Disease-modifying properties of long-term lithium treatment for
                        amnestic mild cognitive impairment: randomised controlled
                        trial

Forlenza, Orestes Vicente; Diniz, Breno S.; Radanovic, Márcia; Santos, Franklin Santana; Talib, Leda Leme; Gattaz, Wagner F.

doi:10.1192/bjp.bp.110.080044

Cited by 322 publications

(261 citation statements)

References 26 publications

Supporting

Mentioning

245

Contrasting

Unclassified

Order By: Relevance

“…A Phase II clinical trial studying the effect of lithium treatment in patients with AD is currently underway (ClinicalTrials.gov identifier: NCT00088387), and in a small cohort of patients lithium reduced the progression from mild cognitive impairment to full AD 55 . In addition to increasing BDNF levels, lithium also inhibits the hyperphosphorylation of Tau mediated by GSK3β and has additional beneficial effects in the activation of pro-survival CREB signalling and the activation of autophagy [56][57][58][59] ( Figure 2, and see below).…”

Section: Increasing Bdnf As a Therapeutic Approachmentioning

confidence: 99%

Convergent pathogenic pathways in Alzheimer's and Huntington's diseases: shared targets for drug development

Ehrnhoefer

Wong

Hayden

2011

Nat Rev Drug Discov

View full text Add to dashboard Cite

Neurodegenerative diseases exemplified by Alzheimer's and Huntington disease are characterized by the progressive neuropsychiatric dysfunction and loss of specific neuronal subtypes. Even though there are differences in the exact sites of pathology and clinical profiles only partially overlap, considerable similarities in disease mechanisms and pathogenic pathways can be observed. These shared mechanisms raise the possibility of common therapeutic targets for drug development. Huntington disease with a monogenic cause and the possibility to accurately identify pre-manifest mutation carriers could be exploited as a 'model' for Alzheimer's disease to test the efficacy of therapeutic interventions targeting shared pathogenic pathways.

show abstract

Section: Increasing Bdnf As a Therapeutic Approachmentioning

confidence: 99%

Convergent pathogenic pathways in Alzheimer's and Huntington's diseases: shared targets for drug development

Ehrnhoefer

Wong

Hayden

2011

Nat Rev Drug Discov

View full text Add to dashboard Cite

show abstract

“…Moreover, in individuals with mild cognitive impairment (MCI), we found that low-dose lithium intake over 4 years reduced the conversion to AD [31]. As MCI is considered a pre-Alzheimer condition [32], these findings suggest that lithium may have disease-modifying properties capable of reducing AD risk.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 86%

Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

Mury

Silva

Barbosa

et al. 2015

Eur Arch Psychiatry Clin Neurosci

Self Cite

View full text Add to dashboard Cite

a significant perdurability of long-term memory, which correlated with increased transcriptional and enzymatic activities of certain members of the Pla2 family (iPla2 and sPla2) after the chronic lithium treatment. Our data suggest new possible targets of lithium, add more information on its pharmacological activity and reinforce the possible use of low doses of lithium for the treatment of neurodegenerative conditions such as the Alzheimer's disease.

show abstract

“…Barthel et al, using positron emission tomography (PET) images of florbetaben (an 18 F-labeled Aβ-targeted PET tracer), demonstrated that nine of ten mildmoderate probable AD participants (DSM-IV and NINCDS-ADRDA criteria) were Aβ-positive, compared to only one of ten healthy controls [49] . Furthermore, in a global phase 2, open-label, non-randomized, multi-center study recruiting a total of 81 men and women with probable mild-to-moderate AD and 69 cognitively unimpaired healthy volunteers aged 55 years and older, florbetaben scans indicated a sensitivity of 80% (95% CI 71-89) and a specificity of 91% (84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98) for discriminating participants with AD from healthy controls [50] .…”

