title: 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.
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.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT01300728.
authors.affiliation: Sutter Neuroscience Institute, Sacramento, California, USA.
authors.forename: Shawn
authors.initials: S
authors.lastname: Kile
authors.affiliation: Sutter Neuroscience Institute, Sacramento, California, USA.
authors.forename: William
authors.initials: W
authors.lastname: Au
authors.affiliation: Sutter Institute for Medical Research (SIMR), Sacramento, California, USA.
authors.forename: Carol
authors.identifier: http://orcid.org/0000-0002-3098-6160
authors.initials: C
authors.lastname: Parise
authors.affiliation: Sutter Neuroscience Institute, Sacramento, California, USA.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Rose
authors.affiliation: Sutter Institute for Medical Research (SIMR), Sacramento, California, USA.
authors.forename: Tammy
authors.initials: T
authors.lastname: Donnel
authors.affiliation: Sutter Institute for Medical Research (SIMR), Sacramento, California, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hankins
authors.affiliation: Sutter Imaging, Neuroradiology, Sacramento, California, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Chan
authors.affiliation: Sutter Imaging, Neuroradiology, Sacramento, California, USA.
authors.forename: Azad
authors.initials: A
authors.lastname: Ghassemi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D000647:Amnesia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000523:psychology; D001284:Atrophy / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000523:psychology; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D003071:Cognition / Q000187:drug effects*; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000523:psychology; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D016896:Treatment Outcome
chemical_list: D016756:Immunoglobulins, Intravenous