A Study to Verify the Clinical Benefit of Aducanumab in Participants With Early Alzheimer's Disease

The Clinical Dementia Rate Scale integrates assessments from 3 domains of cognition (memory, orientation, judgment/problem-solving) and 3 domains of function (community affairs, home/hobbies, personal care). Following the caregiver interview and systematic participant examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. The Sum of boxes scoring methodology sums the score for each of the 6 domains and provides a value ranging from 0 to 18. Higher scores indicate greater impairment. A positive change from baseline indicates greater impairment.

Time frame: Baseline, Week 78

Population: FAS included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis.

ADAS-Cog13 comprises both cognitive tasks and clinical ratings of cognitive performance. The cognitive subscale items capture word recall, ability to follow commands, the ability to correctly copy or draw an image, naming, the ability to interact with everyday objects, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure for delayed word recall and concentration/distractibility. The total score ranges from 0 to 85. Higher scores indicate worse performance. A positive change from baseline indicates decline in cognitive performance.

Time frame: Baseline, Weeks 78 and 106

Population: FAS included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis. Assessment was also planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.

The ADCS-ADL-MCI scale consists of 17 instrumental items (e.g., shopping, preparing meals, using household appliances, etc) and 1 basic item (getting dressed). Ratings reflect caregiver observations about the participant's actual functioning over the previous month and provide an assessment of change in the functional state of the participant over time. The total score ranges from 0 to 53. Higher scores indicate greater independent, healthy functioning. A positive change from baseline indicates healthy functioning while a negative change from baseline indicates a decline in independent functioning.

Time frame: Baseline, Weeks 78 and 106

Population: FAS included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis. Assessment was also planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.

Amyloid PET scan assesses cerebral amyloid load using radiotracers which is standardized into centiloids. Centiloid values on centiloid scale is based on mean composite standardized uptake value ratio (SUVR).

Time frame: Baseline, Weeks 78 and 104

Population: FAS included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis. Due to the decision of early termination, only one participant had an amyloid scan at week 78 and data was reported below. In addition, the assessment planned for Week 104 was not performed due to early termination.

The CDR integrates assessments from 3 domains of cognition (memory, orientation, judgment/problem-solving) and 3 domains of function (community affairs, home/hobbies, personal care). Following caregiver interview and systematic participant examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. The CDR-SB sums the score for each of the 6 domains and provides a value ranging from 0 to 18. Higher scores indicate greater impairment. Positive change from baseline indicates greater impairment.

Time frame: Baseline, Week 106

Population: Assessment was planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.

GST z-score is an average of z-scores of CDR-SB, ADASCog13 and ADCS-ADL-MCI. CDR-SB assesses 3 cognitive (memory,orientation, judgment/problem-solving)and 3 functional(community affairs,home/hobbies,personal care) domains. Sum of Boxes method combines scores across 6 domains, ranging from 0-18(higher scores=greater impairment). ADAS-Cog13 evaluates cognitive tasks like word recall, naming, orientation and memory, with scores from 0-85 (higher scores=worse performance). ADCS-ADL-MCI rates 17 tasks (e.g.,shopping, preparing meal) and 1 basic task(dressing) with scores from 0-53 (higher scores=greater independence/healthy functioning). z-score\>0 indicates greater impairment/worse performance for CDR-SB and ADASCog13 scales and improved functioning for ADCS-ADL-MCI. For ADCS-ADL-MCI, z-score were reversed (new reversed value=original value-1) to make interpretation consistent. The GST z-score of 0 indicates population mean and score\>0 indicate greater impairment/worse performance.

Time frame: Baseline, Weeks 78 and 106

Population: FAS included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis. Assessment was also planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.

The iADRS composite captures a decline in both cognition and daily function. It is a simple linear combination of the Alzheimer's disease assessment scale, cognitive subscale (ADAS-Cog13), and the Alzheimer's disease cooperative study scale for activities of daily living in mild cognitive impairment (ADCS-ADL-MCI). The ADAS-Cog13 scale ranges from 0 to 85 (higher scores indicate worse performance) and the ADCS-ADL-MCI scale ranges from 0 to 53 (higher scores indicate greater independent, healthy functioning). The total score for iADRS scale ranges from 0 to 138, where higher scores indicate better performance.

Time frame: Baseline, Weeks 78 and 106

Population: FAS included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis. Assessment was also planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.

The MMSE scale is a performance-based test of global cognitive status. It consists of 11 tasks that assess orientation, word recall, attention and calculation, language abilities, and visuospatial functions. The scores from the 11 tests are combined to obtain the total score, which ranges from 0 to 30. Higher scores indicate better performance. A negative change from baseline indicates decline in cognitive performance.

Time frame: Baseline, Weeks 78 and 106

Population: FAS included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis. Assessment was also planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.

The NPI-10 is a questionnaire administered to the informant, designed to obtain information on the presence of neuropsychiatric symptoms and behaviors in a participant with Alzheimer's disease. Ten areas are assessed: delusions, hallucinations, agitation/aggression, depression, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability and aberrant motor behavior. The NPI total score ranges from 0 to 120. Higher scores indicate greater impairment. A negative change from baseline indicates improvement (symptom reduction).

Time frame: Baseline, Weeks 78 and 106

Population: FAS included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis. Assessment was also planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.

The cerebral tau level was measured by tau PET imaging. Tau PET imaging was conducted using radiotracer. SUVR is a ratio of PET uptake measured in brain region of interest and a disease-free reference region. A higher SUVR is an indication of increased PET radiotracer uptake and worsening disease.

Time frame: Baseline, Weeks 78 and 104

Population: FAS included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis. Due to decision of early termination, the Tau PET scan was not performed in any participant at scheduled visits of Weeks 78 and 104.