The Cognitive Effects of Lorazepam in Healthy Older Individuals With TOMM40 Variable-length Polymorphisms

Study Overview
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Brief Summary
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The investigators' goal is to determine if certain tests of memory and attention, performed while sleepiness is induced by a single dose of lorazepam, can predict whether or not an individual is at risk for developing Alzheimer's disease.

Official Title
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The Cognitive Effects of Lorazepam in Healthy Older Individuals With TOMM40 Variable-length Polymorphisms

Conditions
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Alzheimer's Disease (AD)

Intervention / Treatment
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* Drug: lorazepam


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Mini-Mental State Examination (MMSE) score of 28-30 Hamilton Depression Rating Scale score of less than 10 participants in longitudinal study of aging and have a TOMM40 genotype of S/S, VL/VL, S/VL, L/S or L/VL. Exclusion criteria: Alzheimer's Disease or Mild Cognitive Impairment any significant medical, psychiatric, and neurological illnesses, e.g., impaired liver or kidney function, prior stroke, traumatic brain injury, memory impairment, cognitive impairment, parkinsonism, a lifetime history of schizophrenia, bipolar disorder, a psychoactive substance use disorder, or current major depression. known allergy to benzodiazepines current use (within the previous four weeks) of benzodiazepines or other medications known to interact with lorazepam, current use of sedating antihistamines, or current use of stimulant medications

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: L/VL APOE e3/e4 carrier<br>long and very long poly - T variants of TOMM40 and APOE e3/e4 carrier | Drug: lorazepam<br>* single dose of 1 mg lorazepam<br>* Other names: Ativan;|
| Other: L/S APOE e3/e4 carrier<br>long and short poly - T variants of TOMM40 and APOE e3/e4 carrier | Drug: lorazepam<br>* single dose of 1 mg lorazepam<br>* Other names: Ativan;|
| Other: S/VL APOE e3/e3 carrier<br>short and Very long poly - T variants of TOMM40 and APOE e3/e3 carrier | Drug: lorazepam<br>* single dose of 1 mg lorazepam<br>* Other names: Ativan;|
| Other: VL/VL APOE e3/e3 carrier<br>Very long poly - T variants of TOMM40 and APOE e3/e3 carrier | Drug: lorazepam<br>* single dose of 1 mg lorazepam<br>* Other names: Ativan;|
| Other: S/S APOE e3/e3 carrier<br>short poly - T variants of TOMM40 and APOE e3/e3 carrier | Drug: lorazepam<br>* single dose of 1 mg lorazepam<br>* Other names: Ativan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Groton Maze Learning Test (GMLT) score | The GMLT assesses visuospatial working memory, error monitoring, information processing speed, and short-term delayed recall for a complex hidden maze. Subjects are familiarized with the task during two untimed practice tests, and once the tester is confident that the subject understands the rules and can move easily around the grid, the timed test is administered. In each of the 5 successive trials of the GMLT exam, the subject is asked to learn to navigate his or her way around a 28-step maze that is hidden beneath a 10 x 10 grid of squares on the computer touch screen. For each trial, the time to completion, number of correct moves, number of wrong moves, and the number of perseverative errors are recorded. | baseline to 5 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Auditory Verbal Learning Test (AVLT) Long-term memory score | The AVLT assesses verbal memory | baseline to 5 hours | 
| Two Back Test (TBK) | The TBK measures working memory | baseline to 5 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease (AD)