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    Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study.

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    Authors
    Hampel, Harald
    Ewers, Michael
    Burger, Katharina
    Annas, Peter
    Mortberg, Anette
    Bogstedt, Anna
    Frolich, Lutz
    Schroder, Johannes
    Schonknecht, Peter
    Riepe, Matthias W
    Kraft, Inga
    Gasser, Thomas
    Leyhe, Thomas
    Moller, Hans-Jurgen
    Kurz, Alexander
    Basun, Hans
    Show allShow less
    Affiliation
    Trinity Center for Health Sciences, The Adelaide and Meath Hospital Incorporating, The National Children's Hospital (AMiNCH), Tallaght, Dublin 24, Ireland., harald.hampel@med.uni-muenchen.de
    Issue Date
    2012-02-01T10:49:06Z
    MeSH
    Aged
    Aged, 80 and over
    Alzheimer Disease/diagnosis/*drug therapy/psychology
    Amyloid beta-Peptides/metabolism
    Enzyme Inhibitors/adverse effects/*therapeutic use
    Female
    Glycogen Synthase Kinase 3/*antagonists & inhibitors
    Humans
    Lithium Carbonate/adverse effects/*therapeutic use
    Male
    Mental Status Schedule/statistics & numerical data
    Middle Aged
    Neuropsychological Tests/statistics & numerical data
    Peptide Fragments/metabolism
    Phosphorylation
    Psychometrics
    Single-Blind Method
    tau Proteins/metabolism
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    Citation
    J Clin Psychiatry. 2009 Jun;70(6):922-31.
    Journal
    The Journal of clinical psychiatry
    URI
    http://hdl.handle.net/10147/207885
    PubMed ID
    19573486
    Abstract
    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.
    Language
    eng
    ISSN
    1555-2101 (Electronic)
    0160-6689 (Linking)
    Collections
    Tallaght University Hospital

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