Cortical gyrification in relation to age and cognition in older adults

Gyrification of the cerebral cortex changes with aging and relates to development of cognitive function during early life and midlife. Little is known about how gyrification relates to age and cognitive function later in life. We investigated this in 4397 individuals (mean age: 63.5 years, range: 45.7 to 97.9) from the Rotterdam Study, a population-based cohort. Global and local gyrification were assessed from T1-weighted images. A measure for global cognition, the g-factor, was calculated from five cognitive tests. Older age was associated with lower gyrification (mean difference per year ​= ​−0.0021; 95% confidence interval ​= ​−0.0025; −0.0017). Non-linear terms did not improve the models. Age related to lower gyrification in the parietal, frontal, temporal and occipital regions, and higher gyrification in the medial prefrontal cortex. Higher levels of the g-factor were associated with higher global gyrification (mean difference per g-factor unit ​= ​0.0044; 95% confidence interval ​= ​0.0015; 0.0073). Age and the g-factor did not interact in relation to gyrification (p ​> ​0.05). The g-factor bilaterally associated with gyrification in three distinct clusters. The first cluster encompassed the superior temporal gyrus, the insular cortex and the postcentral gyrus, the second cluster the lingual gyrus and the precuneus, and the third cluster the orbitofrontal cortex. These clusters largely remained statistically significant after correction for cortical surface area. Overall, the results support the notion that gyrification varies with aging and cognition during and after midlife, and suggest that gyrification is a potential marker for age-related brain and co

Sleep and resting-state functional magnetic resonance imaging connectivity in middle-aged adults and the elderly: A population-based study

Sleep problems increase with ageing. Increasing evidence suggests that sleep problems are not only a consequence of age-related processes, but may independently contribute to developing vascular or neurodegenerative brain disease. Yet, it remains unclear what mechanisms underlie the impact sleep problems may have on brain health in the general middle-aged and elderly population. Here, we studied sleep's relation to brain functioning in 621 participants (median age 62 years, 55% women) from the population-based Rotterdam Study. We investigated cross-sectional associations of polysomnographic and subjectively measured aspects of sleep with intrinsic neural activity measured with resting-state functional magnetic resonance imaging on a different day. We investigated both functional connectivity between regions and brain activity (blood-oxygen-level-dependent signal amplitude) within regions, hierarchically towards smaller topographical levels. We found that longer polysomnographic total sleep time is associated with lower blood-oxygen-level-dependent signal amplitude in (pre)frontal regions. No objective or subjective sleep parameters were associated with functional connectivity between or within resting-state networks. The findings may indicate a pathway through which sleep, in a ‘real-life’ population setting, impacts brain activity or regional brain activity determines t

Genetic Burden for Late-Life Neurodegenerative Disease and Its Association With Early-Life Lipids, Brain, Behavior, and Cognition

Background: Genetics play a significant role in the etiology of late-life neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia. Part of the individual differences in risk for these diseases can be traced back decades before the onset of disease symptoms. Previous studies have shown evidence for plausible links of apolipoprotein E (APOE), the most important genetic marker for Alzheimer’s disease, with early-life cognition and neuroimaging markers. We aimed to assess whether genome-wide genetic burden for the aforementioned neurodegenerative diseases plays a role in early-life processes. Methods: We studied children from the Generation R Study, a prospective birth cohort. APOE genotypes and polygenic genetic burdens for Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia were obtained through genome-wide genotyping. Non-verbal intelligence was assessed through cognitive tests at the research center around the age of 6 years, and educational attainment through a national school performance test around the age of 11 years. The Child Behavior Checklist was administered around the age of 10 years, and data from the anxious/depressed, withdrawn/depressed, and the internalizing behavior problems scales were used. Children participated in a neuroimaging study when they were 10 years old, in which structural brain metrics were obtained. Lipid serum profiles, which may be influenced by APOE genotype, were assessed from venal blood obtained around the age of 6 years. The sample size per analysis varied between 1,641 and 3,650 children due to completeness of data. Results: We did not find evidence that APOE genotype or the polygenic scores impact on childhood nonverbal intelligence, educational attainment, internalizing behavior, and global brain structural measures including total brain volume and whole brain fractional anisotropy (all p > 0.05). Carriership of the APOE ε2 allele was associated with lower and APOE ε4 with higher low-density lipoprotein cholesterol concentrations when compared to APOE ε3/ε3 carriers. Conclusion: We found no evidence that genetic burden for late-life neurodegenerative diseases associates with early-life cognition, internalizing behavior, or global brain structure

A prospective population-based study of gestational vitamin D status and brain morphology in preadolescents

Low vitamin D level during pregnancy has been associated with adverse neurodevelopmental outcomes such as autism spectrum disorders (ASD) in children. However, the underlying neurobiological mechanism remains largely unknown. This study investigated the association between gestational 25-hydroxyvitamin D [25(OH)D] concentration and brain morphology in 2597 children at the age of 10 years in the population-based Generation R Study. We studied both 25(OH)D in maternal venous blood in mid-gestation and in umbilical cord blood at delivery, in relation to brain volumetric measures and surface-based cortical metrics including cortical thickness, surface area, and gyrification using linear regression. We found exposure to higher maternal 25(OH)D concentrations in mid-gestation was associated with a larger cerebellar volume in children (b ​= ​0.02, 95%CI 0.001 to 0.04), however this association did not remain after co

Neonatal critical illness and development: white matter and hippocampus alterations in school-age neonatal ECMO survivors

