Associations between CSF cortisol and CSF norepinephrine in cognitively normal controls and patients with amnestic MCI and AD dementia

Lucy Y. Wang, Murray A. Raskind, Charles W. Wilkinson, Jane B. Shofer, Carl Sikkema, Patricia Szot, Joseph Quinn, Douglas R. Galasko, Elaine R. Peskind

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective: This study evaluated the effects of Alzheimer disease (AD) on the relationship between the brain noradrenergic system and hypothalamic pituitary adrenocortical axis (HPA). Specifically, relationships between cerebrospinal fluid (CSF) norepinephrine (NE) and CSF cortisol were examined in cognitively normal participants and participants with AD dementia and amnestic mild cognitive impairment (aMCI). We hypothesized that there would a positive association between these 2 measures in cognitively normal controls and that this association would be altered in AD. Methods: Four hundred twenty-one CSF samples were assayed for NE and cortisol in controls (n = 305), participants with aMCI (n = 22), and AD dementia (n = 94). Linear regression was used to examine the association between CSF cortisol and NE, adjusting for age, sex, education, and body mass index. Results: Contrary to our hypothesis, CSF cortisol and NE levels were not significantly associated in controls. However, higher cortisol levels were associated with higher NE levels in AD and aMCI participants. Regression coefficients ± standard errors for the change in cortisol per 100- pg/mL increase in NE are as follows: controls 0.0 ± 0.2, P = 1.0; MCI, 1.4 ± 0.7, P =.14; and AD 1.1 ± 0.4, P =.032. Analysis with MCI and AD participants combined strengthened statistical significance (1.2 ± 0.3, P =.007). Conclusions: Enhanced responsiveness of the HPA axis to noradrenergic stimulatory regulation in AD and disruption of the blood brain barrier may contribute to these findings. Because brainstem noradrenergic stimulatory regulation of the HPA axis is substantially increased by both acute and chronic stress, these findings are also consistent with AD participants experiencing higher levels of acute and chronic stress.

Original languageEnglish (US)
Pages (from-to)763-768
Number of pages6
JournalInternational Journal of Geriatric Psychiatry
Volume33
Issue number5
DOIs
StatePublished - Jan 1 2018

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Cerebrospinal Fluid
Hydrocortisone
Norepinephrine
Alzheimer Disease
Sex Education
Blood-Brain Barrier
Brain Stem
Linear Models
Body Mass Index
Brain

Keywords

  • Alzheimer disease
  • Cerebrospinal fluid
  • Cortisol
  • Mild cognitive impairment
  • Norepinephrine
  • Stress

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Associations between CSF cortisol and CSF norepinephrine in cognitively normal controls and patients with amnestic MCI and AD dementia. / Wang, Lucy Y.; Raskind, Murray A.; Wilkinson, Charles W.; Shofer, Jane B.; Sikkema, Carl; Szot, Patricia; Quinn, Joseph; Galasko, Douglas R.; Peskind, Elaine R.

In: International Journal of Geriatric Psychiatry, Vol. 33, No. 5, 01.01.2018, p. 763-768.

Research output: Contribution to journalArticle

Wang, Lucy Y. ; Raskind, Murray A. ; Wilkinson, Charles W. ; Shofer, Jane B. ; Sikkema, Carl ; Szot, Patricia ; Quinn, Joseph ; Galasko, Douglas R. ; Peskind, Elaine R. / Associations between CSF cortisol and CSF norepinephrine in cognitively normal controls and patients with amnestic MCI and AD dementia. In: International Journal of Geriatric Psychiatry. 2018 ; Vol. 33, No. 5. pp. 763-768.
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abstract = "Objective: This study evaluated the effects of Alzheimer disease (AD) on the relationship between the brain noradrenergic system and hypothalamic pituitary adrenocortical axis (HPA). Specifically, relationships between cerebrospinal fluid (CSF) norepinephrine (NE) and CSF cortisol were examined in cognitively normal participants and participants with AD dementia and amnestic mild cognitive impairment (aMCI). We hypothesized that there would a positive association between these 2 measures in cognitively normal controls and that this association would be altered in AD. Methods: Four hundred twenty-one CSF samples were assayed for NE and cortisol in controls (n = 305), participants with aMCI (n = 22), and AD dementia (n = 94). Linear regression was used to examine the association between CSF cortisol and NE, adjusting for age, sex, education, and body mass index. Results: Contrary to our hypothesis, CSF cortisol and NE levels were not significantly associated in controls. However, higher cortisol levels were associated with higher NE levels in AD and aMCI participants. Regression coefficients ± standard errors for the change in cortisol per 100- pg/mL increase in NE are as follows: controls 0.0 ± 0.2, P = 1.0; MCI, 1.4 ± 0.7, P =.14; and AD 1.1 ± 0.4, P =.032. Analysis with MCI and AD participants combined strengthened statistical significance (1.2 ± 0.3, P =.007). Conclusions: Enhanced responsiveness of the HPA axis to noradrenergic stimulatory regulation in AD and disruption of the blood brain barrier may contribute to these findings. Because brainstem noradrenergic stimulatory regulation of the HPA axis is substantially increased by both acute and chronic stress, these findings are also consistent with AD participants experiencing higher levels of acute and chronic stress.",
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T1 - Associations between CSF cortisol and CSF norepinephrine in cognitively normal controls and patients with amnestic MCI and AD dementia

