Alzheimer disease: intranasal insulin is down but maybe not out

  • Craft S & al.
  • JAMA Neurol
  • 22 Jun 2020

  • curated by Susan London
  • Clinical Essentials
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Takeaway

  • A year of treatment with intranasal insulin did not slow cognitive decline in patients with amnestic mild cognitive impairment or Alzheimer disease, but drug delivery was initially problematic.

Why this matters

  • Efficacious interventions for prevention and treatment of Alzheimer disease are lacking.

Key results

  • Among patients treated with device 2, there was a nonsignificant difference between insulin and placebo groups on mean score change on Alzheimer Disease Assessment Scale-cognitive subscale 12 (ADAS-cog-12) at month 12 (0.0258 points; P=.98).
  • Groups also had similar changes in:
    • Clinical Dementia Rating scale Sum of Boxes.
    • Activities of Daily Living Scale for Mild Cognitive Impairment.
    • Memory composite test.
    • Cerebrospinal fluid levels of Alzheimer disease biomarkers.
  • No clinically important adverse events reported.

Study design

  • US phase 2/3 multicenter randomized controlled trial among 289 older adults with amnestic mild cognitive impairment or Alzheimer disease:
    • Score ≥20 on Mini-Mental State Examination.
    • Clinical dementia rating 0.5 or 1.0.
    • Delayed logical memory score.
  • 12-month double-blind phase: daily insulin (40 IU) vs placebo.
  • Intranasal delivery:
    • 49 patients used device 1 (inconsistent reliability).
    • 240 patients used device 2.
  • Main outcome: mean score change on ADAS-cog-12.
  • Funding: National Institute on Aging; Eli Lilly (provided diluent, insulin).

Limitations

  • Switch of devices midtrial.
  • Device 2 not used previously in patients with Alzheimer disease.