Lithium as a Treatment for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Article type: Research Article

Authors: Matsunaga, Shinji^{a; *} | Kishi, Taro^a | Annas, Peter^b | Basun, Hans^{c; d} | Hampel, Harald^{e; *} | Iwata, Nakao^a

Affiliations: [a] Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan | [b] Department of Psychology, Uppsala University, Uppsala, Sweden | [c] Department of Public Care and Family Medicine, Section of Geriatric Medicine, Uppsala University, Uppsala, Sweden | [d] BioArctic Neuroscience AB, Stockholm, Sweden | [e] AXA Research Fund and UPMC Chair, Sorbonne Universités,Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d’Alzheimer & INSERM U1127, Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France

Correspondence: [*] Correspondence to: Shinji Matsunaga, MD, PhD, Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470–1192, Japan. Tel.: +81 562 93 9250; Fax: +81 562 93 1831; E-mail: [email protected]

Correspondence: [*] Correspondence to: Harald Hampel, MD, PhD, MSc, AXA Research Fund and UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A) & INSERM U1127, Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Pavillon François Lhermitte, Hôpital de la Pitié-Salpêtrière, 47 Boulevard de l’Hôpital, 75651 - Paris, CEDEX 13, France. Tel.: +33 1 42 16 75 15; Fax: +33 1 42 16 75 16; [email protected]

Abstract: Background: This is the first meta-analysis of randomized placebo-controlled trials testing lithium as a treatment for patients with Alzheimer’s disease (AD) and individuals with mild cognitive impairment (MCI). Methods: The primary outcome measure was efficacy on cognitive performance as measured through the Alzheimer’s Disease Assessment Scale cognitive subscale or the Mini-Mental State Examination. Other outcome measures were drug discontinuation rate, individual side effects, and biological markers (phosphorylated tau 181, total tau, and amyloid-β42) in cerebrospinal fluid (CSF). Results: Three clinical trials including 232 participants that met the study’s inclusion criteria were identified. Lithium significantly decreased cognitive decline as compared to placebo (standardized mean difference = –0.41, 95% confidence interval = –0.81 to –0.02, p = 0.04, I2 = 47% , 3 studies, n = 199). There were no significant differences in the rate of attrition, discontinuation due to all causes or adverse events, or CSF biomarkers between treatment groups. Conclusions: The results indicate that lithium treatment may have beneficial effects on cognitive performance in subjects with MCI and AD dementia.

Keywords: Alzheimer’s disease, lithium, meta-analysis, mild cognitive impairment, systematic review

DOI: 10.3233/JAD-150437

Journal: Journal of Alzheimer's Disease, vol. 48, no. 2, pp. 403-410, 2015