Lithium: An Old Drug for New Therapeutic Strategy for Alzheimer’s Disease and Related Dementia

Shim, Seong Sool; Berglund, Ken; Yu, Shan Ping

doi:10.1159/000533797

Cited by 3 publications

(1 citation statement)

References 152 publications

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“…However, the precise mechanism of action for treating mood disturbances in bvFTD remains speculative. Translational research suggests neurotrophic and neuroprotective effects that contribute to the modulation of multiple homeostatic mechanisms, which are core pathological processes in dementia ( 22 ). Additional research is necessary to clarify the specific mechanisms through which lithium operates in bvFTD.…”

Section: Discussionmentioning

confidence: 99%

Lithium management of periodic mood fluctuations in behavioural frontotemporal dementia: a case report

Llorca-Bofí,

Batalla,

Ruiz-Julián

et al. 2024

Front. Psychiatry

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The behavioural variant of Frontotemporal Dementia (bvFTD) is a neurodegenerative condition characterized by behavioural and cognitive symptoms. Mood disturbances, including manic-like episodes, can occur in bvFTD, posing diagnostic and therapeutic challenges. This case report presents a 62-year-old male with bvFTD exhibiting weekly mood fluctuations alternating between manic and depressive-like states. While initial treatment with quetiapine and trazodone showed partial improvement, the periodicity of mood fluctuations persisted. Subsequently, lithium was introduced, resulting in a notable reduction in symptom severity for both manic and depressive episodes. This report highlights the potential use of lithium as a mood stabilizer in bvFTD patients with periodic mood fluctuations, refractory to standard treatments. Further research is needed to elucidate the mechanisms underlying lithium’s efficacy in bvFTD and to establish treatment guidelines.

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Section: Discussionmentioning

confidence: 99%

Lithium management of periodic mood fluctuations in behavioural frontotemporal dementia: a case report

Llorca-Bofí,

Batalla,

Ruiz-Julián

et al. 2024

Front. Psychiatry

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Lithium Therapy’s Potential to Lower Dementia Risk and the Prevalence of Alzheimer’s Disease: A Meta-Analysis

Lu,

Lv,

Liu

et al. 2024

Eur Neurol

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Introduction: Dementia is a neurodegenerative disease with insidious onset and progressive progression, of which the most common type is Alzheimer's disease (AD). Lithium, a trace element in the body, has neuroprotective properties. However, whether lithium can treat dementia or AD remains a highly controversial topic. Therefore we conducted a meta-analysis. Methods: A systematic literature review was conducted in PubMed, Embase, and Web of Science. Comparison of the effects of lithium on Alzheimer's disease or dementia in terms of use, duration, and dosage, and meta-analysis to test whether lithium therapy is beneficial in ameliorating the onset of dementia or Alzheimer's disease. Sensitivity analyses were performed using a stepwise exclusion method. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of included studies. We determined the relative risk (RR) between patient groups using a random effects model. Results: A total of seven studies were included. The forest plot results showed that taking lithium therapy reduced the risk of Alzheimer's disease (RR 0.59, 95% CI: 0.44-0.78), and is also protective in reducing the risk of dementia (RR 0.66, 95% CI: 0.56-0.77). The duration of lithium therapy was able to affect the dementia incidence (RR 0.70, 95% CI: 0.55-0.88); however, it is unclear how this effect might manifest in AD. It's also uncertain how many prescriptions for lithium treatment lower the chance of dementia development. Conclusion: The duration of treatment and the usage of lithium therapy seem to lower the risk of AD and postpone the onset of dementia.

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Lithium Ions as Modulators of Complex Biological Processes: The Conundrum of Multiple Targets, Responsiveness and Non-Responsiveness, and the Potential to Prevent or Correct Dysregulation of Systems during Aging and in Disease

Hart

2024

Biomolecules

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Lithium is one of the lightest elements on Earth and it has been in the environment since the formation of the galaxy. While a common element, it has not been found to be an essential element in biological processes, ranging from single cell organisms to Homo sapiens. Instead, at an early stage of evolution, organisms committed to a range of elements such as sodium, potassium, calcium, magnesium, zinc, and iron to serve essential functions. Such ions serve critical functions in ion channels, as co-factors in enzymes, as a cofactor in oxygen transport, in DNA replication, as a storage molecule in bone and liver, and in a variety of other roles in biological processes. While seemingly excluded from a major essential role in such processes, lithium ions appear to be able to modulate a variety of biological processes and “correct” deviation from normal activity, as a deficiency of lithium can have biological consequences. Lithium salts are found in low levels in many foods and water supplies, but the effectiveness of Li salts to affect biological systems came to recent prominence with the work of Cade, who reported that administrating Li salts calmed guinea pigs and was subsequently effective at relatively high doses to “normalize” a subset of patients with bipolar disorders. Because of its ability to modulate many biological pathways and processes (e.g., cyclic AMP, GSK-3beta, inositol metabolism, NaK ATPases, neuro processes and centers, immune-related events, respectively) both in vitro and in vivo and during development and adult life, Li salts have become both a useful tool to better understand the molecular regulation of such processes and to also provide insights into altered biological processes in vivo during aging and in disease states. While the range of targets for lithium action supports its possible role as a modulator of biological dysregulation, it presents a conundrum for researchers attempting to elucidate its specific primary target in different tissues in vivo. This review will discuss aspects of the state of knowledge regarding some of the systems that can be influenced, focusing on those involving neural and autoimmunity as examples, some of the mechanisms involved, examples of how Li salts can be used to study model systems, as well as suggesting areas where the use of Li salts could lead to additional insights into both disease mechanisms and natural processes at the molecular and cell levels. In addition, caveats regarding lithium doses used, the strengths and weaknesses of rodent models, the background genetics of the strain of mice or rats employed, and the sex of the animals or the cells used, are discussed. Low-dose lithium may have excellent potential, alone or in combination with other interventions to prevent or alleviate aging-associated conditions and disease progression.

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Lithium: An Old Drug for New Therapeutic Strategy for Alzheimer’s Disease and Related Dementia

Cited by 3 publications

References 152 publications

Lithium management of periodic mood fluctuations in behavioural frontotemporal dementia: a case report

Lithium management of periodic mood fluctuations in behavioural frontotemporal dementia: a case report

Lithium Therapy’s Potential to Lower Dementia Risk and the Prevalence of Alzheimer’s Disease: A Meta-Analysis

Lithium Ions as Modulators of Complex Biological Processes: The Conundrum of Multiple Targets, Responsiveness and Non-Responsiveness, and the Potential to Prevent or Correct Dysregulation of Systems during Aging and in Disease

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