Alzheimer's Disease
Conditions
Keywords
ASL MRI, perfusion, cognition, donepezil, alzheimer's disease, translational medicine
Brief summary
The study hypothesizes that donepezil will have a positive impact on brain blood flow deficits in subjects with memory deficits and/or mild dementia and that improvements in brain blood flow will be accompanied by improvements in memory.
Interventions
DRUGDonepezil
5 mg tablets once daily for 7 days and then 10mg on 8th day
DRUGPlacebo
matching placebo
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects and caregivers must provide written Informed Consent and be willing to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. * AD: Diagnostic evidence of probable AD consistent with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria met by the site Physician at the time of the Screening visit. This evidence must be fully documented in the participant's file prior to the Baseline Visit. * For amnestic Mild Cognitive Impairment (MCI): A Clinical Dementia Rating (CDR) of 0.5 (with memory box score of at least 0.5) and a memory complaint that is objectively verified using a test of episodic memory: Delayed recall from one paragraph of the Wechsler Logical Memory scale (cutoff scores by education - maximum score of 25). * Less than or equal to 8 for 16 or more years of education; Less than or equal to 4 for 8-15 years of education; Less than or equal to 2 for 0-7 years of education. * Mini Mental State Exam (MMSE) score of 21-30 * Male and female subjects of non child-bearing potential (or using appropriate birth control measures) who are at least 50 years of age. * In generally good health, in the opinion of the Principal Investigator (PI), based on medical history, Body Mass Index (BMI), physical examination, vital signs, 12-lead ECG, and laboratory values, including hematology and chemistry values. * No known genetic AD causes for early onset memory impairment (e.g., presenilin mutation), participants from a family with known autosomal dominant AD associated with mutations in APP, PS1, or PS2 genes or strongly suspected, but not yet identified mutations in APP, PS1 or PS2 genes or Down's syndrome are not eligible to enroll. Individuals from families with late onset AD with 2 or more affected family members may participate. Type II diabetic subjects may be included provided that their disease and serum glucose values are controlled and being actively managed, as assessed by the PI using a fasting blood sugar and/or HgbA1C (per the PI's medical judgment in consultation with the Sponsor). * Rosen-Modified Hachinski Ischemia Score less than or equal to 4.
Exclusion criteria
* Diagnosis or history of other possible cause for or significant contributor to dementia, including but not limited to other neurodegenerative disorders (eg, frontotemporal dementia, Lewy body disease, vascular dementia), vitamin B12 deficiency (reflex Methylmalonic Acid (MMA) and folate if B12 is low), untreated thyroid disease, syphilis, alcoholism, severe or recurrent head injury that is clinically relevant to the disease under study, or onset of dementia following heart surgery or cardiac arrest. * Diagnosis or history of cerebrovascular disease (eg, stroke, transient ischemic attack), severe carotid stenosis, cerebral hemorrhage, intracranial tumor, subarachnoid hemorrhage, or subdural hematoma that could contribute to the subject's current cognitive or functional status, impair ability to fully participate in the trial or that may impact status during the one week study. * Specific exclusionary brain MRI findings identified prior to study or at baseline as determined by the investigator that could either contribute to the subject's current cognitive or functional decline impair ability to fully participate in the trial or that may impact status during the trial: * History of cancer within the last year (except for cutaneous basal cell, squamous cell cancer resolved by excision, colon polyp resolved by excision, or non-progressive prostate cancer per investigator's judgment). * History of clinically significant cardiovascular or renal events. * Subjects with uncontrolled hypertension even with therapeutic intervention * History of clinically significant (as determined by the PI in consultation with the Sponsor) syncope, seizure, head trauma, or clinically significant unexplained loss of consciousness within the last 5 years. * A diagnosis of major depressive disorder or other psychiatric illness as the primary diagnosis per the DSM-IV text revision (TR) criteria per the investigator's judgment. * History of schizophrenia, bipolar disorder, or other severe mental illness. * Known history of alcohol or drug abuse (as defined by the DSM-IV-TR) within 5 years prior to dosing or a positive result regarding use of illicit drugs on the drug screening test. * History of clinically significant symptoms of pulmonary disease that requires treatment (eg. asthma, COPD, or other chronic respiratory conditions). * Known positive Human immunodeficiency virus (HIV) status. * Unwilling or unable to comply with the Life Style guidelines described in this protocol. Exclusions Related to Medications or Procedures * Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) of Study Day 1. * Use of tobacco- or nicotine-containing products within three months of study Day 1. Use of medication(s) for cognitive enhancement ≤ 90 days before the first dose of study medication. * Prescription: including but not limited to donepezil, galantamine, rivastigmine, tacrine, memantine, Axona™; * Reason for stoppage of donepezil may not be related to tolerability issues or to gain entry in this study. * Non-prescription treatments for cognitive enhancement. * Subjects with either non-removable ferromagnetic implants (such as cardiac pacemaker), aneurysm clips or other foreign bodies that would contraindicate a brain MRI scan. * A clinically significant (as determined by the PI) abnormality in the 12-lead ECG, including complete heart block, bradycardia (heart rate \<40 beats/minute), sinus pauses \>2 seconds, second or third degree heart block, QTc \>450 or other abnormalities judged clinically significant by the PI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 1 | Baseline, 4 hours post-dose on Day 1 | Posterior cingulate cortex perfusion was measured by arterial spin labeling (ASL). ASL is a completely noninvasive magnetic resonance method to measure regional cerebral perfusion. Results are reported for average relative perfusion rate. Average relative perfusion rate is defined as the average absolute perfusion rate divided by the whole brain absolute perfusion rate at the same time point. Average absolute perfusion rate is the average of left absolute perfusion rate and right absolute perfusion rate at the same time point. |
| Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 0 on Day 8 | Baseline, 1 minute post-dose (Hour 0) on Day 8 | Posterior cingulate cortex perfusion was measured by ASL. ASL is a completely noninvasive magnetic resonance method to measure regional cerebral perfusion. Results are reported for average relative perfusion rate. Average relative perfusion rate is defined as the average absolute perfusion rate divided by the whole brain absolute perfusion rate at the same time point. Average absolute perfusion rate is the average of left absolute perfusion rate and right absolute perfusion rate at the same time point. |
| Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 8 | Baseline, 4 hours post-dose on Day 8 | Posterior cingulate cortex perfusion was measured by ASL. ASL is a completely noninvasive magnetic resonance method to measure regional cerebral perfusion. Results are reported for average relative perfusion rate. Average relative perfusion rate is defined as the average absolute perfusion rate divided by the whole brain absolute perfusion rate at the same time point. Average absolute perfusion rate is the average of left absolute perfusion rate and right absolute perfusion rate at the same time point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline, 4 hours post-dose on Day 1, 1 minute post-dose (Hour 0), 4 hours post-dose on Day 8 | Perfusion in anterior cingulate cortex, medial prefrontal cortex, precuneus, inferior parietal cortex and other regions of interest (whole brain gray, superior, medial and inferior temporal cortex; inferior and superior prefrontal cortex; insula, amygdala, thalamus, basal ganglia, hippocampus, Landau) was measured by ASL technique. ASL is a completely noninvasive magnetic resonance method to measure regional cerebral perfusion. Results are reported for relative perfusion rate. Relative perfusion rate is defined as the absolute perfusion rate divided by the whole brain absolute perfusion rate at the same time point. |
| Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Baseline, 5 hours post-dose on Day 1; 1, 5 hours post-dose on Day 8 | Computerized test battery used to assess detection and identification task. CogState detection task: a measure of simple reaction time, provided valid assessment of psychomotor function. Participants were required to press a YES response key as soon as they detected an event (a card turning face up presented in center of the computer screen). The software measured the response time to detect each event. CogState identification task: measure of choice reaction time, provided a valid assessment of visual attention. Participants were required to decide YES or NO as to whether the event met a predefined and unchanging criterion (is the color of the card red?) while the event (a card turning face up) occurred in the center of the computer screen. The software measured the speed and accuracy of each response. |
| Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8 | Baseline, 5 hours post-dose on Day 1; 1, 5 hours post-dose on Day 8 | CPAL: a cognitive test which assessed visual episodic learning. Participant was to learn and remember picture locations on the screen and was to tap the target on the central location to begin. As each picture was revealed, the participant was to remember where the picture was located and tap that location. After 4 pictures were placed correctly, second round started. In second round pictures remain in the same locations, but their order of presentation in the center of the screen was different to that of the first round (randomized). The same process was repeated for round 3 and round 4. The outcome was the number of errors made in correctly placing each of the 4 patterns in their location 4 times. |
| Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8 | Baseline, 5 hours post-dose on Day 8 | RAVLT, in immediate recall (IR) list of 15 words (list A) was read aloud to participant 5 times followed by a test of spontaneous retrieval (A1 to A5). After fifth attempt a list of interference, comprising 15 words (list B) was read to participant followed by its retrieval (B1). After attempt B1 examiner asked individual to recall words from list A, without reading it again (A6). Score range: 0-105, higher scores=less impairment. Delayed recall (DR):after a 20-minute interval examiner asked individual to remember words from list A without reading this list; in recognition performance a list comprising 15 words from list A, 15 words from list B, 20 distracting words (similar to words in list A, B) was read to individual. Upon each word read aloud, individual asked to indicate if it belonged to list A, or not. Score range: 0-30, higher scores=less impairment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Donepezil Donepezil 5 mg tablet orally once daily up to Day 7, followed by donepezil 10 mg tablet orally once on Day 8. | 10 |
| Placebo Placebo matched to donepezil 5 mg tablet orally once daily up to Day 7, followed by placebo matched to donepezil 10 mg tablet orally once on Day 8. | 8 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Donepezil | Placebo | Total |
|---|---|---|---|
| Age Continuous | 74.7 years STANDARD_DEVIATION 9.6 | 70.6 years STANDARD_DEVIATION 6.9 | 72.9 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 2 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 10 | 2 / 8 |
| serious Total, serious adverse events | 0 / 10 | 0 / 8 |
Outcome results
Primary
Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 0 on Day 8
Posterior cingulate cortex perfusion was measured by ASL. ASL is a completely noninvasive magnetic resonance method to measure regional cerebral perfusion. Results are reported for average relative perfusion rate. Average relative perfusion rate is defined as the average absolute perfusion rate divided by the whole brain absolute perfusion rate at the same time point. Average absolute perfusion rate is the average of left absolute perfusion rate and right absolute perfusion rate at the same time point.
