45 research outputs found
Applying the genetically based cortical parcellations to independent data.
No full textA) The phenotypic correlation matrix of VETSA twin cohort versus the phenotypic correlation matrix of combined-5-cohort (C5C). The Mantel test confirmed that the similarity between them was highly significant (p = 0.0001). B) Cortical brain phenotypes—surface area measures of 12 cortical regions after controlling for total surface area. The cortex was parceled into 12 genetically based regions of maximal shared genetic influence derived from the VETSA sample [16]. 1. motor & premotor; 2. dorsolateral prefrontal; 3. dorsomedial frontal; 4. orbitofrontal; 5. pars opercularis & subcentral; 6. superior temporal; 7. posterolateral temporal; 8. anteromedial temporal; 9. inferior parietal; 10. superior parietal; 11. precuneus; 12. occipital. C) The phenotypic correlation versus the genetic correlations (rg) matrices of VETSA. The correlation of the two matrices was also highly significant (p S1 Table and S2 Table.</p
Genetics of brain structure: Contributions from the vietnam era twin study of aging
No full textUnderstanding the genetics of neuropsychiatric disorders requires an understanding of the genetics of brain structure and function. The Vietnam Era Twin Study of Aging (VETSA) is a longitudinal behavioral genetic study focused on cognitive and brain aging. Here, we describe basic science work carried out within the VETSA MRI study that provides meaningful contributions toward the study of neuropsychiatric disorders. VETSA produced the first comprehensive assessment of the heritability of cortical and subcortical brain structure sizes, all within the same individuals. We showed that neocortical thickness and surface area are largely genetically distinct. With continuous neocortical thickness maps, we demonstrated regional specificity of genetic influences, and that genetic factors did not conform to traditional regions of interest (ROIs). However, there was some evidence for different genetic factors accounting for different types of cortex, and for genetic relationships across cortical regions corresponding to anatomical and functional connectivity and brain maturation patterns. With continuous neocortical surface area maps, we confirmed the anterior-posterior gradient of genetic influences on cortical area patterning demonstrated in animal models. Finally, we used twin methods to create the first map of cortical ROIs based entirely on genetically informative data. We conclude that these genetically based cortical phenotypes may be more appropriate for genetic studies than traditional ROIs based on structure or function. Our results also suggest that cortical volume-the product of thickness and surface area-is a problematic phenotype for genetic studies because two independent sets of genes may be obscured. Examples supporting the validity of these conclusions are provided
Paradoxical cognitive trajectories in men from earlier to later adulthood
No full textBecause longitudinal studies of aging typically lack cognitive data from earlier ages, it is unclear how general cognitive ability (GCA) changes throughout the life course. In 1,173 Vietnam Era Twin Study of Aging (VETSA) participants, we assessed young adult GCA at average age 20 and current GCA at three VETSA assessments beginning at average age 56. The same GCA index was used throughout. Higher young adult GCA and better GCA maintenance were associated with stronger specific cognitive abilities from age 51-73. Given equivalent GCA at age 56, individuals who had higher age 20 GCA outperformed those whose GCA remained stable in terms of memory, executive function, and working memory abilities from age 51-73. Thus, paradoxically, despite poorer maintenance of GCA, high young adult GCA still conferred benefits. Advanced predicted brain age and the combination of elevated vascular burden and APOE-ε4 status were associated with poorer maintenance of GCA. These findings highlight the importance of distinguishing between peak and current GCA for greater understanding of cognitive aging
The Association between Exposure to Fine Particulate Matter and MRI-Assessed Locus Coeruleus Integrity in the Vietnam Era Twin Study of Aging (VETSA)
No full text
Background:
Increased exposure to ambient air pollution, especially fine particulate matter ≤2.5μm (PM2.5) is associated with poorer brain health and increased risk for Alzheimer’s disease (AD) and related dementias. The locus coeruleus (LC), located in the brainstem, is one of the earliest regions affected by tau pathology seen in AD. Its diffuse projections throughout the brain include afferents to olfactory areas that are hypothesized conduits of cerebral particle deposition. Additionally, extensive contact of the LC with the cerebrovascular system may present an additional route of exposure to environmental toxicants.
Objective:
Our aim was to investigate if exposure to PM2.5 was associated with LC integrity in a nationwide sample of men in early old age, potentially representing one pathway through which air pollution can contribute to increased risk for AD dementia.
Methods:
We examined the relationship between PM2.5 and in vivo magnetic resonance imaging (MRI) estimates of LC structural integrity indexed by contrast to noise ratio (LCCNR) in 381 men [mean age=67.3; standard deviation (SD)=2.6] from the Vietnam Era Twin Study of Aging (VETSA). Exposure to PM2.5 was taken as a 3-year average over the most recent period for which data were available (average of 5.6 years prior to the MRI scan). We focused on LCCNR in the rostral-middle portion of LC due to its stronger associations with aging and AD than the caudal LC. Associations between PM2.5 exposures and LC integrity were tested using linear mixed effects models adjusted for age, scanner, education, household income, and interval between exposure and MRI. A co-twin control analysis was also performed to investigate whether associations remained after controlling for genetic confounding and rearing environment.
