Hippocampal volume varies with educational attainment across the life-span

Socioeconomic disparities—and particularly differences in educational attainment—are associated with remarkable differences in cognition and behavior across the life-span. Decreased educational attainment has been linked to increased exposure to life stressors, which in turn have been associated with structural differences in the hippocampus and the amygdala. However, the degree to which educational attainment is directly associated with anatomical differences in these structures remains unclear. Recent studies in children have found socioeconomic differences in regional brain volume in the hippocampus and amygdala across childhood and adolescence. Here we expand on this work, by investigating whether disparities in hippocampal and amygdala volume persist across the life-span. In a sample of 275 individuals from the BRAINnet Foundation database ranging in age from 17 to 87, we found that socioeconomic status (SES), as operationalized by years of educational attainment, moderates the effect of age on hippocampal volume. Specifically, hippocampal volume tended to markedly decrease with age among less educated individuals, whereas age-related reductions in hippocampal volume were less pronounced among more highly educated individuals. No such effects were found for amygdala volume. Possible mechanisms by which education may buffer age-related effects on hippocampal volume are discussed

Is Residual Memory Variance a Valid Method for Quantifying Cognitive Reserve? A Longitudinal Application

Cognitive reserve describes the mismatch between brain integrity and cognitive performance. Older adults with high cognitive reserve are more resilient to age-related brain pathology. Traditionally, cognitive reserve is indexed indirectly via static proxy variables (e.g., years of education). More recently, cross-sectional studies have suggested that reserve can be expressed as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). The present study extends these methods to a longitudinal framework in a community-based cohort of 244 older adults who underwent two comprehensive neuropsychological and structural magnetic resonance imaging sessions over 4.6 years. On average, residual memory variance decreased over time, consistent with the idea that cognitive reserve is depleted over time. Individual differences in change in residual memory variance predicted incident dementia, independent of baseline residual memory variance. Multiple-group latent difference score models revealed tighter coupling between brain and language changes among individuals with decreasing residual memory variance. These results suggest that changes in residual memory variance may capture a dynamic aspect of cognitive reserve and could be a useful way to summarize individual cognitive responses to brain changes. Change in residual memory variance among initially non-demented older adults was a better predictor of incident dementia than residual memory variance measured at one time-point

Higher BMI is associated with reduced brain volume in heart failure

Abstract Background Heart failure (HF) patients are at risk for structural brain changes due to cerebral hypoperfusion. Past work shows obesity is linked with reduced cerebral blood flow and associated with brain atrophy in healthy individuals, although its effects on the brain in HF are unclear. This study examined the association among body mass index (BMI), cerebral perfusion, and brain volume in HF patients. Results Eighty HF patients underwent transcranial Doppler sonography to quantify cerebral blood flow velocity of the middle cerebral artery (CBF-V of the MCA) and brain magnetic resonance imaging (MRI) to quantify total brain, total and subcortical gray matter, white matter volume, and white matter hyperintensities. Body mass index (BMI) operationalized weight status. Nearly 45% of HF patients exhibited a BMI consistent with obesity. Regression analyses adjusting for medical variables, demographic characteristics, and CBF-V of the MCA, showed increased BMI was associated with reduced white matter volume (p \u3c .05). BMI also interacted with cerebral perfusion to impact total gray matter volume, but this pattern did not emerge for any other MRI indices (p \u3c 0.05). Conclusions Our findings suggest increased BMI negatively affects brain volume in HF, and higher BMI interacts with cerebral perfusion to impact gray matter volume. The mechanisms for these findings remain unclear and likely involve multiple physiological processes. Prospective studies are needed to elucidate the exact pattern and rates of brain changes in obese HF persons

Soluble amyloid beta levels are elevated in the white matter of Alzheimer’s patients, independent of cortical plaque severity

