Longitudinal measure of IVIG treatment effect in patients with Alzheimer's and Lewy Body disease

Abstract

Intravenous immunoglobulin (IVIG) therapy has shown treatment efficacy in patients with mild to moderate Alzheimer's disease (AD). IVIG binds to abnormally folded proteins, such as oligomeric beta amyloid and alpha synuclein, thought to be involved in both AD and Lewy Body disease (LBD) pathogenesis. Therefore, IVIG therapy may be useful in AD and LBD. In this study, we evaluated longitudinal treatment efficacy of IVIG therapy in patients with AD and LBD in mild cognitive impairment to moderately severe stages. Patient with AD (n=13) and with LBD (n=4) received IVIG therapy for average of 18 (stdev=14.5) and 14 (stdev=14) months. Dementia severity was determined using the Functional Assessment Staging Test (FAST). Pre-IVIG monitoring of AD and LBD patients using MCI Screen (a modification of the CERAD Wordlist) and FAST staging tests averaged 21 (σ=12) and 36 (σ=16) months respectively. Cognitive, functional and behavioral testing at baseline and during IVIG therapy consisted of ADAS-Cog, MMSE, MCI Screen, NPI, ADCS-ADL, DAD, FAST, and CGIC tests. Baseline and endpoint CSF Tau and Ab42 levels were obtained when possible. IVIG therapy either stabilized or significantly slowed cognitive and functional decline in most of the AD and LBD patients. Disease delaying effects appeared more significant in patients with AD. Of the AD and LBD patients who discontinued IVIG treatment_primarily due to cost_they declined more rapidly within months after stopping IVIG than while they were on it. CSF studies suggested that IVIG reduces either beta amyloid 1-42 levels, or phosphorylated tau levels, or both. When patients serve as their own control in an off-on or off-on-off design, disease delaying treatment effects can be more easily detected. In this study using such a design, both functional and cognitive improvement (or reduced rate of decline) was demonstrable in LBD and AD patients receiving IVIG therapy. Since both AD and LBD pathologies involve abnormal protein folding, it may be that other neurologic diseases with abnormal protein folding will respond to IVIG therapy. Some examples include Huntington's disease and certain forms of Frontal Temporal Lobe Dementia. More rigorous clinical trials are needed, particularly in LBD.