Aim: Examine the neurobiology of long-term neuropsychological deficits following neonatal extracorporeal membrane oxygenation (ECMO). Method: This cross-sectional study assessed white matter integrity and hippocampal volume of ECMO survivors (8-15yrs) and healthy controls (8-17yrs) using Diffusion Tensor Imaging and structural MRI, respectively. Neuropsychological outcome was evaluated in patients. Included clinical predictors of white matter integrity: age start ECMO, ECMO duration, highest oxygenation index before ECMO, highest mean airway pressure and mechanical ventilation duration. Results: Patients (n=23) had lower global fractional anisotropy than controls (n=54)(patients=.368; controls=.381; p=.02), but similar global mean diffusivity (p=.41). Patients had lower fractional anisotropy in the left cingulum bundle (patients=.345; controls=.399; p<.001) and higher mean diffusivity in a region of the left parahippocampal cingulum (patients=.916; controls=.871; p<.001). Higher global mean diffusivity predicted worse verbal memory in patients (n=17)(β=-.74, p=.01). Patients (n=23) had smaller bilateral hippocampal volume than controls (n=43)(left: p< .001; right: p< .001). In patients, this was related to worse verbal memory (left: β=.65, p=.02; right: β=.71, p=.01). Interpretation: Neonatal ECMO survivors are at risk for long-term brain alterations, which may partly explain long-term neuropsychological impairments. Neuroimaging may contribute to better risk stratification of long-term impairments

Autistic traits and neuropsychological performance in 6- to-10-year-old children: a population-based study

Clinical studies of children with autism spectrum disorder (ASD) provide evidence for poorer neuropsychological performance within specific domains compared to age, gender, and sometimes IQ-matched controls. Since recent evidence suggests that autistic symptoms form a spectrum that extends into the general population, it was our goal to evaluate the nature of the relationship between autistic traits and neuropsychological performance across the continuum in the general population. We examined neuropsychological performance across five different domains in 1019 6-to-10-year-old children participating in a population-based study of child development. Autistic traits were assessed when the children were 6 years of age using the Social Responsiveness Scale and ASD diagnoses were obtained via medical records. Neuropsychological functioning was measured using the NEPSY-II-NL and included the domains of attention and executive function, memory and learning, sensorimotor functioning, language, and visuospatial functioning. We found that children with higher autistic traits showed significantly lower neuropsychological performance in all domains investigated and that this association remained even after excluding children with the highest autistic traits or confirmed ASD. When comparing 41 children with confirmed ASD diagnosis to typically developing controls, children with ASD showed significantly lower neuropsychological performance across all domains. Taken together, our results suggest that children with both ASD and subclinical autistic traits have lower neuropsychological performance. Thus, this may provide an understanding of why some children without an ASD diagnosis may require some additional assistance within academic settings

Cognitive functioning in children with internalising, externalising and dysregulation problems: a population-based study

Psychiatric symptoms in childhood are closely related to neurocognitive deficits. However, it is unclear whether

White matter microstructure correlates of age, sex, handedness and motor ability in a population-based sample of 3031 school-age children

Understanding the development of white matter microstructure in the general population is an imperative precursor to identifying its involvement in psychopathology. Previous studies have reported changes in white matter microstructure associated with age and different developmental patterns between boys and girls. Handedness has also been related to white matter in adults. Motor performance, tightly dependent on overall neuronal myelination, has been related to the corpus callosum. However, the association between motor performance and global white matter microstructure has not been reported in the literature. In general, these age, sex, handedness, and motor performance associations have been observed using small and poorly representative samples. We examined the rela

Polygenic Multiple Sclerosis Risk and Population-Based Childhood Brain Imaging

Objective: Multiple sclerosis (MS) is a neurological disease with a substantial genetic component and immune-mediated neurodegeneration. Patients with MS show structural brain differences relative to individuals without MS, including smaller regional volumes and alterations in white matter (WM) microstructure. Whether genetic risk for MS is associated with brain structure during early neurodevelopment remains unclear. In this study, we explore the association between MS polygenic risk scores (PRS) and brain imaging outcomes from a large, population-based pediatric sample to gain insight into the underlying neurobiology of MS. Methods: We included 8- to 12-year-old genotyped participants from the Generation R Study in whom T1-weighted volumetric (n = 1,136) and/or diffusion tensor imaging (n = 1,088) had been collected. PRS for MS were calculated based on a large genome-wide association study of MS (n = 41,505) and were regressed on regional volumes, global and tract-specific fractional anisotropy (FA), and global mean diffusivity using linear regression. Results: No associations were observed for the regional volumes. We observed a positive association between the MS PRS and global FA (β = 0.098, standard error [SE] = 0.030, p = 1.08 × 10−3). Tract-specific analyses showed higher FA and lower radial diffusivity in several tracts. We replicated our findings in an independent sample of children (n = 186) who were scanned in an earlier phase (global FA; β = 0.189, SE = 0.072, p = 9.40 × 10−3). Interpretation: This is the first study to show that greater genetic predisposition for MS is associated with higher global brain WM FA at an early age in the general population. Our results suggest a preadolescent time window within neurodevelopment in which MS risk variants act upon the brain. ANN NEUROL 2020

Neural Profile of Callous Traits in Children: A Population-Based Neuroimaging Study

Background Callous traits during childhood, e.g., lack of remorse and shallow affect, are a key risk marker for antisocial behavior. Although callous traits have been found to be associated with structural and functional brain alterations, evidence to date has been almost exclusively limited to small, high-risk samples of boys. We characterized gray and white matter brain correlates of callous traits in over 2000 children from the general population. Methods Data on mother-re