Alzheimer’s disease (AD) is the most common neurodegenerative disease and the leading cause of dementia. In addition to grey matter pathology, white matter changes are now recognized as an important pathological feature in the emergence of the disease. Despite growing recognition of the importance of white matter abnormalities in the pathogenesis of AD, the causes of white matter degeneration are still unknown. While multiple studies propose Wallerian-like degeneration as the source of white matter change, others suggest that primary white matter pathology may be due, at least in part, to other mechanisms, including local effects of toxic Aβ peptides. In the current study, we investigated levels of soluble amyloid-beta (Aβ) in white matter of AD patients (n=12) compared with controls (n=10). Fresh frozen white matter samples were obtained from anterior (Brodmann area 9) and posterior (Brodmann area 1, 2 and 3) areas of post-mortem AD and control brains. ELISA was used to examine levels of soluble Aβ -42 and Aβ -40. Total cortical neuritic plaque severity rating was derived from individual ratings in the following areas of cortex: mid-frontal, superior temporal, pre-central, inferior parietal, hippocampus (CA1), subiculum, entorhinal cortex, transentorhinal cortex, inferior temporal, amygdala and basal forebrain. Compared with controls, AD samples had higher white matter levels of both soluble Aβ -42 and Aβ -40. While no regional white matter differences were found in Aβ -40, Aβ -42 levels were higher in anterior regions than in posterior regions across both groups. After statistically controlling for total cortical neuritic plaque severity, differences in both soluble Aβ -42 and Aβ -40 between the groups remained, suggesting that white matter Aβ peptides accumulate independent of overall grey matter fibrillar amyloid pathology and are not simply a reflection of overall amyloid burden. These results shed light on one potential mechanism through which white matter degeneration may occur in AD. Given that white matter degeneration may be an early marker of disease, preceding grey matter atrophy, understanding the mechanisms and risk factors that may lead to white matter loss could help to identify those at high risk and to intervene earlier in the pathogenic process

The Plant Pathogen Phytophthora andina Emerged via Hybridization of an Unknown Phytophthora Species and the Irish Potato Famine Pathogen, P. infestans

Emerging plant pathogens have largely been a consequence of the movement of pathogens to new geographic regions. Another documented mechanism for the emergence of plant pathogens is hybridization between individuals of different species or subspecies, which may allow rapid evolution and adaptation to new hosts or environments. Hybrid plant pathogens have traditionally been difficult to detect or confirm, but the increasing ease of cloning and sequencing PCR products now makes the identification of species that consistently have genes or alleles with phylogenetically divergent origins relatively straightforward. We investigated the genetic origin of Phytophthora andina, an increasingly common pathogen of Andean crops Solanum betaceum, S. muricatum, S. quitoense, and several wild Solanum spp. It has been hypothesized that P. andina is a hybrid between the potato late blight pathogen P. infestans and another Phytophthora species. We tested this hypothesis by cloning four nuclear loci to obtain haplotypes and using these loci to infer the phylogenetic relationships of P. andina to P. infestans and other related species. Sequencing of cloned PCR products in every case revealed two distinct haplotypes for each locus in P. andina, such that each isolate had one allele derived from a P. infestans parent and a second divergent allele derived from an unknown species that is closely related but distinct from P. infestans, P. mirabilis, and P. ipomoeae. To the best of our knowledge, the unknown parent has not yet been collected. We also observed sequence polymorphism among P. andina isolates at three of the four loci, many of which segregate between previously described P. andina clonal lineages. These results provide strong support that P. andina emerged via hybridization between P. infestans and another unknown Phytophthora species also belonging to Phytophthora clade 1c

CIViCdb 2022: evolution of an open-access cancer variant interpretation knowledgebase

CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC’s functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination of structured curated data. To support the full breadth of variant interpretation from basic to translational, including integration of somatic and germline variant knowledge and inference of drug response, we have enabled curation of three new Evidence Types (Predisposing, Oncogenic and Functional). The growing CIViC knowledgebase has over 300 contributors and distributes clinically-relevant cancer variant data currently representing >3200 variants in >470 genes from >3100 publications

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Structural MRI Predictors of Late-Life Cognition Differ Across African Americans, Hispanics, and Whites.

