Intravenous Immunoglobulin Therapy for the Treatment of Alzheimer’s Disease

Background: Alzheimer’s disease (AD) is the 6th leading cause of death and affects 5.4 million Americans. It is thought to be caused, in part, by the deposition of β-amyloid plaques in the brain. Intravenous immunoglobulin (IVIg) is a medication with a reputable safety record that contains natural anti-β-amyloid (Aβ) antibodies. Decades of research have led to the proposal of IVIg for the treatment of AD. Method: An exhaustive search of medical literature was conducted. Key words searched included: intravenous immunoglobulin, Alzheimer’s disease, immunotherapy, and Aβ. Articles were screened to fit criteria and assessed using the GRADE method. Results: Three studies met criteria. Study 1 showed at 9, 18, and 36 months, the group treated with IVIg continuously (n=16) had statistically less decline in cognitive function compared to placebo (n=8). Patients treated with IVIg 0.4g/kg/2weeks continuously over 36 months showed no decline in ADAS-Cog or ADCS-CGIC assessments. Study 2 measured Aβ load and cognitive function of 8 patients during 6 months of therapy, followed by a 3-month washout, and 9 months of resumed therapy. Aβ load was statistically lower at 6 months, returned to baseline after the washout, and was again statistically lower after 9 months of return to therapy (P\u3c0.003). The mean MMSE increased 2.5 points at 6 months and was unchanged from baseline to 18 months. Study 3 measured Aβ load and cognitive function of 5 patients treated with IVIg at baseline and after 6 months of treatment. Aβ load decreased in all patients (mean: 30.1%, P\u3c0.05). A slight improvement of 3.7 ± 2.9 points on the ADAS-Cog was calculated at 6 months. Conclusion: IVIg therapy at a dose of 0.4g/kg/2weeks may be an effective treatment for AD. Limitations of the studies include low number of subjects, potential bias, and flawed study designs. The very low quality of evidence makes a definitive conclusion impractical. There is a need for larger, placebo-controlled, randomized, double-blind clinical trials. The Gammaglobulin Alzheimer Partnership (GAP) study is in progress, and includes 360+ AD patients, has an appropriate design, and may provide further evidence of the efficacy of IVIg in AD