Change in Cognition and Frailty After Shunt Surgery in Idiopathic Normal Pressure Hydrocephalus (iNPH)

The goal of this observational study is to describe changes in cognitive profile and frailty from pre shunt to one year after the shunt surgery and to identify clinical predictors of an improvement in terms of cognition and frailty during the same period. The main objective is to identify predictors of the effect on the planned shunt surgery on cognition and frailty.

Study Overview

• Status: Completed
• Conditions: Idiopathic Normal Pressure Hydrocephalus (INPH)
• Intervention / Treatment: Procedure: Ventriculoperitoneal shunt

Detailed Description

Idiopathic normal pressure hydrocephalus (iNPH) is characterized by one or more of the symptoms gait disturbance, cognitive decline and urinary incontinence. The pathophysiology is not fully understood, but disturbed cerebrospinal fluid (CSF) circulation is considered one of the contributing factors. The CSF disturbance can be treated by shunt surgery with significant improvement in gait velocity and balance, whereas improvements in cognitive function are more uncertain.

Frailty is a consequence of cumulative decline in many physiological systems during a lifetime and implies an increased vulnerability to poor resolution of homoeostasis after a stressor event. Frailty is emerging as an important risk factor for mortality and postoperative complications but has to a limited degree been studied in iNPH.

We have previously, in a cross-sectional design, described cognitive profile and frailty status in patients with iNPH accepted for shunt surgery at Oslo University Hospital. The aims of this longitudinal follow-up of the same patient cohort are twofold:

1. to describe changes in cognitive profile and frailty from pre shunt to one year after the shunt surgery, and
2. to identify clinical predictors of an improvement in terms of cognition and frailty during the same period.

The patient sample consists of 276 patients that were accepted for shunt surgery at Oslo University Hospital in the period from September 2018 to December 2023. Their mean age was 73.1 years (range 52-85), 61% were men, and their mean length of education was 12.5 years. For the cognitive tests, we utilised z-scores (number of standard deviations (SD) from the age and education adjusted mean in a normative dataset).

For frailty, we used a 35 items Frailty Index (FI). Most of the items (frailty indicators) are scored 0 (not present) or 1 (present), while some of them have a graded score. The index is the sum score divided by the number of items, varying from 0.0 (no frailty) to 1.0 (extreme frailty). We used the same approach for assessment of the degree of frailty within each frailty domain. Cognitive decline is considered as one component of frailty. Accordingly, the Mini Mental State Examination (MMSE) is part of the FI and has a graded score. MMSE sum score <21 gives a score of 1 at this particular FI item, an MMSE score of 21-23 gives an item score of 0.7, an MMSE score of 24-26 gives an item score of 0.3, whereas an MMSE score of 27-30 does not contribute to the FI. MMSE is a screening test covering several cognitive domains. We will use MMSE to evaluate the cognitive dimension of frailty as described here, whereas more specific cognitive tests are utilised to assess failure in particular cognitive domains.

Preoperatively, the mean FI score was 0.23, and the most common frailty markers were in the domains of physical function and instrumental activities of daily living (iADL). On the group level, the iNPH patients were impaired on all cognitive domains preoperatively, but compared to patients with Alzheimer's disease, they had relatively better-preserved memory and more severe impairments in phonemic fluency.

220 (80%) patients were assessed one year postoperatively. The same cognitive tests and frailty assessments were carried out, making it possible to calculate simple change scores as score(postop) - score(preop). We will compare baseline characteristics of patients lost to follow-up descriptively with those followed, to assess potential attrition bias.

A detailed Statistical Analysis Plan (SAP) describes the planned analytical approach.

• Study Type: Observational
• Enrollment (Actual): 276

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway
    • Department of Geriatric Medicine, Oslo University Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

see inclusion criteria

Description

Inclusion Criteria:

• Diagnosed with iNPH and accepted for shunt surgery according to the American-European guidelines at Department of Neurosurgery, Oslo University Hospital, Rikshospitalet.

Exclusion Criteria:

• Non-native speakers of Norwegian
• Patients who had completed ≤ 3 cognitive tests

