Landmark Study Confirms Treatment for a Condition that Causes Dementia in Seniors

International study ends decades of controversy, confirming that shunt surgery restores walking thus improving independence in older adults with iNPH 

Bethesda, September 16, 2025: A condition that develops for unknown reasons as people age and causes dementia-like symptoms now has a clear path toward recognition and effective treatment by the medical community. Idiopathic normal pressure hydrocephalus (iNPH) is a form of hydrocephalus that impacts individuals age 60 and older. iNPH is typically characterized by a triad of symptoms that include difficulty walking, cognitive impairment, and impaired bladder control. These symptoms arise when there is a build-up of cerebrospinal fluid (CSF) in the brain’s ventricles, causing them to enlarge and put pressure on the brain.  

Nearly one million older Americans may be living with iNPH, with more than 80% of cases going unrecognized or untreated. The likelihood of developing iNPH increases with age; by age 86 and older, about one in 13 people (7.7%) are affected. Left untreated, iNPH can cause falls, loss of independence, and eventually severe neurological disability and death. With early treatment, however, most patients experience meaningful improvement, often with partial to complete reversal of symptoms. 

Without appropriate diagnostic testing, iNPH is often misdiagnosed as Alzheimer’s disease, Parkinson’s disease, stroke, or dismissed as “normal aging.” The primary treatment, the placement of a shunt (a small tube) to drain fluid from the brain to another part of the body, has been clouded by controversy regarding its effectiveness and safety. 

Now, a landmark international study funded by the National Institutes of Health (NIH) and led by Johns Hopkins University School of Medicine along with the Adult Hydrocephalus Clinical Research Network (AHCRN), has clearly demonstrated that shunt surgery improves walking and balance, restoring mobility, reducing falls and thus improving safety and independence in older adults with iNPH. The Placebo-Controlled Efficacy in iNPH Shunting (PENS) Trial is the first large, double-blind, placebo-controlled study to resolve decades of debate on whether shunts truly help patients. The results are published in The New England Journal of Medicine, one of the most prestigious peer-reviewed medical journals.  

“Completing this randomized clinical trial was necessary because many neurologists and neurosurgeons were unsure if shunts could effectively treat iNPH, which greatly affected patient access to diagnosis and care,” stated Dr. Mark Hamilton, MD, Director of the Calgary Adult Hydrocephalus Program at the Cumming School of Medicine, Calgary, Alberta, Canada and Chair of the AHCRN. “Now, there is no doubt. Shunt surgery for iNPH has been confirmed to improve walking and balance, decrease falls, and restore independence. Shunt surgery for patients with iNPH is both safe and effective.” 

The Road to PENS 

Normal pressure hydrocephalus was first described in 1964 by Salomon Hakim, MD, PhD, ushering in early enthusiasm in the 1960s and 70s for a treatment that could relieve, and even reverse, symptoms in the aging population. By the 1980s, however, skepticism took hold due to inconsistent outcomes and high complication rates.  

The PENS Trial was designed to resolve this long-standing uncertainty through the most rigorous form of clinical research—a double-blind, randomized, placebo-controlled trial. The concept originated in 2008, led by Dr. Mark Luciano, MD, PhD, Director of the Cerebral Fluid Center at Johns Hopkins Medicine; Dr. Michael Williams, MD, FAAN, Director of Adult and Transitional Hydrocephalus and CSF Disorders at the University of Washington; and Dr. Mark Hamilton. All three, founding members of the AHCRN and leading experts in iNPH neurology and neurosurgery, were committed to validating the improvements they had repeatedly observed in their own patients. Yet, despite their persistence, early proposals to the NIH were dismissed as “unnecessary.” 

In 2012, the Hydrocephalus Association supported the start of the AHCRN. For the first time, leading experts from the United States, United Kingdom, and Canada joined forces, pooling their data, resources, and patients to tackle the most pressing research questions in adult hydrocephalus. The AHCRN completed a PENS pilot study with the financial support of the Hydrocephalus Association and an unrestricted grant from a medical device company – Codman, a division of Integra LifeSciences. With data in hand and AHCRN’s proven ability to collaborate across institutions, enroll patients efficiently, and maintain a centralized data coordinating center, a new proposal was submitted to NIH.  

