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lithium and Alzheimer's

Rui-Fang Wang, Guo-Fang Xue, Christian Hölscher, Miao-Jing Tian, Peng Feng, Ji-Ying Zheng, Dong-Fang Li
Glucagon-like peptide-1(GLP-1) is a growth factor that has neuroprotective and anti-inflammatory properties. The protease resistant GLP-1 analogue liraglutide has been shown to be neuroprotective in previous studies in animal models of Alzheimer's disease or Parkinson's disease. Status epilepticus (SE) is a complex disorder, involving many underlying pathological processes, including excitotoxic and chronic inflammatory events. The present pilot study aims to investigate whether liraglutide alleviates the chronic inflammation response and mitochondrial stress induced by SE in the lithium-pilocarpine animal model...
March 9, 2018: Epilepsy Research
Yijun Pan, Jennifer L Short, Stephanie A Newman, Kwok H C Choy, Durgesh Tiwari, Christopher Yap, Danielle Senyschyn, William A Banks, Joseph A Nicolazzo
Epidemiological evidence suggests that people with bipolar disorder prescribed lithium exhibit a lower risk of Alzheimer's disease (AD) relative to those prescribed other mood-stabilizing medicines. Lithium chloride (LiCl) reduces brain β-amyloid (Aβ) levels, and the brain clearance of Aβ is reduced in AD. Therefore, the purpose of this study was to assess whether the cognitive benefits of LiCl are associated with enhanced brain clearance of exogenously-administered Aβ. The brain clearance of intracerebroventricularly (icv) administered125 I-Aβ42 was assessed in male Swiss outbred mice administered daily oral NaCl or LiCl (300 mg/kg for 21 days)...
March 12, 2018: Brain, Behavior, and Immunity
Cheng-Hwang Perng, Yue-Cune Chang, Ruu-Fen Tzang
OBJECTIVE: No cure is currently available for dementia; however, various treatments and interventions have been reported to be effective. The factors influencing the efficacy of dementia treatment have not been comprehensively evaluated. This study evaluated the factors influencing treatment effects on cognitive dysfunction in dementia by comparing the results obtained from a meta-analysis based on meta-regression. METHODS: We searched for articles, clinical trials, and meta-analyses on the efficacy of pharmacotherapy or psychosocial treatment for dementia published between 2000 and 2016 in the MEDLINE/PubMed, Cochrane Library, SCOPUS, and Airiti Library databases...
March 3, 2018: Psychopharmacology
Sarah A Monaco, Brielle R Ferguson, Wen-Jun Gao
Glycogen synthase kinase 3β (GSK3β) is a highly conserved serine/threonine kinase that has been implicated in both psychiatric and neurodegenerative diseases including schizophrenia, bipolar disorder, and Alzheimer's disease; therefore regulating its activity has become an important strategy for treatment of cognitive impairments in these disorders. This study examines the effects of lithium on GSK3β and its interaction with β-catenin and NMDA receptors within the prefrontal cortex. Lithium, a clinically relevant drug commonly prescribed as a mood stabilizer for psychiatric disorders, significantly increased levels of phosphorylated GSK3β serine 9, an inhibitory phosphorylation site, and decreased β-catenin ser33/37/thr41 phosphorylation in vitro , indicating GSK3β inhibition and reduced β-catenin degradation...
2018: Frontiers in Cellular Neuroscience
Élise Morlet, Franz Hozer, Jean-François Costemale-Lacoste
Lithium is used as a first line treatment in bipolar disorder. The neuroprotective effects of lithium in this indication tend to be well known and are mediated by its action on two enzymes: glycogen synthase kinase-3 and inositol monophosphatase-1. Preclinical and clinical studies seek to evaluate the neuroprotective effect of lithium in neurodegenerative disorders. The aims of this literature review is to gather clinical studies that investigated the efficacy of lithium in neurodegenerative diseases, using a systematic method based on PubMed data...
February 5, 2018: Gériatrie et Psychologie Neuropsychiatrie du Vieillissement
Val Andrew Fajardo, Val Andrei Fajardo, Paul J LeBlanc, Rebecca E K MacPherson
BACKGROUND: Alzheimer's disease (AD) mortality rates have steadily increased over time. Lithium, the current gold standard treatment for bipolar disorder, can exert neuroprotective effects against AD. OBJECTIVE: We examined the relationship between trace levels of lithium in drinking water and changes in AD mortality across several Texas counties. METHODS: 6,180 water samples from public wells since 2007 were obtained and averaged for 234 of 254 Texas counties...
