Plasma cortisol levels, brain volumes and cognition in healthy elderly men.
OBJECTIVE
In ageing animals, exposure to chronic high levels of glucocorticoids is associated with cognitive impairment and hippocampal atrophy. However, there are few studies examining relationships among glucocorticoids, brain volumes and cognitive function in healthy older humans. This study examined the hypotheses that higher plasma cortisol levels and altered sensitivity to glucocorticoids are associated with worse cognition and more brain atrophy in elderly men.


METHODS
Ninety-seven healthy men aged 65-70 had plasma cortisol measured at 09:00, 14:30 h, and post-dexamethasone (0.25mg, 09:00 h), and had dermal sensitivity to glucocorticoids measured. They also underwent cognitive testing, with scores adjusted for estimated prior mental ability, and had MRI measurements of intracranial area (a validated estimate of intracranial capacity), and hippocampus, temporal lobe and frontal lobe volumes.


RESULTS
Plasma cortisol levels at 09:00 h were significantly and negatively correlated with a summary General Cognitive Factor accounting for 51% of the variance of cognitive function (rho=-0.22, p=0.035), and specific cognitive tests: delayed paragraph recall (rho=-0.28, p=0.036) and processing speed (rho=-0.23, p=0.026). Regional brain volumes adjusted for intracranial area generally did not correlate with cortisol levels. Tissue glucocorticoid sensitivity did not correlate with any measure of cognition or brain volume.


CONCLUSIONS
In healthy older men, higher plasma cortisol levels are associated with worse ageing-related overall cognitive change but not ageing-related brain atrophy.
MacLullich
Alasdair M J
AM
Geriatric Medicine, University of Edinburgh, Room SU220, The Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
Deary
Ian J
IJ
Starr
John M
JM
Ferguson
Karen J
KJ
Wardlaw
Joanna M
JM
Seckl
Jonathan R
JR
D000368:Aged; D001284:Atrophy; D001921:Brain / Q000033:anatomy & histology*; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D005938:Glucocorticoids / Q000378:metabolism; D006624:Hippocampus / Q000033:anatomy & histology / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D011965:Receptors, Glucocorticoid / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D012867:Skin / Q000098:blood supply; D014661:Vasoconstriction / Q000502:physiology
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone