Cortisol associated with hypometabolism across the Alzheimer's disease spectrum

Miranka Wirth, Catharina Lange, Willem Huijbers

Research output: Contribution to journalArticleScientific

Abstract


Objective: Hypothalamic-pituitary-adrenal (HPA) dysregulation is proposed as a risk factor for Alzheimer's disease (AD). This cross-sectional study assessed relationships between plasma cortisol levels and neuroimaging biomarkers, specifically brain glucose metabolism and gray matter volume, across the AD spectrum. Methods: Cognitively normal older adults and patients with mild cognitive impairment (MCI) and AD dementia were included from the Alzheimer's Disease Neuroimaging Initiative. Participants (n = 556) were selected based on availability of baseline measures of plasma cortisol levels and gray matter volume, as estimated with magnetic resonance imaging. Within a subsample (n = 288), we examined brain glucose metabolism (n = 288) as with positron emission tomography. Relationships between plasma cortisol and AD neuroimaging biomarkers were assessed using regions-of-interest and voxel-wise analyses. Results: Across the entire cohort, higher plasma cortisol was also related to lower gray matter volume, most notably in the left lateral temporal-parietal-occipital regions. Importantly, higher plasma cortisol concentration was also related to hypometabolism, especially in lateral temporo-parietal and medial parietal regions. When stratified by diagnosis, these negative associations were most pronounced in MCI and AD patients. Interpretation: High plasma cortisol was associated with hypometabolism predominantly in AD-sensitive regions. Our results indicate that HPA axis activation could influence brain metabolism and exacerbate existing AD pathological processes. This is consistent with a notion that stress is a conceivable target for intervention to slow down AD progression. Future studies should delineate underlying pathological mechanisms and investigate if clinical or lifestyle interventions could alleviate negative actions of stress on AD.
Original languageEnglish
Pages (from-to)514968
JournalBioRxiv
DOIs
Publication statusPublished - 2019

Fingerprint

Alzheimer Disease
Neuroimaging
Cross-Sectional Studies

Cite this

@article{76e373fc091a47b28e411e6f840f98fa,
title = "Cortisol associated with hypometabolism across the Alzheimer's disease spectrum",
abstract = "Objective: Hypothalamic-pituitary-adrenal (HPA) dysregulation is proposed as a risk factor for Alzheimer's disease (AD). This cross-sectional study assessed relationships between plasma cortisol levels and neuroimaging biomarkers, specifically brain glucose metabolism and gray matter volume, across the AD spectrum. Methods: Cognitively normal older adults and patients with mild cognitive impairment (MCI) and AD dementia were included from the Alzheimer's Disease Neuroimaging Initiative. Participants (n = 556) were selected based on availability of baseline measures of plasma cortisol levels and gray matter volume, as estimated with magnetic resonance imaging. Within a subsample (n = 288), we examined brain glucose metabolism (n = 288) as with positron emission tomography. Relationships between plasma cortisol and AD neuroimaging biomarkers were assessed using regions-of-interest and voxel-wise analyses. Results: Across the entire cohort, higher plasma cortisol was also related to lower gray matter volume, most notably in the left lateral temporal-parietal-occipital regions. Importantly, higher plasma cortisol concentration was also related to hypometabolism, especially in lateral temporo-parietal and medial parietal regions. When stratified by diagnosis, these negative associations were most pronounced in MCI and AD patients. Interpretation: High plasma cortisol was associated with hypometabolism predominantly in AD-sensitive regions. Our results indicate that HPA axis activation could influence brain metabolism and exacerbate existing AD pathological processes. This is consistent with a notion that stress is a conceivable target for intervention to slow down AD progression. Future studies should delineate underlying pathological mechanisms and investigate if clinical or lifestyle interventions could alleviate negative actions of stress on AD.",
author = "Miranka Wirth and Catharina Lange and Willem Huijbers",
year = "2019",
doi = "10.1101/514968",
language = "English",
pages = "514968",
journal = "BioRxiv",
publisher = "Cold Spring Harbor Laboratory Press",

}

Cortisol associated with hypometabolism across the Alzheimer's disease spectrum. / Wirth, Miranka; Lange, Catharina; Huijbers, Willem.

