Memory Disorders
Conditions
Keywords
Memory Disorders, Alzheimer's Disease
Brief summary
The study described in the present application will test the hypothesis that insulin mediated facilitation of memory in Alzheimer's disease (AD) is achieved through enhanced glutamatergic neurotransmission due to improvements in cerebral glucose metabolism. The effect of a single dose of intranasal insulin on memory and cerebral glutamate concentrations in adults with mild AD or amnestic mild cognitive impairment (aMCI), the presumed prodromal phase of AD will be studied. Successful completion of this study may set the stage for a larger-scale treatment trial of intranasal insulin for adults with memory disorders. However, the use of insulin in this manner at this point in time is purely experimental.
Detailed description
The specific aims of this project will be accomplished through a cross sectional repeated measures design in which 15 participants with mild AD or amnestic MCI will undergo assessments of brain structure and function 15 minutes after a single dose of insulin (20 IU) or placebo. Insulin and placebo conditions will be counterbalanced across participants. Intranasal insulin or placebo administration: Saline and insulin (NovoLog) will be ordered though the UT Student Health Services Pharmacy (Sharon Roberson, Chief Pharmacist) and stored at 4°C, according to standard pharmacy protocols. Three ml doses of saline or insulin will be packaged in nasal spray bottles (e.g., Spectrum Pharmacy Products bottles 969-17404P and actuators 551-24362P) designed to deliver 100μL dose with each spray. A total volume of 200μL will be delivered during each administration (one 100μL dose in each nostril).
Interventions
DRUGInsulin
20 IU of insulin was administered once daily on two occasions in either the first intervention period or second intervention period using a nasal spray bottle
OTHERSaline
200 micro liters of saline was administered once daily on two separate occasions in either the first intervention period or second intervention period using a nasal spray bottle
Sponsors
University of Texas at Austin
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of probable AD * Age over 21 * Clinical Dementia Rating of 0.5 or 1.0 * Mini Mental State Exam Score\>15
Exclusion criteria
* preexisting diabetes * significant neurological disease that might affect cognition, other than AD, including stroke, Parkinson's disease, multiple sclerosis * severe head injury with loss of consciousness \> 30 minutes or with permanent neurological sequelae * significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease * current use of anti-psychotic or anti-convulsant medications * current or previous use of hypoglycemic agents or insulin * MRI contraindications * claustrophobia * pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral Glutamate Concentration | 15 minutes post insulin or placebo administration | Glutamate concentration was expressed as the ratio of glutamate to creatine. This was determined using magnetic resonance spectroscopy (MRS), a magnetic resonance technique that uses the same equipment as magnetic resonance imaging (MRI), but allows researchers to extract information about the concentrations of various neurochemicals of neurobiological significance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Memory | 15 minutes post insulin or placebo administration | Memory performance was assessed using delayed recall (number of units recalled) on the Wechsler Memory Scale (WMS-IV) logical memory (story recall) test. Scores represent a sum of recalled units of two different stories after a 30 minute delay. Total scores range from 0 to 50 (0-25 for each story) with higher scores reflecting better memory performance |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Insulin First, Then Saline 20 IU of insulin was administered once daily on two occasions followed by 200 micro liters of saline administered once daily on two occasions | 5 |
| Saline First, Then Insulin 200 micro liters of saline was administered once daily on two occasions followed by 20 IU of insulin administered once daily on two occasions | 6 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (1 Day) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Insulin First, Then Saline | Saline First, Then Insulin | Total |
|---|---|---|---|
| Age, Continuous | 73.8 years STANDARD_DEVIATION 8.58 | 74.33 years STANDARD_DEVIATION 5.92 | 74.09 years STANDARD_DEVIATION 6.54 |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 1 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Cerebral Glutamate Concentration
Glutamate concentration was expressed as the ratio of glutamate to creatine. This was determined using magnetic resonance spectroscopy (MRS), a magnetic resonance technique that uses the same equipment as magnetic resonance imaging (MRI), but allows researchers to extract information about the concentrations of various neurochemicals of neurobiological significance.
Time frame: 15 minutes post insulin or placebo administration
Population: per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin | Cerebral Glutamate Concentration | 1.34 ratio | Standard Deviation 0.12 |
| Saline | Cerebral Glutamate Concentration | 1.34 ratio | Standard Deviation 0.17 |
Secondary
Memory
Memory performance was assessed using delayed recall (number of units recalled) on the Wechsler Memory Scale (WMS-IV) logical memory (story recall) test. Scores represent a sum of recalled units of two different stories after a 30 minute delay. Total scores range from 0 to 50 (0-25 for each story) with higher scores reflecting better memory performance
Time frame: 15 minutes post insulin or placebo administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin | Memory | 6.73 units on a scale | Standard Deviation 6.25 |
| Saline | Memory | 5.36 units on a scale | Standard Deviation 2.69 |