Time frame: Baseline, 1 minute post-dose (Hour 0) on Day 8
Population: FAS included all randomized participants who received at least 1 dose of the study drug (donepezil or placebo). Here, 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Donepezil | Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 0 on Day 8 | 0.263 ratio | Standard Deviation 0.4872 |
| Placebo | Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 0 on Day 8 | 0.093 ratio | Standard Deviation 0.5624 |
Comparison: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.963895% CI: [-0.51, 0.49]Mixed Models Analysis
Primary
Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 1
Posterior cingulate cortex perfusion was measured by arterial spin labeling (ASL). ASL is a completely noninvasive magnetic resonance method to measure regional cerebral perfusion. Results are reported for average relative perfusion rate. Average relative perfusion rate is defined as the average absolute perfusion rate divided by the whole brain absolute perfusion rate at the same time point. Average absolute perfusion rate is the average of left absolute perfusion rate and right absolute perfusion rate at the same time point.
Time frame: Baseline, 4 hours post-dose on Day 1
Population: Full analysis set (FAS) included all randomized participants who received at least 1 dose of the study drug (donepezil or placebo). Here, 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 1 | Baseline | 1.243 ratio | Standard Deviation 0.2586 |
| Donepezil | Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 1 | Change at Hour 4 on Day 1 | 0.156 ratio | Standard Deviation 0.5178 |
| Placebo | Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 1 | Baseline | 1.564 ratio | Standard Deviation 0.2494 |
| Placebo | Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 1 | Change at Hour 4 on Day 1 | -0.017 ratio | Standard Deviation 0.381 |
Comparison: Mixed model for repeated measures (MMRM) was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, Apolipoprotein E (ApoE) genotype, site as covariates.p-value: 0.974295% CI: [-0.6, 0.58]Mixed Models Analysis
Primary
Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 8
Posterior cingulate cortex perfusion was measured by ASL. ASL is a completely noninvasive magnetic resonance method to measure regional cerebral perfusion. Results are reported for average relative perfusion rate. Average relative perfusion rate is defined as the average absolute perfusion rate divided by the whole brain absolute perfusion rate at the same time point. Average absolute perfusion rate is the average of left absolute perfusion rate and right absolute perfusion rate at the same time point.
Time frame: Baseline, 4 hours post-dose on Day 8
Population: FAS included all randomized participants who received at least 1 dose of the study drug (donepezil or placebo). Here, 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Donepezil | Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 8 | -0.008 ratio | Standard Deviation 0.2506 |
| Placebo | Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 8 | -0.004 ratio | Standard Deviation 0.3948 |
Comparison: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.254895% CI: [-0.53, 0.16]Mixed Models Analysis
Secondary
Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8
Perfusion in anterior cingulate cortex, medial prefrontal cortex, precuneus, inferior parietal cortex and other regions of interest (whole brain gray, superior, medial and inferior temporal cortex; inferior and superior prefrontal cortex; insula, amygdala, thalamus, basal ganglia, hippocampus, Landau) was measured by ASL technique. ASL is a completely noninvasive magnetic resonance method to measure regional cerebral perfusion. Results are reported for relative perfusion rate. Relative perfusion rate is defined as the absolute perfusion rate divided by the whole brain absolute perfusion rate at the same time point.
