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Lorazepam Challenge for Individuals at Varying Genetic Risk for Alzheimer Disease

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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 1 mg 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 lorazepam-induced 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.
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Keywords: Alzheimer disease; apolipoprotein E; executive function; lorazepam; memory; presymptomatic

Document Type: Research Article

Affiliations: 1: Departments of Psychiatry and Psychology 2: Cogstate Ltd, Melbourne, Vic., Australia, Neuroscience and Pain Research Unit, Pfizer Worldwide Research & Development, Cambridge, MA 3: Biostatistics, Mayo Clinic in Arizona, Scottsdale, AZ 4: Cogstate Ltd, Melbourne, Vic., Australia 5: Neurology

Publication date: October 1, 2017

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