An association has been observed between the use of lithium and a decreased risk for the development of dementia in a retrospective study published in the journal PLOS Medicine.

Recognizing that dementia ranks as a leading cause of death in elderly Western populations, the researchers noted that preventive interventions designed to delay the onset of dementia, even modestly, could have a major impact on public health. Thus, they sought to evaluate the association between the use of lithium and the incidence of dementia, along with its subtypes, including Alzheimer disease (AD) and vascular dementia (VD).

The primary objective of the study was to explore the relationship between lithium use and the incidence of dementia/dementia subtypes, with an analysis of possible confounding factors, over a 15-year period. The researchers theorized that the use of lithium would be linked to a decreased risk for dementia and its subtypes, and that this association would be observed with both short-term and long-term lithium exposure.


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The study was conducted between January 2, 2005, and December 31, 2019. Data from electronic clinical records of secondary mental health services rendered in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), United Kingdom, were obtained.

A total of 548 patients who had been exposed to lithium and 29,070 who had not experienced any lithium exposure were identified from CPFT routinely collected clinical data. In the cohort of patients exposed to lithium (group Li+), each person’s origin time (ie, start date) was defined as “their earliest recorded exposure to lithium.” In the unexposed cohort (group Li–), each person’s origin time was defined as “the latest of their CPFT registration date or January 1, 2005.” Follow-up took place until the patient’s final record, death, or the initial record of dementia — whichever occurred first.

Eligible patients were 50 years of age or older at baseline and had 1 year or more of follow-up. Patients were excluded if they had a preexisting diagnosis of mild cognitive impairment or dementia, or if they had been diagnosed less than a 1 year after the origin time. Overall, 40.2% of the patients were male, 33.3% were either married or in a civil partnership, and 71.0% were White. The mean patient age was 73.9 years.

Those in group Li+ were more likely to be married, cohabitating, or in a civil partnership; to be a current/former smoker; to have comorbid depression, mania/bipolar affective disorder (BPAD), hypertension, central vascular disease, diabetes, or hyperlipidemia; and to have used antipsychotic agents. There were no significant differences between group Li+ and group Li– with respect to other characteristics, such as age, sex, and alcohol-linked disorders.

In the exposed cohort, 9.7% (53 of 548) of the patients were diagnosed with dementia, which included 6.8% with AD and 2.6% with VD. In the unexposed cohort, 11.2% of the patients were diagnosed with dementia, 8.1% with AD, and 2.6% with VD.

After controlling for other mental comorbidities, physical comorbidities, use of other medications, socioedemographic factors, and smoking status, the use of lithium was associated with a significantly lower risk for dementia (adjusted hazard ratio [aHR], 0.56; 95% CI, 0.37 to 0.82; P =.0006), AD (aHR, 0.55; 95% CI, 0.37 to 0.82; P =.0033), and VD (aHR, 0.36; 95% CI, 0.19 to 0.69; P =.002). Lithium appeared to be protective among both short-term users (1-year or less of exposure) and long-term users (more than 5-year exposure).

A major limitation of the current study is the handling of BPAD, which was the most common reason for lithium prescription but was also a risk factor for dementia. Although such a potential confounder would be likely to cause an increase in dementia in the exposed group, the opposite was actually true, with the sensitivity analysis corroborating these primary results. An additional limitation was the relatively small sample size of patients who were exposed to lithium.

The researchers concluded that study findings show “lithium may be a disease-modifying treatment for dementia and that this is a promising treatment to take forwards to larger randomised controlled trials (RCTs) for this indication.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference  

Chen S, Underwood BR, Jones PB, Lewis JR, Cardinal RN. Association between lithium use and the incidence of dementia and its subtypes: a retrospective cohort study. PLoS Med. Published online March 17, 2022. doi:10.1371/journal.pmed.1003941