White Matter Distortion and Dementia Biomarkers in Normal Pressure Hydrocephalus (NPH)

Observational Study to Investigate the Effect of White Matter Tract Distortion and Neurodegenerative Biomarkers on Shunt-responsiveness in Idiopathic Normal Pressure Hydrocephalus (iNPH)

Idiopathic Normal Pressure Hydrocephalus (iNPH) is a progressive condition of the elderly that results in severe disability. iNPH can dramatically respond to Cerebral spinal fluid(CSF)-shunting where excess ventricular fluid is diverted from the brain. Not all patients with iNPH respond to CSF-shunting however. The reasons for this are uncertain.

Aim 1: To understand if specific nerve pathways (white matter tracts) that are near ventricles are damaged in patients that respond to shunting as opposed to those that do not.

Aim 2: Can we explain shunt non-responsiveness by screening for dementia like illnesses (neurodegeneration) using a large array of methods.

Aim 3: To understand whether wearable activity and bed sleep monitors are palatable in a NPH population and to understand if these metrics relate to quality of life.

Aim 4: To see whether self-administered digital cognitive assessments can measure improvements pre and post surgery.

This single-centre observational cohort study will follow 50 patients diagnosed with symptomatic Normal Pressure Hydrocephalus (NPH) (idiopathic or late presenting congenital hydrocephalus and not secondary hydrocephalus) through their clinical journey, from initial assessment to post-CSF shunt surgery or a time when surgery is decided against. Separate groups of 50 asymptomatic individuals with chronic hydrocephalus and non-hydrocephalus individuals will act as controls.

Participants will undergo comprehensive clinical assessments including gait, cognitive and urinary evaluations, quality of life measures, serum and CSF degenerative biomarker analysis, diffusion-weighted Magnetic Resonance Imaging (MRI) and optional brain and skin biopsies. Data collection will focus on capturing changes in clinical presentation and imaging findings before and after shunting. REDCap will be utilised as the primary tool for data storage.

Primary outcome measures assess pre and post-shunting imaging changes in shunt-responders and non-responders. Shunt response will be defined as 10% improvement in gait speed. Secondary outcomes evaluate the relationship between biomarkers and clinical outcomes. Longitudinal data will help identify factors distinguishing responders from non-responders, with descriptive and inferential statistics used.

Group 1 (communicating hydrocephalus):

Inclusion Criteria:

• Adult patients >60
• With gait apraxia
• With or without cognitive impairment
• Urinary dysfunction
• Communicating Hydrocephalus

Exclusion Criteria:

• Asymptomatic hydrocephalus
• High pressure-hydrocephalus
• Serious head injury within 5 years of presentation or a clear secondary cause (e.g. brain infection)
• History of childhood gait disturbance
• Clear alternative explanation for symptoms (e.g. Parkinson's disease with limb rigidity, peripheral neuropathy with sensory ataxia, cervical myelopathy).
• Too frail for shunt surgery
• Medically unstable (e.g. active angina, respiratory disease, recurrent delirium, active epilepsy).
• Unable to tolerate MRI brain imaging
• Unable to have a lumbar puncture
• Immobile
• Unable to attend the hospital for study visits

Group 2 (asymptomatic and non-hydrocepahlus dementia and healthy controls):

Inclusion Criteria (Any of the following):

• Healthy Carers
• Members of the Public
• Staff of Imperial College/ICHT
• Non-NPH Dementias (including Alzheimer's disease or vascular dementia)
• Asymptomatic Hydrocephalus

Exclusion Criteria:

- Unable to attend the hospital for study visits