title: Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer's type.
abstract: Increased peripheral and central nervous system cortisol levels have been reported in Alzheimer's disease (AD) and may reflect dysfunction of cerebral components of the hypothalamic-pituitary-adrenal (HPA) axis. However, brain exposure to high cortisol concentrations may also accelerate disease progression and cognitive decline. The objectives of this study were to investigate whether HPA-axis dysregulation occurs at early clinical stages of AD and whether plasma and CSF cortisol levels are associated with clinical disease progression. Morning plasma and CSF cortisol concentrations were obtained from the subjects with AD dementia, mild cognitive impairment of AD type (MCI-AD), MCI of other type (MCI-O), and controls with normal cognition included in a multicenter study from the German Dementia Competence Network. A clinical and neuropsychological follow-up was performed in a subgroup of participants with MCI-AD, MCI-O, and AD dementia. CSF cortisol concentrations were increased in the subjects with AD dementia or MCI-AD compared with subjects with MCI-O or normal cognition. After controlling for possible confounders including CSF measures of amyloid beta1-42 and total tau, higher baseline CSF cortisol levels were associated with faster clinical worsening and cognitive decline in MCI-AD. The findings suggest that HPA-axis dysregulation occurs at the MCI stage of AD and may accelerate disease progression and cognitive decline.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; Department of Psychiatry, Leenaards Memory Center, University Hospital of Lausanne, Lausanne, Switzerland; Department of Clinical Neurosciences, Leenaards Memory Center, University Hospital of Lausanne, Lausanne, Switzerland. Electronic address: Julius.Popp@chuv.ch.
authors.forename: Julius
authors.initials: J
authors.lastname: Popp
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Wolfsgruber
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Isabella
authors.initials: I
authors.lastname: Heuser
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Peters
authors.affiliation: Center for Geriatric Medicine and Gerontology, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hüll
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Heidelberg, Heidelberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schröder
authors.affiliation: Department of Psychiatry, Ludwig-Maximilians, University München, München, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Möller
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Piotr
authors.initials: P
authors.lastname: Lewczuk
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schneider
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Hamburg, Hamburg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Jahn
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Luckhaus
authors.affiliation: Department of Psychiatry and Psychotherapy, Technische Universität München, München, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Perneczky
authors.affiliation: Central Institute of Mental Health, Mannheim, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Frölich
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Wiltfang
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Jessen
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000097:blood / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000134:cerebrospinal fluid*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D006854:Hydrocortisone
keywords: Alzheimer's disease; Cerebrospinal fluid; Cognitive decline; Cortisol; Hypothalamic-pituitary-adrenal axis; Mild cognitive impairment