Lithium Treatment and Risk of Dementia

Context: It has been suggested that lithium may have neuroprotective abilities, but it is not clear whether lithium reduces the risk of dementia. Objective: To investigate whether continued treatment with lithium reduces the risk of dementia in a nationwide study. Design: An observational cohort study with linkage of registers of all patients prescribed lithium and diagnosed as having dementia in Denmark from January 1, 1995, through December 31, 2005. Setting: We identified all patients treated with lithium in Denmark within community psychiatry, private specialist, and general practices and a random sample of 30% of the general population. Subjects: A total of 16 238 persons who purchased lithium at least once and 1 487 177 persons from the general population who did not purchase lithium. Main Outcome Measure: Diagnosis of dementia or Alzheimer disease during inpatient or outpatient hospital care. Results: Persons who purchased lithium at least once had an increased rate of dementia compared with persons not exposed to lithium (relative risk, 1.47; 95% confidence interval, 1.22-1.76). For persons who continued to take lithium, the rate of dementia decreased to the same level as the rate for the general population. The rate of dementia decreased early after the consumption of lithium tablets corresponding to 1 prescription (typically 100 tablets) and stayed at a low level, although with a slight increase according to the number of subsequent prescriptions. The association between the number of prescriptions for lithium and dementia was unique and different from the association between the number of prescriptions for anticonvulsants and dementia. All findings were replicated in subanalyses with Alzheimer disease as the outcome. Conclusions: Continued lithium treatment was associated with reduction of the rate of dementia to the same level as that for the general population. Methodological reasons for this finding cannot be excluded, owing to the nonrandomized nature of data.