Time frame: Baseline, 4 hours post-dose on Day 1, 1 minute post-dose (Hour 0), 4 hours post-dose on Day 8
Population: FAS included all randomized participants who received at least 1 dose of the study drug (donepezil or placebo). Here, 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Whole Brain Gray | 0.018 ratio | Standard Deviation 0.2309 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Superior Temporal Cortex | 1.749 ratio | Standard Deviation 0.2774 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Medial Temporal Cortex | 1.753 ratio | Standard Deviation 0.3186 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Inferior Temporal Cortex | 1.260 ratio | Standard Deviation 0.4634 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Medial Prefrontal Cortex | 1.488 ratio | Standard Deviation 0.183 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Medial Temporal Cortex | -0.066 ratio | Standard Deviation 0.5297 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Inferior Prefrontal Cortex | 1.381 ratio | Standard Deviation 0.2205 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Superior Prefrontal Cortex | 1.308 ratio | Standard Deviation 0.1236 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Inferior Parietal Cortex | 1.610 ratio | Standard Deviation 0.2824 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Insula | 1.390 ratio | Standard Deviation 0.1785 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Precuneus | 1.357 ratio | Standard Deviation 0.1904 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Anterior Cingulate Cortex | 1.236 ratio | Standard Deviation 0.2265 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Amygdala | 1.067 ratio | Standard Deviation 0.3025 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Thalamus | 1.417 ratio | Standard Deviation 0.4886 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Basal Ganglia | 1.120 ratio | Standard Deviation 0.2781 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Hippocampus | 1.327 ratio | Standard Deviation 0.2726 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Landau | 1.916 ratio | Standard Deviation 0.3753 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Whole Brain Gray | 1.486 ratio | Standard Deviation 0.1215 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1:Superior Temporal Cortex | 0.031 ratio | Standard Deviation 0.343 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1:Inferior Temporal Cortex | -0.052 ratio | Standard Deviation 0.6289 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1:Medial Prefrontal Cortex | 0.035 ratio | Standard Deviation 0.2704 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour4 on Day1:Inferior Prefrontal Cortex | 0.143 ratio | Standard Deviation 0.1987 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour4 on Day1:Superior Prefrontal Cortex | 0.064 ratio | Standard Deviation 0.2702 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1:Inferior Parietal Cortex | -0.054 ratio | Standard Deviation 0.2411 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Insula | 0.154 ratio | Standard Deviation 0.2813 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Precuneus | -0.024 ratio | Standard Deviation 0.3002 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day1:Anterior Cingulate Cortex | 0.118 ratio | Standard Deviation 0.2168 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Amygdala | 0.187 ratio | Standard Deviation 0.5504 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Thalamus | 0.244 ratio | Standard Deviation 0.5697 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Basal Ganglia | 0.292 ratio | Standard Deviation 0.4557 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Hippocampus | 0.128 ratio | Standard Deviation 0.2115 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Landau | -0.051 ratio | Standard Deviation 0.3923 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Whole Brain Gray | 0.058 ratio | Standard Deviation 0.1024 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8:Superior Temporal Cortex | 0.051 ratio | Standard Deviation 0.2678 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Medial Temporal Cortex | -0.015 ratio | Standard Deviation 0.3095 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8:Inferior Temporal Cortex | 0.084 ratio | Standard Deviation 0.6856 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8:Medial Prefrontal Cortex | -0.198 ratio | Standard Deviation 0.4168 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour0 on Day8:Inferior Prefrontal Cortex | 0.043 ratio | Standard Deviation 0.3353 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour0 on Day8:Superior Prefrontal Cortex | -0.152 ratio | Standard Deviation 0.312 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8:Inferior Parietal Cortex | 0.005 ratio | Standard Deviation 0.5185 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Insula | 0.103 ratio | Standard Deviation 0.2679 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Precuneus | 0.055 ratio | Standard Deviation 0.4065 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day8:Anterior Cingulate Cortex | 0.279 ratio | Standard Deviation 0.4424 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Amygdala | 0.170 ratio | Standard Deviation 0.5388 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Thalamus | 0.195 ratio | Standard Deviation 0.6486 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Basal Ganglia | 0.243 ratio | Standard Deviation 0.3925 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Hippocampus | 0.170 ratio | Standard Deviation 0.2832 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Landau | -0.030 ratio | Standard Deviation 0.5354 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Whole Brain Gray | 0.010 ratio | Standard Deviation 0.1286 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8:Superior Temporal Cortex | 0.126 ratio | Standard Deviation 0.3065 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Medial Temporal Cortex | -0.103 ratio | Standard Deviation 0.2852 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8:Inferior Temporal Cortex | -0.194 ratio | Standard Deviation 0.5644 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8:Medial Prefrontal Cortex | 0.111 ratio | Standard Deviation 0.3606 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour4 on Day8:Inferior Prefrontal Cortex | -0.031 ratio | Standard Deviation 0.2477 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour4 on Day8:Superior Prefrontal Cortex | 0.225 ratio | Standard Deviation 0.346 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8:Inferior Parietal Cortex | -0.175 ratio | Standard Deviation 0.4557 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Insula | 0.148 ratio | Standard Deviation 0.1477 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Precuneus | -0.110 ratio | Standard Deviation 0.3846 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day8:Anterior Cingulate Cortex | 0.180 ratio | Standard Deviation 0.2939 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Amygdala | 0.097 ratio | Standard Deviation 0.4984 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Thalamus | -0.124 ratio | Standard Deviation 0.5028 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Basal Ganglia | 0.084 ratio | Standard Deviation 0.3393 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Hippocampus | 0.041 ratio | Standard Deviation 0.277 |