Results:
Multiple linear regressions revealed a significant association between PM2.5 and rostral-middle LCCNR (β=−0.16; =0.02), whereby higher exposure to PM2.5 was associated with lower LCCNR. A co-twin control analysis found that, within monozygotic pairs, individuals with higher PM2.5 exposure showed lower LCCNR (β=−0.11; =0.02), indicating associations were not driven by genetic or shared environmental confounds. There were no associations between PM2.5 and caudal LCCNR or hippocampal volume, suggesting a degree of specificity to the rostral-middle portion of the LC.
Discussion:
Given previous findings that loss of LC integrity is associated with increased accumulation of AD-related amyloid and tau pathology, impacts on LC integrity may represent a potential pathway through which exposure to air pollution increases AD risk. https://doi.org/10.1289/EHP14344
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Lifestyle and the Aging Brain: Interactive Effects of Modifiable Lifestyle Behaviors and Cognitive Ability in Men From Midlife to Old Age
No full textWe examined the influence of lifestyle on brain aging after nearly 30 years, and tested the hypothesis that young adult general cognitive ability (GCA) would moderate these effects. In the community-dwelling Vietnam Era Twin Study of Aging (VETSA), 431 largely non-Hispanic white men completed a test of GCA at mean age 20. We created a modifiable lifestyle behavior composite from data collected at mean age 40. During VETSA, MRI-based measures at mean age 68 included predicted brain age difference (PBAD), Alzheimer’s disease (AD) brain signature, and abnormal white matter scores. There were significant main effects of young adult GCA and lifestyle on PBAD and the AD signature (ps≤.012), and a GCA-by-lifestyle interaction on both (ps≤.006). Regardless of GCA level, having more favorable lifestyle behaviors predicted less advanced brain age and less AD-like brain aging. Unfavorable lifestyles predicted advanced brain aging in those with lower age 20 GCA, but did not affect brain aging in those with higher age 20 GCA. Targeting early lifestyle modification may promote dementia risk reduction, especially among lower reserve individuals
Vulnerability to memory decline in aging revealed by a mega-analysis of structural brain change
No full textA convergent pattern of genetically mediated relationships among cortical surface areas.
No full textA) Genetic correlations (rg) of VETSA derived by an AE twin model. B) Genetic correlations (rg) of C5C derived by genotype-based GCTA-bivariate model. C) Gene expression or transcriptomic similarities of Allen Human Brain Atlas cohort based on Jaccard coefficient that are scaled to [-1,+1] such that they can be displayed on the same color scale with the correlation coefficients. Subsequent analyses were performed on the original similarity coefficients shown in S4 Table. D) Hierarchical clustering of the genetic correlations between cortical regions averaged over standardized twin rg (A), genotype rg (B), and gene expression similarity (C).</p
Significant associations among correlation matrices.
No full textCorrelation matrices among cortical surface areas derived from a variety of measures are highly consistent with each other as quantified by the Mantel test coefficients with 95% confidence intervals. Each pair of bars represents two correlation methods used in the Mantel test: linear regression with errors-in-both-variables (correlation with EIV) in gray color on the left versus Pearson’s correlation in light-gray color on the right. Variables were standardized in regression analysis. *p≤0.05, **p≤0.01, ***p≤0.001, ****p≤0.0001. Twin refers to VETSA cohort, and twin-based method was used to derive genetic correlations. Genotype-based method was used to derive genetic correlations for ombined-5-cohort. The corresponding matrices are visualized in Figs 1 and 2. See also S1 Fig and S2 Table, S3 Table, and S4 Table.</p
Early identification and heritability of mild cognitive impairment
No full textBackgound Identifying mild cognitive impairment (MCI) in midlife could improve early identification of Alzheimer’s disease (AD). Also, AD is highly heritable, but the heritability of MCI has not been estab-lished. We estimated prevalence rates, association with premorbid general cognitive ability (GCA) and heritability for different defin-itions of neuropsychologically defined MCI in adults in their 50s. Method We examined 1126 twins aged 51–59 years when recruited into the Vietnam Era Twin Study of Aging (VETSA). Six neurocognitive domains were assessed using tests designed to avoid ceiling effects. To differentiate MCI from low overall ability, criteria included adjustment for GCA measured at approximately age 20 years. Results As in older adults, prevalence rates varied widely. Among the lower prevalence rates were some definitions of multiple-domain MCI and single-domain amnestic MCI, which may be less likely than other MCI categories to revert to normal on follow-up. Low prevalenc
