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November 20, 2018; 91 (21) Article

Circulating cortisol and cognitive and structural brain measures

The Framingham Heart Study

Justin B. Echouffo-Tcheugui, Sarah C. Conner, Jayandra J. Himali, Pauline Maillard, Charles S. DeCarli, Alexa S. Beiser, Ramachandran S. Vasan, Sudha Seshadri
First published October 24, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006549
Justin B. Echouffo-Tcheugui
From the Division of Endocrinology, Diabetes and Hypertension (J.B.E.-T.), Brigham and Women's Hospital/Harvard Medical School, Boston; National Heart, Lung, and Blood Institute (J.B.E.-T., S.C.C., J.J.H., A.S.B., R.S.V., S.S.), Framingham Heart Study, MA; Department of Neurology (S.C.C., J.J.H., A.S.B., S.S.) and Sections of Preventive Medicine and Epidemiology (R.S.V.) and Cardiology (R.S.V.), Department of Medicine, Boston University School of Medicine; Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (P.M., C.S.D.), University of California, Davis, Sacramento; and Glenn Biggs Institute of Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio.
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Sarah C. Conner
From the Division of Endocrinology, Diabetes and Hypertension (J.B.E.-T.), Brigham and Women's Hospital/Harvard Medical School, Boston; National Heart, Lung, and Blood Institute (J.B.E.-T., S.C.C., J.J.H., A.S.B., R.S.V., S.S.), Framingham Heart Study, MA; Department of Neurology (S.C.C., J.J.H., A.S.B., S.S.) and Sections of Preventive Medicine and Epidemiology (R.S.V.) and Cardiology (R.S.V.), Department of Medicine, Boston University School of Medicine; Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (P.M., C.S.D.), University of California, Davis, Sacramento; and Glenn Biggs Institute of Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio.
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Jayandra J. Himali
From the Division of Endocrinology, Diabetes and Hypertension (J.B.E.-T.), Brigham and Women's Hospital/Harvard Medical School, Boston; National Heart, Lung, and Blood Institute (J.B.E.-T., S.C.C., J.J.H., A.S.B., R.S.V., S.S.), Framingham Heart Study, MA; Department of Neurology (S.C.C., J.J.H., A.S.B., S.S.) and Sections of Preventive Medicine and Epidemiology (R.S.V.) and Cardiology (R.S.V.), Department of Medicine, Boston University School of Medicine; Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (P.M., C.S.D.), University of California, Davis, Sacramento; and Glenn Biggs Institute of Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio.
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Pauline Maillard
From the Division of Endocrinology, Diabetes and Hypertension (J.B.E.-T.), Brigham and Women's Hospital/Harvard Medical School, Boston; National Heart, Lung, and Blood Institute (J.B.E.-T., S.C.C., J.J.H., A.S.B., R.S.V., S.S.), Framingham Heart Study, MA; Department of Neurology (S.C.C., J.J.H., A.S.B., S.S.) and Sections of Preventive Medicine and Epidemiology (R.S.V.) and Cardiology (R.S.V.), Department of Medicine, Boston University School of Medicine; Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (P.M., C.S.D.), University of California, Davis, Sacramento; and Glenn Biggs Institute of Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio.
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Charles S. DeCarli
From the Division of Endocrinology, Diabetes and Hypertension (J.B.E.-T.), Brigham and Women's Hospital/Harvard Medical School, Boston; National Heart, Lung, and Blood Institute (J.B.E.-T., S.C.C., J.J.H., A.S.B., R.S.V., S.S.), Framingham Heart Study, MA; Department of Neurology (S.C.C., J.J.H., A.S.B., S.S.) and Sections of Preventive Medicine and Epidemiology (R.S.V.) and Cardiology (R.S.V.), Department of Medicine, Boston University School of Medicine; Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (P.M., C.S.D.), University of California, Davis, Sacramento; and Glenn Biggs Institute of Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio.
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Alexa S. Beiser
From the Division of Endocrinology, Diabetes and Hypertension (J.B.E.-T.), Brigham and Women's Hospital/Harvard Medical School, Boston; National Heart, Lung, and Blood Institute (J.B.E.-T., S.C.C., J.J.H., A.S.B., R.S.V., S.S.), Framingham Heart Study, MA; Department of Neurology (S.C.C., J.J.H., A.S.B., S.S.) and Sections of Preventive Medicine and Epidemiology (R.S.V.) and Cardiology (R.S.V.), Department of Medicine, Boston University School of Medicine; Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (P.M., C.S.D.), University of California, Davis, Sacramento; and Glenn Biggs Institute of Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio.
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Ramachandran S. Vasan
From the Division of Endocrinology, Diabetes and Hypertension (J.B.E.-T.), Brigham and Women's Hospital/Harvard Medical School, Boston; National Heart, Lung, and Blood Institute (J.B.E.-T., S.C.C., J.J.H., A.S.B., R.S.V., S.S.), Framingham Heart Study, MA; Department of Neurology (S.C.C., J.J.H., A.S.B., S.S.) and Sections of Preventive Medicine and Epidemiology (R.S.V.) and Cardiology (R.S.V.), Department of Medicine, Boston University School of Medicine; Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (P.M., C.S.D.), University of California, Davis, Sacramento; and Glenn Biggs Institute of Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio.
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Sudha Seshadri
From the Division of Endocrinology, Diabetes and Hypertension (J.B.E.-T.), Brigham and Women's Hospital/Harvard Medical School, Boston; National Heart, Lung, and Blood Institute (J.B.E.-T., S.C.C., J.J.H., A.S.B., R.S.V., S.S.), Framingham Heart Study, MA; Department of Neurology (S.C.C., J.J.H., A.S.B., S.S.) and Sections of Preventive Medicine and Epidemiology (R.S.V.) and Cardiology (R.S.V.), Department of Medicine, Boston University School of Medicine; Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (P.M., C.S.D.), University of California, Davis, Sacramento; and Glenn Biggs Institute of Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio.
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Circulating cortisol and cognitive and structural brain measures
The Framingham Heart Study
Justin B. Echouffo-Tcheugui, Sarah C. Conner, Jayandra J. Himali, Pauline Maillard, Charles S. DeCarli, Alexa S. Beiser, Ramachandran S. Vasan, Sudha Seshadri
Neurology Nov 2018, 91 (21) e1961-e1970; DOI: 10.1212/WNL.0000000000006549

