Abstract 483: External Counterpulsation Therapy (Renew™ NCP-5) For The Treatment Of Mild Cognitive Impairment Due To Alzheimer’s Disease Or Mild Dementia Of The Alzheimer’s Type

Abstract

Introduction: Research is elucidating vascular impairment in the pathophysiology of Alzheimer’s disease (AD) and as a treatment target. NCP-5 is external counterpulsation (ECP) therapy approved for treating unstable angina and granted FDA Breakthrough Status for mild cognitive impairment (MCI) and AD. It increases cardiac output and improves endothelial function. A study was done to assess NCP-5 on cognitive function. Methods: Randomized, single-blind, sham-controlled; 10 US sites. Subjects 55-85 years (Montreal Cognitive Assessment score ≥11) were given NCP-5 (n=95) or active sham (n=95). Primary endpoint: mean change from baseline in Vascular Dementia Assessment Scale-cognitive subscale (VADAS-Cog) at 12, 18, and 24 weeks, powered for a 2-point change. Results: Primary endpoint met (change, -4.45 points); NCP-5 showed statistically significantly greater improvement from baseline vs active sham on VADAS-Cog. In subjects with type 2 diabetes (T2D; n=36), NCP-5 improved cognition from baseline (change, -17.01 points; p <0.005). NCP-5 was statistically significantly superior to active sham on Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change at weeks 12 (odds ratio [OR], 2.13; p =0.013) and 24 (OR, 2.56; p =0.002). NCP-5 had a statistically significant decrease on Neuropsychiatric Inventory Aggression Index vs active sham at week 24 ( p =0.041). Neuroimaging showed a decline in right hippocampal volume (HV) that was statistically significantly greater with NCP-5 at week 24 ( p =0.012) and at longitudinal assessment to 12 months ( p =0.008), possibly related to smaller HV seen at baseline with NCP-5. However, the decline in regional cerebral blood flow (rCBF) in the left hippocampus from baseline to month 12 and for the longitudinal assessment was statistically significantly less with NCP-5 than with active sham ( p =0.010 and 0.019, respectively). NCP-5 had a low-risk safety profile (10,644 exposures), and the most common AE was mild skin irritation/injury. Conclusions: Renew NCP-5 improved cognitive performance and global function, particularly in those with T2D. Findings support the role of targeting vascular dysfunction, specifically with NCP-5, for the treatment of MCI and mild dementia of the Alzheimer’s type.