In 2021, the NIH awarded $14 million — its largest-ever grant for hydrocephalus research — to launch PENS under the leadership of Dr. Mark Luciano at Johns Hopkins University School of Medicine, along with Dr. Michael Williams, Dr. Mark Hamilton, and the AHCRN. Six AHCRN sites—which included Johns Hopkins University, University of Washington, University of Calgary, University of British Columbia, New York University, and the Cleveland Clinic participated in the PENS trial. The University of Utah Data Coordinating Center and the Johns Hopkins BIOS Clinical Trials Coordinating Centre coordinated the PENS trial. There were 21 active sites in the United States, Canada, and Sweden in the study, with 17 enrolling patients. 

New Hope for Patients: Improving Mobility 

The incidence of iNPH for individuals age 85 and older is comparable with that of Alzheimer’s Disease. Yet, a lack of understanding and recognition of iNPH often puts patients on a multi-year diagnostic odyssey trying to find the cause of the triad of symptoms they are experiencing. Left untreated, iNPH can cause progressive disability, loss of independence, and early death for the individual, and an increasing burden of care and medical expenses for loved ones.  

The PENS trial enrolled 99 patients in the United States, Canada, and Sweden. Every participant received a programmable shunt. On the day of surgery, the patients shunt was randomized to either open or placebo, with the placebo setting effectively preventing the shunt from functioning. The main outcome of the study was the speed of walking (gait velocity). After three months, the gait velocity in the open shunt group was significantly faster than before surgery, while in the placebo group, gait speed was virtually unchanged. Patients in the open shunt group also had improved balance and reported fewer falls. Eventually, after three months, all patients had their shunts opened. Neither patients nor their doctors knew which group they were in to avoid biasing the results.  

The PENS Trial will continue to follow participants for 12 months to measure long-term outcomes, including cognition, daily functioning, and quality of life. Early findings already suggest gains beyond walking. 

For the first time, patients and families have clear evidence that iNPH is not simply “old age.” It is a condition with a clear, effective treatment. By restoring mobility, reducing falls, and preserving independence, shunt surgery directly addresses the issues most feared in aging: disability, loss of independence, and nursing home placement. 

“We hear testimonials from individuals who are active with the Hydrocephalus Association that their iNPH diagnosis and subsequent treatment allowed them to slowly return to the activities that they loved,” shared Diana Gray, President and CEO of the Hydrocephalus Association. “This study is an important step in raising awareness of iNPH among the medical community so that individuals can be referred early in order to get the treatment they need. We are proud to have played a critical role in funding research that directly improves the lives of the community we serve.” 

Learn More about idiopathic Normal Pressure Hydrocephalus 

iNPH is typically characterized by a triad of symptoms:  

• Gait Disturbance – difficulty walking or making turns, feeling like it’s hard to take the first step, balance issues, falling 

• Cognitive Impairment – problems organizing or planning tasks, hard time multitasking, trouble listening or paying attention, short-term memory issues, feeling withdrawn, talking less, poor handwriting, trouble with simple math calculations.  

• Impaired Bladder Control – trouble “holding it”, inability to get to the bathroom fast enough, experiencing accidents 

These three symptoms may not all occur at the same time. They can also emerge at different stages of the disease with varying levels of severity. If you or a loved one is experiencing these symptoms, ask your doctor about normal pressure hydrocephalus. Learn more about diagnosis and treatment on the Hydrocephalus Association website.  

About the Hydrocephalus Association 

Founded in 1983 by the parents of children with hydrocephalus, the Hydrocephalus Association (HA) is now the nation’s largest and most widely respected organization dedicated to those living with hydrocephalus across the entire age spectrum. Since 2009, HA has invested over $16.4 million in research, making it the largest non-profit and non-governmental funder of hydrocephalus research in the United States. The Hydrocephalus Association’s mission is to find a cure for hydrocephalus and improve the lives of those impacted by the condition.