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  1. Article ; Online: Mitochondrial dysfunction in Alzheimer's disease: Therapeutic implications of lithium.

    Singulani, Monique P / De Paula, Vanessa J R / Forlenza, Orestes V

    Neuroscience letters

    2021  Volume 760, Page(s) 136078

    Abstract: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by the accumulation of abnormal tau proteins within neurons and amyloid plaques in the brain parenchyma, which leads to progressive loss of neurons in the ... ...

    Abstract Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by the accumulation of abnormal tau proteins within neurons and amyloid plaques in the brain parenchyma, which leads to progressive loss of neurons in the brain. While the detailed mechanism of the pathogenesis of AD is still unknown, evidence suggests that mitochondrial dysfunction likely plays a fundamental role in the pathogenesis of this disease. Due to the relevance of mitochondrial alterations in AD, recent works have suggested the therapeutic potential of mitochondrial-targeted lithium. Lithium has been shown to possess neuroprotective and neurotrophic properties that could also be related to the upregulation of mitochondrial function. In the current work, we perform a comprehensive investigation of the significance of mitochondrial dysfunction in AD and pharmacological treatment with lithium as imperative in this pathology, through a brief review of the major findings on the effects of lithium as a therapeutic approach targeting mitochondria in the context of AD.
    MeSH term(s) Alzheimer Disease/drug therapy ; Alzheimer Disease/pathology ; Brain/cytology ; Brain/drug effects ; Brain/pathology ; Cell Line ; Clinical Trials as Topic ; Drug Evaluation, Preclinical ; Glycogen Synthase Kinase 3 beta/antagonists & inhibitors ; Glycogen Synthase Kinase 3 beta/metabolism ; Humans ; Lithium Compounds/pharmacology ; Lithium Compounds/therapeutic use ; Mitochondria/drug effects ; Mitochondria/metabolism ; Mitochondria/pathology ; Neurons/cytology ; Neurons/drug effects ; Neurons/metabolism ; Oxidative Phosphorylation/drug effects ; Oxidative Stress/drug effects
    Chemical Substances Lithium Compounds ; GSK3B protein, human (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1)
    Language English
    Publishing date 2021-06-20
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 194929-9
    ISSN 1872-7972 ; 0304-3940
    ISSN (online) 1872-7972
    ISSN 0304-3940
    DOI 10.1016/j.neulet.2021.136078
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Lithium and Stroke Recovery: A Systematic Review and Meta-Analysis of Stroke Models in Rodents and Human Data.

    Almeida, Osvaldo P / Singulani, Monique P / Ford, Andrew H / Hackett, Maree L / Etherton-Beer, Christopher / Flicker, Leon / Hankey, Graeme J / De Paula, Vanessa J R / Penteado, Camila T / Forlenza, Orestes V

    Stroke

    2022  Volume 53, Issue 9, Page(s) 2935–2944

    Abstract: Background: Lithium has neuroprotective effects in animal models of stroke, but benefits in humans remain uncertain. This article aims to systematically review the available evidence of the neuroprotective and regenerative effects of lithium in animal ... ...

    Abstract Background: Lithium has neuroprotective effects in animal models of stroke, but benefits in humans remain uncertain. This article aims to systematically review the available evidence of the neuroprotective and regenerative effects of lithium in animal models of stroke, as well as in observational and trial stroke studies in humans.
    Methods: This systematic review and meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched Medline, Embase, and PsycINFO for preclinical and clinical studies published between January 2000 and September 2021. A random-effects meta-analysis was conducted from observational studies.
    Results: From 1625 retrieved studies, 42 were included in the systematic review. Of those, we identified 36 rodent models of stroke using preinsult or postinsult treatment with lithium, and 6 studies were conducted in human samples, of which 4 could be meta-analyzed. The review of animal models was stratified according to the type of stroke and outcomes. Human data were subdivided into observational and intervention studies. Treatment of rodents with lithium was associated with smaller stroke volumes, decreased apoptosis, and improved poststroke function. In humans, exposure to lithium was associated with a lower risk of stroke among adults with bipolar disorder in 2 of 4 studies. Two small trials showed equivocal clinical benefits of lithium poststroke.
    Conclusions: Animal models of stroke show consistent biological and functional evidence of benefits associated with lithium treatment, whereas human evidence remains sparse and inconclusive. The potential role of lithium in poststroke recovery is yet to be adequately tested in humans.
    MeSH term(s) Adult ; Animals ; Humans ; Lithium/pharmacology ; Lithium/therapeutic use ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Observational Studies as Topic ; Rodentia ; Stroke/drug therapy
    Chemical Substances Neuroprotective Agents ; Lithium (9FN79X2M3F)
    Language English
    Publishing date 2022-08-15
    Publishing country United States
    Document type Journal Article ; Meta-Analysis ; Systematic Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 80381-9
    ISSN 1524-4628 ; 0039-2499 ; 0749-7954
    ISSN (online) 1524-4628
    ISSN 0039-2499 ; 0749-7954
    DOI 10.1161/STROKEAHA.122.039203
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Anti-dementia medications: current prescriptions in clinical practice and new agents in progress.

