Initial Findings Of A Randomized Double-Blinded Placebo-Controlled Study Of Intravenous Immunoglobulin In Mild Cognitive Impairment Due To Alzheimer Disease

OBJECTIVE: Determine the effect of IVIG in mild cognitive impairment (MCI) due to Alzheimer Disease on brain atrophy. BACKGROUND: MCI patients convert to dementia due to Alzheimer Disease (AD) at a rate of approximately15% per year and exhibit significant beta-amyloid (Aβ) burden. IVIG contains Aβ antibodies. Recent investigations have shown IVIG to improve cognitive function in AD and slow brain atrophy as measured by ventricular volume with the optimal dosing of 0.4g/kg every 2wks. Retrospective analysis reported standard doses of IVIG for other clinical indications were associated with lower rates of developing AD. DESIGN/METHODS: Fifty-one subjects 50 to 84 years of age with MCI by Petersen criteria and NIA-AA criteria were administered 0.4 g/kg 10% Newgam IVIG or 0.9% saline every 2 weeks x 5 doses. APOE status and CSF Alzheimer signature were recorded (lumbar puncture was optional). Cognitive testing (MMSE and CDR-SB) was conducted every 4 months. MRI brain was completed at baseline, 12 months, and 24 months for Neuroquant volumetric analysis. RESULTS: Fifty-one subjects (59% female) with a mean age of 72.4±7.4 years have been enrolled. Forty-three patients completed all infusions with no serious adverse events. Eighteen subjects completed 1-year follow-up. MMSE remained similar: 26.4±2.3 baseline to 25.4±3.9 1-year with IVIG; 26.4±2.6 to 25.8±3.8 with placebo. CDR-SB at 1-year improved with IVIG 1.9±0.9 to 1.8±1.9 and worsened with placebo 1.7±0.9 to 2.4±2.0. MRI ventricular volumetric analysis demonstrated lower brain atrophy with IVIG: mean percent change of 5.2%±3.3% for IVIG and 8.1%±4.2% for placebo. CONCLUSIONS: IVIG in subjects with MCI was associated with decreased brain atrophy and improvement of cognitive function on CDR-SB. Affect on conversion rate to AD is yet to be determined. These preliminarily positive but non-statistically significant results indicate that a relatively short course of IVIG in MCI may have disease-modulating effects in AD. Supported by: Sutter Institute for Medical Research; Octapharma. Disclosure: Dr. Kile9s institution has received research support from Octapharma. Dr. Au has received research support from Octapharma. Dr. Parise9s institution received personal compensation for activities with Octopharma as a consultation. Dr. Low has received research support from Celgene and UCB Pharma.