Dataset Information

Brain white matter integrity and cortisol in older men: the Lothian Birth Cohort 1936.

ABSTRACT: Elevated glucocorticoid (GC) levels are hypothesized to be deleterious to some brain regions, including white matter (WM). Older age is accompanied by increased between-participant variation in GC levels, yet relationships between WM integrity and cortisol levels in older humans are underexplored. Moreover, it is unclear whether GC-WM associations might be general or pathway specific. We analyzed relationships between salivary cortisol (diurnal and reactive) and general measures of brain WM hyperintensity (WMH) volume, fractional anisotropy (gFA), and mean diffusivity (gMD) in 90 males, aged 73 years. Significant associations were predominantly found between cortisol measures and WMHs and gMD but not gFA. Higher cortisol at the start of a mild cognitive stressor was associated with higher WMH and gMD. Higher cortisol at the end was associated with greater WMHs. A constant or increasing cortisol level during cognitive testing was associated with lower gMD. Tract-specific bases of these associations implicated anterior thalamic radiation, uncinate, and arcuate and inferior longitudinal fasciculi. The cognitive sequelae of these relationships, above other covariates, are a priority for future study.

SUBMITTER: Cox SR

PROVIDER: S-EPMC4274312 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Brain white matter integrity and cortisol in older men: the Lothian Birth Cohort 1936.

Cox Simon R SR Bastin Mark E ME Ferguson Karen J KJ Maniega Susana Muñoz SM MacPherson Sarah E SE Deary Ian J IJ Wardlaw Joanna M JM MacLullich Alasdair M J AM

Neurobiology of aging 20140628 1

Elevated glucocorticoid (GC) levels are hypothesized to be deleterious to some brain regions, including white matter (WM). Older age is accompanied by increased between-participant variation in GC levels, yet relationships between WM integrity and cortisol levels in older humans are underexplored. Moreover, it is unclear whether GC-WM associations might be general or pathway specific. We analyzed relationships between salivary cortisol (diurnal and reactive) and general measures of brain WM hype ...[more]

PMID: 25066239

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Project description:Apolipoprotein E (APOE) ε genotype has previously been significantly associated with cognitive, brain imaging, and Alzheimer's disease-related phenotypes (e.g., age of onset). In the TOMM40 gene, the rs10524523 ("523") variable length poly-T repeat polymorphism has more recently been associated with similar ph/enotypes, although the allelic directions of these associations have varied between initial reports. Using diffusion magnetic resonance imaging tractography, the present study aimed to investigate whether there are independent effects of apolipoprotein E (APOE) and TOMM40 genotypes on human brain white matter integrity in a community-dwelling sample of older adults, the Lothian Birth Cohort 1936 (mean age = 72.70 years, standard deviation = 0.74, N approximately = 640-650; for most analyses). Some nominally significant effects were observed (i.e., covariate-adjusted differences between genotype groups at p < 0.05). For APOE, deleterious effects of ε4 "risk" allele presence (vs. absence) were found in the right ventral cingulum and left inferior longitudinal fasciculus. To test for biologically independent effects of the TOMM40 523 repeat, participants were stratified into APOE genotype subgroups, so that any significant effects could not be attributed to APOE variation. In participants with the APOE ε3/ε4 genotype, effects of TOMM40 523 status were found in the left uncinate fasciculus, left rostral cingulum, left ventral cingulum, and a general factor of white matter integrity. In all 4 of these tractography measures, carriers of the TOMM40 523 "short" allele showed lower white matter integrity when compared with carriers of the "long" and "very-long" alleles. Most of these effects survived correction for childhood intelligence test scores and vascular disease history, though only the effect of TOMM40 523 on the left ventral cingulum integrity survived correction for false discovery rate. The effects of APOE in this older population are more specific and restricted compared with those reported in previous studies, and the effects of TOMM40 on white matter integrity appear to be novel, although replication is required in large independent samples.

Project description:Structural measures of the hippocampus have been linked to a variety of memory processes and also to broader cognitive abilities. Gross volumetry has been widely used, yet the hippocampus has a complex formation, comprising distinct subfields which may be differentially sensitive to the deleterious effects of age, and to different aspects of cognitive performance. However, a comprehensive analysis of multidomain cognitive associations with hippocampal deformations among a large group of cognitively normal older adults is currently lacking. In 654 participants of the Lothian Birth Cohort 1936 (mean age = 72.5, SD = 0.71 years), we examined associations between the morphology of the hippocampus and a variety of memory tests (spatial span, letter-number sequencing, verbal recall, and digit backwards), as well as broader cognitive domains (latent measures of speed, fluid intelligence, and memory). Following correction for age, sex, and vascular risk factors, analysis of memory subtests revealed that only right hippocampal associations in relation to spatial memory survived type 1 error correction in subiculum and in CA1 at the head (β = 0.201, p = 5.843 × 10-4, outward), and in the ventral tail section of CA1 (β = -0.272, p = 1.347 × 10-5, inward). With respect to latent measures of cognitive domains, only deformations associated with processing speed survived type 1 error correction in bilateral subiculum (βabsolute ≤ 0.247, p < 1.369 × 10-4, outward), bilaterally in the ventral tail section of CA1 (βabsolute ≤ 0.242, p < 3.451 × 10-6, inward), and a cluster at the left anterior-to-dorsal region of the head (β = 0.199, p = 5.220 × 10-6, outward). Overall, our results indicate that a complex pattern of both inward and outward hippocampal deformations are associated with better processing speed and spatial memory in older age, suggesting that complex shape-based hippocampal analyses may provide valuable information beyond gross volumetry.

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Dataset Information

Brain white matter integrity and cortisol in older men: the Lothian Birth Cohort 1936.

Publications

Brain white matter integrity and cortisol in older men: the Lothian Birth Cohort 1936.

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