Alzheimer's Disease, Apathy
Conditions
Keywords
apathy, Alzheimer's disease, activities of daily living performance, caregiver burden
Brief summary
This study examined the effects of modafinil on apathetic symptomatology, performance of activities of daily living (ADLs) and caregiver burden in individuals with Alzheimer's disease (AD).
Interventions
DRUGModafinil
100 mg in the morning for the first week and 200 mg in the morning for the remaining seven weeks
DRUGPlacebo
100 mg in the morning for the first week and 200 mg in the morning for the remaining seven weeks
Sponsors
National Institute of Mental Health (NIMH)
Cephalon
Brown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to 95 Years
Healthy volunteers
Yes
Inclusion criteria
* diagnosis of mild to moderate stage Probable Alzheimer's disease * on a stable dose of a cholinesterase inhibitor medication for at least 30 days * clinically elevated levels of apathy as measured by the Frontal Systems Behavior Scale
Exclusion criteria
* diagnosis of Major Depression * focal brain lesion on neuroimaging * history of significant substance abuse * history of significant head trauma with loss if consciousness \>10 minutes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apathy | at baseline | The Frontal Systems Behavior Scale. Raw scores are converted to T-Scores using published norms. T-Scores have a mean of 50 and a standard deviation of 10. T-scores less than or equal to 64 are within average range. T-scores equal to or greater than 65 are indicative of a clinically significant problem. Higher scores indicate greater problem severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lawton Brody Activities of Daily Living Questionnaire | at baseline | Caregiver reported performance of personal and instrumental activities of daily living (ADLs. There are 6 personal ADLs (i.e. dressing, grooming, eating, etc) and 8 instrumental ADLs (i.e. managing finances, transportation, food preparation) which are assessed. Each item is awarded 2 points for fully independent, 1 point for minimal or moderate support required, and 0 points for full support. Maximum score for independence with all personal and instrumental ADL's is 28. |
| The Direct Assessment of Functional Status Scale | at baseline | A direct, examiner observed assessment of basic and instrumental activities of daily living. Participants are awarded points for correct performance of activities. Raw score is used for statistical comparison. |
| Zarit Burden Inventory | at baseline | Measure of Caregiver Burden. Caregiver rates each item assessing burden on a 0 to 4 point scale with higher numbers reflecting more frequent occurence of the behavior or feeling being assessed. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from a Memory Disorders Clinic and the community between 2005 and 2007
Participants by arm
| Arm | Count |
|---|---|
| Cholinesterase Inhibitor Only participants who received placebo | 11 |
| Cholinesterase Plus Modafinil participants who received modafinil (200 mg per day) | 11 |
| Total | 22 |
Baseline characteristics
| Characteristic | Cholinesterase Plus Modafinil | Cholinesterase Inhibitor Only | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 11 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Age Continuous | 75.27 years STANDARD_DEVIATION 8.34 | 79.36 years STANDARD_DEVIATION 7.62 | 77.32 years STANDARD_DEVIATION 8.07 |
| Region of Enrollment United States | 11 participants | 11 participants | 22 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 7 Participants | 4 Participants | 11 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
Apathy
The Frontal Systems Behavior Scale. Raw scores are converted to T-Scores using published norms. T-Scores have a mean of 50 and a standard deviation of 10. T-scores less than or equal to 64 are within average range. T-scores equal to or greater than 65 are indicative of a clinically significant problem. Higher scores indicate greater problem severity.
Time frame: at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholinesterase Inhibitor Only | Apathy | 88.91 T-score | Standard Deviation 11.95 |
| Cholinesterase Plus Modafinil | Apathy | 95.64 T-score | Standard Deviation 10.79 |
p-value: 0.18195% CI: [-16.86, 3.4]t-test, 2 sided
Primary
Apathy
The Frontal Systems Behavior Scale.Raw scores are converted to T-Scores using published norms. T-Scores have a mean of 50 and a standard deviation of 10. T-scores less than or equal to 64 are within the average range. T-scores equal to or greater than 65 are indicative of a clinically significant problem. Higher scores indicate greater problem severity.