| Donepezil | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Landau | -0.208 ratio | Standard Deviation 0.3152 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8:Superior Temporal Cortex | -0.037 ratio | Standard Deviation 0.1319 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8:Superior Temporal Cortex | 0.038 ratio | Standard Deviation 0.3095 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Superior Temporal Cortex | 1.773 ratio | Standard Deviation 0.1732 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Hippocampus | 0.017 ratio | Standard Deviation 0.1225 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Medial Temporal Cortex | 1.718 ratio | Standard Deviation 0.2778 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Medial Temporal Cortex | -0.052 ratio | Standard Deviation 0.2575 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Inferior Temporal Cortex | 1.173 ratio | Standard Deviation 0.4024 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Medial Temporal Cortex | -0.110 ratio | Standard Deviation 0.2551 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Medial Prefrontal Cortex | 1.709 ratio | Standard Deviation 0.1441 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8:Inferior Temporal Cortex | -0.012 ratio | Standard Deviation 0.3842 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day8:Anterior Cingulate Cortex | 0.062 ratio | Standard Deviation 0.1423 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Inferior Prefrontal Cortex | 1.486 ratio | Standard Deviation 0.1673 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8:Medial Prefrontal Cortex | -0.173 ratio | Standard Deviation 0.305 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Superior Prefrontal Cortex | 1.443 ratio | Standard Deviation 0.2046 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8:Inferior Temporal Cortex | -0.102 ratio | Standard Deviation 0.3114 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Inferior Parietal Cortex | 1.714 ratio | Standard Deviation 0.1628 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour0 on Day8:Inferior Prefrontal Cortex | 0.010 ratio | Standard Deviation 0.2188 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Insula | 1.533 ratio | Standard Deviation 0.213 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Basal Ganglia | -0.066 ratio | Standard Deviation 0.2787 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Precuneus | 1.505 ratio | Standard Deviation 0.2781 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour0 on Day8:Superior Prefrontal Cortex | -0.019 ratio | Standard Deviation 0.2863 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Anterior Cingulate Cortex | 1.442 ratio | Standard Deviation 0.1753 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8:Medial Prefrontal Cortex | -0.038 ratio | Standard Deviation 0.2262 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Amygdala | 1.256 ratio | Standard Deviation 0.2966 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8:Inferior Parietal Cortex | -0.106 ratio | Standard Deviation 0.2009 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Thalamus | 1.468 ratio | Standard Deviation 0.3061 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Amygdala | 0.019 ratio | Standard Deviation 0.31 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Basal Ganglia | 1.241 ratio | Standard Deviation 0.2461 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Insula | 0.154 ratio | Standard Deviation 0.1816 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Hippocampus | 1.389 ratio | Standard Deviation 0.1229 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour4 on Day8:Inferior Prefrontal Cortex | -0.001 ratio | Standard Deviation 0.2342 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Landau | 2.025 ratio | Standard Deviation 0.094 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Precuneus | 0.059 ratio | Standard Deviation 0.3475 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Whole Brain Gray | 0.050 ratio | Standard Deviation 0.101 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Landau | 0.008 ratio | Standard Deviation 0.1418 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1:Superior Temporal Cortex | 0.023 ratio | Standard Deviation 0.3002 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Medial Temporal Cortex | -0.006 ratio | Standard Deviation 0.2549 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day8:Anterior Cingulate Cortex | 0.167 ratio | Standard Deviation 0.3681 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour4 on Day8:Superior Prefrontal Cortex | -0.007 ratio | Standard Deviation 0.1348 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1:Medial Prefrontal Cortex | -0.164 ratio | Standard Deviation 0.2054 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Amygdala | 0.083 ratio | Standard Deviation 0.4233 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour4 on Day1:Inferior Prefrontal Cortex | -0.061 ratio | Standard Deviation 0.2299 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Thalamus | -0.077 ratio | Standard Deviation 0.533 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour4 on Day1:Superior Prefrontal Cortex | -0.062 ratio | Standard Deviation 0.2361 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Thalamus | -0.063 ratio | Standard Deviation 0.4992 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1:Inferior Parietal Cortex | -0.016 ratio | Standard Deviation 0.1848 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8:Inferior Parietal Cortex | -0.017 ratio | Standard Deviation 0.156 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Insula | 0.096 ratio | Standard Deviation 0.3276 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Basal Ganglia | 0.040 ratio | Standard Deviation 0.3106 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Precuneus | 0.053 ratio | Standard Deviation 0.2952 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Baseline: Whole Brain Gray | 1.500 ratio | Standard Deviation 0.0869 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day1:Anterior Cingulate Cortex | 0.173 ratio | Standard Deviation 0.2709 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Hippocampus | 0.047 ratio | Standard Deviation 0.2551 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Amygdala | 0.175 ratio | Standard Deviation 0.3785 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Insula | 0.078 ratio | Standard Deviation 0.2317 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Thalamus | -0.038 ratio | Standard Deviation 0.2209 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Landau | -0.105 ratio | Standard Deviation 0.2642 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Basal Ganglia | 0.014 ratio | Standard Deviation 0.1761 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1:Inferior Temporal Cortex | 0.090 ratio | Standard Deviation 0.2734 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Hippocampus | 0.036 ratio | Standard Deviation 0.2915 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Whole Brain Gray | -0.022 ratio | Standard Deviation 0.0945 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 1: Landau | -0.033 ratio | Standard Deviation 0.1952 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 4 on Day 8: Precuneus | 0.074 ratio | Standard Deviation 0.3035 |
| Placebo | Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8 | Change at Hour 0 on Day 8: Whole Brain Gray | 0.028 ratio | Standard Deviation 0.1569 |