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with idiopathic normal pressure hydrocephalus accepted for shunt surgery	Procedure: Ventriculoperitoneal shunt; Patients are already accepted for shunt surgery. We will describe changes in cognitve profile and frailty from pre shunt to one year after to identify clinical predictors for shunt response.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Trail Making Test A (TMT A) from preoperative to postoperative in patients with idiopathic normal pressure hydrocephalus (iNPH).	TMT A is a cognitive test assessing attention and psychomotor speed and z-scores are calculated using age and educational adjusted norms. The lowest/highest possible z-score is - 3/+ 3 and indicates - 3/+ 3 SD from the mean. Higher z-score reflects better performance. We have defined a Minimum Clinically Important Difference (MCID) as an increase in the z-score (number of standard deviations (SD)) from the age and education adjusted mean in a normative dataset of 0.5 or more for TMT A.	12 month
Change in Frailty Index (FI) from preoperative to postoperative in patients with idiopathic normal pressure hydrocephalus (iNPH).	For frailty, a 35 items FI was used. Most of the items (frailty indicators) are scored 0 (not present) or 1 (present), while some of them have a graded score. The index is the sum score divided by the numbers of items, varying from 0.0 (no frailty) to 1.0 (extreme frailty). We have defined a Minimum Clinically Important Difference (MCID) as a decrease in the FI of 0.05 (5 %) or more.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other measures of cognition and frailty	Cognitive variables: For assessing memory, delayed word recall (z score from either Consortium to Establish a Registry for Alzheimer's disease (CERAD) ten words memory test or the Rey Auditory Learning Test were used. The lowest/highest possible z-score is - 3/+ 3 and indicates - 3/+ 3 SD from the mean. Higher z-score reflects better performance. MCID: Z-score difference 0.5.	12 months
Other measures of cognition and frailty	Figure Construction Test from CERAD is a cognitive test assessing visuoconstructive abilities. The lowest/highest possible z-score is - 3/+ 3 and indicates - 3/+ 3 SD from the mean. Higher z-score reflects better performance. MCID: Z-score difference 0.5.	12 months
Other measures of cognition and frailty	Trail Making Test B is a cognitive test assessing attention, psychomotor speed and executive function. The lowest/highest possible z-score is - 3/+ 3 and indicates - 3/+ 3 SD from the mean. Higher z-score reflects better performance. MCID: Z-score difference 0.5.	12 months
Other measures of cognition and frailty	The Phonemic Fluency Test is a cognitive test assessing language abilities and executive function. The lowest/highest possible z-score is - 3/+ 3 and indicates - 3/+ 3 SD from the mean. Higher z-score reflects better performance. MCID: Z-score difference 0.5.	12 months
Other measures of cognition and frailty	Mini Mental State Examination (MMSE-NR3) is a cognitive screening test from 0 - 30 covering several cognitive domains. Higher score indicates better function. MMSE is part of the FI and has a graded score. MMSE sum score <21 gives a score of 1 at this particular FI item, an MMSE score of 21-23 gives an item score of 0.7, an MMSE score of 24-26 gives an item score of 0.3, whereas an MMSE score of 27-30 does not contribute to the FI. MCID: 2 points.	12 months
Other measures of cognition and frailty	Personal activities in daily living (pADL) are subscales of the FI and are scored from 0-7, higher score indicates more need for help in daily living. An improvement is set to at least 5 % for subscale as a limit for MCID.	12 months
Other measures of cognition and frailty	Instrumental activities in daily living (iADL) are subscales of the FI and are scored from 0-7, higher score indicates more need for help in daily living. An improvement is set to at least 5 % for subscale as a limit for MCID.	12 months
Other measures of cognition and frailty	Gait speed (m/s) is measured from 10 m walk and 0.1 m/s or more is accepted as clinically meaningful. MCID is set to 0.1 m/s.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder analysis	Based on the MCID limits for each outcome, we will define a responder for each outcome as a patient improving that much or more from the preoperative to the one-year postoperative assessment and will calculate the percentage of responders for each of the outcomes. We will then analyse predictors for shunt response on each of the ten outcome variables. Candidate variables in the prediction models are: 1. Age. 2. Sex. 3. MMSE-NR3 score. 4. Gait speed. 5. FI score. 6. Difference in z-score between phonemic fluency and delayed recall at baseline. 7. Cluster affiliation (based on a previously published cluster analysis. The analytic strategy is described in detail in the Statistical Analysis Plan (SAP) that is uploaded as a separate document.	12 months

Collaborators and Investigators

• Sponsor: Oslo University Hospital

Publications and helpful links

General Publications

• Dejgaard MS, Eide PK, Tangen GG, Skovlund E, Selbaek G, Wyller TB. Correction: Cognitive profile and frailty in patients with idiopathic normal pressure hydrocephalus. Front Neurol. 2025 Oct 13;16:1708210. doi: 10.3389/fneur.2025.1708210. eCollection 2025.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Actual): June 19, 2025
• Study Completion (Actual): June 19, 2025

Study Registration Dates

• First Submitted: May 27, 2026
• First Submitted That Met QC Criteria: June 5, 2026
• First Posted (Actual): June 11, 2026

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: dementia; frailty; mild cognitive impairment; gait disorder; normative data
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Neurocognitive Disorders; Cognition Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Frailty; Cognitive Dysfunction; Mobility Limitation; Dementia; Surgical Procedures, Operative; Neurosurgical Procedures; Anastomosis, Surgical; Cerebrospinal Fluid Shunts; Ventriculoperitoneal Shunt
• Other Study ID Numbers: 10150 (formerly 2019/547); Funded by (Other Identifier: Department of Geriatric Medicine Oslo University Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The raw data supporting the conclsion of the article will be made available, following ethic committee guidelines on resonable request from any qualified investigators.
• IPD Sharing Access Criteria: Data sets are available from the PI on request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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