Parkinson's Disease
Conditions
Keywords
amyloid burden, Parkinson's disease, florbetapir PET, amyloid PET imaging
Brief summary
The primary aim of this study is to compare regional amyloid burden in Parkinson's disease (PD) to normal control subjects. We hypothesize that there will be significant differences in overall amyloid burden in PD patients compared to age-matched normal controls.
Interventions
DRUGflorbetapir F 18
10 millicurie (mCi) (370 MBq) florbetapir F 18 Injection
Sponsors
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Avid Radiopharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects may be enrolled if they (inclusion criteria): * Are males or females ≥60 years of age * Meet research diagnostic criteria for Parkinson's disease: * Diagnosis of a parkinsonian syndrome * Bradykinesia (slowness of initiation of voluntary movement with progressive reduction in speed and amplitude of repetitive actions) * At least one of the following: muscle rigidity, rest tremor, postural instability not due to visual, vestibular, cerebellar or proprioceptive causes * Supportive criteria for diagnosis of PD (two or more required) * Unilateral onset of symptoms and persistent asymmetry * Rest tremor present * Progressive illness * Excellent response to levodopa with dyskinesias * Levodopa response for 5 years or more * Clinical course of 10 years or more * Have the ability to lie flat and tolerate a 10 minute PET scan.
Exclusion criteria
* Subjects may not be enrolled if any of the following are present (
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Cortical Amyloid Burden | 50-60 min after injection | Standardized uptake value ratios (SUVR) were calculated and compared between subjects with PD and controls. Subjects with Parkinson's Disease (PD) were stratified into one of three groups based on performance on the age and education adjusted Mattis Dementia Rating Scale (DRS-2). The age and education adjusted DRS-2 ranges from 0 (lowest cognitive function) to 20 (highest cognitive function). SUVR is the ratio of tracer uptake in predefined cortical regions, relative to uptake in the whole cerebellum. SUVR values higher than 1 indicate greater amyloid burden in the predefined cortical regions as compared to cerebellum whereas scores less than 1 indicate the opposite. This outcome measure only reports data from the subjects analyzed in this study, the data from normal controls was obtained from a pre-existing database and is not reported here. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Global Amyloid Burden and Clinical Measures of Cognitive Decline. | 50-60 min after injection | Correlation between amyloid burden (global florbetapir SUVR) and cognitive decline (DRS-2 score) was determined using Spearman's rank order correlation method where SUVR was the dependent variable and the DRS-2 score was the independent variable. This analysis was performed for total DRS-2 score and the five DRS-2 subscale scores. The subscales (score range) are: Attention (0-37), Initiation/Perseveration (0-37), Construction (0-6), Conceptualization (0-39) and Memory (0-25). The total DRS-2 score is the sum of the subscale scores and ranges from 0-144. Higher DRS-2 scores indicate greater cognitive function. |
| Correlation of Florbetapir SUVR With CSF Biomarker Values | 50-60 min after injection | Correlation between amyloid burden (florbetapir SUVR) and cerebrospinal fluid (CSF) biomarker values (amyloid beta, tau and phospho-tau) was determined using Spearman's rank order correlation in a subset of subjects undergoing CSF analysis where SUVR was the dependent variable and CSF biomarker values were the independent variables. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Subjects With Parkinson's Disease Subjects with diagnosed Parkinson's Disease received a 370 MBq injection of florbetapir F 18 followed by a 10 minute PET scan 50 minutes post-injection. | 31 |
| Total | 31 |
Baseline characteristics
| Characteristic | Subjects With Parkinson's Disease |
|---|---|
| Age Continuous | 71.3 years STANDARD_DEVIATION 6.72 |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 31 |
| serious Total, serious adverse events | 0 / 31 |
Outcome results
Primary
Mean Cortical Amyloid Burden
Standardized uptake value ratios (SUVR) were calculated and compared between subjects with PD and controls. Subjects with Parkinson's Disease (PD) were stratified into one of three groups based on performance on the age and education adjusted Mattis Dementia Rating Scale (DRS-2). The age and education adjusted DRS-2 ranges from 0 (lowest cognitive function) to 20 (highest cognitive function). SUVR is the ratio of tracer uptake in predefined cortical regions, relative to uptake in the whole cerebellum. SUVR values higher than 1 indicate greater amyloid burden in the predefined cortical regions as compared to cerebellum whereas scores less than 1 indicate the opposite. This outcome measure only reports data from the subjects analyzed in this study, the data from normal controls was obtained from a pre-existing database and is not reported here.
Time frame: 50-60 min after injection
Population: All subjects who were enrolled in the study and received florbetapir scans.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects With Normal Cognitive Performance | Mean Cortical Amyloid Burden | 0.990 SUVR | Standard Deviation 0.141 |
| Subjects With Mild Cognitive Deficits | Mean Cortical Amyloid Burden | 1.051 SUVR | Standard Deviation 0.194 |
| Subjects With Moderate to Severe Cognitive Impairment | Mean Cortical Amyloid Burden | 1.146 SUVR | Standard Deviation 0.237 |
Secondary
Correlation Between Global Amyloid Burden and Clinical Measures of Cognitive Decline.