Comparison: Change at Hour 4 on Day 1, Whole Brain Gray: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.631695% CI: [-0.18, 0.12]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Whole Brain Gray: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.625695% CI: [-0.12, 0.19]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Whole Brain Gray: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.584795% CI: [-0.12, 0.19]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Superior Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.155595% CI: [-0.46, 0.09]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Superior Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.241695% CI: [-0.51, 0.14]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Superior Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.80795% CI: [-0.33, 0.26]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Medial Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.682895% CI: [-0.59, 0.43]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Medial Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.898795% CI: [-0.26, 0.29]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Medial Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.892295% CI: [-0.28, 0.25]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Inferior Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.755595% CI: [-0.39, 0.52]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Inferior Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.192895% CI: [-0.18, 0.79]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Inferior Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.494695% CI: [-0.26, 0.49]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Medial Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.702995% CI: [-0.56, 0.4]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Medial Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.108595% CI: [-0.68, 0.08]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Medial Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.358895% CI: [-0.44, 0.18]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Inferior Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.305395% CI: [-0.2, 0.53]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Inferior Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.986195% CI: [-0.36, 0.36]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Inferior Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.655895% CI: [-0.41, 0.28]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Superior Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.947195% CI: [-0.53, 0.51]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Superior Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.213695% CI: [-0.77, 0.23]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Superior Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.643595% CI: [-0.47, 0.67]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Inferior Parietal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.065995% CI: [-0.41, 0.02]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Inferior Parietal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.768795% CI: [-0.41, 0.31]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Inferior Parietal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.106195% CI: [-0.73, 0.1]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Insula: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.392595% CI: [-0.41, 0.19]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Insula: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.199195% CI: [-0.58, 0.14]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Insula: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.517695% CI: [-0.45, 0.24]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Precuneus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.31495% CI: [-0.5, 0.18]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Precuneus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.634895% CI: [-0.46, 0.29]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Precuneus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.149195% CI: [-0.64, 0.12]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Anterior Cingulate Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.422695% CI: [-0.59, 0.27]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Anterior Cingulate Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.977895% CI: [-0.49, 0.5]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Anterior Cingulate Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.945695% CI: [-0.4, 0.43]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Amygdala: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.229995% CI: [-0.55, 0.15]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Amygdala: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.506995% CI: [-0.54, 0.28]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Amygdala: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.352495% CI: [-0.45, 0.17]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Thalamus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.418295% CI: [-0.8, 1.47]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Thalamus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.36395% CI: [-0.42, 1.04]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Thalamus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.983795% CI: [-0.73, 0.74]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Basal Ganglia: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.097495% CI: [-0.04, 0.42]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Basal Ganglia: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.124695% CI: [-0.04, 0.27]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Basal Ganglia: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.61995% CI: [-0.2, 0.32]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Hippocampus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.63595% CI: [-0.39, 0.25]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Hippocampus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.820595% CI: [-0.4, 0.32]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Hippocampus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.295995% CI: [-0.42, 0.14]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 1, Landau: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.55295% CI: [-0.56, 0.32]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Landau: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.904695% CI: [-0.5, 0.45]Mixed Models Analysis
Comparison: Change at Hour 4 on Day 8, Landau: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.040295% CI: [-0.62, -0.02]Mixed Models Analysis
Secondary
Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8
CPAL: a cognitive test which assessed visual episodic learning. Participant was to learn and remember picture locations on the screen and was to tap the target on the central location to begin. As each picture was revealed, the participant was to remember where the picture was located and tap that location. After 4 pictures were placed correctly, second round started. In second round pictures remain in the same locations, but their order of presentation in the center of the screen was different to that of the first round (randomized). The same process was repeated for round 3 and round 4. The outcome was the number of errors made in correctly placing each of the 4 patterns in their location 4 times.