Time frame: after 8 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholinesterase Inhibitor Only | Apathy | 82.09 T-score | Standard Deviation 13.52 |
| Cholinesterase Plus Modafinil | Apathy | 89.09 T-score | Standard Deviation 9.61 |
Secondary
Lawton Brody Activities of Daily Living Questionnaire
Caregiver reported performance of personal and instrumental activities of daily living (ADLs. There are 6 personal ADLs (i.e. dressing, grooming, eating, etc) and 8 instrumental ADLs (i.e. managing finances, transportation, food preparation) which are assessed. Each item is awarded 2 points for fully independent, 1 point for minimal or moderate support required, and 0 points for full support. Maximum score for independence with all personal and instrumental ADL's is 28.
Time frame: at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholinesterase Inhibitor Only | Lawton Brody Activities of Daily Living Questionnaire | 19.00 raw score | Standard Deviation 5.25 |
| Cholinesterase Plus Modafinil | Lawton Brody Activities of Daily Living Questionnaire | 16.18 raw score | Standard Deviation 4.81 |
Secondary
Lawton Brody Activities of Daily Living Questionnaire
Caregiver reported performance of personal and instrumental activities of daily living (ADLs. There are 6 personal ADLs (i.e. dressing, grooming, eating, etc) and 8 instrumental ADLs (i.e. managing finances, transportation, food preparation) which are assessed. Each item is awarded 2 points for fully independent, 1 point for minimal or moderate support required, and 0 points for full support. Maximum score for independence with all personal and instrumental ADL's is 28.
Time frame: after 8 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholinesterase Inhibitor Only | Lawton Brody Activities of Daily Living Questionnaire | 19.00 raw score | Standard Deviation 5.54 |
| Cholinesterase Plus Modafinil | Lawton Brody Activities of Daily Living Questionnaire | 15.64 raw score | Standard Deviation 5.43 |
Secondary
The Direct Assessment of Functional Status Scale
A direct, examiner observed assessment of basic and instrumental activities of daily living. Participants are awarded points for correct performance of activities. Raw score is used for statistical comparison.
Time frame: after 8 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholinesterase Inhibitor Only | The Direct Assessment of Functional Status Scale | 88.36 raw score | Standard Deviation 8.35 |
| Cholinesterase Plus Modafinil | The Direct Assessment of Functional Status Scale | 85.27 raw score | Standard Deviation 14.16 |
Secondary
The Direct Assessment of Functional Status Scale
A direct, examiner observed assessment of basic and instrumental activities of daily living. Participants are awarded points for correct performance of activities. Raw score is used for statistical comparison.
Time frame: at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholinesterase Inhibitor Only | The Direct Assessment of Functional Status Scale | 89.09 raw score | Standard Deviation 7.84 |
| Cholinesterase Plus Modafinil | The Direct Assessment of Functional Status Scale | 84.55 raw score | Standard Deviation 16.11 |
Secondary
Zarit Burden Inventory
Measure of Caregiver Burden. Caregiver rates each item assessing burden on a 0 to 4 point scale with higher numbers reflecting more frequent occurence of the behavior or feeling being assessed.
Time frame: after 8 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholinesterase Inhibitor Only | Zarit Burden Inventory | 30.00 raw score | Standard Deviation 20.56 |
| Cholinesterase Plus Modafinil | Zarit Burden Inventory | 30.00 raw score | Standard Deviation 4.17 |
Secondary
Zarit Burden Inventory
Measure of Caregiver Burden. Caregiver rates each item assessing burden on a 0 to 4 point scale with higher numbers reflecting more frequent occurence of the behavior or feeling being assessed.
Time frame: at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholinesterase Inhibitor Only | Zarit Burden Inventory | 28.36 raw score | Standard Deviation 21.09 |
| Cholinesterase Plus Modafinil | Zarit Burden Inventory | 31.18 raw score | Standard Deviation 8.73 |