    Stella, Florindo / Radanovic, Márcia / Canineu, Paulo Renato / de Paula, Vanessa J R / Forlenza, Orestes V

    Therapeutic advances in drug safety

    2015  Volume 6, Issue 4, Page(s) 151–165

    Abstract: Almost three decades after the publication of the first clinical studies with tacrine, the pharmacological treatment of Alzheimer's disease (AD) remains a challenge. Randomized clinical trials have yielded evidence of significant - although modest and ... ...

    Abstract Almost three decades after the publication of the first clinical studies with tacrine, the pharmacological treatment of Alzheimer's disease (AD) remains a challenge. Randomized clinical trials have yielded evidence of significant - although modest and transient - benefit from cholinergic replacement therapy for people diagnosed with AD, and disease modification with antidementia compounds is still an urgent, unmet need. The natural history of AD is very long, and its pharmacological treatment must acknowledge different needs according to the stage of the disease process. Cognitive and functional deterioration evolves gradually since the onset of clinical symptoms, which may be preceded by several years or perhaps decades of silent, presymptomatic neurodegeneration. Therefore, the pharmacological treatment of AD must ideally comprise both a symptomatic effect to preserve or improve cognition and a disease-modifying effect to tackle the progression of the pathological process. Primary prevention is the ultimate goal, should these strategies be delivered to patients with preclinical AD. In this article, we briefly address the pharmaceutical compounds that are currently used for the symptomatic treatment of AD and discuss the ongoing strategies designed to modify its natural course.
    Language English
    Publishing date 2015-06-27
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2583589-0
    ISSN 2042-0994 ; 2042-0986
    ISSN (online) 2042-0994
    ISSN 2042-0986
    DOI 10.1177/2042098615592116
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Demographic and clinical characteristics of lithium-treated older adults with bipolar disorder.

    Forlenza, Orestes V / Hajek, Tomas / Almeida, Osvaldo P / Beunders, Alexandra J M / Blumberg, Hilary P / Briggs, Farren B S / De-Paula, Vanessa J R / Dols, Annemiek / Eyler, Lisa T / Forester, Brent P / Gildengers, Ariel / Jimenez, Esther / Korten, Nicole C M / Lafer, Beny / McWhinney, Sean R / Mulsant, Benoit / Rej, Soham / Sarna, Kaylee / Schouws, Sigfried /
    Sutherland, Ashley / Tsai, Shangying / Vieta, Eduard / Yala, Joy / Sajatovic, Martha

    Acta psychiatrica Scandinavica

    2022  Volume 146, Issue 5, Page(s) 442–455

    Abstract: Objectives: There is limited information on the characteristics of older adults with bipolar disorder (OABD) treated with lithium, along with safety concerns about its use by older adults. The aim of the present study is to describe the demographic and ... ...

    Abstract Objectives: There is limited information on the characteristics of older adults with bipolar disorder (OABD) treated with lithium, along with safety concerns about its use by older adults. The aim of the present study is to describe the demographic and clinical characteristics of OABD receiving lithium therapy, using data from the Global Ageing & Geriatric Experiments in Bipolar Disorder (GAGE-BD).
    Experimental procedures: Cross-sectional analysis of the GAGE-BD dataset to determine differences and similarities between lithium users and non-users. We analysed data from 986 participants aged 50 years or older (mean age 63.5 years; 57.5% females) from 12 study sites. Two subgroups ('Lithium'; 'Non-lithium') were defined according to the current prescription of lithium. We compared several outcomes between these groups, controlling for age, gender, and study site.
    Results: OABD treated with lithium had lower scores on depression rating scales and were less likely to be categorised as with moderate or severe depression. There was a lower proportion of lithium users than non-users among those with evidence of rapid cycling and non-bipolar psychiatric diagnoses. Assessment of global cognitive state and functionality indicated better performance among lithium users. The current use of antipsychotics was less frequent among lithium users, who also reported fewer cardiovascular comorbidities than non-users.
    Conclusion: We found several potentially relevant differences in the clinical profile of OABD treated with lithium compared with those treated with other mood stabilisers. However, the interpretation of the present results must take into account the methodological limitations inherent to the cross-sectional approach and data harmonisation.
    MeSH term(s) Aged ; Antipsychotic Agents/therapeutic use ; Bipolar Disorder/diagnosis ; Bipolar Disorder/drug therapy ; Bipolar Disorder/epidemiology ; Demography ; Female ; Humans ; Lithium/therapeutic use ; Lithium Compounds/therapeutic use ; Male ; Middle Aged
    Chemical Substances Antipsychotic Agents ; Lithium Compounds ; Lithium (9FN79X2M3F)
    Language English
    Publishing date 2022-07-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 103-x
    ISSN 1600-0447 ; 0001-690X
    ISSN (online) 1600-0447
    ISSN 0001-690X
    DOI 10.1111/acps.13474
    Database MEDical Literature Analysis and Retrieval System OnLINE

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