Five-year outcomes after IVIG for mild cognitive impairment due to alzheimer disease

Shawn Kile, William Au, Carol Parise, Kimberley Rose, Tammy Donnel, Andrea Hankins, Yvonne Au, Matthew Chan, Azad Ghassemi, Shawn Kile, William Au, Carol Parise, Kimberley Rose, Tammy Donnel, Andrea Hankins, Yvonne Au, Matthew Chan, Azad Ghassemi

Abstract

Background: The purpose of this study was to assess the five-year treatment effects of a short course of intravenous immunoglobulin (IVIG) in subjects with mild cognitive impairment (MCI) due to Alzheimer disease (AD).

Methods: Fifty subjects 50 to 84 years of age with MCI due to AD were administered 0.4 g/kg 10% IVIG or 0.9% saline every two weeks x five doses in a randomized double-blinded design as part of a two-year study. Twenty-seven subjects completed an additional three-year extension study. MRI brain imaging, cognitive testing, and conversion to dementia were assessed annually. Participants were stratified into early MCI (E-MCI) and late MCI (L-MCI). The primary endpoint was brain atrophy measured as annualized percent change in ventricular volume (APCV) annually for five years. ANOVA was used to compare annualized percent change in ventricular volume from baseline between the groups adjusting for MCI status (E-MCI, L-MCI).

Results: Differences in brain atrophy between the groups, which were statistically significant after one year, were no longer significant after five years. IVIG-treated L-MCI subjects did demonstrate a delay in conversion to dementia of 21.4 weeks.

Conclusion: An eight-week course of IVIG totaling 2 g/kg in MCI is safe but is not sufficient to sustain an initial reduction in brain atrophy or a temporary delay in conversion to dementia at five years. Other dosing strategies of IVIG in the early stages of AD should be investigated to assess more sustainable disease-modifying effects. Trial registration ClinicalTrials.gov NCT01300728. Registered 23 February 2011.

Keywords: Alzheimer’s disease; Intravenous immunoglobulin (IVIG); Mild cognitive impairment (MCI); Ventricular volume.

Conflict of interest statement

No authors have disclosures or competing interests to report.

© 2021. The Author(s).

Figures

Fig 1.
Fig 1.
Consort flow diagram
Fig. 2
Fig. 2
Annualized percent change in ventricular volume (cm3) at 1, 2, 3, 4, and 5 years following IVIG or placebo
Fig. 3
Fig. 3
Annualized percent change in ventricular volume (cm3) at 1, 2, 3, 4, and 5 years following IVIG or placebo stratified into E-MCI and L-MCI mild cognitive impairment
Fig. 4
Fig. 4
MMSE (Panel A), ADAS-Cog (Panel B), and CDR-SB (Panel C) at baseline and 1, 2, 3, 4, and 5 years following IVIG or placebo
Fig. 5
Fig. 5
MMSE (Panel A), ADAS-Cog (Panel B), and CDR-SB (Panel C) at baseline and 1, 2, 3, 4, and 5 years following IVIG or placebo stratified into E-MCI and L-MCI
Fig. 6
Fig. 6
Kaplan–Meier survival analysis for conversion to Alzheimer’s disease dementia for subjects with L-MCI following IVIG or placebo

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