Aging
Conditions
Brief summary
The purpose of this research study is to understand the neural mechanisms underlying long-term memory formation in older adults. Both sleep and memory decrease with age. The investigators are interested in discovering whether these two biological changes are related. This study is specifically focused on understanding what are the critical components of sleep that facilitate memory formation and are they impaired in older adults. The investigators will be using the hypnotic zolpidem, a sleep drug that has been shown to increase a specific aspect of sleep that have been shown to correlate with memory improvement in young adults. The Food and Drug Administration (FDA) have approved zolpidem for use in certain sleep disorders, specifically in the treatment of sleeplessness (i.e., insomnia). In the current study, the investigators will examine whether zolpidem (5mg), compared with placebo, increases memory-related sleep events in older adults and test the impact of these drug-related sleep changes on post-sleep memory recall. This is a research study because the investigators are using pharmacological interventions to investigate our hypotheses about memory consolidation. The investigators are not studying the efficacy of zolpidem to treat conditions for which the FDA has already approved it.
Interventions
DRUGZolpidem
The research involves oral administration of zolpidem (ZOL) or placebo during sleep with EEG recording. This study will employ a within-subject, crossover design, in which every subject experiences each of the following study conditions: Nap/5mg, Nap/placebo, plus an adaptation nap to be scheduled one week prior to the first experimental day. One condition will be tested per week, with condition order counterbalanced. Each subject will have 2 visits (plus an adaptation nap), each separated by 5-7 days (although this may be extended based on participant availability) to ensure that the drug is completely eliminated from the body. The order of drug conditions will be randomized and counterbalanced.
Sponsors
University of California, Irvine
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* English speaking * non-smoker * between the ages of 60 to 75, without major medical problems * have a regular sleep wake schedule, defined as obtaining 6-9 hours of sleep per night, with a habitual bedtime before 2am and a habitual wake time before 10am * must have experience with Ambien to participate in the study.
Exclusion criteria
* have a sleeping disorder (reported or detected on questionnaires) * have any personal or immediate family history of diagnosed mental disorders * have any personal history of head injury with loss of consciousness greater than 2 minutes or seizures * have a history of substance dependence * currently use any medications that could affect sleep and/or thought processes * have any cardiac, respiratory or other medical condition which may affect cerebral metabolism * have dementia * have non-correctable vision and hearing impairments, due to the nature of the stimulus and its presentation, will also be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Memory Recall | baseline to 12 hour recall test | The investigators will assess change in performance on a memory task that will be tested before and after the drug intervention. Subjects will study word lists before the intervention and their recall will be tested after the intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Electroencephalography (EEG) Activity During the Naps | second intervention occurs at least 7 days after the first intervention | The investigators will measure electroencephalography (EEG) during the sleep, we are measuring spindle density, where higher density means more spindles. More spindles would be a sign of greater hippocampal memory consolidation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zolpidem Then Placebo The research involves oral administration of zolpidem (ZOL, 5mg) or placebo during sleep with EEG recording. This study will employ a within-subject, crossover design, in which every subject experiences each of the following study conditions: Nap/5mg, Nap/placebo, plus an adaptation nap to be scheduled one week prior to the first experimental day.The order of drug conditions will be randomized and counterbalanced. During the experimental phase, each drug condition will include one day in the sleep lab, two encoding test sessions, and one retrieval test session. Multiple subjects will be in the experimental phase concurrently, and multiple subjects will be tested on each day.
Zolpidem: The research involves oral administration of zolpidem (ZOL) or placebo during sleep with EEG recording. This study will employ a within-subject, crossover design, in which every subject experiences each of the following study conditions: Nap/5mg, Nap/placebo, plus an adaptation nap to be scheduled one week prior to the first experimental day. One condition will be tested per week, with condition order counterbalanced. Each subject will have 2 visits (plus an adaptation nap), each separated by 5-7 days (although this may be extended based on participant availability) to ensure that the drug is completely eliminated from the body. The order of drug conditions will be randomized and counterbalanced. | 5 |
| Placebo Then Zolpidem The research involves oral administration of zolpidem (ZOL, 5mg) or placebo during sleep with EEG recording. This study will employ a within-subject, crossover design, in which every subject experiences each of the following study conditions: Nap/5mg, Nap/placebo, plus an adaptation nap to be scheduled one week prior to the first experimental day.The order of drug conditions will be randomized and counterbalanced. During the experimental phase, each drug condition will include one day in the sleep lab, two encoding test sessions, and one retrieval test session. Multiple subjects will be in the experimental phase concurrently, and multiple subjects will be tested on each day.
Zolpidem: The research involves oral administration of zolpidem (ZOL) or placebo during sleep with EEG recording. This study will employ a within-subject, crossover design, in which every subject experiences each of the following study conditions: Nap/5mg, Nap/placebo, plus an adaptation nap to be scheduled one week prior to the first experimental day. One condition will be tested per week, with condition order counterbalanced. Each subject will have 2 visits (plus an adaptation nap), each separated by 5-7 days (although this may be extended based on participant availability) to ensure that the drug is completely eliminated from the body. The order of drug conditions will be randomized and counterbalanced. | 5 |
| Total | 10 |
Baseline characteristics
| Characteristic | Zolpidem Then Placebo | Placebo Then Zolpidem | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 10 Participants |
| Age, Continuous | 60 years STANDARD_DEVIATION 4 | 60 years STANDARD_DEVIATION 4 | 60 years STANDARD_DEVIATION 4 |
| Epworth Sleepiness Scale | 11 units on a scale STANDARD_DEVIATION 3 | 10 units on a scale STANDARD_DEVIATION 3 | 10 units on a scale STANDARD_DEVIATION 3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment United States | 5 participants | 5 participants | 10 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
| Stanford Sleepiness Scale | 4.5 units on a scale STANDARD_DEVIATION 1.5 | 5 units on a scale STANDARD_DEVIATION 1.5 | 4.75 units on a scale STANDARD_DEVIATION 1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Memory Recall
The investigators will assess change in performance on a memory task that will be tested before and after the drug intervention. Subjects will study word lists before the intervention and their recall will be tested after the intervention.
Time frame: baseline to 12 hour recall test
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nap/5mg Zolpidem | Memory Recall | 80 percent correct | Standard Deviation 3.5 |
| Nap/Placebo | Memory Recall | 81 percent correct | Standard Deviation 4.3 |
Secondary
Electroencephalography (EEG) Activity During the Naps
The investigators will measure electroencephalography (EEG) during the sleep, we are measuring spindle density, where higher density means more spindles. More spindles would be a sign of greater hippocampal memory consolidation.
Time frame: second intervention occurs at least 7 days after the first intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nap/5mg Zolpidem | Electroencephalography (EEG) Activity During the Naps | 6 spindles per minutes | Standard Deviation 3 |
| Nap/Placebo | Electroencephalography (EEG) Activity During the Naps | 5 spindles per minutes | Standard Deviation 3.5 |