Cognitive ability across the life course and cortisol levels in older age

Elevated cortisol levels have been hypothesised to contribute to cognitive ageing, but study findings are inconsistent. In the present study, we examined the association between salivary cortisol in older age and cognitive ability across the life course. We used data from 370 members of the 36-Day Sample of the Scottish Mental Survey 1947, who underwent cognitive testing at age 11, and were then followed up at around age 78, completing further cognitive tests and providing diurnal salivary cortisol samples. We hypothesised that higher cortisol levels would be associated with lower cognitive ability in older age and greater cognitive decline from childhood to older age, but also lower childhood cognitive ability. Few of the tested associations were significant, and of those that were, most suggested a positive relationship between cortisol and cognitive ability. Only one cognitive measure showed any sign of cortisol-related impairment. However, after correcting for multiple comparisons, no results remained significant. These findings suggest that cortisol may not play an important role in cognitive ageing across the life course

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

AbstractElevated 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

Correlational structure of ‘frontal’ tests and intelligence tests indicates two components with asymmetrical neurostructural correlates in old age

AbstractBoth general fluid intelligence (gf) and performance on some ‘frontal tests’ of cognition decline with age. Both types of ability are at least partially dependent on the integrity of the frontal lobes, which also deteriorate with age. Overlap between these two methods of assessing complex cognition in older age remains unclear. Such overlap could be investigated using inter-test correlations alone, as in previous studies, but this would be enhanced by ascertaining whether frontal test performance and gf share neurobiological variance. To this end, we examined relationships between gf and 6 frontal tests (Tower, Self-Ordered Pointing, Simon, Moral Dilemmas, Reversal Learning and Faux Pas tests) in 90 healthy males, aged ~73years. We interpreted their correlational structure using principal component analysis, and in relation to MRI-derived regional frontal lobe volumes (relative to maximal healthy brain size). gf correlated significantly and positively (.24≤r≤.53) with the majority of frontal test scores. Some frontal test scores also exhibited shared variance after controlling for gf. Principal component analysis of test scores identified units of gf-common and gf-independent variance. The former was associated with variance in the left dorsolateral (DL) and anterior cingulate (AC) regions, and the latter with variance in the right DL and AC regions. Thus, we identify two biologically-meaningful components of variance in complex cognitive performance in older age and suggest that age-related changes to DL and AC have the greatest cognitive impact

Maternal separation alters nerve growth factor and corticosterone levels but not the DNA methylation status of the exon 17 glucocorticoid receptor promoter region

Separating rat pups from their mothers during the early stages of life is an animal model commonly used to study the development of psychiatric disorders such as anxiety and depression. The present study investigated how soon after the termination of the maternal separation period behavioural and neuroendocrine abnormalities relevant to above-mentioned illnesses would manifest. Sprague Dawley rat pups were subjected to maternal separation (3 h per day from postnatal day 2 through 14) and their behaviour and HPA axis activity determined 7 d later. We also measured nerve growth factor levels in their hippocampi and assessed the DNA methylation status of the promoter region of exon 17 of the glucocorticoid receptor in this brain region. As early as 7 d after the termination of the adverse event, a change in behaviour was observed that was associated with increased plasma corticosterone release and elevated nerve growth factor levels in the hippocampus. No alteration in the methylation status of the exon 17 glucocorticoid receptor promoter region was observed. Our data indicate that early life adversity may lead to the rapid development of abnormal behaviours and HPA axis dysregulation though no epigenetic changes to the exon 17 glucocorticoid receptor promoter region occurred. We further propose that the observed increased neurotrophin levels reflect compensatory mechanisms that attempt to combat the long-term deleterious effects of maternal separation. © 2009 Springer Science+Business Media, LLC.Articl