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Treatment with lithium may be protective against dementia and its subtypes, a retrospective cohort study indicated.

Among patients receiving mental health care, those exposed to lithium at standard clinical dosages had a 44% lower risk of receiving a diagnosis of dementia versus those unexposed over an average follow-up of 4.8 years (HR 0.56, 95% CI 0.40-0.78), Shanquan Chen, PhD, of the University of Cambridge, England, and colleagues reported in .

Lithium use was tied to a significantly reduced risk for both dementia subtypes considered:

• Alzheimer's disease: HR 0.55 (95% CI 0.37-0.82)
• Vascular dementia: HR 0.36 (95% CI 0.19-0.69)

The researchers didn't measure risk for other dementia subtypes though, such as Lewy body or Parkinson disease dementia.

Of note, lithium use was protective both with 1 year or less of use and with long-term use of 5 or more years. However, medium-term exposures -- between 1 and 5 years of treatment -- weren't significantly protective, although Chen's group said this was likely just an effect of being statistically underpowered.

"The number of people with dementia continues to grow, which puts huge pressure on healthcare systems," Chen explained in a statement. "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."

Not surprisingly, 73% of the patients in the lithium-treated group had mania or bipolar affective disorders -- one of the most common indications for lithium. Because of this, the researchers adjusted for this common comorbidity, as well as depression, age, sex, marital status, ethnicity, smoking status, alcohol disorders, antipsychotic use, hypertension, central vascular disease, diabetes mellitus, and hyperlipidemia.

"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," Chen noted.

For the analysis, the researchers used electronic health record data from 29,618 patients at a secondary care mental health service in the U.K. The cohort was exclusive to patients ages 50 and older (average 73.9) without a diagnosis of mild cognitive impairment or dementia at baseline.

Of these patients, only 548 had exposure to lithium. Patients treated with lithium were more likely to be married or in a civil partnership, be a former or current smoker, to have used antipsychotics, and have comorbid depression, mania/bipolar affective disorder, hypertension, central vascular disease, diabetes mellitus, or hyperlipidemia.

A total of 9.7% of the lithium-exposed patients were subsequently diagnosed with dementia, while 11.2% of the unexposed group were. "The frequency of dementia in our control cohort was higher than in the general population, as would be expected for a [mental health] service," the researchers pointed out.

Chen's group noted that lithium levels weren't consistently available throughout follow-up, but generally fell between in standard therapeutic range and well above the typical 0.00029 to 0.00386 mmol/L found in drinking water.

"The main unanswered question from this work is the dose-response association between lithium within its therapeutic range and the incidence of dementia," the researchers wrote. "The clinical context means that lithium levels primarily lay within its therapeutic range of 0.4 to 1.0 mmol/L...but at times, lithium levels in some patients may have been >1.0 mmol/L, with resultant potential for neurotoxicity, or subtherapeutic, either might alter the estimate of the protective effects of lithium, and the optimal level for any such protective effect is unknown."

The next steps to confirm a protective effect would involve large-scale dose and effect studies, particularly those that include the general population and measure outcomes for other types of dementia, Chen's group concluded. Also, randomized trials of lithium for the prevention of progression to dementia in those with mild cognitive impairment or early disease are warranted, they said.

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