Section: Aβ As a Promising Target For Ad Treatmentmentioning

confidence: 99%

Section: Other Therapeutic Approaches To Admentioning

confidence: 99%

“…The role of GSK-3 in the development of AD-like cognitive decline was supported by Liu et al [86] who found that inhibition of phosphoinositol-3 kinase and protein kinase C results in overactivation of GSK-3, leading to tau hyperphosphorylation and eventually impaired spatial memory. Lithium, a GSK-3 inhibitor, has been shown to reduce the amount of altered tau protein in animal studies and improve cognitive and biological outcomes in participants with amnestic mild cognitive impairment in a phase 2 clinical study [87] .Besides, since inflammation may participate in the neurodegenerative process of AD, the use of non-steroidal anti-inflammatory medications such as naproxen may reduce AD incidence in vulnerable subjects [88] . Oxidative stress is also reported to play a role in the process of AD, as strongly proposed by Smith and Perry [89,90] , and antioxidants may be associated with a lower risk of AD [91] .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Combination of Aβ clearance and neurotrophic factors as a potential treatment for Alzheimer’s disease

et al. 2012

View full text Add to dashboard Cite

There is no effective drug to treat Alzheimer's disease (AD), a neurodegenerative disease affecting an estimated 30 million people around the world. Strongly supported by preclinical and clinical studies, amyloid-beta (Aβ) may be a target for developing drugs against AD. Meanwhile, the fact that localized neuronal death/loss and synaptic impairment occur in AD should also be considered. Neuronal regeneration, which does not occur normally in the mammalian central nervous system, can be promoted by neurotrophic factors (NTFs). Evidence from clinical trials has shown that both Aβ clearance and NTFs are potentially effective in treating AD, thus a new approach combining Aβ clearance and administration of NTFs may be an effective therapeutic strategy.Keywords: Alzheimer's disease; amyloid-beta; neurotrophic factors; treatment IntroductionAlzheimer's disease (AD) is an age-related, progressive and irreversible neurodegenerative disease that causes serious cognitive dysfunction. Its pathological hallmarks are extracellular deposits of amyloid-beta (Aβ) and intracellular neurofibrillary tangles, together with drastic synaptic and neuronal reduction or loss [1] . It has been estimated that AD affects 30 million people around the world [2] , and the past two decades have witnessed an explosion in research into the underlying mechanisms as well as potential therapeutic strategies. Although it was first described by German psychiatrist Alois Alzheimer in 1906, there is still no cure for AD, partly because the cellular and molecular mechanisms underlying it are far from clear. The Food and Drug Administration in the United Stateshas approved a limited range of drugs to treat AD, including acetylcholinesterase inhibitors (AChEIs) and N-methyl-Daspartate receptor (NMDAR) antagonists [3] , although their effects are merely symptomatic and memory-improvement occurs within a limited period. Donepezil, galantamine, rivastigmine and tacrine are AChEIs that prevent the breakdown of acetylcholine released from presynaptic terminals, increasing the residence time of the neurotransmitter within the synapse and thereby prolonging the duration of its interaction with postsynaptic receptors [4] . Memantine, an NMDAR antagonist, has been approved for the treatment of moderate and severe AD; it works by preventing the excitatory neurotoxicity induced by excessive glutamate [5] .Currently, no available pharmacological agents cure or reverse the progression of this devastating neurological disorder. It is therefore urgent to improve our understanding of its pathogenesis, and then develop an effective treatment strategy. This review aimed to provide insights Neurosci Bull February 1, 2013, 29(1): 111-120 112 into the design of potentially effective pharmaceutical treatments for AD by targeting two seemingly separate but tightly connected components, Aβ and neurotrophic factors (NTFs). Aβ as a Promising Target for AD TreatmentAβ is a peptide of 36-43 amino-acids produced from amyloid precursor protein (APP) through aberrant cleavage by...

show abstract

Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial

Abstract: The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer's disease.

Cited by 322 publications

References 26 publications

Convergent pathogenic pathways in Alzheimer's and Huntington's diseases: shared targets for drug development

Convergent pathogenic pathways in Alzheimer's and Huntington's diseases: shared targets for drug development

Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

Combination of Aβ clearance and neurotrophic factors as a potential treatment for Alzheimer’s disease

Contact Info

Product

Resources

About