Integrated Multimodal Assessment to Optimize Diagnosis and Surgical Selection in Idiopathic Normal Pressure Hydrocephalus (NPH-OPTIMIZE)

Integrated Multimodal Approach for Diagnostic Optimization and Surgical Candidate Selection in Idiopathic Normal Pressure Hydrocephalus: The Role of CSF Biomarkers, Cognitive-Motor Assessment, and Neuroimaging

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological condition that can cause walking difficulties, cognitive impairment, and urinary incontinence. Although iNPH can be treated with cerebrospinal fluid (CSF) shunt surgery, diagnosis is often challenging because its symptoms and brain imaging findings may overlap with those of other neurodegenerative disorders, such as Alzheimer's disease or vascular parkinsonism. As a result, some patients may experience delayed diagnosis or may not be referred for potentially beneficial surgical treatment.

This observational study aims to evaluate whether combining different types of clinical information can improve the diagnosis of iNPH and help identify patients who are more likely to benefit from surgery. The study integrates cognitive testing, motor performance assessment, CSF biomarker analysis, and brain magnetic resonance imaging.

Patients aged over 60 years with suspected iNPH who are evaluated within a standardized diagnostic care pathway will be included. Cognitive and motor performance will be assessed before and after a cerebrospinal fluid tap test, which is part of routine clinical practice. Results will be compared between patients who receive a confirmed diagnosis of iNPH and undergo CSF shunt surgery and patients who receive an alternative diagnosis and do not undergo surgical treatment.

The results of this study may help improve diagnostic accuracy, reduce false-negative test results, and support better clinical decision-making in patients with suspected idiopathic normal pressure hydrocephalus.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Normal Pressure Hydrocephalus

Detailed Description

This is an observational, non-interventional cohort study designed to assess the diagnostic and prognostic value of a multimodal approach in patients with suspected idiopathic normal pressure hydrocephalus (iNPH).

The study includes patients aged over 60 years who are referred to a standardized diagnostic, therapeutic, and care pathway for suspected iNPH at a tertiary referral center. All data are collected as part of routine clinical practice after informed consent.

Clinical data collection includes demographic and medical information, standardized neuropsychological assessments, motor performance tests, cerebrospinal fluid (CSF) analysis, and brain magnetic resonance imaging. Cognitive and motor assessments are performed before and after the CSF tap test, which is routinely used to support diagnostic and therapeutic decision-making in iNPH.

The exposed cohort consists of patients with confirmed iNPH who undergo CSF shunt surgery, while the non-exposed cohort includes patients who receive an alternative diagnosis and are managed without surgical intervention. The two groups will be compared with respect to changes in cognitive and motor performance, CSF biomarker profiles, and neuroimaging parameters.

Secondary analyses will explore associations between changes in cognitive and motor outcomes, CSF biomarkers, neuroimaging features, and surgical outcomes, including clinical response at 6 months following surgery when available within the study timeframe.

The study combines prospectively collected data with retrospectively available clinical data to provide a comprehensive characterization of patients with suspected iNPH and to support improved diagnostic accuracy and surgical candidate selection.

• Study Type: Observational
• Enrollment (Estimated): 116

Contacts and Locations

• Study Contact: Name: Andrea Arighi, MD; Phone Number: +39 0255033814; Email: andrea.arighi@policlinico.mi.it
• Study Contact Backup: Name: Francesca Mameli, PsyD; Phone Number: +39 0255038671; Email: francesca.mameli@policlinico.mi.it

Study Locations

• Italy
  • Milan, Italy, 20122
    • Recruiting
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
    • Contact: Milena Scauso; Phone Number: +39-02-5503-6197; Email: milena.scauso@policlinico.mi.it
  • Milan, Italy, 20122
    • Active, not recruiting
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population includes adults aged 60 years or older with suspected idiopathic normal pressure hydrocephalus who are referred to a standardized diagnostic, therapeutic, and care pathway at a tertiary referral center. Participants undergo clinical, cognitive, motor, cerebrospinal fluid, and neuroimaging evaluations as part of routine clinical practice.

