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

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

doi:10.1002/gps.4856

Cited by 26 publications

(24 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is evidence from experimental studies that cortisol might exacerbate Aβ and tau pathology in the brain, while mifepristone, a glucocorticoid antagonist, can decrease cerebral Aβ and tau load in a mouse model of AD ( Ouanes and Popp, 2019 ). In human subjects, one study from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) found CSF cortisol levels to be positively correlated with CSF tau and p-tau, but not CSF Aβ 1–42 ( Wang et al, 2018 ). Findings of studies that measured cortisol levels in the serum have been contradictory ( Laske et al, 2009 ; Pena-Bautista et al, 2019 ), possibly due to methodological differences and to the relationship between cortisol, Aβ and tau changing as the disease progresses.…”

Section: Discussionmentioning

confidence: 99%

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

Ouanes

Clark

Richiardi

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Ouanes

Clark

Richiardi

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…Carroll et al (2011) [81] have observed that the prolonged stress caused by this hyperactivation also causes an increase in the accumulation of hyperphosphorylated tau and neurodegeneration in mice. In humans, increased levels of cortisol were observed in patients with AD compared to the control group [82–84]. Huang et al (2009) [85] observed in a 2-year follow-up of patients with AD that the higher cortisol levels correlated with the faster progression of the disease, worsened in the MMSE and smaller volume of the hippocampus region when observed by resonance.…”

Section: Acquired Risk Factorsmentioning

confidence: 99%

Alzheimer’s disease: risk factors and potentially protective measures

et al. 2019

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the most common type of dementia and typically manifests through a progressive loss of episodic memory and cognitive function, subsequently causing language and visuospatial skills deficiencies, which are often accompanied by behavioral disorders such as apathy, aggressiveness and depression. The presence of extracellular plaques of insoluble β-amyloid peptide (Aβ) and neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein (P-tau) in the neuronal cytoplasm is a remarkable pathophysiological cause in patients’ brains. Approximately 70% of the risk of developing AD can be attributed to genetics. However, acquired factors such as cerebrovascular diseases, diabetes, hypertension, obesity and dyslipidemia increase the risk of AD development. The aim of the present minireview was to summarize the pathophysiological mechanism and the main risk factors for AD. As a complement, some protective factors associated with a lower risk of disease incidence, such as cognitive reserve, physical activity and diet will also be addressed.

show abstract

“…Given that altered cortisol secretion plays a role in the etiology of many diseases marked by cognitive impairments [e.g., Addison's disease, Cushing's syndrome, Alzheimer's disease, major depressive disorder, post-traumatic stress disorder, and metabolic syndrome; (130,181,185,(198)(199)(200)(201)(202)], and given the known alterations in cortisol concentrations in patients with AD on replacement therapy, it is important to determine the physiological mechanisms by which chronically altered circadian rhythms impact cognitive functioning. One such mechanism may be through sleep, given that a bidirectional relationship exists between circadian rhythmicity and the sleep-wake cycle, and because successful memory consolidation of information learned during the day is known to rely on sleep (1,90,203).…”

Section: Variations In Cortisol Concentrations and Their Effects On Cognitionmentioning

confidence: 99%

Sleep, Cognition and Cortisol in Addison’s Disease: A Mechanistic Relationship

2021

View full text Add to dashboard Cite

Sleep is a critical biological process, essential for cognitive well-being. Neuroscientific literature suggests there are mechanistic relations between sleep disruption and memory deficits, and that varying concentrations of cortisol may play an important role in mediating those relations. Patients with Addison’s disease (AD) experience consistent and predictable periods of sub- and supra-physiological cortisol concentrations due to lifelong glucocorticoid replacement therapy, and they frequently report disrupted sleep and impaired memory. These disruptions and impairments may be related to the failure of replacement regimens to restore a normal circadian rhythm of cortisol secretion. Available data provides support for existing theoretical frameworks which postulate that in AD and other neuroendocrine, neurological, or psychiatric disorders, disrupted sleep is an important biological mechanism that underlies, at least partially, the memory impairments that patients frequently report experiencing. Given the literature linking sleep disruption and cognitive impairment in AD, future initiatives should aim to improve patients’ cognitive performance (and, indeed, their overall quality of life) by prioritizing and optimizing sleep. This review summarizes the literature on sleep and cognition in AD, and the role that cortisol concentrations play in the relationship between the two.

show abstract

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

Cited by 26 publications

References 39 publications

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

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

Alzheimer’s disease: risk factors and potentially protective measures

Sleep, Cognition and Cortisol in Addison’s Disease: A Mechanistic Relationship

Contact Info

Product

Resources

About