The Impact of Lorazepam on Cognition in APOE e4 Carriers

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Impact of Lorazepam on Cognition in APOE e4 Carriers

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: lorazepam
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>single 2 mg dose of lorazepam | Drug: lorazepam<br>* single 2 mg dose of lorazepam<br>* Other names: Ativan;|
| Placebo Comparator: 2<br>single dose of placebo | Drug: placebo<br>* single dose of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Groton Maze Learning Task |  | baseline, 2.5 hours and 5 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Auditory Verbal Learning Test |  | baseline, 2.5 hours and 5 hours | 
| 1-back test |  | baseline, 2.5 hours and 5 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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apolipoprotein E e4, Alzheimer's disease, somnolence, Early detection