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

Hdl Handle:
http://hdl.handle.net/10147/207885
Title:
Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study.
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
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
Citation:
J Clin Psychiatry. 2009 Jun;70(6):922-31.
Journal:
The Journal of clinical psychiatry
Issue Date:
1-Feb-2012
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
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
ISSN:
1555-2101 (Electronic); 0160-6689 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorHampel, Haralden_GB
dc.contributor.authorEwers, Michaelen_GB
dc.contributor.authorBurger, Katharinaen_GB
dc.contributor.authorAnnas, Peteren_GB
dc.contributor.authorMortberg, Anetteen_GB
dc.contributor.authorBogstedt, Annaen_GB
dc.contributor.authorFrolich, Lutzen_GB
dc.contributor.authorSchroder, Johannesen_GB
dc.contributor.authorSchonknecht, Peteren_GB
dc.contributor.authorRiepe, Matthias Wen_GB
dc.contributor.authorKraft, Ingaen_GB
dc.contributor.authorGasser, Thomasen_GB
dc.contributor.authorLeyhe, Thomasen_GB
dc.contributor.authorMoller, Hans-Jurgenen_GB
dc.contributor.authorKurz, Alexanderen_GB
dc.contributor.authorBasun, Hansen_GB
dc.date.accessioned2012-02-01T10:49:06Z-
dc.date.available2012-02-01T10:49:06Z-
dc.date.issued2012-02-01T10:49:06Z-
dc.identifier.citationJ Clin Psychiatry. 2009 Jun;70(6):922-31.en_GB
dc.identifier.issn1555-2101 (Electronic)en_GB
dc.identifier.issn0160-6689 (Linking)en_GB
dc.identifier.pmid19573486en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207885-
dc.description.abstractOBJECTIVE: 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAgeden_GB
dc.subject.meshAged, 80 and overen_GB
dc.subject.meshAlzheimer Disease/diagnosis/*drug therapy/psychologyen_GB
dc.subject.meshAmyloid beta-Peptides/metabolismen_GB
dc.subject.meshEnzyme Inhibitors/adverse effects/*therapeutic useen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGlycogen Synthase Kinase 3/*antagonists & inhibitorsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshLithium Carbonate/adverse effects/*therapeutic useen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMental Status Schedule/statistics & numerical dataen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshNeuropsychological Tests/statistics & numerical dataen_GB
dc.subject.meshPeptide Fragments/metabolismen_GB
dc.subject.meshPhosphorylationen_GB
dc.subject.meshPsychometricsen_GB
dc.subject.meshSingle-Blind Methoden_GB
dc.subject.meshtau Proteins/metabolismen_GB
dc.titleLithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study.en_GB
dc.contributor.departmentTrinity 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.deen_GB
dc.identifier.journalThe Journal of clinical psychiatryen_GB
dc.description.provinceLeinster-

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