This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s Terms & Conditions.

Focus on Alzheimer's Disease and Related Disorders

Lithium Trial in Alzheimer’s Disease: A Randomized, Single-Blind, Placebo-Controlled, Multicenter 10-Week Study

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

Published: June 18, 2009

Article 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 = 21 and = 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-amyloid1-42 (Abeta1-42), plasma levels of Abeta1-42, 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.

Conclusion: 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

Volume: 70

Quick Links: Dementia , Neurologic and Neurocognitive

Continue Reading…

Subscribe to read the entire article

$40.00

Buy this Article as a PDF

Sign-up to stay
up-to-date today!

SUBSCRIBE

Already registered? Sign In

Original Research

Telehealth of Coordinated Specialty Care in Early Psychosis During COVID-19

As the COVID-19 pandemic emerged in 2020, access to in-person clinical care was restricted. This study explored...

Read More...