Dehydroepiandrosterone sulfate (DHEA‐S) and Alzheimer's dementia in older subjects

Bo, Mario; Massaia, Massimiliano; Zannella, Patrizia; Cappa, Giorgetta; Ferrario, E.; Rainero, Innocenzo; Arvat, Emanuela; Giordano, Roberta; Molaschi, M

doi:10.1002/gps.1608

Cited by 13 publications

(4 citation statements)

References 37 publications

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“…Despite biologic evidence for the neuroprotective effects of androgens against amyloid-β induced apoptosis and tau hyperphosphorylation, we found no association between DHEA-S and disease progression. Our findings are consistent with an earlier study in which plasma DHEA-S was not associated with presence of AD, impairment in cognitive domains, or cumulative mortality (Bo et al, 2006), albeit in contradiction to a subsequent study reporting lower plasma DHEA in AD patients respective to age-matched controls (Aldred and Mecocci, 2010). Further, DHEA levels within cerebrospinal fluid were significantly higher in AD patients compared with cognitively normal controls and correlated with Braak neuropathological disease stage.…”

Section: Discussionsupporting

confidence: 86%

Elevations in Serum Dickkopf-1 and Disease Progression in Community-Dwelling Older Adults With Mild Cognitive Impairment and Mild-to-Moderate Alzheimer’s Disease

Tay

Leung

Yeo

et al. 2019

Front. Aging Neurosci.

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Background: Disruption of Wnt signaling has been implicated in dysfunctional synaptic plasticity, the degree of which correlates with Alzheimer’s disease severity. We sought to examine whether serum levels of Dickkopf-1 (Dkk-1), a Wnt antagonist, are associated with global disease progression in older adults with mild cognitive impairment (MCI) and mild-to-moderate AD.Methods: We prospectively followed 88 older adults with MCI and mild-to-moderate AD attending a Memory Clinic. Cognitive performance, functional performance and neuropsychological symptoms were assessed at baseline and after 1 year. We reviewed neuroimaging for white matter changes and medial temporal atrophy, and performed ApoE genotyping at baseline. Serum Dkk-1 was assayed at baseline and 1 year, along with blood biomarkers of inflammation and endocrine dysfunction. We defined global disease progression (“progressors”) as an increase in Clinical Dementia Rating Sum-of-Boxes (CDR-SB) score by >2 points at 1 year.Results: Fifteen (17.0%) participants had global disease progression. At baseline, there was no difference in cognitive performance and neuropsychiatric symptoms between groups, although progressors were more impaired in instrumental activities of daily living (p = 0.008). Progressors had significantly greater deterioration in cognitive performance (p = 0.002), with significantly worse functional performance and more severe neuropsychiatric symptoms (p = 0.042) at follow-up. Serum inflammatory and endocrine biomarkers at baseline and 1 year were similar between progressors and non-progressors. Serum Dkk-1 had increased significantly from baseline amongst progressors, while non-progressors exhibited decremental Dkk-1 over time (Dkk-1change: 354.304 ± 670.467 vs. −173.582 ± 535.676 ng/ml, p = 0.001). Adjusting for age, gender and baseline cognitive performance, incremental Dkk-1 independently predicted global cognitive decline (p = 0.012).Conclusion: Our results suggest progressively dysfunctional Wnt signaling through Dkk-1 antagonism contributes to disease progression amongst older adults with MCI and mild-moderate AD.

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Section: Discussionsupporting

confidence: 86%

Elevations in Serum Dickkopf-1 and Disease Progression in Community-Dwelling Older Adults With Mild Cognitive Impairment and Mild-to-Moderate Alzheimer’s Disease

Tay

Leung

Yeo

et al. 2019

Front. Aging Neurosci.

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“…DHEA(S) concentrations are not clearly associated with cognition in dementia; however, it may be important to compare relative concentrations of DHEA-to-DHEAS and other metabolites of DHEA. Patients with Alzheimer’s disease and/or multi-infarct dementia have been reported to exhibit decreased [17; 34; 62; 91; 216; 223; 288; 304; 306; 344], as well as increased or unchanged [38; 40; 92; 172; 276; 291] plasma, serum and CSF DHEA(S) concentrations. In several instances, plasma and serum DHEA(S)-to-cortisol ratios distinguish demented participants from controls better than DHEA(S) or cortisol concentrations alone [12; 73; 170; 171; 192].…”

Section: Dhea(s) Concentrations and Neuropsychiatric Illnessesmentioning

confidence: 99%

Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)

Maninger

Wolkowitz

Reus

et al. 2009

Frontiers in Neuroendocrinology

646

603

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DHEA and DHEAS are steroids synthesized in human adrenals, but their function is unclear. In addition to adrenal synthesis, evidence also indicates that DHEA and DHEAS are synthesized in the brain, further suggesting a role of these hormones in brain function and development. Despite intensifying research into the biology of DHEA and DHEAS, many questions concerning their mechanisms of action and their potential involvement in neuropsychiatric illnesses remain unanswered. We review and distill the preclinical and clinical data on DHEA and DHEAS, focusing on (i) biological actions and putative mechanisms of action, (ii) differences in endogenous circulating concentrations in normal subjects and patients with neuropsychiatric diseases, and (iii) the therapeutic potential of DHEA in treating these conditions. Biological actions of DHEA and DHEAS include neuroprotection, neurite growth, and antagonistic effects on oxidants and glucocorticoids. Accumulating data suggest abnormal DHEA and/or DHEAS concentrations in several neuropsychiatric conditions. The evidence that DHEA and DHEAS may be fruitful targets for pharmacotherapy in some conditions is reviewed.

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“…Conversely, DHEAS is significantly lower in the CSF [20], but not in the serum from people affected with Alzheimer's disease in comparison to controls [12]. Although more studies are required to determine the actual status of DHEA levels in Alzheimer's disease, the majority of published studies indicated that DHEA levels were elevated in Alzheimer's disease.…”

Section: Androgens In Alzheimer's Diseasementioning

confidence: 95%

“…Many studies have confirmed that total testosterone declines at a rate between 0.9 and 1.6% per year after the third decade of life, whereas bioavailable testosterone declines at a higher annual rate due to the concurrent increase in SHBG at an average rate of approximately 1.3% per year, compounding the effect of depleting total testosterone [6][7][8][9][10][11]. DHEA and DHEAS also decline with age [12,13].…”

Section: Androgens In Normal Agingmentioning

confidence: 97%

Androgens and Alzheimer's disease

Drummond

Harvey²,

Martins³

2009

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Dehydroepiandrosterone sulfate (DHEA‐S) and Alzheimer's dementia in older subjects

Abstract: In a sample of newly-diagnosed DAT patients, we did not find significant association between presence of DAT or impairment in cognitive domains and DHEA-S levels; baseline DHEA-S levels are not associated with cumulative mortality in patients and controls.

Cited by 13 publications

References 37 publications

Elevations in Serum Dickkopf-1 and Disease Progression in Community-Dwelling Older Adults With Mild Cognitive Impairment and Mild-to-Moderate Alzheimer’s Disease

Elevations in Serum Dickkopf-1 and Disease Progression in Community-Dwelling Older Adults With Mild Cognitive Impairment and Mild-to-Moderate Alzheimer’s Disease

Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)

Androgens and Alzheimer's disease

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