Normal pressure hydrocephalus (NPH) is a neurological disorder characterized by the triad of gait disturbance, cognitive decline, and urinary incontinence, occurring in the presence of enlarged cerebral ventricles but normal cerebrospinal fluid (CSF) pressure on lumbar puncture[1][2]. NPH represents one of the few potentially reversible causes of dementia, making its accurate diagnosis critically important. The condition was first described by Hakim and Adams in 1965, who reported a distinctive syndrome of ventricular enlargement, walking difficulty, and dementia that improved following CSF drainage[3].
Despite being recognized for over 60 years, NPH remains underdiagnosed, with an estimated 80% of cases going unrecognized. Common misdiagnoses include Alzheimer's disease and Parkinson's disease, underscoring the need for improved awareness among clinicians. When appropriately diagnosed and treated, 50-80% of patients experience significant clinical improvement following shunt surgery.
Idiopathic NPH (iNPH) primarily affects individuals over 60 years, with peak prevalence in the 70-79 age group. Population-based studies estimate the prevalence of iNPH at approximately 0.5-2.9% in individuals over 65 years, making it a significant contributor to reversible dementia in the elderly[4]. Some studies suggest that up to 5-10% of individuals with dementia may have NPH as a contributing or sole factor.
The incidence of iNPH increases with age, estimated at 5.5 per 100,000 person-years overall, rising to 18 per 100,000 in those over 70. Men may be slightly more affected than women (ratio ~1.3:1).
NPH is widely considered the most underdiagnosed reversible cause of dementia. Several factors contribute[5]:
The most common form, occurring in older adults without an identifiable cause. iNPH accounts for approximately 50-80% of all NPH cases and is considered a disease of aging, with emerging evidence linking it to cerebrovascular risk factors, glymphatic system dysfunction, and impaired CSF absorption at the arachnoid granulations[4:1].
Results from known underlying conditions including[6]:
Secondary NPH may occur at any age and often has a more acute onset and a better response to shunt surgery than idiopathic NPH.
NPH involves a complex disturbance of CSF production, circulation, and absorption. The traditional model emphasizes impaired CSF absorption through the arachnoid granulations, but contemporary understanding recognizes a more nuanced pathophysiology[7]:
Emerging research has implicated glymphatic system dysfunction as a key mechanism in iNPH pathogenesis. The glymphatic system relies on perivascular spaces and AQP4 water channels on astrocyte endfeet to facilitate CSF-interstitial fluid exchange and clearance of metabolic waste products from the brain[6:1][8].
In iNPH[9]:
Periventricular White Matter: The frontal and parietal white matter is most vulnerable to damage from ventricular expansion, transependymal CSF flow, and chronic ischemia. Disruption of frontal-subcortical circuits that control gait, executive function, and bladder regulation produces the classic triad.
Corpus Callosum: Progressive thinning and callosal angle narrowing due to chronic ventricular enlargement disrupt interhemispheric communication.
Corona Radiata: Compression of descending corticospinal tract fibers contributes to the characteristic gait disorder.
Basal Ganglia: Distortion of basal ganglia circuits due to ventricular expansion may contribute to parkinsonian features.
Hippocampal and Cortical Structures: Secondary cortical atrophy may develop in advanced or longstanding cases, potentially indicating comorbid neurodegeneration.
Cerebrovascular disease is frequently comorbid with iNPH and may contribute to its pathogenesis:
The classic Hakim-Adams triad of symptoms typically develops insidiously over months to years:
Gait Disturbance: Often the first and most prominent symptom, present in over 90% of cases[1:1]. Characteristic features include:
Cognitive Impairment: Subcortical dementia pattern characterized by:
Urinary Incontinence: Typically the last symptom to appear and progresses through stages:
Only 50-60% of patients present with the complete triad. The most common presentation is gait disturbance alone or gait combined with cognitive decline. Isolated dementia or urinary symptoms without gait impairment is atypical and should prompt consideration of alternative diagnoses.
Probable iNPH:
Possible iNPH: Less stringent criteria allowing for incomplete triad or atypical features.
