Sex and ApoE genotype differences in treatment response to two doses of intranasal insulin in adults with mild cognitive impairment or Alzheimer's disease

J Alzheimers Dis. 2013;35(4):789-97. doi: 10.3233/JAD-122308.


A previous clinical trial demonstrated that four months of treatment with intranasal insulin improves cognition and function for patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI), but prior studies suggest that response to insulin treatment may differ by sex and ApoE ε4 carriage. Thus, responder analyses using repeated measures analysis of covariance were completed on the trial's 104 participants with MCI or AD who received either placebo or 20 or 40 IU of insulin for 4 months, administered by a nasal delivery device. Results indicate that men and women with memory impairment responded differently to intranasal insulin treatment. On delayed story memory, men and women showed cognitive improvement when taking 20 IU of intranasal insulin, but only men showed cognitive improvement for the 40 IU dose. The sex difference was most apparent for ApoE ε4 negative individuals. For the 40 IU dose, ApoE ε4 negative men improved while ApoE ε4 negative women worsened. Their ApoE ε4 positive counterparts remained cognitively stable. This sex effect was not detected in functional measures. However, functional abilities were relatively preserved for women on either dose of intranasal insulin compared with men. Unlike previous studies with young adults, neither men nor women taking intranasal insulin exhibited a significant change in weight over 4 months of treatment.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Intranasal
  • Aged
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / psychology
  • Apolipoprotein E4 / genetics*
  • Body Mass Index
  • Body Weight / physiology
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / psychology
  • Female
  • Genotype
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / administration & dosage
  • Insulin / blood
  • Insulin / therapeutic use*
  • Male
  • Neuropsychological Tests
  • Sex Characteristics
  • Treatment Outcome


  • Apolipoprotein E4
  • Hypoglycemic Agents
  • Insulin