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Research paper
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
  1. Shawn Kile1,
  2. William Au1,
  3. Carol Parise2,
  4. Kimberley Rose1,
  5. Tammy Donnel2,
  6. Andrea Hankins2,
  7. Matthew Chan3,
  8. Azad Ghassemi3
  1. 1Sutter Neuroscience Institute, Sacramento, California, USA
  2. 2Sutter Institute for Medical Research (SIMR), Sacramento, California, USA
  3. 3Sutter Imaging, Neuroradiology, Sacramento, California, USA
  1. Correspondence to Shawn Kile, Sutter Neuroscience Institute, 2800 L Street, suite 500, Sacramento, CA 95816, USA; kiles{at}sutterhealth.org

Abstract

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.

Trial registration number ClinicalTrials.gov, NCT01300728.

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Footnotes

  • Contributors SK: Study concept and design, data acquisition, interpretation of data, drafting/revising the manuscript. WA: Study design, data acquisition, interpretation of data, drafting/revising the manuscript. CP: Study design, statistical analysis, drafting/revising the manuscript. KR: Data acquisition, cognitive data analysis and interpretation, drafting/revising the manuscript. TD: Study coordination, study design, drafting/revising the manuscript. AH: Data acquisition, revising the manuscript. MC: MRI data acquisition and analysis, drafting/revising the manuscript. AG: MRI data acquisition and analysis, drafting/revising the manuscript.

  • Funding This study was funded by grant 947110-1107542 from the Sutter Medical Center Foundation and supported by Octapharma.

  • Competing interests None declared.

  • Ethics approval Sutter Health Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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