Description

Inclusion Criteria:

• Age 60 years or older.
• Patients with suspected idiopathic normal pressure hydrocephalus referred to the institutional diagnostic, therapeutic, and care pathway.
• Ability to provide written informed consent.

Exclusion Criteria:

• Refusal or inability to provide informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Idiopathic Normal Pressure Hydrocephalus - Surgical Cohort; Patients with confirmed idiopathic normal pressure hydrocephalus who undergo cerebrospinal fluid shunt surgery as part of standard clinical care. All diagnostic procedures, surgical decisions, and follow-up assessments are performed according to routine clinical practice. No experimental interventions are assigned within this observational study.
Non-Surgical Comparison Cohort; Patients evaluated for suspected idiopathic normal pressure hydrocephalus who receive an alternative diagnosis and do not undergo cerebrospinal fluid shunt surgery. All diagnostic procedures, surgical decisions, and follow-up assessments are performed according to routine clinical practice. No experimental interventions are assigned within this observational study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montreal Cognitive Assessment (MoCA) total score after CSF tap test	Difference in MoCA total score between baseline (pre-CSF tap test) and 72 hours after CSF tap test in patients with suspected iNPH. Higher scores indicate better cognitive performance (range 0-30).	Baseline and 72 hours post-CSF tap test

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Simple Visual Reaction Time After CSF Tap Test	Difference in mean reaction time (milliseconds) between baseline and 72 hours after CSF tap test. Lower values indicate better performance.	Baseline and 72 hours post-CSF tap test
Change in Go/No-Go Test Accuracy After CSF Tap Test	Difference in response accuracy (%) between baseline and 72 hours after CSF tap test. Higher percentages indicate better inhibitory control and executive function.	Baseline and 72 hours post-CSF tap test
Change in Timed Up and Go (TUG) Test Score After CSF Tap Test	Difference in time required to complete the Timed Up and Go test (seconds) between baseline and 72 hours after CSF tap test. Lower times indicate better mobility performance.	Baseline and 72 hours post-CSF tap test
Change in Short Physical Performance Battery (SPPB) Score After CSF Tap Test	Difference in SPPB total score (range 0-12) between baseline and 72 hours after CSF tap test. Higher scores indicate better lower-extremity function.	Baseline and 72 hours post-CSF tap test
Change in Tinetti Performance-Oriented Mobility Assessment Score After CSF Tap Test	Difference in total Tinetti score (range 0-28) between baseline and 72 hours after CSF tap test. Higher scores indicate better gait and balance performance.	Difference in total Tinetti score (range 0-28) between baseline and 72 hours after CSF tap test. Higher scores indicate better gait and balance performance.
Cerebrospinal Fluid Biomarker Profile Differences Between Surgical and Non-Surgical Patients	Comparison of CSF biomarker concentrations measured at diagnostic lumbar puncture, including Aβ42, Aβ40, total tau, phosphorylated tau, Aβ42/Aβ40 ratio, p-tau/Aβ42 ratio, and aquaporin-4. Analyses will evaluate differences between patients undergoing CSF shunt surgery and those receiving an alternative diagnosis without surgery.	Baseline (at diagnostic lumbar puncture)
Association Between Multimodal Markers and Six-Month Surgical Outcome	Correlation between pre- to post-tap-test changes in cognitive and motor measures, CSF biomarkers, neuroimaging parameters, and clinical response at 6 months following CSF shunt surgery.	Baseline through 6 months post-surgery

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Study record dates

Study Major Dates

• Study Start (Estimated): February 11, 2026
• Primary Completion (Estimated): July 1, 2034
• Study Completion (Estimated): January 1, 2035

Study Registration Dates

• First Submitted: February 3, 2026
• First Submitted That Met QC Criteria: February 16, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Cognition; Gait assessment; CSF biomarkers; CSF tap test
• Other Study ID Numbers: 0048426-U

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared because the study dataset contains sensitive personal health information and, despite de-identification, there remains a risk of re-identification. Data sharing is therefore limited to aggregated results to protect participant privacy and comply with applicable data protection regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No