Cortisol hypersecretion and the risk of Alzheimer’s disease: A systematic review and meta-analysis

Zheng, Bang; Tal, Roy; Yang, Zhirong; Middleton, Lefkos T.; Udeh-Momoh, Chinedu

doi:10.1016/j.arr.2020.101171

Cited by 38 publications

(37 citation statements)

References 73 publications

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“…Musculature is also affected by androgens, known to be decreased in AD [ 63, 64 ], and negatively impacted by corticosteroids [ 65 ]. Consistent with the hypothesis of hormonal link to AD muscle loss, we found increased levels of corticosteroids and decreased DHEAS (in the diagnostic prediction model), validating previous reports [ 66, 67 ]. This increase is sometimes explained by chronic stress response or dysregulated circadian cycle and sleep disorders, a common theme in AD, negatively impacting glymphatic clearance and hippocampal volume [ 68 ].…”

Section: Discussionsupporting

confidence: 92%

Targeted Metabolomic Analysis in Alzheimer’s Disease Plasma and Brain Tissue in Non-Hispanic Whites

Kalecky

German

Montillo

2022

JAD

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Background: Metabolites are biological compounds reflecting the functional activity of organs and tissues. Understanding metabolic changes in Alzheimer’s disease (AD) can provide insight into potential risk factors in this multifactorial disease and suggest new intervention strategies or improve non-invasive diagnosis. Objective: In this study, we searched for changes in AD metabolism in plasma and frontal brain cortex tissue samples and evaluated the performance of plasma measurements as biomarkers. Methods: This is a case-control study with two tissue cohorts: 158 plasma samples (94 AD, 64 controls; Texas Alzheimer’s Research and Care Consortium – TARCC) and 71 postmortem cortex samples (35 AD, 36 controls; Banner Sun Health Research Institute brain bank). We performed targeted mass spectrometry analysis of 630 compounds (106 small molecules: UHPLC-MS/MS, 524 lipids: FIA-MS/MS) and 232 calculated metabolic indicators with a metabolomic kit (Biocrates MxP® Quant 500). Results: We discovered disturbances (FDR≤0.05) in multiple metabolic pathways in AD in both cohorts including microbiome-related metabolites with pro-toxic changes, methylhistidine metabolism, polyamines, corticosteroids, omega-3 fatty acids, acylcarnitines, ceramides, and diglycerides. In AD, plasma reveals elevated triglycerides, and cortex shows altered amino acid metabolism. A cross-validated diagnostic prediction model from plasma achieves AUC = 82% (CI95 = 75–88%); for females specifically, AUC = 88% (CI95 = 80–95%). A reduced model using 20 features achieves AUC = 79% (CI95 = 71–85%); for females AUC = 84% (CI95 = 74–92%). Conclusion: Our findings support the involvement of gut environment in AD and encourage targeting multiple metabolic areas in the design of intervention strategies, including microbiome composition, hormonal balance, nutrients, and muscle homeostasis.

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Section: Discussionsupporting

confidence: 92%

Targeted Metabolomic Analysis in Alzheimer’s Disease Plasma and Brain Tissue in Non-Hispanic Whites

Kalecky

German

Montillo

2022

JAD

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“…Cortisol has been associated with impeding normal amyloid β (Aβ) and tau processing in the brain, exacerbating Aβ and tau toxicity, promoting oxidative stress and neurodegeneration, inducing synaptic dysfunction, and reducing dendritic plasticity in the hippocampus and prefrontal cortex in animal models ( Ouanes and Popp, 2019 ). Higher cortisol levels have been reported in patients with clinically diagnosed AD dementia or mild cognitive impairment (MCI) compared to controls, in plasma, saliva, urine, and cerebrospinal fluid (CSF) ( Zheng et al, 2020 ). Previous studies also found that elevated cortisol levels were associated with more pronounced cognitive impairment in patients with AD dementia ( Zverova et al, 2013 ; Pena-Bautista et al, 2019 ), as well as with faster cognitive decline in cognitively healthy older individuals ( Pietrzak et al, 2017 ) and in patients with MCI or dementia of AD type ( Huang et al, 2009 ; Popp et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Cortisol and Dehydroepiandrosterone Sulfate, Alzheimer’s Disease Pathology, and Cognitive Decline

Ouanes

Clark

Richiardi

et al. 2022

Front. Aging Neurosci.

