Lorazepam Challenge for Individuals at Varying Genetic Risk for Alzheimer Disease

Cynthia M. Stonnington, Brian Harel, Dona E.C. Locke, Joseph G. Hentz, Nan Zhang, Paul Maruff, Richard J. Caselli

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Introduction: This study set out to clarify the differential acute cognitive impact of lorazepam based on varying genetic risk for Alzheimer disease. Methods: Fifty-seven cognitively unimpaired individuals aged 51 to 88, genotyped according to apolipoprotein E (APOE) and translocase of outer mitochondrial membrane (40 homolog) poly-T lengths, completed cognitive testing before, 2.5 and 5 hours after receiving a 1mg dose of lorazepam. Results: Post-lorazepam, there were significant (P<0.05) declines from baseline in memory, psychomotor processing speed, and executive function. At 2.5 hours, the magnitude of this lorazepaminduced cognitive change was significantly greater in the APOE3/4 group than in the APOE3/3 group for tests of working memory and visuospatial memory/executive function. At 5 hours postchallenge, verbal memory and working memory deficits persisted in the APOE3/4 group compared with the APOE3/3 group. At 5 hours after lorazepam challenge, as compared with the very long/very long group, the short/short group performed slightly worse on a test of working memory (P<0.05), but no other differences were observed among translocase of the outer mitochondrial membrane 40 homolog poly-T variant groups. Discussion: The lorazepam challenge may be unmasking presymptomatic cognitive dysfunction associated with APOE4 carriage.

Original languageEnglish (US)
Pages (from-to)271-277
Number of pages7
JournalAlzheimer disease and associated disorders
Issue number4
StatePublished - 2017


  • Alzheimer disease
  • apolipoprotein E
  • executive function
  • lorazepam
  • memory
  • presymptomatic

ASJC Scopus subject areas

  • Clinical Psychology
  • Gerontology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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