Study of Octagam (Intravenous Immunoglobulin [IVIG]) 10% on the Treatment of Mild to Moderate Alzheimer's Disease

For participants who received infusions every 2 weeks, plasma samples were collected at the trough level at Week 22 and on Days 1, 4, 7, and 14 after Week 22. For participants who received infusions every 4 weeks, plasma samples were collected at the trough level at Week 20 and on Days 1, 4, 7, 14, 21, and 28 after Week 20. Samples for determining Aβ1-40 in blood plasma were processed at a central laboratory using a commercially available kit from Innogenetics NV (INNO-BIA plasma Aβ forms; Gent, Belgium).

Samples for determining Aβ1-40 and Aβ1-42 in blood plasma were processed at a central laboratory using a commercially available kit from Innogenetics NV (INNO-BIA plasma Aβ forms; Gent, Belgium).

Samples for determining anti-Aβ autoantibodies in blood plasma were processed at a central laboratory using a commercially available kit from DRG Instruments GmbH, (EIA-5099; Marburg, Germany) using methods established at the Department of Neurology, Philipps-University, Marburg, Germany (Professor Dr. med. Richard Dodel). The kit includes 6 standard concentrations of anti-Aβ antibody against which the results of the assay are compared. The standards contain 1, 5, 15, 30, 60, and 120 Relative Units (RTU) which contain 0.03, 0.17, 0.5, 1, 2, and 4 mg IgG/mL, respectively.

For participants who received infusions every 2 weeks, plasma samples were collected at the trough level at Week 22 and on Days 1, 4, 7, and 14 after Week 22. For participants who received infusions every 4 weeks, plasma samples were collected at the trough level at Week 20 and on Days 1, 4, 7, 14, 21, and 28 after Week 20. Samples for determining Aβ1-42 in blood plasma were processed at a central laboratory using a commercially available kit from Innogenetics NV (INNO-BIA plasma Aβ forms; Gent, Belgium).

For participants who received infusions every 2 weeks, plasma samples were collected at the trough level at Week 22 and on Days 1, 4, 7, and 14 after Week 22. For participants who received infusions every 4 weeks, plasma samples were collected at the trough level at Week 20 and on Days 1, 4, 7, 14, 21, and 28 after Week 20. Samples for determining anti-Aβ autoantibodies in blood plasma were processed at a central laboratory using a commercially available kit from DRG Instruments GmbH, (EIA-5099; Marburg, Germany) using methods established at the Department of Neurology, Philipps-University, Marburg, Germany (Professor Dr. med. Richard Dodel). The kit includes 6 standard concentrations of anti-Aβ antibody against which the results of the assay are compared. The standards contain 1, 5, 15, 30, 60, and 120 Relative Units (RTU) which contain 0.03, 0.17, 0.5, 1, 2, and 4 mg IgG/mL, respectively.

Samples for determining Aβ1-40 and Aβ1-42 in cerebral spinal fluid were processed at a central laboratory using a commercially available kit from Meso Scale Discovery (MSD 96-Well Multi-Spot Human/Rodent (4G8) Abeta Triplex Ultra-Sensitive Assay; Rockville, MD, USA).

Samples for determining anti-Aβ autoantibodies in blood plasma were processed at a central laboratory using a commercially available kit from DRG Instruments GmbH, (EIA-5099; Marburg, Germany) using methods established at the Department of Neurology, Philipps-University, Marburg, Germany (Professor Dr. med. Richard Dodel). The kit includes 6 standard concentrations of anti-Aβ antibody against which the results of the assay are compared. The standards contain 1, 5, 15, 30, 60, and 120 Relative Units (RTU) which contain 0.03, 0.17, 0.5, 1, 2, and 4 mg IgG/mL, respectively.

Samples for determining tau and phosphorylated tau in cerebral spinal fluid were processed at a central laboratory using commercially available kits from Innogenetics NV (INNOTEST® hTau Ag, INNOTEST PHOSPHO-TAU (181P); Gent, Belgium). To measure phosphorylated tau, tau phosphorylated at threonine 181 (pTau181) was determined.

The MMSE test contains 30 questions that assess 8 cognitive domains (orientation to time, orientation to place, registration, attention and calculation, recall, language, repetition, and complex commands). The test is administered by a neuropsychologist, psychometrician, or certified study coordinator. The total score ranges from 0 (severe impairment) to 30 (no impairment), with a higher score indicating a better mental status. A positive change score indicates improvement.

The ADAS cog consists of 11 items that assess cognitive areas that are often impaired in Alzheimer's disease, specifically learning (word list), naming (objects), following commands (1 to 5 elements), ideational praxis (mail a letter), constructional praxis (copy 4 figures), orientation (person, time and place), recognition memory (from a second word list), and remembering test instructions (from the recognition subtest). The test includes 3 additional subjective scales that assess spoken language ability, word finding difficulty, and comprehension. The test is administered by a neuropsychologist, psychometrician, or certified study coordinator. The total score ranges from 0 to 70 with a higher score indicating greater cognitive impairment. A negative change score indicates improvement.

The ADAS-ADL consists of 23 questions that measure the ability of a person to perform basic activities of daily living, such as eating, walking, bathing, grooming, and dressing. The test is administered by a neuropsychologist, psychometrician, or certified study coordinator. The total score ranges from 0 to 78 with a lower score indicating more impaired ability. A positive change score indicates improvement.

A semi-structured interview was conducted by a physician, neuropsychologist, psychometrician, or certified study coordinator with the patient and a caregiver. Based on the results of the interview, the patient was rated on 6 domains of cognition and function: Memory, orientation, judgment/problem solving, community activities, home and hobbies, and personal care. Each domain is rated from 0 = no dementia; 0.5 = questionable dementia, mild cognitive impairment; 1 = mild dementia; 2 = moderate dementia; 3 = severe dementia. The total score ranges from 0 to 18 with a higher score indicating more dementia. A negative change score indicates improvement.

The volume of the whole brain and of the left and right hippocampus was measured using high-resolution structural coronal 3D heavily T1-weighted gradient-echo sequence magnetic resonance imaging. All evaluations were done centrally by Professor Frederik Barkhof at the Image Analysis Centre, VU Medical Center, Amsterdam, Netherlands. A negative change score indicates loss of brain volume.

Cerebral glucose metabolism was measured in validated 3 dimensional statistic surface projection analysis (Cortex ID®, GE Healthcare), transversal/coronal/sagittal-slice analysis (HERMES BRASS), and voxel-wise whole brain analysis (SPM5) using [18F]fluorodeoxyglucose positron emission tomography.