Salivary cortisol, brain volumes, and cognition in community-dwelling elderly without dementia.
OBJECTIVE
We investigated the associations of morning and evening salivary cortisol levels with regional brain volumes and cognitive functioning in community-dwelling older persons without dementia.


METHODS
From the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,244 persons without dementia (age 76 ± 5 years, 58% women) who had 1.5T brain MRI, assessment of cognitive functioning, and saliva collected at home 45 minutes after awakening and at night. Linear regression analysis was used to estimate the cross-sectional relationship among cortisol levels, brain volumes, and cognitive functioning, adjusting for covariates.


RESULTS
Higher evening cortisol was associated with smaller total brain volume (highest vs lowest tertile -16.0 mL; 95% confidence interval -19.7 to -12.2 mL, adjusted for age, sex, education, intracranial volume, smoking, steroid use, white matter lesions, and brain infarcts on MRI). The smaller volumes were observed in all brain regions, but were significantly smaller in gray matter than in white matter regions. Poorer cognitive functioning across all domains was also associated with higher evening cortisol. Higher levels of morning cortisol were associated with slightly greater normal white matter volume and better processing speed and executive functioning, but not with gray matter volume or with memory performance.


CONCLUSIONS
In older persons, evening and morning cortisol levels may be differentially associated with tissue volume in gray and white matter structures and cognitive function. Understanding these differential associations may aid in developing strategies to reduce the effects of hypothalamic-pituitary-adrenal axis dysfunction on late-life cognitive impairment.
From the Laboratory of Epidemiology and Population Sciences (M.I.G., M.E.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Julius Center for Health Sciences and Primary Care (M.I.G.), University Medical Center Utrecht, the Netherlands; Icelandic Heart Association (S.S., G.E., V.G.), Kopavogur, Iceland; and the University of Iceland (V.G.), Reykjavik.
Mirjam I
MI
Geerlings
From the Laboratory of Epidemiology and Population Sciences (M.I.G., M.E.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Julius Center for Health Sciences and Primary Care (M.I.G.), University Medical Center Utrecht, the Netherlands; Icelandic Heart Association (S.S., G.E., V.G.), Kopavogur, Iceland; and the University of Iceland (V.G.), Reykjavik.
Sigurdur
S
Sigurdsson
From the Laboratory of Epidemiology and Population Sciences (M.I.G., M.E.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Julius Center for Health Sciences and Primary Care (M.I.G.), University Medical Center Utrecht, the Netherlands; Icelandic Heart Association (S.S., G.E., V.G.), Kopavogur, Iceland; and the University of Iceland (V.G.), Reykjavik.
Gudny
G
Eiriksdottir
From the Laboratory of Epidemiology and Population Sciences (M.I.G., M.E.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Julius Center for Health Sciences and Primary Care (M.I.G.), University Medical Center Utrecht, the Netherlands; Icelandic Heart Association (S.S., G.E., V.G.), Kopavogur, Iceland; and the University of Iceland (V.G.), Reykjavik.
Melissa E
ME
Garcia
From the Laboratory of Epidemiology and Population Sciences (M.I.G., M.E.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Julius Center for Health Sciences and Primary Care (M.I.G.), University Medical Center Utrecht, the Netherlands; Icelandic Heart Association (S.S., G.E., V.G.), Kopavogur, Iceland; and the University of Iceland (V.G.), Reykjavik.
Tamara B
TB
Harris
From the Laboratory of Epidemiology and Population Sciences (M.I.G., M.E.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Julius Center for Health Sciences and Primary Care (M.I.G.), University Medical Center Utrecht, the Netherlands; Icelandic Heart Association (S.S., G.E., V.G.), Kopavogur, Iceland; and the University of Iceland (V.G.), Reykjavik.
Vilmundur
V
Gudnason
From the Laboratory of Epidemiology and Population Sciences (M.I.G., M.E.G., T.B.H., L.J.L.), National Institute on Aging, Bethesda, MD; Julius Center for Health Sciences and Primary Care (M.I.G.), University Medical Center Utrecht, the Netherlands; Icelandic Heart Association (S.S., G.E., V.G.), Kopavogur, Iceland; and the University of Iceland (V.G.), Reykjavik. launerl@nia.nih.gov.
Lenore J
LJ
Launer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001921:Brain / Q000473:pathology*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000503:physiopathology; D003430:Cross-Sectional Studies; D003704:Dementia / Q000473:pathology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D010913:Pituitary-Adrenal System / Q000473:pathology; D012463:Saliva / Q000737:chemistry / Q000502:physiology*
D006854:Hydrocortisone