Effects of adult education on cognitive function and risk of dementia in older adults: a longitudinal analysis.

Introduction: Mid/late-life cognitive activities are associated with a lower rate of subsequent cognitive decline and lower subsequent dementia risk over time. Methods: In this study, we investigated the association between adult education class participation and subsequent cognitive decline and dementia risk over time after adjusting for baseline cognitive function and genetic risk of dementia, correcting for several potential confounding variables, using a large prospective cohort data of participants from the UK Biobank study followed from 2006 to 2010. Results: The results revealed that participation in adult education classes at baseline was associated with greater subsequent retention of fluid intelligence score. Cox proportional hazard models revealed that subjects who participated in adult education classes showed a significantly lower risk of incident dementia 5 years after baseline compared with those that did not at baseline. Discussion: In this study, we show that participation in adult education classes preceded greater retention of subsequent fluid intelligence and a lower risk of developing dementia after 5 years: this association did not change after adjusting for cognitive function at baseline or genetic predisposition to dementia. Accordingly, participation in such classes could reduce the risk of developing dementia.

Effects of television viewing on brain structures and risk of dementia in the elderly: Longitudinal analyses.

Introduction: TV viewing in the elderly and in children is associated with subsequent greater decline of various cognitive functions including verbal working memory, but results of its association with subsequent risk of dementia were divided. Methods: In this longitudinal cohort study of UK Biobank, we investigated the associations of TV viewing length with subsequent risk of dementia and longitudinal changes of brain structural measures after corrections of a wide range of potential confounders. Results: Our results showed longer TV viewing was associated with increased risk of subsequent onset of dementia, as well as subsequent greater decline in intracellular volume fraction (ICVF) in the extensive areas of right lateral temporal cortex and the right medial temporal cortex, in the area around the left middle and inferior temporal cortex as well as the left fusiform gyrus, and the area adjacent to the left inferior frontal gyrus, and left insula. Discussion: These results may suggest prolonged TV viewing was associated with decline in density of neurites (axon, dendrites) in areas particularly implicated in language, communication, and memory, which are altered in dementia.

Nutrients and Dementia: Prospective Study.

The association of diet and nutrients with dementia risk is an interesting research topic. Middle-aged and older Europeans not diagnosed with dementia within two years of baseline were followed up and their data were analysed until 2021. The association between the nutrient quintiles measured by the web-based 24 h dietary and the risk of developing dementia was examined using a Cox proportional hazard model after adjusting for potential confounding factors. Approximately 160,000 subjects and 1200 cases were included in the analysis of each nutrient. A greater risk of dementia was associated with (a) no alcohol intake (compared with moderate to higher intake), (b) higher intake of total sugars and carbohydrates (compared with lower intake), (c) highest or lowest fat intake (compared with moderate intake), (d) quintiles of highest or lowest magnesium intake (compared with the quintile of the second highest intake), and (e) highest protein intake (compared with moderate intake). Overall, the present results are congruent with the importance of a moderate intake of certain nutrients.

Disappearance and Re-Emergence of Influenza during the COVID-19 Pandemic: Association with Infection Control Measures.

During the coronavirus disease 2019 (COVID-19) pandemic, the influenza virus had a very low prevalence, and in many areas, outbreaks were almost non-existent. In this study, the associations between infection control measures taken for COVID-19 and the global disappearance of the influenza virus were investigated. The detection rate of influenza from baseline was investigated during four seasons (12 weeks from epidemiological week 49 in 2020 and 2021 and 12 weeks from epidemiological week 23 in 2020 and 2021) in each country participating in the surveillance system of the World Health Organization. Three measures of infection control: mask use ratio, social distancing index (an index of human mobility and physical distance obligations), and an index of stringency of measures taken by authorities were studied. In mid-2020, most countries analyzed had high levels of infection control measures, and in most countries, influenza was drastically reduced compared to previous years. Multiple regression analyses compared the study data with data from other seasons. There was an association between high mask use with low influenza detection in all three remaining seasons, an association between a low social distancing index (low mobility and more social contact obligations) with a low influenza detection rate in two seasons, and a marginal significant association of high stringency index with a low influenza detection rate(in 2020-end-seasons). These results support the notion that seasonal influenza is controllable through effective preventive measures, especially those of mask use and human social contact, and these measures should be recommended during future waves of novel influenza virus infection.

A Prospective Study on the Relationship between Iron Supplement Intake, Hemoglobin Concentration, and Risk of Parkinsonism.

The findings regarding whether the greater iron level or intake is a risk factor to Parkinson's disease (PD) or parkinsonism was not clear. The purpose of this study is to establish a consistent association between iron supplementation and parkinsonism risk, we conducted a large-scale prospective cohort study using comprehensive longitudinal data from the UK Biobank. The longitudinal cohort data of 385,898 participants (including 911 cases) who were middle to old aged British adults and joined the UK Biobank study from 2006 to 2010 and were followed up until 2018 was analyzed. The associations between iron supplement intake, hemoglobin levels and all cause subsequent parkinsonism risk after corrections of potential confounders (sex, age, household income, education length, employment status, deprivation level, body mass index, physical activity level, household numbers, smoking and drinking levels, health status, blood pressure) were investigated. Analyses revealed that (a) iron supplementation was significantly associated with higher parkinsonism risk, (b) greater hemoglobin was weakly and insignificantly associated with lower parkinsonism risk, and (c) multivitamin or vitamin C supplement intake was not significantly associated with parkinsonism risk. Regardless of whether the subjects were classified as anemic, normal, or polycythemic or in the hemoglobin level quintile, there was no nonlinear association between hemoglobin and parkinsonism risk. Parkinsonism risk did not differ between participants reporting supplementary iron intake with or without vitamin C or multivitamin supplement intake. Furthermore, polygenic risk score of PD negatively correlated with hemoglobin level, while it did not associate with intake of iron supplement or multivitamin or vitamin C supplement intake. The results suggest excessive iron intake may increase parkinsonism risk. Interventional studies are warranted to examine whether iron intake restriction is beneficial for individuals without clinical iron deficiency.

Reduced prosaposin levels in HepG2 cells with long-term coenzyme Q10 deficiency.

Glycosphingolipids are involved in intercellular signaling, adhe-sion, proliferation, and differentiation. Saposins A, B, C, and D are cofactors required for glycosphingolipid hydrolysis. Saposins A-D are present in series in a common precursor protein, prosaposin. Thus, glycosphingolipids amounts depend on prosaposin cellular levels. We previously reported that prosaposin and saposin B bind coenzyme Q10 in human cells. Coenzyme Q10 is an essential lipid of the mitochondrial electron transport system, and its reduced form is an important antioxidant. Coenzyme Q10 level decrease in aging and in various progressive diseases. Therefore, it is interesting to understand the cellular response to long-term coenzyme Q10 deficiency. We established a long-term coenzyme Q10 deficient cell model by using the coenzyme Q10 biosynthesis inhibitor, 4-nitrobenzoate. The levels of coenzyme Q10 were reduced by 4-nitrobenzoate in HepG2 cells. Administration of 4-nitrobenzoate also decreased prosaposin protein and mRNA levels. The cellular levels of coenzyme Q10 and prosaposin were recovered by treatment with 4-hydroxybenzoquinone, a substrate for coenzyme Q10 synthesis that counteracts the effect of 4-nitrobenzoate. Furthermore, the ganglioside levels were altered in 4-nitrobenzoate treated cells. These results imply that long-term coenzyme Q10 deficiency reduces cellular prosaposin levels and disturbs glycosphingolipid metabolism.

Brain Anatomy Alterations and Mental Health Challenges Correlate to Email Addiction Tendency.

