Date of Graduation
Master of Science in Physician Assistant Studies
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<0.003). 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<0.05). 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.
Williams, Kathryn L., "Intravenous Immunoglobulin Therapy for the Treatment of Alzheimer’s Disease" (2013). School of Physician Assistant Studies. 451.