The Impact of Lorazepam on Cognition in APOE e4 Carriers

Mayo Clinic

Status: Completed

Conditions: Alzheimer's Disease

Treatments: Drug: placebo; Drug: lorazepam

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00586430

929-05

Details and patient eligibility

About

We expect the results of this pilot study to justify a larger study that follows people to determine if certain tests of memory and attention, performed while sleepiness is induced by a single dose of lorazepam (a widely used anti-anxiety medication) could predict an individual's risk of developing AD. We plan to compare cognitively normal people who possess a common gene that increases risk for AD- the apolipoprotein E (APOE) e4 allele-to individuals without this gene. We hypothesize that a single 2 mg dose of lorazepam will cause more cognitive impairment in carriers of the APOE e4 allele than in noncarriers, and that the carriers will recover more slowly from these impairments than noncarriers.

Full description

We aim to compare measures of memory and information processing speed at 2.5 hours and 5 hours after the administration of a 2 mg dose of lorazepam or placebo in cognitively normal, 50-65 year old APOE e4 carriers and noncarriers, and determine the differential impact of lorazepam on cognition at each time point. Twenty carriers and 20 noncarriers matched for age, sex, and education will be drawn from a database of persons who have already undergone genotyping for an ongoing study at the Mayo Clinic, excluding people with evidence of depression or cognitive impairment and other medical, neurological or psychiatric conditions. Using a double blind, crossover design, subjects will receive either placebo or a 2 mg dose of lorazepam after baseline testing. Equivalent tests will be repeated 2.5 and 5 hours post challenge. The data analysis will compare APOE e4 carriers to noncarriers.

Enrollment: 36 patients

Sex: All

Ages: 50 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• a score of at least 28 on the MMSE
• a score of less than 10 points on the HAM-D-17
• age 50-65
• genotype APOE e3/e4 or APOE e4 non-carriers
• cognitively normal

Exclusion criteria

• significant medical, psychiatric, or neurological illnesses
• use of benzodiazepines within the previous four weeks
• currently using sedating antihistamines

Trial design

Primary purpose: Screening

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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36 participants in 2 patient groups, including a placebo group

1

Active Comparator group

Description:

single 2 mg dose of lorazepam

Treatment:

Drug: lorazepam

2

Placebo Comparator group

Description:

single dose of placebo

Treatment:

Drug: placebo