Lithium slows decline in mild cognitive impairment

  • Forlenza OV & al.
  • Br J Psychiatry
  • 5 Apr 2019

  • International Clinical Digest
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Takeaway

  • Long-term therapy with lithium (Eskalith, others) at subtherapeutic doses stabilized cognitive and functional measures among community-dwelling older adults with mild cognitive impairment (MCI).

Why this matters

  • Lack of disease-modifying therapies for Alzheimer’s disease.

Key results

  • 24-month changes in outcomes favored lithium over placebo:
    • Alzheimer’s Disease Assessment Scale–cognitive subscale (0.83 vs 1.80; P<.05>
    • Clinical Dementia Rating–Sum of Boxes (−0.22 vs 0.53; P<.05>
    • Delayed recall (F=16.48; P<.001>
    • Figure recall (F=6.16; P=.02); and
    • Trail-Making Test–A (−0.80 vs 1.60; P<.05>
  • Rate of conversion to dementia: 16% with lithium vs 30% with placebo (P=.06).
  • Lithium group had 30% greater increase in cerebrospinal fluid amyloid-β peptide Aβ1-42 at 36 months (P=.003); difference driven by change among patients with high baseline level.
  • Adverse events not reported in detail; included lithium intolerance (tremor, nausea).

Study design

  • Brazilian single-center randomized controlled trial among 61 community-dwelling, physically healthy older adults with MCI.
  • Randomization: lithium (subtherapeutic concentrations of 0.25-0.5 mEq/L) vs placebo for 24 months (double-blind phase); follow-up for additional 24 months (single-blinded phase).
  • Main outcomes: Alzheimer's Disease Assessment Scale–cognitive subscale; Clinical Dementia Rating–Sum of Boxes.
  • Funding: Alzheimer’s Association; others.

Limitations

  • Small sample.
  • Lack of biological eligibility criteria.
  • Optimal lithium window, dose unknown.

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