Open label studies of patients with Alzheimer′s disease (AD) dementia treated with IVIG therapy have found evidence of modest cognitive improvement. This study was designed to determine whether a short treatment course of IVIG, given at the mild cognitive impairment (MCI) stage of AD, can reduce rates of brain atrophy, cognitive decline and/or conversion to AD dementia.
METHODSSubjects were patients 50 to 84 years of age diagnosed with amnesic MCI. At baseline, the patients underwent physical and neurologic evaluation with laboratory testing, cognitive testing and MRI. The subjects were randomized to receive either 0.4 g/kg IVIG or 0.9% IV saline placebo once every two weeks for eight weeks. Patients were reassessed with the Mini-Mental State Exam (MMSE), the Clinical Dementia Rating (CDR) scale and the ADAS-Cog at four-month intervals. Brain imaging was completed at 12 and 24 months. The primary endpoint was the annualized percent change in ventricular volume (APCV).
RESULTSThe ventricular APCV percentages were 8.14% at 12 months and 7.08% at 24 months in the placebo group and 5.87% and 6.26% in the IVIG group, respectively. The unadjusted analysis of APCV between groups at 12 months demonstrated a 28% reduction in the rate of atrophy in the treatment group compared with the placebo subjects. This effect was statistically significant when adjusted for MCI status (P＝0.037). At both 12 months and 24 months, patients in the treatment group had higher scores on the MMSE than did those in the placebo group (P＝0.004 and P＝0.012, respectively). At both 12 and 24 months, the ADAS-Cog scores were more favorable in the treatment group than in the placebo group (P＝0.01 and P＝0.027, respectively). Conversion to AD dementia occurred in 33.3% of the treatment group and 58.3% of the control group.
CONCLUSIONThis study found that IVIG, administered over eight weeks, a can reduce brain atrophy and cognitive decline for the first year after administration.