2018: Journal of Alzheimer's Disease: JAD
Xiangchang Zeng, Siyu Chen, Qing Gao, Wenjing Zong, Dejian Jiang, Guirong Zeng, Luping Zhou, Lulu Chen, Wei Luo, Jian Xiao, Bo Xiao, Dongsheng Ouyang, Kai Hu
OBJECTIVE: Acute seizures induced dendritic formation and synaptogenesis promotes aberrant circuitry development and further aggravates underlying conditions towards chronic epilepsy. The G protein-coupled receptor kinase-5 (GRK5) served as a key modulator in neurogenesis and the establishment of functional neuronal circuitry. This included dendritic development, as its dysfunction could cause different central nervous system disorders, including Alzheimer's disease. However, the involvement of GRK5 in the progression of epilepsy remains unclear...
October 13, 2017: Epilepsy Research
Magali Roux, Anthony Dosseto
Metal ions are critical to a wide range of biological processes. Among them, lithium (Li) has been recognised for its benefit as a treatment for bipolar disorder (BD). However, we are yet to grasp the extent of its role in biological processes, despite its molecular targets having been extensively studied. Here we review a wide range of transcriptomic, proteomic and metabolomic studies in order to obtain a full picture of Li effects at various levels. Multifarious patterns of Li-regulated genes, proteins and metabolites are identified...
October 18, 2017: Metallomics: Integrated Biometal Science
S M Wittenberg, K A Toxopeus, P F J Schulte
Lithium is associated with adverse effects on cognitive functioning. However, there are published trials that have investigated the protective effects of lithium in cognitive decline.<br/> AIM: To review studies that investigate the potentially protective effects of lithium on cognitive disorders.<br/> METHOD: We studied English-language and Dutch reports on controlled, clinical trials published up to October 2016.<br/> RESULTS: We found four relevant articles. Two studies indicated that cognitive functioning remained more stable when patients were given lithium than when they were given a placebo...
2017: Tijdschrift Voor Psychiatrie
Lars Vedel Kessing, Thomas Alexander Gerds, Nikoline Nygård Knudsen, Lisbeth Flindt Jørgensen, Søren Munch Kristiansen, Denitza Voutchkova, Vibeke Ernstsen, Jörg Schullehner, Birgitte Hansen, Per Kragh Andersen, Annette Kjær Ersbøll
Importance: Results from animal and human studies suggest that lithium in therapeutic doses may improve learning and memory and modify the risk of developing dementia. Additional preliminary studies suggest that subtherapeutic levels, including microlevels of lithium, may influence human cognition. Objective: To investigate whether the incidence of dementia in the general population covaries with long-term exposure to microlevels of lithium in drinking water. Design, Setting, and Participants: This Danish nationwide, population-based, nested case-control study examined longitudinal, individual geographic data on municipality of residence and data from drinking water measurements combined with time-specific data from all patients aged 50 to 90 years with a hospital contact with a diagnosis of dementia from January 1, 1970, through December 31, 2013, and 10 age- and sex-matched control individuals from the Danish population...
October 1, 2017: JAMA Psychiatry
E N Wilson, S Do Carmo, M F Iulita, H Hall, A Ducatenzeiler, A R Marks, S Allard, D T Jia, J Windheim, A C Cuello
Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer's disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology...
August 1, 2017: Translational Psychiatry
Osamu Shibahara, Masaki Watanabe, Shoya Yamada, Masaru Akehi, Takanori Sasaki, Akiya Akahoshi, Takahisa Hanada, Hiroyuki Hirano, Shunsuke Nakatani, Hiromi Nishioka, Yasuo Takeuchi, Hiroki Kakuta
The retinoid X receptor (RXR) partial agonist 1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid (1; CBt-PMN, Emax = 75%, EC50 = 143 nM) is a candidate for treatment of central nervous system (CNS) diseases such as Alzheimer's and Parkinson's diseases based on reports that RXR-full agonist 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) shows therapeutic effects on these disease in rodent models. Here, we synthesized carbon-11-labeled ([(11)C]1) as a tracer for positron emission tomography (PET) and used it in a PET imaging study to examine the brain uptake and biodistribution of 1...
August 24, 2017: Journal of Medicinal Chemistry
Ahsan Habib, Darrell Sawmiller, Song Li, Yang Xiang, David Rongo, Jun Tian, Huayan Hou, Jin Zeng, Adam Smith, Shengnuo Fan, Brian Giunta, Takashi Mori, Glenn Currier, Douglas Ronald Shytle, Jun Tan
Lithium has been marketed in the United States of America since the 1970s as a treatment for bipolar disorder. More recently, studies have shown that lithium can improve cognitive decline associated with Alzheimer's disease (AD). However, the current United States Food and Drug Administration-approved lithium pharmaceutics (carbonate and citrate chemical forms) have a narrow therapeutic window and unstable pharmacokinetics that, without careful monitoring, can cause serious adverse effects. Here, we investigated the safety profile, pharmacokinetics, and therapeutic efficacy of LISPRO (ionic co-crystal of lithium salicylate and l-proline), lithium salicylate, and lithium carbonate (Li2CO3)...
