IVIG treatment of mild cognitive impairment due to Alzheimer's disease: a randomised double-blinded exploratory study of the effect on brain atrophy, cognition and conversion to dementia

OBJECTIVE: To determine the effect of intravenous immunoglobulin (IVIG) on brain atrophy and cognitive function in mild cognitive impairment (MCI) due to Alzheimer's disease (AD). METHODS: 50 participant 50-84 years of age with amnestic MCI were administered 0.4 g/kg 10% IVIG or 0.9% saline every 2 weeks for a total of 5 infusions (2 g/kg total dose) in a randomised double-blinded design. MRI brain was completed at baseline, 12 and 24 months. Cognitive testing was completed at baseline and every 4 months. Participants were stratified into early and late (LMCI) MCI stages. Average annualised per cent change in ventricular volume was computed as a measure of brain atrophy. RESULTS: There was significantly less brain atrophy (p=0.037, adjusted for MCI status) in the IVIG group (5.87%) when compared with placebo (8.14%) at 12 months; at 24 months, the reduction in brain atrophy no longer reached statistical significance. The LMCI participants who received IVIG performed better on Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog; p=0.011) and Mini-Mental State Examination (MMSE; p=0.004) at 1 year; these differences were not present after 2 years. There was no difference in conversion to AD dementia between the treatment and control groups after 2 years; however, at 1 year, there were fewer conversions from LMCI to AD dementia in the IVIG group (33.3%) when compared with control group (58.3%). CONCLUSIONS: This exploratory study provides limited evidence that a short course of IVIG administered in the MCI stage of AD reduces brain atrophy, prevents cognitive decline in LMCI and delays conversion to AD dementia for at least 1 year; however, this effect of IVIG appears to wane by 2 years.