Neuroimaging methods in the randomized pivotal study of Renew NCP‐5 for the treatment of mild cognitive impairment (MCI) due to Alzheimer's disease or mild dementia of the Alzheimer's type

Abstract

AbstractBackgroundVascular disease and even subclinical variation in vascular health are known contributors to cognitive impairment and hasten the progression of symptoms in individuals with Alzheimer’s disease. Recent trials have demonstrated the therapeutic benefit of pharmacological treatments for enhancing vascular health on the incidence of cognitive impairment and on the progression of vascular brain injury measured by magnetic resonance imaging (MRI). Thus, novel vascular therapeutics provide a promising approach to slowing or preventing impairment in older adults. RenewTM NCP‐5 is an FDA‐cleared, external counterpulsation (ECP) device used clinically to improve coronary and peripheral vascular hemodynamics by sequential compression and decompression of vascular beds in synchrony with the cardiac cycle. ECP is currently used to treat patients with chronic angina and congestive heart failure and has been demonstrated to alter cerebral hemodynamics.MethodNeuroimaging was coordinated across 12 sites (10 in the US and 2 outside of the US) for safety screening as well as for acquisition of exploratory neuroimaging markers of disease stage and treatment modification. Imaging protocols were in created based on a modified cross‐platform protocols developed for the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Additional sequences were added for safety. Coded data are uploaded to the central imaging coordinating site (CICS) at Massachusetts General Hospital. Patient characterization and exploratory outcome measures include T1‐weighted hippocampal volume measures and arterial spin labeling (ASL)‐based measures of cerebral blood flow (CBF). Imaging protocols include phantom scanning and test‐retest at each scan session to evaluate platform specific data quality. Imaging is performed at baseline, 6 months, and 12 months after initial treatment.ResultImaging has been performed on 214 individuals to date with 76 6 month and 6 12‐month scans. The imaging protocol is tolerated with minimal motion. ASL imaging is variable quality across scanners due to differences in hardware, software, and imaging support. This study is ongoing and initial study analyses are expected by November 2020.ConclusionRenewTM NCP‐5 treatment in Alzheimer's disease may impact cerebral hemodynamics and the ongoing clinical trial will test the effect of this treatment on cognitive symptoms as well the impact on Alzheimer’s or vascular‐associated disease processes in the brain.