AU - Wang, Lucy Y.

AU - Raskind, Murray A.

AU - Wilkinson, Charles W.

AU - Shofer, Jane B.

AU - Sikkema, Carl

AU - Szot, Patricia

AU - Quinn, Joseph

AU - Galasko, Douglas R.

AU - Peskind, Elaine R.

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N2 - Objective: This study evaluated the effects of Alzheimer disease (AD) on the relationship between the brain noradrenergic system and hypothalamic pituitary adrenocortical axis (HPA). Specifically, relationships between cerebrospinal fluid (CSF) norepinephrine (NE) and CSF cortisol were examined in cognitively normal participants and participants with AD dementia and amnestic mild cognitive impairment (aMCI). We hypothesized that there would a positive association between these 2 measures in cognitively normal controls and that this association would be altered in AD. Methods: Four hundred twenty-one CSF samples were assayed for NE and cortisol in controls (n = 305), participants with aMCI (n = 22), and AD dementia (n = 94). Linear regression was used to examine the association between CSF cortisol and NE, adjusting for age, sex, education, and body mass index. Results: Contrary to our hypothesis, CSF cortisol and NE levels were not significantly associated in controls. However, higher cortisol levels were associated with higher NE levels in AD and aMCI participants. Regression coefficients ± standard errors for the change in cortisol per 100- pg/mL increase in NE are as follows: controls 0.0 ± 0.2, P = 1.0; MCI, 1.4 ± 0.7, P =.14; and AD 1.1 ± 0.4, P =.032. Analysis with MCI and AD participants combined strengthened statistical significance (1.2 ± 0.3, P =.007). Conclusions: Enhanced responsiveness of the HPA axis to noradrenergic stimulatory regulation in AD and disruption of the blood brain barrier may contribute to these findings. Because brainstem noradrenergic stimulatory regulation of the HPA axis is substantially increased by both acute and chronic stress, these findings are also consistent with AD participants experiencing higher levels of acute and chronic stress.

AB - Objective: This study evaluated the effects of Alzheimer disease (AD) on the relationship between the brain noradrenergic system and hypothalamic pituitary adrenocortical axis (HPA). Specifically, relationships between cerebrospinal fluid (CSF) norepinephrine (NE) and CSF cortisol were examined in cognitively normal participants and participants with AD dementia and amnestic mild cognitive impairment (aMCI). We hypothesized that there would a positive association between these 2 measures in cognitively normal controls and that this association would be altered in AD. Methods: Four hundred twenty-one CSF samples were assayed for NE and cortisol in controls (n = 305), participants with aMCI (n = 22), and AD dementia (n = 94). Linear regression was used to examine the association between CSF cortisol and NE, adjusting for age, sex, education, and body mass index. Results: Contrary to our hypothesis, CSF cortisol and NE levels were not significantly associated in controls. However, higher cortisol levels were associated with higher NE levels in AD and aMCI participants. Regression coefficients ± standard errors for the change in cortisol per 100- pg/mL increase in NE are as follows: controls 0.0 ± 0.2, P = 1.0; MCI, 1.4 ± 0.7, P =.14; and AD 1.1 ± 0.4, P =.032. Analysis with MCI and AD participants combined strengthened statistical significance (1.2 ± 0.3, P =.007). Conclusions: Enhanced responsiveness of the HPA axis to noradrenergic stimulatory regulation in AD and disruption of the blood brain barrier may contribute to these findings. Because brainstem noradrenergic stimulatory regulation of the HPA axis is substantially increased by both acute and chronic stress, these findings are also consistent with AD participants experiencing higher levels of acute and chronic stress.

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KW - Cortisol

KW - Mild cognitive impairment

KW - Norepinephrine

KW - Stress

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