Department of Geriatric Medicine, Oslo University Hospital
Oslo, Norway
NCT Number: NCT07642726
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.
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Observational
Oslo, Norway
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:
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.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
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.
Time frame: 12 month
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.
Time frame: 12 months
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.
Time frame: 12 months
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.
Time frame: 12 months
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.
Time frame: 12 months
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.
Time frame: 12 months
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.
Time frame: 12 months
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.
Time frame: 12 months
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.
Time frame: 12 months
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.
Time frame: 12 months
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.
Time frame: 12 months
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:
Oslo University Hospital
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