Dehydroepiandrosterone sulphate in Alzheimer's disease

Leblhuber, Friedrich; Windhager, Elmar; Reisecker, F; Steinparz, F.X.; Dienstl, E; Cuckle, H. S.; Stone, R.; Smith, David H.G.; Wald, Nicholas; Brammer, Michael; Hajimohammedreza, I.; Levy, Raymond; Chard, Tim; Perry, Les

doi:10.1016/0140-6736(90)92006-4

Cited by 35 publications

(13 citation statements)

References 6 publications

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“…Five subsequent reports [8][9][10][11][12] have not supported these findings, while one report by Nasman et al [6] studying 45 AD patients, the largest sample size so far, has demonstrated a lower concentration of serum DHEA-S not only in patients with AD but also in patients with multi-infarct dementia (MID). Such a discrepancy may be attributed to slight differences in the sample size, age and gender distribution.…”

Section: Statisticsmentioning

confidence: 74%

“…However, the exact concentrations of serum in DHEA-S must still be regarded as controversial, since five other studies found no difference in serum DHEA-S level between AD patients and controls [8][9][10][11][12]. All of the previous studies have focused only on circulating DHEA-S levels and have not yet examined another important index, namely serum DHEA levels in AD.…”

Section: Dehydroepiandrosteronementioning

confidence: 99%

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Serum Dehydroepiandrosterone (DHEA) and DHEA-Sulfate (DHEA-S) in Alzheimer's Disease and in Cerebrovascular Dementia.

et al. 1996

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Section: Statisticsmentioning

confidence: 74%

Section: Dehydroepiandrosteronementioning

confidence: 99%

Serum Dehydroepiandrosterone (DHEA) and DHEA-Sulfate (DHEA-S) in Alzheimer's Disease and in Cerebrovascular Dementia.

et al. 1996

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“…The decline of DHEAS with age has led to considering the intriguing possibility that its serum levels are related to the development of age-associated ''normal'' changes, as well as diseases such as cancer, atherosclerosis, or Alzheimer disease (14)(15)(16)(17)(18)(19)(20)(21)(22). Results to date have not been conclusive.…”

mentioning

confidence: 90%

Relationships of dehydroepiandrosterone sulfate in the elderly with functional, psychological, and mental status, and short-term mortality: A French community-based study

Berr

Lafont

Debuire

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

258

128

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In human beings of both sexes, dehydroepiandrosterone sulfate (DHEAS) circulating in blood is mostly an adrenally secreted steroid whose serum concentration (in the micromolar range and 30-50% higher in men than in women) decreases with age, toward Ϸ20-10% of its value in young adults during the 8th and 9th decades. The mechanism of action of DHEA and DHEAS is poorly known and may include partial transformation into sex steroids, increase of bioavailable insulin-like growth factor I, and effects on neurotransmitter receptors. Whether there is a cause-to-effect relationship between the decreasing levels of DHEAS with age and physiological and pathological manifestations of aging is still undecided, but this is of obvious theoretical and practical interest in view of the easy restoration by DHEA administration. Here we report on 622 subjects over 65 years of age, studied for the 4 years since DHEAS baseline values had been obtained, in the frame of the PAQUID program, analyzing the functional, psychological, and mental status of a communitybased population in the south-west of France. We confirm the continuing decrease of DHEAS serum concentration with age, more in men than in women, even if men retain higher levels. Significantly lower values of baseline DHEAS were recorded in women in cases of functional limitation (Instrumental Activities of Daily Living), confinement, dyspnea, depressive symptomatology, poor subjective perception of health and life satisfaction, and usage of various medications. In men, there was a trend for the same correlations, even though not statistically significant in most categories. No differences in DHEAS levels were found in cases of incident dementia in the following 4 years. In men (but not in women), lower DHEAS was significantly associated with increased short-term mortality at 2 and 4 years after baseline measurement. These results, statistically established by taking into account corrections for age, sex, and health indicators, suggest the need for further careful trials of the administration of replacement doses of DHEA in aging humans. Indeed, the first noted results of such ''treatment'' are consistent with correlations observed here between functional and psychological status and endogenous steroid serum concentrations.

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“…For instance, Weill-Engerer and colleagues [108] reported that not only are brain levels of DHEAS significantly lower in AD, but also the lower levels are inversely correlated with the presence of phosphorylated tau and β-amyloid. A few studies have not detected differences in serum DHEAS concentrations between AD patients and controls [120,123], and there is one report that serum DHEAS levels are increased in mild-moderate AD [124]. The reasons for these differences between studies have not yet been elucidated.…”

Section: Dhea and Admentioning

confidence: 91%

“…Several other clinical studies have reported lower serum concentrations of DHEAS in patients with AD [14,[118][119][120], a reduction paralleled by decreases in the brain and cerebral spinal fluid [121,122]. For instance, Weill-Engerer and colleagues [108] reported that not only are brain levels of DHEAS significantly lower in AD, but also the lower levels are inversely correlated with the presence of phosphorylated tau and β-amyloid.…”

Section: Dhea and Admentioning

confidence: 99%

Dehydroepiandrosterone (DHEA) and DHEA Sulfate: Roles in Brain Function and Disease

Quinn¹,

Robinson²,

Walker³

2018

Sex Hormones in Neurodegenerative Processes and Diseases

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Among the neuroactive steroids, dehydroepiandrosterone (3b-hydroxyandrost-5-ene-17-one, [DHEA]) and its sulfated metabolite DHEA sulfate (DHEAS) have been shown to be potent modulators of neural function, including neurogenesis, neuronal growth and differentiation, and neuroprotection. Highlighting the potential health significance of DHEA and DHEAS in humans, serum concentrations decrease steadily with age, with lowest concentrations present at the time many diseases of aging and neurodegeneration become apparent. This temporal association has led to the suggestion that pathology associated with cognitive decline, age-related neurological disorders such as Alzheimer's disease, dementia, amyotrophic lateral sclerosis (ALS), and adult onset schizophrenia may, in part at least, be attributed to decreased secretion of DHEA. Animal studies suggest neuroprotective functions for DHEA and DHEAS through reduction of glutamate-induced excitotoxicity. Reduced myelin loss and reactive gliosis after spinal cord injury by DHEA treatment also suggest a role for DHEA in the treatment of white matter pathologies such as multiple sclerosis. In this chapter, we discuss the physiological roles of DHEA and DHEAS in the central nervous system (CNS), their potential as neuroprotective hormones with reference to documented effects on excitotoxicity and oxidative stress, and their anti-glucocorticoid actions during chronic stress. The potential for metabolic derivatives of DHEA, such as estrogens and testosterone on brain function, and their contribution to neurodevelopment and neurodegenerative conditions are also discussed.

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Dehydroepiandrosterone sulphate in Alzheimer's disease

Cited by 35 publications

References 6 publications

Serum Dehydroepiandrosterone (DHEA) and DHEA-Sulfate (DHEA-S) in Alzheimer's Disease and in Cerebrovascular Dementia.

Serum Dehydroepiandrosterone (DHEA) and DHEA-Sulfate (DHEA-S) in Alzheimer's Disease and in Cerebrovascular Dementia.

Relationships of dehydroepiandrosterone sulfate in the elderly with functional, psychological, and mental status, and short-term mortality: A French community-based study

Dehydroepiandrosterone (DHEA) and DHEA Sulfate: Roles in Brain Function and Disease

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