Neuroimaging is the preferred imaging modality:
CSF Tap Test: Removal of 30-50 mL CSF via lumbar puncture with assessment of gait improvement over 30 minutes to 72 hours[5:1]. A positive response (>10% improvement in gait speed or step length) has:
Extended Lumbar Drainage (ELD): Continuous external CSF drainage for 48-72 hours via lumbar catheter. More sensitive than the tap test:
Infusion Test: Measurement of CSF outflow resistance (Rout) during controlled CSF infusion. Rout >12 mmHg/mL/min suggests impaired CSF absorption and predicts shunt response.
Intracranial Pressure Monitoring: Overnight ICP monitoring may reveal B-waves (intermittent pressure elevations at 0.5-2/minute) suggestive of reduced intracranial compliance.
The overlap between NPH and Alzheimer's disease is clinically significant and represents a major diagnostic challenge[11]:
Approximately 30-50% of iNPH patients show concomitant Alzheimer's pathology on biopsy or at autopsy. This overlap likely reflects shared risk factors (age, vascular disease) and a potential mechanistic link through impaired amyloid-beta clearance due to glymphatic dysfunction.
CSF biomarkers can help differentiate iNPH from AD[11:1]:
Bidirectional Mendelian randomization studies have confirmed shared genetic architecture between iNPH and Alzheimer's disease[12], suggesting convergent pathogenic pathways involving:
VP shunt placement remains the standard of care for iNPH[5:2]:
Procedure: A catheter is placed in the lateral ventricle and tunneled subcutaneously to the peritoneal cavity, allowing CSF diversion. Modern systems include:
Outcomes:
Predictors of Good Shunt Response:
Complications:
ETV creates an alternative CSF pathway by fenestrating the floor of the third ventricle, allowing CSF to bypass obstructed absorption pathways. Its role in iNPH is evolving:
For patients who decline surgery or are not surgical candidates:
Without treatment, iNPH progresses over months to years, leading to severe disability with wheelchair dependence, profound dementia, and total incontinence. Untreated NPH significantly increases morbidity and mortality from falls, aspiration, and immobility-related complications.
With appropriate shunt surgery:
Current research focuses on:
Adams RD, Fisher CM, Hakim S, et al. Symptomatic occult hydrocephalus with normal cerebrospinal-fluid pressure. N Engl J Med. 1965. ↩︎ ↩︎
Hakim S, Adams RD. The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal-fluid pressure. J Neurol Sci. 1965. ↩︎
Hakim CA, Hakim R, Hakimi Z, et al. Normal pressure hydrocephalus: the role of cerebrospinal-fluid dynamics in the genesis of dementia. Front Neurol Neurosci. 2009. ↩︎
Relkin N, Marmarou A, Klinge P, et al. Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery. 2005. ↩︎ ↩︎
Marmarou A, Young HF, Aygok GA, et al. Diagnosis and management of idiopathic NPH: a prospective study in 151 patients. J Neurosurg. 2005. ↩︎ ↩︎ ↩︎
Ringstad G, et al. Neuroimaging biomarkers of CSF tracer dynamics in idiopathic NPH. Brain Commun. 2020. ↩︎ ↩︎
Kitagaki H, Mori E, Ishii K, et al. CSF spaces in idiopathic NPH: morphology and pathophysiology. Radiology. 1998. ↩︎
Wang Z, et al. Implications of the glymphatic system in the pathogenesis of NPH. Acta Neurochir. 2025. ↩︎ ↩︎
Mori E, et al. Guidelines for management of idiopathic normal pressure hydrocephalus (third edition). Neurol Med Chir. 2021. ↩︎
Ding J, et al. The pathogenesis of idiopathic NPH based on AQP1 and AQP4. Front Mol Neurosci. 2022. ↩︎
Muller-Schmitz K, et al. Normal pressure hydrocephalus associated with Alzheimer's. Ann Neurol. 2020. ↩︎ ↩︎
Bidirectional Mendelian randomization authors. Bidirectional Mendelian randomization study of iNPH and Alzheimer's. Sci Rep. 2024. ↩︎ ↩︎
Unbiased proteomics authors. Unbiased CSF proteomics in patients with iNPH to identify molecular signatures. Neurology. 2024. ↩︎