Alzheimer Disease
Conditions
Keywords
18F-MK-6240, Cognitive Impairment, Alzheimer's
Brief summary
This study is being done to learn about tau tangles in Alzheimer's disease. A type of positron emission tomography (PET) scan is used to measure the abnormal accumulation of protein called tau in the brain. These are thought to be involved in Alzheimer's disease. The investigators will also perform brain MRI and to tests to measure the participant's memory and thinking.
Detailed description
This study is being done to determine the relationship between tau tangles and cognitive impairment in elderly subjects with and without Alzheimer's disease (AD). Subjects will undergo screen that includes neuropsychological testing and brain MRI. This study uses a special type of scan called a PET scan to take pictures of the brain. During the PET scan, a special radioactive dye called 18F-MK-6240 is injected into the body. 18F-MK-6240 sticks to abnormal tangles made of the protein tau. Subjects will have the option to have lumbar puncture performed to measure CSF concentrations of biomarkers.
Interventions
DRUG18F-MK-6240
18F-MK-6240 is a PET radioligand that binds abnormal tangles made of the protein tau. These tau tangles develop in the brain in people with Alzheimer's disease.
PROCEDURELumbar Puncture (optional)
Subjects have the option to have lumbar puncture performed for the measurement of Alzheimer's disease biomarkers in cerebrospinal fluid.
Sponsors
National Institute on Aging (NIA)
Patrick Lao
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 50 and older. 2. Meet criteria for either 1. amnestic mild cognitive impairment (MCI) (single or mixed domain) or mild Alzheimer's disease (AD), or 2. have no cognitive impairment, based on history, exam, neuropsychological testing, and consensus diagnosis. MCI and mild AD patients must have Clinical Dementia Rating scale score of 0.5 or 1. Unimpaired subjects must have Clinical Dementia Rating scale score of 0. 3. Subjects unable to provide informed consent must have a surrogate decision maker. 4. Written and oral fluency in English or Spanish. 5. Able to participate in all scheduled evaluations and to complete all required tests and procedures. 6. In the opinion of the investigator, the subject must be considered likely to comply with the study protocol and to have a high probability of completing the study.
Exclusion criteria
1. Past or present history of certain brain disorders other than MCI or AD. 2. Certain significant medical conditions, which make study procedures of the current study unsafe. Such serious medical conditions include uncontrolled epilepsy and multiple serious injuries. 3. Contraindication to magnetic resonance imaging (MRI) scanning. 4. Conditions precluding entry into the scanners (e.g. morbid obesity, claustrophobia, etc.). 5. History of kidney disease or presence of impaired kidney function based on laboratory tests at screening visit. 6. History of liver disease or presence of impaired liver function based on laboratory tests at screening visit. 7. Participation in the last year in a clinical trial for a disease modifying drug for AD. 8. Inability to have a catheter in subject's vein for the injection of radioligand. 9. Inability to have blood drawn from subject's veins.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 18F-MK-6240 Binding | 1 day | Standardized uptake value ratio (SUVr) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Tau, Neurodegeneration and Inflammation Using PET and CSF Biomarkers. | One year follow-up | Correlation of 18F-MK-6240 binding and CSF markers of neurodegeneration and inflammation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| No Cognitive Impairment Healthy participants without cognitive impairment | 43 |
| Cognitive Impairment Participants with mild cognitive impairment or mild stage Alzheimer's disease dementia | 28 |
| Total | 71 |
Baseline characteristics
| Characteristic | No Cognitive Impairment | Total | Cognitive Impairment |
|---|---|---|---|
| Age, Continuous | 70.6 years STANDARD_DEVIATION 8.6 | 70.1 years STANDARD_DEVIATION 9.2 | 69.5 years STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 66 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 18 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 | 27 Participants | 53 Participants | 26 Participants |
| Region of Enrollment United States | 43 participants | 71 participants | 28 participants |
| Sex: Female, Male Female | 21 Participants | 28 Participants | 7 Participants |
| Sex: Female, Male Male | 22 Participants | 43 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 28 |
| other Total, other adverse events | 4 / 43 | 4 / 28 |
| serious Total, serious adverse events | 0 / 43 | 0 / 28 |
Outcome results
Primary
18F-MK-6240 Binding
Standardized uptake value ratio (SUVr)
Time frame: 1 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Cognitive Impairment | 18F-MK-6240 Binding | 1.41 SUVr | Standard Deviation 0.43 |
| Cognitive Impairment | 18F-MK-6240 Binding | 2.30 SUVr | Standard Deviation 0.92 |
Secondary
Correlation Between Tau, Neurodegeneration and Inflammation Using PET and CSF Biomarkers.
Correlation of 18F-MK-6240 binding and CSF markers of neurodegeneration and inflammation.
Time frame: One year follow-up
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| No Cognitive Impairment | Correlation Between Tau, Neurodegeneration and Inflammation Using PET and CSF Biomarkers. | Correlation between Tau and Neurodegeneration | -0.347 correlation coefficient (r) |
| No Cognitive Impairment | Correlation Between Tau, Neurodegeneration and Inflammation Using PET and CSF Biomarkers. | Correlation between Tau and Inflammation | -0.295 correlation coefficient (r) |
| Cognitive Impairment | Correlation Between Tau, Neurodegeneration and Inflammation Using PET and CSF Biomarkers. | Correlation between Tau and Neurodegeneration | 0.013 correlation coefficient (r) |
| Cognitive Impairment | Correlation Between Tau, Neurodegeneration and Inflammation Using PET and CSF Biomarkers. | Correlation between Tau and Inflammation | 0.181 correlation coefficient (r) |