External Counterpulsation (ECP) for patients with early Alzheimer's disease

Theauthors propose that Alzheimer's disease is influenced not only by amyloid andtau pathology but also by vascular dysfunction and reduced cerebral bloodflow. ECP may help by:

• Increasing cerebral blood flow
• Improving endothelial function
• Enhancing vascular reactivity
• Reducing inflammation
• Potentially improving brain perfusion over the long term.

Thisrepresents a fundamentally different therapeutic approach from currentanti-amyloid drugs.

Original Research Article
American Journal of Alzheimer's
Disease & Other Dementias®
Volume 41: 1–16
© The Author(s) 2026
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/15333175261451918
journals.sagepub.com/home/aja
Treatment of Clinically Diagnosed Alzheimer’s
Disease by External Counterpulsation A
Randomized Clinical Trial
Jack E. Juni, MD1, Jeffrey M. Burns, MD, MS2, David H. Salat, PhD3, Drew Hill, MSE1,
Steven Tally, PhD4, Jeffrey S. Martin, PhD5 , Michael D. Devous, PhD6, and
Patrick M. Moriarty, MD7
Abstract
Objective: To assess external counterpulsation (ECP) effects on cognitive and functional decline in early AD. Methods: This 12-month, multicenter, blinded, randomized, sham-controlled trial enrolled 190 patients with early AD (MCI due to AD or mild AD per NIA-AA clinical criteria). Participants received either full-pressure ECP (150-300 mmHg) or sham (25 mmHg): 3-5 weekly one-hour sessions for 35 treatments, then twice-weekly through six months. Assessments occurred at baseline and weeks 6,
12, 18, 24, 36, and 52. Primary endpoints included ADCS-ADL, ADAS-cog-14, and VADAS-cog. Results: Full-pressure ECP significantly improved ADCS-ADL scores versus sham (mean change 2.57 vs. -0.49; p=0.036) and VADAS-cog scores (9.95 vs. 5.22; p=0.005) at 12-24 weeks. Benefits persisted through 52 weeks despite treatment cessation at 6 months. No serious device-related adverse events occurred. Conclusions: Full-pressure ECP therapy significantly improved cognition and ADL compared to sham treatment in early AD.

ECP represents a novel therapeutic approach warranting further investigation.
Keywords
Alzheimer’s disease, external counterpulsation, mild cognitive impairment, vascular therapy, cognitive function, activities of
daily living
Received: 30 December 2025; Revised: 23 April 2026; Accepted: 4 May 2026
Introduction
The pathophysiology of Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) is complex. Although research has
focused on amyloid and tau protein buildup, these alone do not fully explain the clinical disease. More than simply a cooccurrence, multiple lines of evidence indicate that vascular disease, especially intra-cranial cerebrovascular disease, is 

1 Medical Device Development, Renew Research, LLC, Farmington Hills, MI, USA
2 University of Kansas Alzheimer's Disease Center, University of Kansas, Kansas City, KS, USA
3 MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA
4 Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, CA, USA
5 Department of Basic Medical Sciences, Lincoln Memorial University, Knoxville, TN, USA
6 MDD Enterprises, Nogal, New Mexico, USA
7 University of Kansas Medical Center, Kansas City, KS, USA
Corresponding author:
Jack E. Juni, MD, Medical Device Development, Renew Research 26800 Haggerty Road Farmington Hills, MI 48331, USA.
Email: [email protected] 
Data Availability Statement included at the end of the article
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