Despite the widespread use of email, our knowledge regarding the consequences of email addiction is lacking. The purpose of this study was to develop an email addiction tendency scale to evaluate its correlation to behavior and brain structure. Following this, the validity and reliability of the developed scale was investigated. We used voxel-based morphometry, correlation, and univariate regression analysis to assess the relationships between email addiction tendency scores and regional gray and white matter volumes, depression, and nonverbal reasoning abilities in a large sample of healthy young adults (n = 1152; mean age, 20.69 ± 1.84 years). The content validity ratio, content validity index, principal component analysis, and confirmatory factorial analysis all showed that the email addiction tendency scale (EATS) has high validity. Additionally, the Cronbach's alpha internal consistency and split-half reliability coefficient showed that the EATS has high reliability. We found that email addiction tendency scores were significantly negatively correlated with nonverbal reasoning. We also observed that the email addiction tendency scores were significantly and positively correlated with depression symptom severity and gray matter volume of the left rostrolateral prefrontal cortex (RLPC) in subjects. These results indicate that email addiction tendency is associated with lower mental health outcomes and increased GMV in the left RLPC.

Mercury levels in hair are associated with reduced neurobehavioral performance and altered brain structures in young adults.

The detrimental effects of high-level mercury exposure on the central nervous system as well as effects of low-level exposure during early development have been established. However, no previous studies have investigated the effects of mercury level on brain morphometry using advance imaging techniques in young adults. Here, utilizing hair analysis which has been advocated as a method for biological monitoring, data of regional gray matter volume (rGMV), regional white matter volume (rWMV), fractional anisotropy (FA) and mean diffusivity (MD), cognitive functions, and depression among 920 healthy young adults in Japan, we showed that greater hair mercury levels were weakly but significantly associated with diminished cognitive performance, particularly on tasks requiring rapid processing (speed measures), lower depressive tendency, lower rGMV in areas of the thalamus and hippocampus, lower rWMV in widespread areas, greater FA in bilaterally distributed white matter areas overlapping with areas of significant rWMV reductions and lower MD of the widely distributed gray and white matter areas particularly in the bilateral frontal lobe and the right basal ganglia. These results suggest that even normal mercury exposure levels in Japan are weakly associated with differences of brain structures and lower neurobehavioral performance and altered mood among young adults.

A Prospective Study on the Relationship Between Driving and Non-occupational Computer Use With Risk of Dementia.

Sedentary behaviors have been associated with the risk of dementia in older adults. Whether driving and computer use are associated with the risk of dementia in older adults is an important research question. The participants of a longitudinal cohort study that included European middle- and old-aged adults at the baseline (2006-2010) who had not been diagnosed with dementia before 5 years after the baseline and had not died within 5 years after the baseline were followed up (until 2018) and analyzed. The associations between driving and non-occupational computer use time measured by the questionnaire at the baseline and incident dementia 5 years after the baseline were analyzed after correcting for confounding variables. Each analysis included approximately 370,000 participants and 1,000 cases. According to Cox proportional hazard models that divide subjects into four groups of habit duration levels [(a) 0 h; (b) less than 1 h, 1 h; (c), 2 h, 3 h; (d) 4 h or more, per/day)], the group with 0 h < driving time ≤1 h at the baseline exhibited a significantly lower risk of incident dementia than the other groups. In addition, in the analysis of non-occupational computer use duration, the 0 h group exhibited a significantly higher risk than the other groups. Our results indicate that different sedentary behaviors have different associations with dementia risk over time and have no simple dose-response relationship with dementia risk. The sedentary behavior risk assessments must consider these factors.

Effects of Diastolic Blood Pressure on Brain Structures and Cognitive Functions in Middle and Old Ages: Longitudinal Analyses.

Hypertension is a pervasive public health concern due to strong associations with cardiovascular diseases and stroke. Alternatively, the associations between hypertension and the risk of Alzheimer's disease are complex and recent large sample studies reported positive associations. In this paper, we examine the associations between diastolic blood pressure (BP) and subsequent changes in brain structure and cognitive function over several years by multiple regression analyses (with adjustment for a wide range of potential confounding variables) among a large cohort from the UK Biobank. Higher baseline diastolic BP was associated with a slightly smaller relative increase (relative improvements) in reaction time and a slightly greater reduction in depression scores. Higher baseline diastolic BP was also associated with a greater total gray matter volume (GMV) retention, while aging alone was associated with GMV reduction. White matter microstructural analyses revealed that a greater diastolic BP was associated with reduced longitudinal mean and regional fractional anisotropy, greater increases in mean and regional mean diffusivity, radial diffusivity, and axial diffusivity, a greater decline in mean intracellular volume fraction, and greater increases in mean and regional isotropic volume fraction. These white matter microstructural changes were consistent with those seen in the aging process. Additional analyses revealed a greater cheese intake level at baseline, which is associated with a subsequent decline in diastolic BP and a relative subsequent increase in depressive tendency together with a relative increase in fluid intelligence and visuospatial memory performance. These results are congruent with the view that a higher BP in the aging brain has a complex role.

