Two recent studies have reported on the effects of intravenous immunoglobulin in patients with cognitive impairment due to Alzheimer’s disease.

The first study found a short-term benefit of IVIG in 50 subjects with mild cognitive impairment (MCI) due to AD (Kile et al. J Neurol Neurosurg Psychiatry 2017;88:106-112). Study participants were aged 50-84 years and had amnestic MCI.

They were randomized to receive IVIG 0.4 g/kg or placebo infusions every two weeks for 10 weeks; total IVIG dose was 2 g/kg. MRI was obtained at baseline, and months 12 and 24. Cognitive testing was performed at baseline and every four months thereafter. Improvements were seen with IVIG versus placebo in the rate of brain atrophy (5.87% vs. 8.14%) at 12 months, but differences were no longer significant at 24 months. Subjects with late MCI showed better performance on ADAS-cog and MMSE, and were less likely to develop AD dementia (33.3% vs. 58.3%) at 12 months, but treatment effects were no longer significant at 24 months.

A separate phase III trial examined the effect of IVIG in subjects with mild to moderate AD (Relkin et al. Neurology 2017;88:1768-1775). A total of 390 participants were randomized to low-dose albumin or IVIG 0.2 or 0.4 g/kg every two weeks for 18 months. The primary endpoints were change from baseline in ADAS-cog and the Alzheimer’s Disease Cooperative Study-ADL Inventory. No benefit was seen on the two scales with either dose at endpoint. There was a significant decrease in plasma beta-amyloid42 levels (but not beta-amyloid40) with IVIG, but there was no difference with IVIG versus placebo in the rate of amyloid-related imaging abnormalities (brain edema, microhemorrhage).

The results suggest that IVIG may have some beneficial effects over the short term in patients with MCI, but has no effect on cognitive or functional outcomes in patients with AD.