging-related immune changes positively correlated not only with increasing age but also with longer dialysis vintage. In multivariable-adjusted logistic regression models, the combination of high terminally differentiated CD8+ T cell level and high intermediate monocyte level, as a composite predictive immunophenotype, was independently associated with prevalent coronary artery disease as well as cardiovascular disease, after adjustment for age, sex, systemic inflammation and presence of diabetes. Levels of terminally differentiated CD8+ T cells also positively correlated with the level of uremic toxin p-cresyl sulfate. CONCLUSIONS: Aging-associated adaptive and innate immune changes are aggravated in ESRD and are associated with cardiovascular diseases. For the first time, our study demonstrates the potential link between immunosenescence in ESRD and duration of exposure to the uremic milieu.