Effects of Body Mass Index on Brain Structures in the Elderly: Longitudinal Analyses.

The relationship between obesity and neurocognitive consequences is complex. Here we investigated associations between body mass index (BMI) and subsequent changes in brain structures, cognitive changes, and the onset of dementia after adjustment of a wide range of potential confounding variables using a large prospective cohort data of UK Biobank. After correcting for confounding factors, higher BMI was associated with greater retention in visuospatial memory performance (decline in error numbers) [beta = -0.019 (CI:-0.027~-0.016), N = 39191], increase in depression tendency scores [beta = 0.036(0.027~0.045)] as well as decreased risk of incident dementia [increasing BMI by 1 is associated with HR of 0.981 (CI:0.969~0.992), N = 398782], but not changes in fluid intelligence or reaction time. Whole brain multiple regression analyses (volumetric analyses: N = 1253, other analyses: N = 1241) revealed positive associations between BMI and subsequent changes in regional gray matter volume (rGMV) in multiple areas, regional white matter volume changes in widespread white matter (WM) tracts, fractional anisotropy changes in several tracts, and intracellular volume fraction (ICVF) and orientation dispersion (OD) in widespread areas, and isotropic volume fraction (ISOVF) in a few areas, and negative associations between BMI and subsequent changes in rGMV in the bilateral medial temporal lobe areas, mean, axial and radial diffusivity, and ISOVF in widespread areas. These results are mostly consistent with the view that less BMI precedes greater neurocognitive aging or atrophy, with a few exceptions including OD findings and the rGMV finding of the medial temporal lobes as most of significant longitudinal associations of higher BMI were opposite to those seen in higher age and dementia. Future epidemiological studies should consider separating effects of higher BMI itself from potential confounders.

Loneliness inside of the brain: evidence from a large dataset of resting-state fMRI in young adult.

Although loneliness itself is a natural emotion, prolonged loneliness is detrimental to human health. Despite its detrimental effect, few loneliness-related neuroimaging studies have been published and some have limitations on the sample size number. This study aims to find the difference in resting-state functional connectivity associated with loneliness within a big sample size via the seed-based approach. Functional connectivity analysis was performed on a large cohort of young adults (N = 1336) using the seed-based functional connectivity approach to address the concern from previous studies. The analysis yielded statistically significant positive correlations between loneliness and functional connectivities between the inferior frontal gyrus and supplementary motor area, precentral gyrus, and superior parietal lobule. Additionally, the analysis replicated a finding from a previous study, which is increased functional connectivities between the inferior frontal gyrus and supplementary motor area. In conclusion, greater loneliness is reflected by stronger functional connectivity of the visual attention brain area.

RELN rs7341475 Associates with Brain Structure in Japanese Healthy Females.

Although temperament has been regarded as an innate aspect of human personality, its association with proteins involved in embryonic development is unclear. Reelin, encoded by RELN, plays an important role in brain development. Herein, we investigated the association between the RELN rs7341475 (G/A) single nucleotide polymorphism, detected as a female-specific risk factor for schizophrenia, brain structure, and temperament to elucidate the role of RELN in the development of human personality. In this study, 1580 healthy young Japanese adults were genotyped for RELN rs7341475 and completed the Temperament and Character Inventory. Whole-brain analysis of covariance was conducted to investigate differences between genotypes in regional gray matter volume (rGMV) and cortical morphology. Additionally, multiple regression analysis was performed to examine the association of four temperaments with rGMV. Those statistical analyses were performed separately for males and females. Individuals with G/G homozygosity showed significantly greater rGMV in several areas of the brain, particularly the bilateral cingulate and temporal gyrus, as well as a larger value of fractal dimension in the left lateral occipital cortex. Furthermore, of the four temperaments, the novelty seeking was significantly and positively associated with rGMV in the right superior temporal gyrus, partially overlapping with areas where differences between the rs7341475 genotypes were detected. The above findings were detected only in females, but not in males. This is the first study to demonstrate the contribution of RELN rs7341475 to differences in brain structure in Japanese females, which may indicate vulnerability to schizophrenia and variations in human personality.