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Abstract

Objective To assess the association of early morning serum cortisol with cognitive performance and brain structural integrity in community-dwelling young and middle-aged adults without dementia.

Methods We evaluated dementia-free Framingham Heart Study (generation 3) participants (mean age 48.5 years, 46.8% men) who underwent cognitive testing for memory, abstract reasoning, visual perception, attention, and executive function (n = 2,231) and brain MRI (n = 2018) to assess total white matter, lobar gray matter, and white matter hyperintensity volumes and fractional anisotropy (FA) measures. We used linear and logistic regression to assess the relations of cortisol (categorized in tertiles, with the middle tertile as referent) to measures of cognition, MRI volumes, presence of covert brain infarcts and cerebral microbleeds, and voxel-based microstructural white matter integrity and gray matter density, adjusting for age, sex, APOE, and vascular risk factors.

Results Higher cortisol (highest tertile vs middle tertile) was associated with worse memory and visual perception, as well as lower total cerebral brain and occipital and frontal lobar gray matter volumes. Higher cortisol was associated with multiple areas of microstructural changes (decreased regional FA), especially in the splenium of corpus callosum and the posterior corona radiata. The association of cortisol with total cerebral brain volume varied by sex (p for interaction = 0.048); higher cortisol was inversely associated with cerebral brain volume in women (p = 0.001) but not in men (p = 0.717). There was no effect modification by the APOE4 genotype of the relations of cortisol and cognition or imaging traits.

Conclusion Higher serum cortisol was associated with lower brain volumes and impaired memory in asymptomatic younger to middle-aged adults, with the association being evident particularly in women.

Glossary

BP=
blood pressure;
CES-D=
Center for Epidemiologic Studies Depression Scale;
DTI=
diffusion tensor imaging;
FA=
fractional anisotropy;
FLAIR=
fluid-attenuated inversion recovery;
HPA=
hypothalamic-pituitary-adrenal;
HRT=
hormone replacement therapy;
HVOT=
Hooper Visual Organization Test;
OCP=
oral contraceptive pill;
SE=
standard error;
TrA=
Trails A;
TrB=
Trails B;
WMH=
white matter hyperintensities

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received March 6, 2018.
  • Accepted in final form August 10, 2018.
  • © 2018 American Academy of Neurology
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Letters: Rapid online correspondence

  • Author response: Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study
    • Justin Echouffo-Tcheugui, Physician, Johns Hopkins University
    • Sarah C. Conner, Biostatistician, Boston University
    • Jayandra J. Himali, Biostatistician, Boston University
    • Alexa S. Beiser, Biostatistician, Boston University
    • Sudha Seshadri, Physician, University of Texas Health Sciences Center, San Antonio
    Submitted May 10, 2019
  • Author response: Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study
    • Jutsin B. Echouffo-Tcheugui, Physician, Johns Hopkins University
    • Sarah C. Conner, Biostatistician, Boston University
    • Jayandra J. Himali, Biostatistician, Boston University
    • Alexa S. Beiser, Biostatistician, Boston University
    • Sudha Seshadri, Physician, UT Health San Antonio
    Submitted May 10, 2019
  • Reader response: Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study
    • Breno J.A.P. Barbosa, Neurologist, Department of Neurology, School of Medicine, Universidade de São Paulo
    • Juliana N. de Souza-Talarico, Associate Professor, Department of Medical-Surgical Nursing, School of Nursing, Universidade de São Paulo
    • Ricardo Nitrini, Department director, Department of Neurology, School of Medicine, Universidade de São Paulo
    • Sônia M.D. Brucki, Neurologist, Department of Neurology, School of Medicine, Universidade de São Paulo
    Submitted December 14, 2018
  • Reader response: Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study
    • David Jiménez-Pavón, "Ramón & Cajal" Researcher in exercise physiology, physical activity and health, MOVE-IT Research group, University of Cádiz (Cádiz, Spain)
    • Ana Carbonell-Baeza, Senior Researcher in Physical Activity and Health, MOVE-IT Research group, University of Cádiz (Cádiz, Spain)
    Submitted October 29, 2018
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