Is lithium helpful for preventing dementia in geriatric individuals?

Lithium for Dementia Prevention

Based on the most recent and highest quality evidence, lithium shows promise for reducing dementia risk in observational studies, but the 2025 systematic review and meta-analysis of randomized controlled trials demonstrates that lithium does not provide consistent cognitive or functional benefits in patients with established Alzheimer's disease dementia, and therefore cannot be recommended for dementia prevention at this time. 1

Current Evidence Quality and Limitations

The evidence base consists primarily of retrospective cohort studies rather than prospective randomized trials specifically designed for dementia prevention:

• The 2025 meta-analysis of 6 RCTs (394 participants) found no significant improvement in global cognition (MMSE: MD -1.61,95% CI -4.11 to 0.88; ADAS-Cog: MD -1.82, -3.05 to -0.60), with high heterogeneity across studies and no consistent benefits for memory, functional outcomes, or neuropsychiatric symptoms. 1

• This represents the highest quality evidence available and directly contradicts the observational data, highlighting the critical distinction between association and causation. 1

Observational Data Showing Association (Not Causation)

While observational studies suggest potential benefit, they cannot establish causation:

• A 2024 meta-analysis of 7 observational studies showed lithium therapy was associated with reduced risk of Alzheimer's disease (RR 0.59,95% CI: 0.44-0.78) and dementia overall (RR 0.66,95% CI: 0.56-0.77). 2

• A 2022 retrospective cohort study from UK mental health services (29,618 patients, 548 lithium-exposed) found lithium use associated with lower dementia risk (HR 0.56,95% CI 0.40 to 0.78), including Alzheimer's disease (HR 0.55,95% CI 0.37 to 0.82) and vascular dementia (HR 0.36,95% CI 0.19 to 0.69). 3

• However, these studies are confounded by the fact that lithium-exposed patients had bipolar disorder, which itself is a dementia risk factor, and the small sample sizes of lithium users (n=548) limit generalizability. 3

Why Observational Data Cannot Guide Clinical Practice Here

The fundamental problem is confounding by indication: patients prescribed lithium have bipolar disorder, which independently affects dementia risk, and the observational studies cannot adequately control for this despite statistical adjustments. 3

• The 2022 cohort study acknowledged that bipolar disorder is both the most common reason for lithium prescription and a risk factor for dementia, creating an unmeasured confounder that likely biases results. 3

• The 2025 RCT meta-analysis, which eliminates this confounding through randomization, found no benefit—this is the gold standard evidence that should guide practice. 1

Evidence-Based Alternatives for Dementia Prevention

Rather than lithium, focus on interventions with proven efficacy:

• Resistance training shows superior effects over other exercise modalities for cognitive function, with clinically meaningful benefits achievable at 724 METs-min per week (approximately 150 minutes of moderate-intensity exercise weekly). 4, 5

• The American College of Physicians recommends group or individual physical exercise for all older adults with cognitive decline as a Level 1B recommendation—the strongest evidence-based intervention available. 5

• Mediterranean diet adherence decreases cognitive decline risk through high mono- and polyunsaturated fatty acid consumption and low saturated fat intake. 5

Critical Safety Considerations if Lithium Were Considered

Even if future evidence emerges supporting lithium for dementia prevention, significant monitoring burdens exist:

• Lithium requires monitoring every 3-6 months during maintenance therapy, with baseline and annual thyroid function tests, renal function tests, and electrolytes. 6

• Patients with reduced kidney function (eGFR <60 mL/min/1.73 m²) require monthly monitoring, and lithium must be discontinued if creatinine increases >100% or >310 μmol/L. 6

• Up to 30% of older adults have eGFR <60 mL/min/1.73 m², making them high-risk for lithium toxicity and requiring intensive monitoring that is impractical for a preventive indication. 6

Common Pitfalls to Avoid

• Do not prescribe lithium off-label for dementia prevention based on observational data alone—the highest quality RCT evidence shows no benefit. 1

• Do not ignore the proven non-pharmacological interventions (resistance exercise, aerobic exercise, Mediterranean diet) that have demonstrated efficacy with minimal risk. 4, 5

• Do not underestimate the monitoring burden and toxicity risk of lithium in older adults with age-related renal decline. 6

• Do not confuse association with causation—the observational studies showing reduced dementia risk in lithium users are confounded by bipolar disorder and cannot establish that lithium causes the risk reduction. 3

Bottom Line for Clinical Practice

Lithium cannot be recommended for dementia prevention. The 2025 meta-analysis of RCTs—the highest quality evidence available—demonstrates no cognitive or functional benefit in patients with Alzheimer's disease dementia. 1 Instead, prescribe resistance and aerobic exercise (≥724 METs-min weekly), which has Level 1B evidence for cognitive benefit with minimal risk. 4, 5