BackgroundStructural magnetic resonance imaging (MRI) provides key biomarkers to predict onset and track progression of Alzheimer's disease (AD). However, most published reports of relationships between MRI variables and cognition in older adults include racially, ethnically, and socioeconomically homogenous samples. Racial/ethnic differences in MRI variables and cognitive performance, as well as health, socioeconomic status and psychological factors, raise the possibility that brain-behavior relationships may be stronger or weaker in different groups. The current study tested whether MRI predictors of cognition differ in African Americans and Hispanics, compared with non-Hispanic Whites.MethodsParticipants were 638 non-demented older adults (29% non-Hispanic White, 36% African American, 35% Hispanic) in the Washington Heights-Inwood Columbia Aging Project. Composite scores of memory, language, speed/executive functioning, and visuospatial function were derived from a neuropsychological battery. Hippocampal volume, regional cortical thickness, infarcts, and white matter hyperintensity (WMH) volumes were quantified with FreeSurfer and in-house developed procedures. Multiple-group regression analysis, in which each cognitive composite score was regressed onto MRI variables, demographics, and cardiovascular health, tested which paths differed across groups.ResultsLarger WMH volume was associated with worse language and speed/executive functioning among African Americans, but not among non-Hispanic Whites. Larger hippocampal volume was more strongly associated with better memory among non-Hispanic Whites compared with Hispanics. Cortical thickness and infarcts were similarly associated with cognition across groups.ConclusionThe main finding of this study was that certain MRI predictors of cognition differed across racial/ethnic groups. These results highlight the critical need for more diverse samples in the study of cognitive aging, as the type and relation of neurobiological substrates of cognitive functioning may be different for different groups

Reconsidering harbingers of dementia: progression of parietal lobe white matter hyperintensities predicts Alzheimer's disease incidence

Accumulating evidence implicates small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH) on T2-weighted MRI, in the pathogenesis and diagnosis of Alzheimer's disease (AD). Cross-sectional volumetric measures of WMH, particularly in the parietal lobes, are associated with increased risk of AD. In the current study, we sought to determine whether the longitudinal regional progression of WMH predicts incident AD above-and-beyond traditional radiological markers of neurodegeneration (i.e., hippocampal atrophy, cortical thickness). Three hundred three non-demented older adults (mean age = 79.24±5.29) received high-resolution MRI at baseline and then again 4.6 years (SD=1.01) later. Over the follow-up interval 26 participants progressed to AD. Using structural equation modeling (SEM), we calculated latent difference scores of parietal/non-parietal WMH, hippocampus volumes, and cortical thickness values in ADrelated regions. Within the SEM framework, we determined whether baseline or change scores or both predicted AD conversion, while controlling for several time-invariant relevant variables. Smaller baseline hippocampus volume, change in hippocampus volume (i.e., atrophy), higher baseline parietal lobe WMH, and increasing parietal lobe WMH volume but not WMH in other regions or measures of cortical thickness, independently predicted progression to AD. The findings provide strong evidence that regionally accumulating WMH, in addition to degenerative changes in the medial temporal lobe, predict AD onset in addition to hallmark neurodegenerative changes typically associated with AD

Hippocampal volume varies with educational attainment across the life-span

Socioeconomic disparities – and particularly differences in educational attainment – are associated with remarkable differences in cognition and behavior across the life-span. Decreased educational attainment has been linked to increased exposure to life stressors, which in turn have been associated with structural differences in the hippocampus and the amygdala. However, the degree to which educational attainment is directly associated with anatomical differences in these structures remains unclear. Recent studies in children have found socioeconomic differences in regional brain volume in the hippocampus and amygdala across childhood and adolescence. Here we expand on this work, by investigating whether disparities in hippocampal and amygdala volume persist across the life-span. In a sample of 275 individuals from the BRAINnet Foundation database ranging in age from 17 to 87, we found that socioeconomic status, as operationalized by years of educational attainment, moderates the effect of age on hippocampal volume. Specifically, hippocampal volume tended to markedly decrease with age among less educated individuals, whereas age-related reductions in hippocampal volume were less pronounced among more highly educated individuals. No such effects were found for amygdala volume. Possible mechanisms by which education may buffer age-related effects on hippocampal volume are discussed