DHEA treatment of Alzheimer’s disease

Wolkowitz, Owen M.; Kramer, Joel H.; Reus, Victor I.; Costa, Martin; Yaffe, Kristine; Walton, Pam; Raskind, Murray A.; Peskind, Elaine R.; Newhouse, Paul; Sack, David A.; Souza, EB De; Sadowsky, Carl; Roberts, Eugene

doi:10.1212/01.wnl.0000052994.54660.58

Cited by 92 publications

(37 citation statements)

References 28 publications

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“…It is unclear what dose would be required to produce similar effects, if these are possible, in a population with lower baseline DHEA concentrations. Secondly, the use of such high doses of DHEA as used here over the long term, could theoretically lead, via metabolism into active sex steroids, to adverse effects, such as enhanced hormone-sensitive tumour growth (Wolkowitz et al 2003). As a result, future investigations need to proceed with caution.…”

Section: Discussionmentioning

confidence: 99%

“…However, the extrapolation of such findings in animals to humans is problematic because DHEA concentrations in rodents are significantly lower than in man (Vallee et al 2001). Further, in humans, results have been inconsistent and almost all placebo-controlled trials have found no beneficial effects on memory in healthy old subjects (Barnhart et al 1999;Wolf et al 1997Wolf et al , 1998van Niekerk et al 2001) or patients with Alzheimer's disease (Wolkowitz et al 2003). This could be due to the use of different dosage, variation of period of DHEA administration and age of subjects.…”

Section: Introductionmentioning

confidence: 99%

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Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study

2005

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study

2005

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“…The majority of trials (n = 94) used at least one cognitive outcome, 25,27-29, 51,52,55,57,64,66,68,75,78,[86][87][88][89][90][91][92][93]97,104,106,107,110,112,115,118,119,121,123,125,126,130,131,133,134,[137][138][139][140]143,145,146 with a variety of 16 measures used. ADLs were measured in 55 trials, using 12 measures.…”

Section: Published Trialsmentioning

confidence: 99%

Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations

Webster

Groskreutz

Grinbergs-Saull

et al. 2017

Health Technol Assess

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Background: There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials. Objectives: To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI). Data sources: We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches. Review methods: The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes. Results: We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally. Limitations: Most of the trials inclu...

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“…Further studies, however, mostly with small series of patients, did not confirm these results (Cuckle et al, 1990;Spath-Schwalbe et al, 1990;Leblhuber et al, 1993). More recently, observational longitudinal studies failed to demonstrate a predictive role of DHEA levels with respect to development of cognitive decline (Barret-Connor and Edelstein, 1994;Berr et al, 1996;Yaffe et al, 1998), and a randomized trial did not show evidence of benefit from treatment with DHEA in patients with Alzheimer's disease (Wolkowitz et al, 2003). Despite this lack of evidence, negative results in previous studies might originate from heterogeneous sample (including different subtypes of dementia) and from inadequacy to focus on selected neuropsychologic fields, as memory and attention, which in experimental models have proven to be favourably affected by DHEA-S administration.…”

Section: Introductionmentioning

confidence: 99%

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

Massaia

Zannella

et al. 2006

Int J Geriat Psychiatry

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DHEA treatment of Alzheimer’s disease

Abstract: DHEA did not significantly improve cognitive performance or overall ratings of change in severity in this small-scale pilot study. A transient effect on cognitive performance may have been seen at month 3, but narrowly missed significance.

Cited by 92 publications

References 28 publications

Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study

Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study

Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations

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

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