Summary: A retrospective study indicates that people treated with lithium, a medication commonly used for bipolar disorder, had a lower incidence of dementia compared with those who did not receive lithium.
Source: University of Cambridge
Researchers at the University of Cambridge report an association suggesting lithium use may reduce the risk of developing dementia, a condition that affects millions worldwide and nearly one million people in the UK alone.
The research team analyzed electronic health records from Cambridgeshire and Peterborough NHS Foundation Trust, reviewing data for 29,618 patients aged 50 and over who accessed secondary mental health services between 2005 and 2019. None of the patients had a diagnosis of mild cognitive impairment (MCI) or dementia at baseline or within the first year after their start date.
Of those patients, 548 had received lithium treatment and 29,070 had not. The average age across the cohort was 73.9 years and approximately 40.2% of participants were male. In the lithium-exposed group, 53 individuals (9.7%) were later diagnosed with dementia, while 3,244 individuals (11.2%) in the unexposed group received a dementia diagnosis.
After adjusting for potential confounders such as smoking status, concurrent medications, and other physical and mental health conditions, the investigators found that lithium use was associated with a lower risk of developing dementia. The adjusted hazard ratio (HR) for dementia among lithium users was 0.56 (95% confidence interval [CI] 0.40–0.78). Similar reductions were observed for Alzheimer’s disease (HR 0.55, 95% CI 0.37–0.82) and vascular dementia (HR 0.36, 95% CI 0.19–0.69).
The protective association was seen in both short-term (≤1 year) and long-term (>5 years) lithium users. Findings for intermediate exposure durations were less clear, likely limited by smaller numbers in those subgroups, but there was some evidence that longer exposure could confer greater benefit.
Lithium is a well-established mood stabilizer used primarily to treat bipolar disorder and sometimes depression. Because conditions such as bipolar disorder and depression are themselves associated with higher dementia risk, the authors took care to account for these diagnoses in their analyses. Notably, although bipolar disorder is a common reason for prescribing lithium and is typically linked to increased dementia risk, the study’s analysis suggested the opposite within the lithium-treated group—raising the possibility that lithium might mitigate dementia risk among people with bipolar disorder. The authors caution that this observation is preliminary and requires further investigation.
The study has several important limitations. It is observational and retrospective, meaning it cannot establish causation. The subgroup of patients taking lithium was small relative to the whole cohort, which reduces statistical power for some comparisons and yields wider confidence intervals for certain exposure durations. In addition, the specific clinical characteristics of patients selected for lithium treatment may differ from the broader population, so results may not generalize to everyone.
Despite these constraints, the results are consistent with prior research that has proposed lithium as a candidate for dementia prevention or modification. The findings support the rationale for larger, prospective randomized controlled trials to test whether lithium can prevent or delay dementia onset and to determine optimal dosing and exposure duration for neuroprotection.
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Author: Press Office
Source: University of Cambridge
Contact: Press Office – University of Cambridge
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Original Research: Open access. “Association between lithium use and the incidence of dementia and its subtypes: A retrospective cohort study” by Shanquan Chen et al., PLOS Medicine.
Abstract — Association between lithium use and the incidence of dementia and its subtypes: A retrospective cohort study
Background
Dementia is a leading cause of death in older adults in Western populations. Even modest delays in the onset of dementia could substantially reduce prevalence and economic burden. Currently there are no disease-modifying interventions proven to prevent dementia. Lithium has been proposed as a potential candidate for reducing dementia risk; this study evaluated the association between lithium exposure and subsequent incidence of dementia and its major subtypes.
Methods and findings
This retrospective cohort study used electronic clinical records from secondary mental health services in Cambridgeshire and Peterborough NHS Foundation Trust between January 1, 2005 and December 31, 2019. Eligible patients were aged 50 or older with at least one year of follow-up and without prior diagnoses of MCI or dementia. The primary exposure was lithium use. Outcomes were diagnoses of dementia and its subtypes, classified according to ICD-10 criteria.
In total, 29,618 patients met inclusion criteria; 548 were exposed to lithium. Exposed patients were more likely to have certain comorbidities and to have used antipsychotics, but there were no meaningful differences in age or sex distribution between groups. Dementia diagnoses occurred in 9.7% of lithium-exposed patients and 11.2% of unexposed patients. After multivariable adjustment, lithium use was associated with lower risks of all-cause dementia, Alzheimer’s disease, and vascular dementia. Sensitivity analyses accounting for bipolar disorder and other confounders supported the main findings, though the small number of lithium users limits precision for some analyses.
Conclusions
The researchers observed an association between lithium therapy and reduced risk of developing dementia. These results strengthen the case for investigating lithium further as a potential disease-modifying agent for dementia and support advancing to larger randomized controlled trials to evaluate its efficacy and safety for this purpose.