Sex interaction of white matter microstructure and verbal IQ in corpus callosum in typically developing children and adolescents.

BACKGROUND: Childhood is an extremely important time for neural development that has a critical role in human intelligence. Efficient information processing is crucial for higher intelligence, so the intra- or inter-hemispheric interaction is vital. However, the relationship between neuroanatomical connections and intelligence in typically developing children, as well as sex differences in this relationship, remains unknown. METHODS: Participants were 253 typically developing children (121 boys and 132 girls) aged 5-18. We acquired diffusion tensor imaging data and intelligence using an age-appropriate version of the IQ test; Wechsler Intelligence Scale for Children (WISC) or Wechsler Adult Intelligence Scale (WAIS). We conducted whole-brain multiple regression analysis to investigate the association between fractional anisotropy (FA), which reflects white matter microstructural properties, and each composite score of IQ test (full-scale IQ, performance IQ, and verbal IQ). RESULTS: FA was positively correlated with full-scale IQ in bilateral inferior occipitofrontal fasciculus, genu, and splenium of corpus callosum (CC). FA in the right superior longitudinal fasciculus, bilateral inferior longitudinal fasciculus, and splenium of CC were also positively correlated with performance IQ. Furthermore, we found significant sex interaction between FA in the CC and verbal IQ. FA was positively correlated in boys, and negatively correlated in girls. CONCLUSION: Results suggest that efficient anatomical connectivity between parietal and frontal regions is crucial for children's intelligence. Moreover, inter-hemispheric connections play a critical role in verbal abilities in boys.

Shame proneness is associated with individual differences in temporal pole white matter structure.

Shame and guilt are distinct negative moral emotions, although they are usually regarded as overlapping affective experiences. Of these two emotions, shame is more closely related to concerns about other people's judgment, whereas guilt is more related to concerns about one's own judgment. Although some studies have tried to identify the psychological process underlying shame as opposed to guilt, there is no clear evidence of brain regions that are specifically relevant to the experience of shame rather than guilt and, more generally, self-blame. We therefore investigated associations between individual differences in shame- and guilt-proneness and the gray and white matter structures of the brain using magnetic resonance imaging and voxel-based morphometry while controlling for associations with guilt- or shame-proneness. To accomplish this goal, we enrolled 590 healthy, right-handed individuals (338 men and 252 women; age, 20.6 ± 1.8 years). We administered a questionnaire to assess shame proneness and guilt proneness. Based on our hypothesis, we found that high shame proneness was associated with decreased regional white matter density only in the right inferior temporal pole, whereas no significant region was associated with guilt. The function of this area may be important for the underlying processes differentiating shame from guilt.

The influence of NRXN1 on systemizing and the brain structure in healthy adults.

Certain behavioral characteristics of autism spectrum disorder can be found in otherwise healthy people. Individuals with difficulties in social adaptation may have subclinical autistic traits; however, effective biomarkers of these traits have not yet been established. There is a dire need for objective indices of these traits that combine behavior, brain images, and genetic information. In this study, we examined the association among a single nucleotide polymorphism of NRXN1 (rs858932; C/G), autistic traits, and brain structure in 311 healthy adults. We found that carriers of minor alleles (carriers of the G-allele) had significantly higher systemizing scores than major-allele (C-allele) homozygotes. Furthermore, the regional white matter volume in the right anterior limb of the internal capsule was significantly greater in carriers of the G-allele than in C-allele homozygotes. To the best of our knowledge, this is the first report of NRXN1 rs858932 being involved in systemizing and the brain structure of healthy adults. Our findings provide insight into the effects of genetics on autistic traits and their respective neural substrates.