Time frame: Baseline, 5 hours post-dose on Day 1; 1, 5 hours post-dose on Day 8
Population: FAS included all randomized participants who received at least 1 dose of the study drug (donepezil or placebo). Here, 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure. n=participants who were evaluable at specified time points for each arm group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8 | Baseline (n=9, 8) | 46.222 errors | Standard Deviation 28.7436 |
| Donepezil | Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8 | Change at Hour 1 on Day 8 (n=9, 6) | -5.444 errors | Standard Deviation 31.9653 |
| Donepezil | Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8 | Change at Hour 5 on Day 8 (n=9, 6) | 2.000 errors | Standard Deviation 16.3325 |
| Donepezil | Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8 | Change at Hour 5 on Day 1 (n=9, 8) | 4.333 errors | Standard Deviation 24.0936 |
| Placebo | Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8 | Change at Hour 1 on Day 8 (n=9, 6) | -15.833 errors | Standard Deviation 15.8293 |
| Placebo | Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8 | Baseline (n=9, 8) | 37.625 errors | Standard Deviation 17.8641 |
| Placebo | Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8 | Change at Hour 5 on Day 1 (n=9, 8) | -2.625 errors | Standard Deviation 28.9084 |
| Placebo | Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8 | Change at Hour 5 on Day 8 (n=9, 6) | -8.000 errors | Standard Deviation 17.4126 |
Comparison: Change at Hour 5 on Day 1: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.68895% CI: [-21.82, 31.82]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.315795% CI: [-11.3, 30.87]Mixed Models Analysis
Comparison: Change at Hour 5 on Day 8: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.322895% CI: [-13.56, 33.28]Mixed Models Analysis
Secondary
Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8
Computerized test battery used to assess detection and identification task. CogState detection task: a measure of simple reaction time, provided valid assessment of psychomotor function. Participants were required to press a YES response key as soon as they detected an event (a card turning face up presented in center of the computer screen). The software measured the response time to detect each event. CogState identification task: measure of choice reaction time, provided a valid assessment of visual attention. Participants were required to decide YES or NO as to whether the event met a predefined and unchanging criterion (is the color of the card red?) while the event (a card turning face up) occurred in the center of the computer screen. The software measured the speed and accuracy of each response.
