Lithium, a therapy for ad: Current evidence from clinical trials of neurodegenerative disorders

Orestes V. Forlenza; Ivan Aprahamian; Vanessa J. De Paula; Tomas Hajek

doi:10.2174/1567205013666160219112854

Lithium, a therapy for ad: Current evidence from clinical trials of neurodegenerative disorders

Orestes V. Forlenza, Ivan Aprahamian, Vanessa J. De Paula, Tomas Hajek

Medicine

Research output: Contribution to journal › Article › peer-review

41 Citations (Scopus)

Abstract

Background: Preclinical studies have shown that lithium modifies pathological cascades implicated in certain neurodegenerative disorders, such as Alzheimer’s disease (AD), Huntigton`s disease (HD), multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS). A critical question is whether these pharmacodynamic properties of lithium translate into neurodegenerative diseases modifying effects in human subjects. Methods: We reviewed all English controlled clinical trials published in PubMed, PsycINFO, Embase, SCOPUS, ISI-Web with the use of lithium for the treatment of neurodegenerative disorders between July 2004 and July 2014. Results: Lithium showed evidence for positive effects on cognitive functions and biomarkers in amnestic mild cognitive impairment (aMCI, 1 study) and AD (2 studies), even with doses lower than those used for mood stabilisation. Studies of Li in HD, MSA and CSI did not show benefits of lithium. However, due to methodological limitations and small sample size, these studies may be inconclusive. Studies in ALS showed consistently negative results and presented evidence against the use of lithium for the treatment of this disease. Conclusion: In absence of disease modifying treatments for any neurodegenerative disorders, the fact that at least 3 studies supported the effect of lithium in aMCI/AD is noteworthy. Future studies should focus on defining the dose range necessary for neuroprotective effects to occur.

Original language	English
Pages (from-to)	879-886
Number of pages	8
Journal	Current Alzheimer Research
Volume	13
Issue number	8
DOIs	https://doi.org/10.2174/1567205013666160219112854
Publication status	Published - Aug 1 2016

Bibliographical note

Funding Information:
Fundação de Amparo á Pesquisa de São Paulo (FAPESP Grant nº 09/52825-8, Brazil), Associação Beneficente Alzira Denise Hertzog da Silva (ABADHS) e JNK Empreendimentose Incorporações.

Publisher Copyright:
© 2016 Bentham Science Publishers.

ASJC Scopus Subject Areas

Neurology
Clinical Neurology

PubMed: MeSH publication types

Journal Article
Review
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.2174/1567205013666160219112854

Cite this

@article{c20354cabc6b4bab94e99375295d7b89,

title = "Lithium, a therapy for ad: Current evidence from clinical trials of neurodegenerative disorders",

abstract = "Background: Preclinical studies have shown that lithium modifies pathological cascades implicated in certain neurodegenerative disorders, such as Alzheimer{\textquoteright}s disease (AD), Huntigton`s disease (HD), multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS). A critical question is whether these pharmacodynamic properties of lithium translate into neurodegenerative diseases modifying effects in human subjects. Methods: We reviewed all English controlled clinical trials published in PubMed, PsycINFO, Embase, SCOPUS, ISI-Web with the use of lithium for the treatment of neurodegenerative disorders between July 2004 and July 2014. Results: Lithium showed evidence for positive effects on cognitive functions and biomarkers in amnestic mild cognitive impairment (aMCI, 1 study) and AD (2 studies), even with doses lower than those used for mood stabilisation. Studies of Li in HD, MSA and CSI did not show benefits of lithium. However, due to methodological limitations and small sample size, these studies may be inconclusive. Studies in ALS showed consistently negative results and presented evidence against the use of lithium for the treatment of this disease. Conclusion: In absence of disease modifying treatments for any neurodegenerative disorders, the fact that at least 3 studies supported the effect of lithium in aMCI/AD is noteworthy. Future studies should focus on defining the dose range necessary for neuroprotective effects to occur.",

author = "Forlenza, {Orestes V.} and Ivan Aprahamian and {De Paula}, {Vanessa J.} and Tomas Hajek",