June 15, 2017: Cell Death & Disease
Jeffrey Fessel
OBJECTIVE: The aim of this study is to examine the hypotheses stating the importance of amyloid or of its oligomers in the pathogenesis of Alzheimer's disease (AD). METHODS: Published studies were examined. RESULTS: The importance of amyloid in the pathogenesis of AD is well established, yet accepting it as the main cause for AD is problematic, because amyloid-centric treatments have provided no clinical benefit and about one-third of cognitively normal, older persons have cerebral amyloid plaques...
May 16, 2017: International Journal of Geriatric Psychiatry
Stefan Frisch, Frank Grünwald, Benedikt Friedrichs
Lithium intoxication is known to induce cognitive deficits along with motor and behavioral changes, even in association with normal serum levels. However, cases with comprehensive neuropsychological assessment of the deficits are rare. In our patient, we initially found severe cognitive deficits, including apraxia and visuo-constructive problems, and temporo-parietal FDG-PET hypometabolism. Neuropsychological and imaging findings were highly suggestive of Alzheimer's disease. However, lithium intoxication was suspected to account for these findings because of a Parkinson's syndrome, despite serum levels being in the upper therapeutic range...
April 24, 2017: International Psychogeriatrics
W J Fessel
The pathogenesis of Alzheimer's disease involves multiple pathways that, at the macrolevel, include decreased proliferation plus increased loss affecting neurons, astrocytes, and capillaries and, at the subcellular level, involve several elements: amyloid/amyloid precursor protein, presenilins, the unfolded protein response, the ubiquitin/proteasome system, the Wnt/catenin system, the Notch signaling system, mitochondria, mitophagy, calcium, and tau. Data presented show the intimate, anatomical interactions between neurons, astrocytes, and capillaries; the interactions between the several subcellular factors affecting those cells; and the treatments that are currently available and that might correct dysfunctions in the subcellular factors...
May 2017: American Journal of Alzheimer's Disease and Other Dementias
J Budni, D P Feijó, H Batista-Silva, M L Garcez, F Mina, T Belletini-Santos, L R Krasilchik, A P Luz, G L Schiavo, J Quevedo
Alzheimer's disease (AD) is the most common cause of dementia in the elderly. The main hallmarks of this disease include progressive cognitive dysfunction and an accumulation of soluble oligomers of β-amyloid (Aβ) 1-42 peptide. In this research, we show the effects of lithium and memantine on spatial memory and neuroinflammation in an Aβ1-42 oligomers-induced animal model of dementia in rats. Aβ 1-42 oligomers were administered intrahippocampally to male wistar rats to induce dementia. Oral treatments with memantine (5mg/kg), lithium (5mg/kg), or both drugs in combination were performed over a period of 17days...
May 2017: Neurobiology of Learning and Memory
Fiona Kerr, Oyinkan Sofola-Adesakin, Dobril K Ivanov, Jemma Gatliff, Beatriz Gomez Perez-Nievas, Hélène C Bertrand, Pedro Martinez, Rebecca Callard, Inge Snoeren, Helena M Cochemé, Jennifer Adcott, Mobina Khericha, Jorge Iván Castillo-Quan, Geoffrey Wells, Wendy Noble, Janet Thornton, Linda Partridge
Nrf2, a transcriptional activator of cell protection genes, is an attractive therapeutic target for the prevention of neurodegenerative diseases, including Alzheimer's disease (AD). Current Nrf2 activators, however, may exert toxicity and pathway over-activation can induce detrimental effects. An understanding of the mechanisms mediating Nrf2 inhibition in neurodegenerative conditions may therefore direct the design of drugs targeted for the prevention of these diseases with minimal side-effects. Our study provides the first in vivo evidence that specific inhibition of Keap1, a negative regulator of Nrf2, can prevent neuronal toxicity in response to the AD-initiating Aβ42 peptide, in correlation with Nrf2 activation...
March 2017: PLoS Genetics
Francesca Gelfo, Debora Cutuli, Annalisa Nobili, Paola De Bartolo, Marcello D'Amelio, Laura Petrosini, Carlo Caltagirone
Alzheimer's disease (AD) is an age-related neurodegenerative disorder with multifactorial etiopathogenesis, characterized by progressive loss of memory and other cognitive functions. A fundamental neuropathological feature of AD is the early and severe brain cholinergic neurodegeneration. Lithium is a monovalent cation classically utilized in the treatment of mood disorders, but recent evidence also advances a beneficial potentiality of this compound in neurodegeneration. Interestingly, lithium acts on several processes whose alterations characterize the brain cholinergic impairment at short and long term...
2017: Journal of Alzheimer's Disease: JAD
Edward C Lauterbach
The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), has been largely unrewarding. Preclinical evidence suggests that repurposing quetiapine, lithium, valproate, fluoxetine, donepezil, and memantine for early and pre-symptomatic disease-modification in NDDs may be promising and can spare regulatory barriers. The literature of these psychotropics in early stage and pre-symptomatic AD, PD, and HD is reviewed and propitious findings follow...
November 2016: Neural Regeneration Research
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