Time frame: Baseline, 5 hours post-dose on Day 1; 1, 5 hours post-dose on Day 8
Population: FAS included all randomized participants who received at least 1 dose of the study drug (donepezil or placebo). Here, 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure. n=participants who were evaluable at specific time points for each arm group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Baseline: Detection Task (n=9, 8) | 2.572 log10 milliseconds | Standard Deviation 0.1192 |
| Donepezil | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Change at Hour 5 on Day 1: Detection Task (n=9, 8) | 0.002 log10 milliseconds | Standard Deviation 0.0931 |
| Donepezil | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Change at Hour5 on Day1:Identification Task(n=9,8) | 0.020 log10 milliseconds | Standard Deviation 0.0355 |
| Donepezil | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Change at Hour 0 on Day 8: Detection Task (n=9, 6) | 0.004 log10 milliseconds | Standard Deviation 0.1184 |
| Donepezil | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Change at Hour0 on Day8:Identification Task(n=9,6) | 0.005 log10 milliseconds | Standard Deviation 0.063 |
| Donepezil | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Change at Hour 5 on Day 8: Detection Task (n=9, 6) | -0.005 log10 milliseconds | Standard Deviation 0.1001 |
| Donepezil | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Change at Hour5 on Day8:Identification Task(n=9,6) | 0.034 log10 milliseconds | Standard Deviation 0.0782 |
| Donepezil | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Baseline: Identification Task (n=9, 8) | 2.708 log10 milliseconds | Standard Deviation 0.0635 |
| Placebo | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Change at Hour 0 on Day 8: Detection Task (n=9, 6) | -0.032 log10 milliseconds | Standard Deviation 0.0512 |
| Placebo | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Baseline: Detection Task (n=9, 8) | 2.542 log10 milliseconds | Standard Deviation 0.0953 |
| Placebo | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Baseline: Identification Task (n=9, 8) | 2.727 log10 milliseconds | Standard Deviation 0.054 |
| Placebo | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Change at Hour 5 on Day 8: Detection Task (n=9, 6) | 0.004 log10 milliseconds | Standard Deviation 0.0508 |
| Placebo | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Change at Hour 5 on Day 1: Detection Task (n=9, 8) | 0.024 log10 milliseconds | Standard Deviation 0.0706 |
| Placebo | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Change at Hour0 on Day8:Identification Task(n=9,6) | 0.004 log10 milliseconds | Standard Deviation 0.0493 |
| Placebo | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Change at Hour5 on Day1:Identification Task(n=9,8) | 0.012 log10 milliseconds | Standard Deviation 0.0371 |
| Placebo | Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8 | Change at Hour5 on Day8:Identification Task(n=9,6) | 0.004 log10 milliseconds | Standard Deviation 0.0625 |
Comparison: Change at Hour 5 on Day 1, Detection Task: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.49495% CI: [-0.09, 0.17]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Detection Task: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.103195% CI: [-0.02, 0.22]Mixed Models Analysis
Comparison: Change at Hour 5 on Day 8, Detection Task: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.327795% CI: [-0.06, 0.16]Mixed Models Analysis
Comparison: Change at Hour 5 on Day 1, Identification Task: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.658595% CI: [-0.05, 0.08]Mixed Models Analysis
Comparison: Change at Hour 0 on Day 8, Identification Task: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.886395% CI: [-0.07, 0.08]Mixed Models Analysis
Comparison: Change at Hour 5 on Day 8, Identification Task: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.438895% CI: [-0.06, 0.13]Mixed Models Analysis
Secondary
Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8
RAVLT, in immediate recall (IR) list of 15 words (list A) was read aloud to participant 5 times followed by a test of spontaneous retrieval (A1 to A5). After fifth attempt a list of interference, comprising 15 words (list B) was read to participant followed by its retrieval (B1). After attempt B1 examiner asked individual to recall words from list A, without reading it again (A6). Score range: 0-105, higher scores=less impairment. Delayed recall (DR):after a 20-minute interval examiner asked individual to remember words from list A without reading this list; in recognition performance a list comprising 15 words from list A, 15 words from list B, 20 distracting words (similar to words in list A, B) was read to individual. Upon each word read aloud, individual asked to indicate if it belonged to list A, or not. Score range: 0-30, higher scores=less impairment.
Time frame: Baseline, 5 hours post-dose on Day 8
Population: FAS included all randomized participants who received at least 1 dose of the study drug (donepezil or placebo). Here, 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure. n=participants who were evaluable at specified time points for each arm group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8 | Baseline: Total IR (n=9, 8) | 25.667 units on a scale | Standard Deviation 7.3144 |
| Donepezil | Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8 | Baseline: Total DR (n=9, 8) | 2.444 units on a scale | Standard Deviation 2.3511 |
| Donepezil | Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8 | Change at Hour 5 on Day 8:Total IR (n=9, 6) | 3.333 units on a scale | Standard Deviation 4.1833 |
| Donepezil | Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8 | Change at Hour 5 on Day 8: Total DR (n=9, 6) | 0.444 units on a scale | Standard Deviation 1.9437 |
| Placebo | Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8 | Change at Hour 5 on Day 8: Total DR (n=9, 6) | 0.333 units on a scale | Standard Deviation 3.0111 |
| Placebo | Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8 | Baseline: Total IR (n=9, 8) | 27.000 units on a scale | Standard Deviation 9.396 |
| Placebo | Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8 | Change at Hour 5 on Day 8:Total IR (n=9, 6) | 5.667 units on a scale | Standard Deviation 4.3665 |
| Placebo | Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8 | Baseline: Total DR (n=9, 8) | 2.375 units on a scale | Standard Deviation 2.1998 |
Comparison: Total IR: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.25495% CI: [-12.9, 4.12]Mixed Models Analysis
Comparison: Total DR: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.p-value: 0.768495% CI: [-4.17, 5.37]Mixed Models Analysis