Low‐level lithium in drinking water and subsequent risk of dementia: Cohort study

Duthie, Ashleigh C.; Hannah, Jean; Batty, G. David; Deary, Ian J.; Starr, John M.; Smith, Daniel J.; Russ, Tom C.

doi:10.1002/gps.5890

Cited by 6 publications

(8 citation statements)

References 40 publications

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“…Even so, this exposure appears to maintain the potential to exert noticeable physiological effects (Harari et al 2015 ). A growing body of evidence suggests that exposure to sub-therapeutic lithium concentration through drinking water may impact a variety of clinically significant outcomes for the neuropsychiatric field, such as reducing dementia risk (Duthie et al 2023 ; Parker et al 2018 ), suicide risk (Barjasteh-Askari et al 2020 ), homicide risk (Giotakos et al 2015 ), psychiatric hospital admissions (Eyre-Watt et al 2021 ), but potentially increase autism spectrum disorder risk in prenatal exposure (Liew et al 2023 ). These data were further and robustly supported by a recent meta-analysis of 9 studies (Memon et al 2020 ), which suggested that naturally occurring lithium in drinking water may reduce the risk of suicide and possibly help in mood stabilisation.…”

Section: Methodsmentioning

confidence: 99%

“…Overall, the interpretation of the available evidence appears particularly complex considering the difficulty in addressing possible confounders influencing the outcomes (e.g., socioeconomic factors on suicides), heterogeneity in the reported outcomes, sex differences in the observed associations, and the unfeasibility of assessing the amount of lithium exposure through routes other than drinking water (e.g., food) (Duthie et al 2023 ). Critical for the field is to define the impact of prenatal exposure to lithium in drinking water on fetal development, as past reports have suggested the potential for some health benefits, albeit non-unanimously, but also for possible detrimental effects (Harari et al 2015 ) even at comparatively similar concentrations (Eyre-Watt et al 2021 ; Liew et al 2023 ).…”

Section: Methodsmentioning

confidence: 99%

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Lithium and its effects: does dose matter?

Manchia,

Paribello,

Pinna

et al. 2024

Int J Bipolar Disord

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Background Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium’s clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations. Content This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors’ preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections. Conclusions Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium’s ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Lithium and its effects: does dose matter?

Manchia,

Paribello,

Pinna

et al. 2024

Int J Bipolar Disord

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“…Interestingly, it has been reported that the concentration of lithium in drinking water is inversely correlated with not only the suicide rate (25, 26) but also the incidence of dementia (27,28). Other studies support an association between lithium levels in drinking water and the risk of dementia in females (29,30); however, a consensus has not been reached yet.…”

Section: Effect Of Lithium On Preventing Recurrence and Onset Of Deme...mentioning

confidence: 99%

Bipolar disorder and Lewy body dementia: case report and literature review

Nakamura,

Sugawara,

Asada

et al. 2024

Front. Psychiatry

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Depressive episodes with psychotic symptoms are prevalent among the older adults, emphasizing the need to differentiate them from dementia with Lewy bodies (DLB), in which depressive and psychotic symptoms commonly coexist. In contrast, psychotic symptoms occur more frequently in depressive episodes of bipolar disorder (BD) than in major depressive disorder (MDD). Although MDD is a significant risk factor for dementia, studies exploring the relationship between BD and dementia are lacking. This report details the case of a 74-year-old female who experienced severe psychotic depression that led to suicide attempts during a long-term course of young-onset BD. Ultimately, she was diagnosed with DLB based on her neurocognitive symptoms and results of the neuroimaging examination. She had experienced multiple relapses in the past, predominantly characterized by depressive episodes in her old age. Notably, she had never undergone lithium treatment, which is known for its potential efficacy in preventing relapse and dementia. Recent systematic reviews and meta-analyses have suggested that patients with BD have a higher risk of dementia than the general population, and that lithium usage is associated with a reduced risk. Moreover, patients with BD have been suggested to have an elevated risk of developing Parkinson’s disease (PD), and the pathophysiological relationship between BD and PD may be attributed to dopamine dysregulation resulting from multiple relapses. Future research is imperative to identify strategies for preventing dementia in patients with BD and to develop interventions for the comorbidities of BD and DLB.

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“…Additionally, lithium levels in drinking water were associated with greater risk of dementia in women. 93…”

Section: Psychosocial Factors: Psychosocial Factors Such As Social Is...mentioning

confidence: 99%

Assessing Risk Factors for Cognitive Decline Using Electronic Health Records: A Scoping Review

Wang,

Yang,

Sha

et al. 2023

Preprint

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BackgroundElectronic health records (EHR) provide rich, diverse, longitudinal real-world data, offering valuable opportunities to study antecedent risk factors for cognitive decline. However, the extent to which such records have been utilized to understand the risk factors of cognitive decline remains unclear.MethodsWe conducted a systematic review following PRISMA guidelines. We retrieved relevant articles published between January 1, 2010, and April 30, 2023, from PubMed, Web of Science, and CINAHL. Inclusion criteria were studies utilizing EHR to study risk factors for cognitive decline, including subjective cognitive decline, mild cognitive impairment, and dementia. Each article was screened by at least two reviewers. Data elements were manually extracted based on a predefined schema. The studied risk factors were reported.ResultsOf 1,593 articles identified, 80 research articles were selected. Seventy (87.5%) were retrospective cohort studies, 53 (66.3%) used datasets with greater than 10,000 patients, and 69 (86.3%) used EHR datasets from the United States or United Kingdom. Furthermore, 39 (48.8%) targeted medical conditions, 23 (28.8%) related to medical interventions, and 14 (17.5%) related to lifestyle, socioeconomic status, and environmental factors. The majority of studied medical conditions were associated with an elevated risk of cognitive decline, whereas medical interventions addressing these conditions often reduced the risk.ConclusionEHRs have significantly advanced our understanding of medical conditions, interventions, lifestyle, socioeconomic status, and environmental factors related to the risk of cognitive decline.HighlightsElectronic health records are increasingly analyzed to discern dementia risk factors.Eighty articles have been published and most of them were retrospective cohort studies.Most risk factors addressed were related to medical conditions and interventions.A few articles studied lifestyle, socioeconomic status, and environmental factors.

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Low‐level lithium in drinking water and subsequent risk of dementia: Cohort study

Cited by 6 publications

References 40 publications

Lithium and its effects: does dose matter?

Lithium and its effects: does dose matter?

Bipolar disorder and Lewy body dementia: case report and literature review

Assessing Risk Factors for Cognitive Decline Using Electronic Health Records: A Scoping Review

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