Diet and Dementia: A Prospective Study.

Whether dietary and nutrition and dietary patterns are associated with the development of dementia is an interesting research question. Participants of a longitudinal cohort study that included European adults who were middle to old aged at baseline and who had not been diagnosed with dementia at baseline (2006-2010) and had not been diagnosed with dementia or died within 5 years after baseline were followed up (until 2018) and analyzed. Associations between intake frequency of each food class measured by the food-frequency questionnaire at baseline and incident dementia 5 years after baseline were analyzed after correcting for confounding variables. A total of approximately 340,000 participants and 900 cases were included in the analysis for each food class. Cox proportional hazard models with self-reported intake level of each food category divided into four mostly equally divided categorical variables revealed a high intake of bread, moderate total meat and total fish intake and low vegetable and fruit intake were thus associated with a small but significant decrease in the onset risk of dementia, while poultry and cereal were not. These findings are mostly inconsistent with the idea that Mediterranean diet is associated with lower risk of subsequent incident dementia.

Brain structures and activity during a working memory task associated with internet addiction tendency in young adults: A large sample study.

The structural and functional brain characteristics associated with the excessive use of the internet have attracted substantial research attention in the past decade. In current study, we used voxel-based morphometry (VBM) and multiple regression analysis to assess the relationship between internet addiction tendency (IAT) score and regional gray and white matter volumes (rGMVs and rWMVs) and brain activity during a WM task in a large sample of healthy young adults (n = 1,154, mean age, 20.71 ± 1.78 years). We found a significant positive correlation between IAT score and gray matter volume (GMV) of right supramarginal gyrus (rSMG) and significant negative correlations with white matter volume (WMV) of right temporal lobe (sub-gyral and superior temporal gyrus), right sublobar area (extra-nuclear and lentiform nucleus), right cerebellar anterior lobe, cerebellar tonsil, right frontal lobe (inferior frontal gyrus and sub-gyral areas), and the pons. Also, IAT was significantly and positively correlated with brain activity in the default-mode network (DMN), medial frontal gyrus, medial part of the superior frontal gyrus, and anterior cingulate cortex during a 2-back working memory (WM) task. Moreover, whole-brain analyses of rGMV showed significant effects of interaction between sex and the IAT scores in the area spreading around the left anterior insula and left lentiform. This interaction was moderated by positive correlation in women. These results indicate that IAT is associated with (a) increased GMV in rSMG, which is involved in phonological processing, (b) decreased WMV in areas of frontal, sublobar, and temporal lobes, which are involved in response inhibition, and (c) reduced task-induced deactivation of the DMN, indicative of altered attentional allocation.

Polygenic risk score for bipolar disorder associates with divergent thinking and brain structures in the prefrontal cortex.

It has been hypothesized that a higher genetic risk of bipolar disorder (BD) is associated with greater creativity. Given the clinical importance of bipolar disorder and the importance of creativity to human society and cultural development, it is essential to reveal their associations and the neural basis of the genetic risk of bipolar disorder to gain insight into its etiology. However, despite the previous demonstration of the associations of polygenic risk score (PRS) of BD and creative jobs, the associations of BD-PRS and creativity measured by the divergent thinking (CMDT) and regional gray matter volume (rGMV) as well as regional white matter volume (rWMV) have not been investigated. Using psychological analyses and whole-brain voxel-by-voxel analyses, we examined these potential associations in 1558 young, typically developing adult students. After adjusting for confounding variables and multiple comparisons, a greater BD-PRS was associated with a greater total CMDT fluency score, and a significant relationship was found in fluency subscores. A greater BD-PRS was also associated with lower total mood disturbance. Neuroimaging analyses revealed that the BD-PRS was associated with greater rGMV in the right inferior frontal gyrus, which is a consistently affected area in BD, as well as a greater rWMV in the left middle frontal gyrus, which has been suggested to play a central role in the increased creativity associated with the risk of BD with creativity. These findings suggest a relationship between the genetic risk of BD and CMDT and prefrontal cortical structures among young educated individuals.