AD: concomitant ChEI, memantine speed cognitive decline in meta-analysis

  • JAMA Netw Open

  • curated by Susan London
  • Clinical Essentials
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Takeaway

  • The majority of patients participating in Alzheimer's disease studies used cholinesterase inhibitors (ChEIs) or memantine (Namenda), in addition to their assigned study treatment.
  • Users had more rapid decline of cognition than nonusers.

Why this matters

  • Concomitant use of these drugs could confound results.

Key results

  • 33.4% of patients used ChEIs only, 5.3% used memantine only, and 34.0% used both.
  • Annual rate of decline on the Alzheimer Disease Assessment Scale-cognitive subscale was faster for users of ChEIs and/or memantine vs nonusers:
    • in studies overall (difference, 1.4 points/year; 95% CI, 0.1-2.7); and
    • in randomized trials (difference, 1.5 points/year; 95% CI, 0.1-2.8).
  • Difference in rate of decline:
    • nonsignificant for patients using only ChEIs (difference, 0.9 points/year; 95% CI, −0.6 to 2.3); and
    • significant for patients using memantine with or without ChEIs (difference, 2.0 points/year; 95% CI, 1.3-2.7).

Study design

  • Meta-analysis: 10 collaborative studies with 2714 patients having dementia or mild cognitive impairment resulting from Alzheimer's disease, or normal cognition.
  • Main outcome: change in Alzheimer Disease Assessment Scale-cognitive subscale score.
  • Funding: NIH; Aging and Disability Resource Center; others.

Limitations

  • Reasons for use unknown.
  • Potential effect of dropout of more severely affected patients.
  • Most studies conducted in academic medical centers.

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