Lucy Y Wang1,2, Murray A Raskind1,2, Charles W Wilkinson3,2, Jane B Shofer2, Carl Sikkema3, Patricia Szot1, Joseph F Quinn4, Douglas R Galasko5, Elaine R Peskind1,2. 1. Mental Illness Research, Education, and Clinical Center (MIRECC), VA Puget Sound Health Care System, Seattle, WA, USA. 2. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA. 3. Geriatric Research, Education, and Clinical Center (GRECC), VA Puget Sound Health Care System, Seattle, WA, USA. 4. Department of Neurology, Oregon Health and Science University, Portland, OR, USA. 5. Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
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.
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 aMCIparticipants. 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 ADparticipants 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 ADparticipants experiencing higher levels of acute and chronic stress.
Authors: D C German; K F Manaye; C L White; D J Woodward; D D McIntire; W K Smith; R N Kalaria; D M Mann Journal: Ann Neurol Date: 1992-11 Impact factor: 10.422
Authors: Lucy Y Wang; Jane B Shofer; Kirsten Rohde; Kim L Hart; David J Hoff; Yun H McFall; Murray A Raskind; Elaine R Peskind Journal: Am J Geriatr Psychiatry Date: 2009-09 Impact factor: 4.105
Authors: Lucy Y Wang; Richard R Murphy; Brett Hanscom; Ge Li; Steven P Millard; Eric C Petrie; Douglas R Galasko; Carl Sikkema; Murray A Raskind; Charles W Wilkinson; Elaine R Peskind Journal: Neurobiol Aging Date: 2013-04-30 Impact factor: 4.673
Authors: Henriette Beyer; Nicole Lange; Armin H Podtschaske; Jan Martin; Lucia Albers; Alexander von Werder; Jürgen Ruland; Gerhard Schneider; Bernhard Meyer; Simone M Kagerbauer; Jens Gempt Journal: touchREV Endocrinol Date: 2022-06-13
Authors: Sami Ouanes; Christopher Clark; Jonas Richiardi; Bénédicte Maréchal; Piotr Lewczuk; Johannes Kornhuber; Clemens Kirschbaum; Julius Popp Journal: Front Aging Neurosci Date: 2022-07-07 Impact factor: 5.702