Could CSF hold the key to earlier and more accurate NPH diagnosis?

New research published by de Guis et al. 2025 reveals that there are distinctive changes in the proteins found in the cerebrospinal fluid (CSF) of patients with normal pressure hydrocephalus (NPH). The CSF biomarkers identified in the study could potentially aid future diagnosis. 

NPH is a progressive neurological disorder characterised by symptoms of walking difficulties, cognitive impairment and urinary incontinence. Clinical findings show enlargement of the fluid-filled chambers of the brain (ventricles) with no/minimal associated rise in pressure. NPH is a cause of dementia and one of the only forms that can be reversed/significantly improved with treatment, which is usually with the surgical placement of a shunt. Diagnosis of NPH is often missed, delayed, or misdiagnosed due to overlapping symptoms with other dementia types, including Alzheimer’s disease and conditions such as Parkinson's disease. ​Early and accurate NPH diagnosis is essential as it means treatment can begin sooner, which generally makes it more effective.  

In the new study, researchers measured the different types and amounts of proteins in CSF samples from people with or without NPH or Alzheimer’s disease. They then used a form of artificial intelligence called 'machine learning' to analyse the differences. The key findings were: 

• Overall, patients with NPH had reduced levels of proteins in their CSF compared to the levels in individuals without cognitive impairments.  
• There were changes in the levels of proteins involved in different processes and functions in the brain, including how the nerves link and communicate, the immune system, and blood clotting.  
• There were also changes associated with key brain systems, including the blood-brain barrier, which surrounds and protects the brain, and the glymphatic system, which is involved in clearing waste.  
• The Researchers found 12 proteins that may, in the future, help doctors distinguish NPH from Alzheimer’s disease and other conditions.

How will this study help? 

These findings could lead to better diagnostic tests for NPH, reducing misdiagnosis and helping patients receive more timely and effective treatment. ​ 

Characterising the unique protein signature of the CSF in NPH gives us clues to the disease processes involved, including the importance of the BBB and glymphatic systems. This furthers our understanding of what underlies NPH symptoms and will potentially shape future research and treatment. ​ 

This NPH Awareness Week, we are aligned with the wider Dementia Action Week in our focus on the importance of diagnosis. Overall, the Neurology publication offers hope for improving the diagnosis and management of NPH.