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


Hampel, Harald, Ewers, Michael, Bürger, Katharina, Annas, Peter, Mörtberg, Anette, Bogstedt, Anna, Frölich, Lutz, Schröder, Johannes, Schönknecht, Peter, Riepe, Matthias W., Kraft, Inga, Gasser, Thomas, Leyhe, Thomas, Möller, Hans-Jürgen, Kurz, Alexander, Basun, Hans


The Journal Of Clinical Psychiatry, Volume: 70, No.: 6, Pages.: 922-931

Year of Publication



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: ( Identifier: ISRCTN72046462.; Copyright 2009 Physicians Postgraduate Press, Inc.


adverse effects, aged, aged, 80 and over, alzheimer disease, antagonists inhibitors, cerebrospinal, diagnosis, drug therapy, enzyme inhibitors, female, fluid, glycogen synthase kinase 3, humans, lithium, lithium carbonate, male, mental status schedule, metabolism, middle aged, neuropsychological tests, peptide fragments, phosphorylation, psychology, psychometrics, statistics & numerical data, tau proteins, therapeutic use

Countries of Study


Types of Dementia

Alzheimer’s Disease

Types of Study

Randomised Controlled Trial

Type of Outcomes

Behaviour, Cognition, Other


Specialist Dementia Centre Care / Memory Clinic

Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Antipsychotics and antidepressants