note = "Funding Information: Funda{\c c}{\~a}o de Amparo {\'a} Pesquisa de S{\~a}o Paulo (FAPESP Grant nº 09/52825-8, Brazil), Associa{\c c}{\~a}o Beneficente Alzira Denise Hertzog da Silva (ABADHS) e JNK Empreendimentose Incorpora{\c c}{\~o}es. Publisher Copyright: {\textcopyright} 2016 Bentham Science Publishers.",

year = "2016",

month = aug,

day = "1",

doi = "10.2174/1567205013666160219112854",

language = "English",

volume = "13",

pages = "879--886",

journal = "Current Alzheimer Research",

issn = "1567-2050",

publisher = "Bentham Science Publishers B.V.",

number = "8",

}

TY - JOUR

T1 - Lithium, a therapy for ad

T2 - Current evidence from clinical trials of neurodegenerative disorders

AU - Forlenza, Orestes V.

AU - Aprahamian, Ivan

AU - De Paula, Vanessa J.

AU - Hajek, Tomas

N1 - Funding Information: Fundação de Amparo á Pesquisa de São Paulo (FAPESP Grant nº 09/52825-8, Brazil), Associação Beneficente Alzira Denise Hertzog da Silva (ABADHS) e JNK Empreendimentose Incorporações. Publisher Copyright: © 2016 Bentham Science Publishers.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Background: Preclinical studies have shown that lithium modifies pathological cascades implicated in certain neurodegenerative disorders, such as Alzheimer’s disease (AD), Huntigton`s disease (HD), multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS). A critical question is whether these pharmacodynamic properties of lithium translate into neurodegenerative diseases modifying effects in human subjects. Methods: We reviewed all English controlled clinical trials published in PubMed, PsycINFO, Embase, SCOPUS, ISI-Web with the use of lithium for the treatment of neurodegenerative disorders between July 2004 and July 2014. Results: Lithium showed evidence for positive effects on cognitive functions and biomarkers in amnestic mild cognitive impairment (aMCI, 1 study) and AD (2 studies), even with doses lower than those used for mood stabilisation. Studies of Li in HD, MSA and CSI did not show benefits of lithium. However, due to methodological limitations and small sample size, these studies may be inconclusive. Studies in ALS showed consistently negative results and presented evidence against the use of lithium for the treatment of this disease. Conclusion: In absence of disease modifying treatments for any neurodegenerative disorders, the fact that at least 3 studies supported the effect of lithium in aMCI/AD is noteworthy. Future studies should focus on defining the dose range necessary for neuroprotective effects to occur.

AB - Background: Preclinical studies have shown that lithium modifies pathological cascades implicated in certain neurodegenerative disorders, such as Alzheimer’s disease (AD), Huntigton`s disease (HD), multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS). A critical question is whether these pharmacodynamic properties of lithium translate into neurodegenerative diseases modifying effects in human subjects. Methods: We reviewed all English controlled clinical trials published in PubMed, PsycINFO, Embase, SCOPUS, ISI-Web with the use of lithium for the treatment of neurodegenerative disorders between July 2004 and July 2014. Results: Lithium showed evidence for positive effects on cognitive functions and biomarkers in amnestic mild cognitive impairment (aMCI, 1 study) and AD (2 studies), even with doses lower than those used for mood stabilisation. Studies of Li in HD, MSA and CSI did not show benefits of lithium. However, due to methodological limitations and small sample size, these studies may be inconclusive. Studies in ALS showed consistently negative results and presented evidence against the use of lithium for the treatment of this disease. Conclusion: In absence of disease modifying treatments for any neurodegenerative disorders, the fact that at least 3 studies supported the effect of lithium in aMCI/AD is noteworthy. Future studies should focus on defining the dose range necessary for neuroprotective effects to occur.

UR - http://www.scopus.com/inward/record.url?scp=84975764391&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975764391&partnerID=8YFLogxK

U2 - 10.2174/1567205013666160219112854

DO - 10.2174/1567205013666160219112854

M3 - Article

C2 - 26892289

AN - SCOPUS:84975764391

SN - 1567-2050

VL - 13

SP - 879

EP - 886

JO - Current Alzheimer Research

JF - Current Alzheimer Research

IS - 8

ER -

Lithium, a therapy for ad: Current evidence from clinical trials of neurodegenerative disorders

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this