Grand Rounds

Does Lithium Exposure Decrease Risk for Dementia?

BACKGROUND AND PURPOSE:

Animal studies show lithium improves learning and memory
Human observational studies suggest lithium treatment may reduce the risk of dementia in individuals with bipolar disorder
Kessing et al. (JAMA Psychiatry, 2017) sought to assess whether incidence of dementia is associated with long-term exposure to microlevels of lithium in drinking water

Population-based, nested case-control study
Longitudinal data on municipality of residence, lithium levels drinking water measurements and incidence of dementia (inpatient and outpatient)
Primary outcome
- Dementia diagnosis
Secondary outcomes
- Alzheimer disease
- Vascular dementia diagnoses

A total of 73,731 patients with dementia and 733,653 controls were included in the study, age 50-90 years
Lithium exposure differed between patients with a diagnosis of dementia (median, 11.5 µg/L) and controls (median, 12.2 µg/L; (P < .001)
Compared with individuals exposed to 2.0 – 5.0 µg/L, the incidence rate ratio (IRR) of dementia was
- Decreased in those exposed to more than 15.0 µg/L (IRR, 0.83; 95% CI 0.81-0.85; P < .001) and 10.1 to 15.0 µg/L (IRR, 0.98; 95% C 0.96-1.01; P = .17)
- Increased with 5.1 to 10.0 µg/L (IRR, 1.22; 95% CI 1.19-1.25; P < .001)
Secondary outcomes: Similar patterns to the above were identified when Alzheimer disease and vascular dementia were studied

Long-term increased lithium exposure in drinking water is correlated with lower incidence of dementia, with lower levels associated with higher risk
Confounding factors could not be excluded, such as differing availability of healthcare which could impact whether a patient would receive a formal diagnosis

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