In: BioRxiv, 2019, p. 514968.

Research output: Contribution to journalArticleScientific

TY - JOUR

T1 - Cortisol associated with hypometabolism across the Alzheimer's disease spectrum

AU - Wirth, Miranka

AU - Lange, Catharina

AU - Huijbers, Willem

PY - 2019

Y1 - 2019

N2 - Objective: Hypothalamic-pituitary-adrenal (HPA) dysregulation is proposed as a risk factor for Alzheimer's disease (AD). This cross-sectional study assessed relationships between plasma cortisol levels and neuroimaging biomarkers, specifically brain glucose metabolism and gray matter volume, across the AD spectrum. Methods: Cognitively normal older adults and patients with mild cognitive impairment (MCI) and AD dementia were included from the Alzheimer's Disease Neuroimaging Initiative. Participants (n = 556) were selected based on availability of baseline measures of plasma cortisol levels and gray matter volume, as estimated with magnetic resonance imaging. Within a subsample (n = 288), we examined brain glucose metabolism (n = 288) as with positron emission tomography. Relationships between plasma cortisol and AD neuroimaging biomarkers were assessed using regions-of-interest and voxel-wise analyses. Results: Across the entire cohort, higher plasma cortisol was also related to lower gray matter volume, most notably in the left lateral temporal-parietal-occipital regions. Importantly, higher plasma cortisol concentration was also related to hypometabolism, especially in lateral temporo-parietal and medial parietal regions. When stratified by diagnosis, these negative associations were most pronounced in MCI and AD patients. Interpretation: High plasma cortisol was associated with hypometabolism predominantly in AD-sensitive regions. Our results indicate that HPA axis activation could influence brain metabolism and exacerbate existing AD pathological processes. This is consistent with a notion that stress is a conceivable target for intervention to slow down AD progression. Future studies should delineate underlying pathological mechanisms and investigate if clinical or lifestyle interventions could alleviate negative actions of stress on AD.

AB - Objective: Hypothalamic-pituitary-adrenal (HPA) dysregulation is proposed as a risk factor for Alzheimer's disease (AD). This cross-sectional study assessed relationships between plasma cortisol levels and neuroimaging biomarkers, specifically brain glucose metabolism and gray matter volume, across the AD spectrum. Methods: Cognitively normal older adults and patients with mild cognitive impairment (MCI) and AD dementia were included from the Alzheimer's Disease Neuroimaging Initiative. Participants (n = 556) were selected based on availability of baseline measures of plasma cortisol levels and gray matter volume, as estimated with magnetic resonance imaging. Within a subsample (n = 288), we examined brain glucose metabolism (n = 288) as with positron emission tomography. Relationships between plasma cortisol and AD neuroimaging biomarkers were assessed using regions-of-interest and voxel-wise analyses. Results: Across the entire cohort, higher plasma cortisol was also related to lower gray matter volume, most notably in the left lateral temporal-parietal-occipital regions. Importantly, higher plasma cortisol concentration was also related to hypometabolism, especially in lateral temporo-parietal and medial parietal regions. When stratified by diagnosis, these negative associations were most pronounced in MCI and AD patients. Interpretation: High plasma cortisol was associated with hypometabolism predominantly in AD-sensitive regions. Our results indicate that HPA axis activation could influence brain metabolism and exacerbate existing AD pathological processes. This is consistent with a notion that stress is a conceivable target for intervention to slow down AD progression. Future studies should delineate underlying pathological mechanisms and investigate if clinical or lifestyle interventions could alleviate negative actions of stress on AD.

U2 - 10.1101/514968

DO - 10.1101/514968

M3 - Article

SP - 514968

JO - BioRxiv

JF - BioRxiv

ER -