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IntroductionElevated cortisol levels have been reported in Alzheimer’s disease (AD) and may accelerate the development of brain pathology and cognitive decline. Dehydroepiandrosterone sulfate (DHEAS) has anti-glucocorticoid effects and it may be involved in the AD pathophysiology.ObjectivesTo investigate associations of cerebrospinal fluid (CSF) cortisol and DHEAS levels with (1) cognitive performance at baseline; (2) CSF biomarkers of amyloid pathology (as assessed by CSF Aβ levels), neuronal injury (as assessed by CSF tau), and tau hyperphosphorylation (as assessed by CSF p-tau); (3) regional brain volumes; and (4) clinical disease progression.Materials and MethodsIndividuals between 49 and 88 years (n = 145) with mild cognitive impairment or dementia or with normal cognition were included. Clinical scores, AD biomarkers, brain MRI volumetry along with CSF cortisol and DHEAS were obtained at baseline. Cognitive and functional performance was re-assessed at 18 and 36 months from baseline. We also assessed the following covariates: apolipoprotein E (APOE) genotype, BMI, and education. We used linear regression and mixed models to address associations of interest.ResultsHigher CSF cortisol was associated with poorer global cognitive performance and higher disease severity at baseline. Cortisol and cortisol/DHEAS ratio were positively associated with tau and p-tau CSF levels, and negatively associated with the amygdala and insula volumes at baseline. Higher CSF cortisol predicted more pronounced cognitive decline and clinical disease progression over 36 months. Higher CSF DHEAS predicted more pronounced disease progression over 36 months.ConclusionIncreased cortisol in the CNS is associated with tau pathology and neurodegeneration, and with decreased insula and amygdala volume. Both CSF cortisol and DHEAS levels predict faster clinical disease progression. These results have implications for the identification of patients at risk of rapid decline as well as for the development of interventions targeting both neurodegeneration and clinical manifestations of AD.

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“…Alternately, religious participation has been shown to exert a beneficial effect on diurnal variations in cortisol secretion [ 32 ]. Elevations in morning cortisol have been found to be associated with both mild cognitive impairment and AD, and it is possible that some aspects of religious belief or practice may attenuate such elevations and thus reduce the risk of cognitive deterioration, independent of their effects on depressive symptoms [ 33 ]. In this connection, it has also been observed that increased cortisol reactivity is associated with telomere shortening, which is a potential risk factor for some forms of dementia [ 13 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

The Relationship Between Four Measures of Religiosity and Cross-National Variations in the Burden of Dementia

Rajkumar¹

2021

Cureus

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Background Several researchers have identified a possible protective effect of religiosity on the risk of dementia. Specific aspects of religiosity may be associated with this attenuation of risk, and it may be partially mediated through an effect on depressive symptoms or social support. However, this effect has only been demonstrated in selected cohorts to date. Methods This study was based on a cross-national analysis of associations. Correlations between World Health Organization estimates of the burden of dementia and four survey-derived measures of religiosity were examined across 101 countries, while controlling for estimates of late-life depression and social capital. Results Specific aspects of religiosity, such as attendance at religious services (Pearson’s r= -0.57), daily prayer (r = - 0.58), and perception of religion as very important (r = -0.65), were associated with lower national levels of Alzheimer’s and other dementias (p< 0.01 for all correlations). This effect was partially mediated through an inverse relationship between religiosity and depression, but remained significant even after controlling for it and on multivariate analyses (β = -0.38 to -0.57, p< 0.01 for all measures). There was no evidence for a mediating effect of social capital. Conclusions Specific religious beliefs and practices may have a protective effect on dementia risk at the population level. These may involve group effects that require further study, such as reductions in depression in the elderly, or may involve beneficial effects on the stress response and cellular ageing in vulnerable individuals; however, the latter cannot be inferred with certainty from a group-level analysis. These results are consistent with earlier research and suggest a potential role for religious-based preventive strategies at the population level.

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Cortisol hypersecretion and the risk of Alzheimer’s disease: A systematic review and meta-analysis

Cited by 38 publications

References 73 publications

Targeted Metabolomic Analysis in Alzheimer’s Disease Plasma and Brain Tissue in Non-Hispanic Whites

Targeted Metabolomic Analysis in Alzheimer’s Disease Plasma and Brain Tissue in Non-Hispanic Whites

Cerebrospinal Fluid Cortisol and Dehydroepiandrosterone Sulfate, Alzheimer’s Disease Pathology, and Cognitive Decline

The Relationship Between Four Measures of Religiosity and Cross-National Variations in the Burden of Dementia

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