Summary: A small study found people who received lithium, a drug commonly associated with the treatment of bipolar disorder, are less likely to develop dementia.
Source: University of Cambridge
Researchers have identified a link suggesting that lithium could decrease the risk of developing dementia, which affects nearly one million people in the UK.
The researchers, from the University of Cambridge, conducted a retrospective analysis of the health records of nearly 30,000 patients from Cambridgeshire and Peterborough NHS Foundation Trust. The patients were all over the age of 50 and accessed NHS mental health services between 2005 and 2019.
The analysis suggested that patients who received lithium were less likely to develop dementia than those who did not, although the overall number of patients who received lithium was small.
Their findings, reported in the journal PLoS Medicine, support the possibility that lithium could be a preventative treatment for dementia, and could be progressed to large randomized controlled trials.
Dementia is the leading cause of death in elderly Western populations, but no preventative treatments are currently available: more than 55 million people worldwide have dementia, with Alzheimer’s disease the most common form.
“The number of people with dementia continues to grow, which puts huge pressure on healthcare systems,” said Dr. Shanquan Chen from Cambridge’s Department of Psychiatry, the paper’s first author. “It’s been estimated that delaying the onset of dementia by just five years could reduce its prevalence and economic impact by as much as 40 percent.”
Previous studies have proposed lithium as a potential treatment for those who have already been diagnosed with dementia or early cognitive impairment, but it is unclear whether it can delay or even prevent the development of dementia altogether, as these studies have been limited in size.
Lithium is a mood stabilizer usually prescribed for conditions such as bipolar affective disorder and depression. “Bipolar disorder and depression are considered to put people at increased risk of dementia, so we had to make sure to account for this in our analysis,” said Chen.
Chen and his colleagues analyzed data from patients who accessed mental health services from Cambridgeshire and Peterborough NHS Foundation Trust between 2005 and 2019. Patients were all over 50 years of age, received at least a one-year follow-up appointment, and had not been previously diagnosed with either mild cognitive impairment or dementia.
Of the 29,618 patients in the study cohort, 548 patients had been treated with lithium and 29,070 had not. Their mean age was just under 74 years, and approximately 40% of patients were male.
For the group that had received lithium, 53, or 9.7%, were diagnosed with dementia. For the group that had not received lithium, 3,244, or 11.2%, were diagnosed with dementia.
After controlling for factors such as smoking, other medications, and other physical and mental illnesses, lithium use was associated with a lower risk of dementia, both for short and long-term users. However, since the overall number of patients receiving lithium was small and this was an observational study, larger clinical trials would be needed to establish lithium as a potential treatment for dementia.
Another limitation of the study was the number of patients who had been diagnosed with bipolar disorder, which is normally associated with an increased risk of dementia. “We expected to find that patients with bipolar disorder were more likely to develop dementia, since that is the most common reason to be prescribed lithium, but our analysis suggested the opposite,” said Chen. “It’s far too early to say for sure, but it’s possible that lithium might reduce the risk of dementia in people with bipolar disorder.”
This paper supports others which have suggested lithium might be helpful in dementia. Further experimental medicine and clinical studies are now needed to see if lithium really is helpful in these conditions.
Dementia is the leading cause of death in elderly Western populations. Preventative interventions that could delay dementia onset even modestly would provide a major public health impact. There are no disease-modifying treatments currently available. Lithium has been proposed as a potential treatment. We assessed the association between lithium use and the incidence of dementia and its subtypes.
Methods and findings
We conducted a retrospective cohort study comparing patients treated between January 1, 2005 and December 31, 2019, using data from electronic clinical records of secondary care mental health (MH) services in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), United Kingdom (catchment area population approximately 0.86 million). Eligible patients were those aged 50 years or over at baseline and who had at least 1 year follow-up, excluding patients with a diagnosis of mild cognitive impairment (MCI) or dementia before, or less than 1 year after, their start date. The intervention was the use of lithium.
The main outcomes were dementia and its subtypes, diagnosed and classified according to the International Classification of Diseases-10th Revision (ICD-10).
In this cohort, 29,618 patients (of whom 548 were exposed to lithium) were included. Their mean age was 73.9 years. A total of 40.2% were male, 33.3% were married or in a civil partnership, and 71.0% were of white ethnicity. Lithium-exposed patients were more likely to be married, cohabiting or in a civil partnership, to be a current/former smoker, to have used antipsychotics, and to have comorbid depression, mania/bipolar affective disorder (BPAD), hypertension, central vascular disease, diabetes mellitus, or hyperlipidemia.
No significant difference between the 2 groups was observed for other characteristics, including age, sex, and alcohol-related disorders. In the exposed cohort, 53 (9.7%) patients were diagnosed with dementia, including 36 (6.8%) with Alzheimer disease (AD) and 13 (2.6%) with vascular dementia (VD). In the unexposed cohort, corresponding numbers were the following: dementia 3,244 (11.2%), AD 2,276 (8.1%), and VD 698 (2.6%).
After controlling for sociodemographic factors, smoking status, other medications, other mental comorbidities, and physical comorbidities, lithium use was associated with a lower risk of dementia (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.40 to 0.78), including AD (HR 0.55, 95% CI 0.37 to 0.82) and VD (HR 0.36, 95% CI 0.19 to 0.69). Lithium appeared protective in short-term (≤1-year exposure) and long-term lithium users (>5-year exposure); a lack of difference for intermediate durations was likely due to lack of power, but there was some evidence for additional benefit with longer exposure durations.
The main limitation was the handling of BPAD, the most common reason for lithium prescription but also a risk factor for dementia. This potential confounder would most likely cause an increase in dementia in the exposed group, whereas we found the opposite, and the sensitivity analysis confirmed the primary results.
However, the specific nature of the group of patients exposed to lithium means that caution is needed in extending these findings to the general population. Another limitation is that our sample size of patients using lithium was small, reflected in the wide CIs for results relating to some durations of lithium exposure, although again sensitivity analyses remained consistent with our primary findings.
We observed an association between lithium use and a decreased risk of developing dementia. This lends further support to the idea that 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.