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.
Subject(s)
Alzheimer Disease/diagnostic imaging , Alzheimer Disease/drug therapy , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/drug therapy , Immunoglobulins, Intravenous/administration & dosage , Aged , Aged, 80 and over , Alzheimer Disease/cerebrospinal fluid , Cognitive Dysfunction/cerebrospinal fluid , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Middle Aged , Time Factors , Treatment Outcome , tau Proteins/cerebrospinal fluidABSTRACT
OBJECTIVE: To assess whether intravenous immunoglobulin (IVIG) in subjects with mild cognitive impairment (MCI) results in a reduction in amyloid in the central nervous system (CNS). METHODS: Five subjects with MCI underwent baseline Florbetapir positron emission tomography and retinal autofluorescent imaging. All were administered IVIG (Octagam 10%) at 0.4 g/kg every 14 days for a total of 5 infusions. After 3 months, standard uptake value ratio (SUVR) and amyloid retinal deposits were reassessed. RESULTS: Three subjects had a reduction in amyloid SUVR and all 5 subjects had a reduction in amyloid retinal deposits in at least 1 eye. CONCLUSIONS: A short course of IVIG over 2 months removes a measurable amount of amyloid from the CNS in persons with MCI.
Subject(s)
Amyloid beta-Peptides/metabolism , Brain/diagnostic imaging , Cognitive Dysfunction , Immunoglobulins, Intravenous/administration & dosage , Retina/diagnostic imaging , Aged , Aniline Compounds , Brain/metabolism , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/drug therapy , Ethylene Glycols , Female , Humans , Male , Positron-Emission TomographyABSTRACT
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 50-84â years of age with amnestic MCI were administered 0.4â g/kg 10% IVIG or 0.9% saline every 2â weeks for a total of 5 infusions (2â g/kg total dose) in a randomised double-blinded design. MRI brain was completed at baseline, 12â and 24â months. Cognitive testing was completed at baseline and every 4â 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 12â months; at 24â 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 1â year; these differences were not present after 2â years. There was no difference in conversion to AD dementia between the treatment and control groups after 2â years; however, at 1â 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 1â year; however, this effect of IVIG appears to wane by 2â years. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT01300728.