Correlation between amyloid burden (global florbetapir SUVR) and cognitive decline (DRS-2 score) was determined using Spearman's rank order correlation method where SUVR was the dependent variable and the DRS-2 score was the independent variable. This analysis was performed for total DRS-2 score and the five DRS-2 subscale scores. The subscales (score range) are: Attention (0-37), Initiation/Perseveration (0-37), Construction (0-6), Conceptualization (0-39) and Memory (0-25). The total DRS-2 score is the sum of the subscale scores and ranges from 0-144. Higher DRS-2 scores indicate greater cognitive function.
Time frame: 50-60 min after injection
Population: All subjects who were enrolled in the study and received florbetapir scans.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects With Normal Cognitive Performance | Correlation Between Global Amyloid Burden and Clinical Measures of Cognitive Decline. | Attention | -0.413 Correlation Coefficient |
| Subjects With Normal Cognitive Performance | Correlation Between Global Amyloid Burden and Clinical Measures of Cognitive Decline. | Initiation/Perseveration | -0.332 Correlation Coefficient |
| Subjects With Normal Cognitive Performance | Correlation Between Global Amyloid Burden and Clinical Measures of Cognitive Decline. | Construction | -0.169 Correlation Coefficient |
| Subjects With Normal Cognitive Performance | Correlation Between Global Amyloid Burden and Clinical Measures of Cognitive Decline. | Conceptualization | -0.206 Correlation Coefficient |
| Subjects With Normal Cognitive Performance | Correlation Between Global Amyloid Burden and Clinical Measures of Cognitive Decline. | Memory | -0.263 Correlation Coefficient |
| Subjects With Normal Cognitive Performance | Correlation Between Global Amyloid Burden and Clinical Measures of Cognitive Decline. | DRS-2 Total Score | -0.369 Correlation Coefficient |
Comparison: P-value for Attention correlation coefficient. Null hypothesis is that there is no correlation between florbetapir SUVR and DRS-2 attention score.p-value: 0.021Spearman's Rank Order Correlation
Comparison: P-value for Initiation/Perseveration correlation coefficient. Null hypothesis is that there is no correlation between florbetapir SUVR and DRS-2 initiation/perseveration score.p-value: 0.077Spearman's Rank Order Correlation
Comparison: P-value for Construction correlation coefficient. Null hypothesis is that there is no correlation between florbetapir SUVR and DRS-2 construction score.p-value: 0.364Spearman's Rank Order Correlation
Comparison: P-value for Conceptualization correlation coefficient. Null hypothesis is that there is no correlation between florbetapir SUVR and DRS-2 conceptualization score.p-value: 0.266Spearman's Rank Order Correlation
Comparison: P-value for Memory correlation coefficient. Null hypothesis is that there is no correlation between florbetapir SUVR and DRS-2 memory score.p-value: 0.152Spearman's Rank Order Correlation
Comparison: P-value for DRS-2 Total correlation coefficient. Null hypothesis is that there is no correlation between florbetapir SUVR and DRS-2 total score.p-value: 0.041Spearman's Rank Order Correlation
Secondary
Correlation of Florbetapir SUVR With CSF Biomarker Values
Correlation between amyloid burden (florbetapir SUVR) and cerebrospinal fluid (CSF) biomarker values (amyloid beta, tau and phospho-tau) was determined using Spearman's rank order correlation in a subset of subjects undergoing CSF analysis where SUVR was the dependent variable and CSF biomarker values were the independent variables.
Time frame: 50-60 min after injection
Population: Participants were a subset of all subjects enrolled in this study who were also part of an ongoing study looking at the usefulness of CSF biomarkers.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects With Normal Cognitive Performance | Correlation of Florbetapir SUVR With CSF Biomarker Values | Amyloid beta | -0.4387 Correlation Coefficient |
| Subjects With Normal Cognitive Performance | Correlation of Florbetapir SUVR With CSF Biomarker Values | Tau | -0.1248 Correlation Coefficient |
| Subjects With Normal Cognitive Performance | Correlation of Florbetapir SUVR With CSF Biomarker Values | Phospho-tau | -0.0525 Correlation Coefficient |
Comparison: P-value for Amyloid beta correlation coefficient. Null hypothesis is that there is no correlation between florbetapir SUVR and amyloid beta.p-value: 0.0411Spearman's Rank Order Correlation
Comparison: P-value for Tau correlation coefficient. Null hypothesis is that there is no correlation between florbetapir SUVR and tau.p-value: 0.58Spearman's Rank Order Correlation
Comparison: P-value for Phospho-Tau correlation coefficient. Null hypothesis is that there is no correlation between florbetapir SUVR and phospho-tau.p-value: 0.8164Spearman's Rank Order Correlation