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Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study
Hampel H, Ewers M, Bürger K, Annas P, Mörtberg A, Bogstedt A, Frölich L, Schröder J et al.. The Journal of clinical psychiatry, 2009-06-01
Topic: Plasma and spinal-fluid biomarkers
Objective Lithium, a first-line drug for the treatment of bipolar depression, has recently been shown to regulate glycogen synthase kinase-3 (GSK-3), a kinase that is involved in the phosphorylation of the tau protein. Since hyperphosphorylation of tau is a core pathological feature in Alzheimer's disease, lithium-induced inhibition of GSK-3 activity may have therapeutic effects in Alzheimer's disease. In the current study, we tested the effect of short-term lithium treatment in patients with Alzheimer's disease. Method A total of 71 patients with mild Alzheimer's disease (Mini-Mental State Examination score > or = 21 and < or = 26) were successfully randomly assigned to placebo (N = 38) or lithium treatment (N = 33) at 6 academic expert memory clinics. The 10-week treatment included a 6-week titration phase to reach the target serum level of lithium (0.5-0.8 mmol/L). The primary outcome measures were cerebrospinal fluid (CSF) levels of phosphorylated tau (p-tau) and GSK-3 activity in lymphocytes. Secondary outcome measures were CSF concentration of total tau and beta-amyloid(1-42) (Abeta(1-42)), plasma levels of Abeta(1-42), Alzheimer's Disease Assessment Scale (ADAS)-Cognitive summary scores, MMSE, and Neuropsychiatric Inventory (NPI). Patients were enrolled in the study from November 2004 to July 2005. Results No treatment effect on GSK-3 activity or CSF-based biomarker concentrations (P > .05) was observed. Lithium treatment did not lead to change in global cognitive performance as measured by the ADAS-Cog subscale (P = .11) or in depressive symptoms. Conclusions The current results do not support the notion that lithium treatment may lead to reduced hyperphosphorylation of tau protein after a short 10-week treatment in the Alzheimer's disease target population. Trial registration (Controlled-Trials.com) Identifier: ISRCTN72046462.
Key findings
- Results No treatment effect on GSK-3 activity or CSF-based biomarker concentrations (P > .05) was observed.
- Conclusions The current results do not support the notion that lithium treatment may lead to reduced hyperphosphorylation of tau protein after a short 10-week treatment in the Alzheimer's disease target population.
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Study details
- Participants38
- Evidence strengthLow
How this study scored 66/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record and institution's track record, so those were left out: it earned 40 of the 61 points we could judge it on, which is 66 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of clinical psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2009 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 38 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19573486) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 40 / 61 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 40 of the 61 points we could judge it on is 66 out of 100. |
| Total | 66 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. This record has no DOI, so the citation leaves it out. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Hampel, H., Ewers, M., Bürger, K., Annas, P., Mörtberg, A., Bogstedt, A., et al. (2009). Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. The Journal of clinical psychiatry.
Vancouver
Hampel H, Ewers M, Bürger K, Annas P, Mörtberg A, Bogstedt A, et al. Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. The Journal of clinical psychiatry. 2009. PMID: 19573486.
BibTeX
@article{hampel2009-19573486,
author = {Hampel, H. and Ewers, M. and Bürger, K. and Annas, P. and Mörtberg, A. and Bogstedt, A. and Frölich, L. and Schröder, J. and others},
title = {{Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study}},
journal = {The Journal of clinical psychiatry},
year = {2009},
pmid = {19573486}
}
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