Normal Pressure Hydrocephalus in the Elderly: A Narrative Review of Diagnostic Complexity, Biomarker Potential, and Surgical Outcomes
DOI:
https://doi.org/10.54112/bcsrj.v6i9.1977Keywords:
Normal Pressure Hydrocephalus, Elderly, Dementia, Ventriculoperitoneal Shunt, Gait Disturbance, Pakistan, Narrative ReviewAbstract
Normal pressure hydrocephalus (NPH) is a reversible cause of dementia in older adults, characterized by the clinical triad of gait disturbance, cognitive decline, and urinary incontinence. Owing to overlapping symptoms and low cerebrospinal fluid (CSF) Aβ42 levels, NPH is frequently misdiagnosed as Alzheimer's or Parkinson's disease. Objective: To provide a comprehensive narrative review of the pathophysiology, diagnostic challenges, treatment options, and prognostic markers of NPH, with a particular focus on implications for low- and middle-income countries (LMICs). Methods: Relevant literature published between 2000 and 2025 was retrieved from PubMed, Scopus, and Google Scholar using the keywords "normal pressure hydrocephalus," "cerebrospinal fluid dynamics," "ventriculoperitoneal shunting," and "biomarkers." Both clinical and experimental studies addressing NPH's pathophysiology, diagnostic modalities, and treatment outcomes were reviewed, with emphasis on studies applicable to LMIC contexts such as Pakistan. Results: Evidence indicates that disrupted CSF circulation and ventriculomegaly underlie NPH, with diffusion tensor imaging and arterial spin-labelling MRI offering diagnostic refinement. However, limited access to advanced neuroimaging and cultural perceptions of symptoms as "normal aging" contribute to underdiagnosis in LMICs. Ventriculoperitoneal shunting, particularly with fixed-pressure devices, consistently improves gait performance, while cognitive and urinary outcomes are variable. Post-shunt changes in CSF biomarkers (Aβ42, tau) and serum markers (BDNF, TRPV4) demonstrate potential prognostic value. Functional imaging further correlates reduced cerebral blood flow with symptom severity. Conclusion: NPH remains an under-recognized yet treatable neurological disorder. Increasing awareness, developing simplified diagnostic approaches, and ensuring cost-effective treatment strategies are essential to optimizing patient outcomes, particularly in resource-constrained settings.
Downloads
References
Verny M, Berrut G. Diagnostic de l'hydrocéphalie à pression normale: revue et propositions chez le sujet âgé. Geriatr Psychol Neuropsychiatr Vieil. 2012;10(4):415–25. https://doi.org/10.1684/pnv.2012.0373
Fathalla H, Ghoneim MA, Katatny AE. Managing Normal Pressure Hydrocephalus in Developing Countries: Personalizing Treatment. Neurosurg Rev. 2025;48(1):356. https://doi.org/10.1007/s10143-025-03474-5
Olazarán J, Martínez MD, Rábano A. Normal pressure hydrocephalus mimicking Alzheimer's disease: such an infrequent case? Clin Neuropathol. 2013;32(6):502–7. https://doi.org/10.5414/NP300614
Factora R, Luciano M. When to consider normal pressure hydrocephalus in the patient with gait disturbance. Geriatrics. 2008;63(2):32–7. [No DOI assigned]
Fraser JJ, Fraser C. Gait disorder is the cardinal sign of normal pressure hydrocephalus: a case study. J Neurosci Nurs. 2007;39(3):132–92. https://doi.org/10.1097/01376517-200706000-00002
Tipton PW, Elder BD, Cogswell PM, Graff-Radford N. Normal pressure hydrocephalus, or Hakim syndrome: review and update. Neurol Neurochir Pol. 2024;58(1):8–20. https://doi.org/10.5603/pjnns.97343
Aoki Y, Kazui H, Pascual-Marqui RD, Ishii R, Yoshiyama K, Kanemoto H, et al. EEG resting-state networks responsible for gait disturbance features in idiopathic normal pressure hydrocephalus. Clin EEG Neurosci. 2019;50(3):210–8. https://doi.org/10.1177/1550059418812156
Soon SXY, Kumar AA, Tan AJL, Lo YT, Lock C, Kumar S, et al. The impact of multimorbidity burden, frailty risk scoring, and 3-directional morphological indices vs testing for CSF responsiveness in normal pressure hydrocephalus. Front Neurosci. 2021;15:751145. https://doi.org/10.3389/fnins.2021.751145
Müller-Schmitz K, Krasavina-Loka N, Yardimci T, Lipka T, Kolman AGJ, Robbers S, et al. Normal pressure hydrocephalus associated with Alzheimer's disease. Ann Neurol. 2020;88(4):703–11. https://doi.org/10.1002/ana.25847
Black PM, Ojemann RG, Tzouras A. CSF shunts for dementia, incontinence, and gait disturbance. Clin Neurosurg. 1985;32:632–51. [No DOI assigned]
Chen J, Xian J, Wang F, Zuo C, We L, Chen Z, et al. Long-term outcomes of ventriculoperitoneal shunt therapy in idiopathic normal pressure hydrocephalus. BMC Surg. 2025;25(1):157. https://doi.org/10.1186/s12893-025-02895-9
Nikaido Y, Kajimoto Y, Tucker A, Kuroda K, Ohno H, Akisue T, et al. Intermittent gait disturbance in idiopathic normal pressure hydrocephalus. Acta Neurol Scand. 2018;137(2):238–44. https://doi.org/10.1111/ane.12853
Allali G, Laidet M, Armand S, Assal F. Brain comorbidities in normal pressure hydrocephalus. Eur J Neurol. 2018;25(3):542–8. https://doi.org/10.1111/ene.13543
Pomeraniec IJ, Bond AE, Lopes MB, Jane JA Sr. Concurrent Alzheimer's pathology in patients with clinical normal pressure hydrocephalus: correlation of high-volume lumbar puncture results, cortical brain biopsies, and outcomes. J Neurosurg. 2016;124(2):382–8. https://doi.org/10.3171/2015.2.JNS142318
Reddy GK, Bollam P, Caldito G. Long-term outcomes of ventriculoperitoneal shunt surgery in patients with hydrocephalus. World Neurosurg. 2014;81(2):404–10. https://doi.org/10.1016/j.wneu.2013.01.096
Caruso JP, El Ahmadieh TY, Trent T, Stutzman SE, Anderson R, Schneider N, et al. Neurologic quality of life outcomes in patients with normal pressure hydrocephalus after ventriculoperitoneal shunt placement: a prospective assessment of cognition, mobility, and social participation. World Neurosurg. 2024;190:e26–33. https://doi.org/10.1016/j.wneu.2024.06.068
Hoza D, Vlasák A, Hořínek D, Sameš M, Alfieri A. DTI-MRI biomarkers in the search for normal pressure hydrocephalus aetiology: a review. Neurosurg Rev. 2015;38(2):239–44. https://doi.org/10.1007/s10143-014-0584-0
Graff-Radford NR. Alzheimer's CSF biomarkers may be misleading in normal-pressure hydrocephalus. Neurology. 2014;83(17):1573–5. https://doi.org/10.1212/WNL.0000000000000916
Taghdiri F, Gumus M, Algarni M, Fasano A, Tang-Wai D, Tartaglia MC. Association between cerebrospinal fluid biomarkers and age-related brain changes in patients with normal pressure hydrocephalus. Sci Rep. 2020;10(1):9106. https://doi.org/10.1038/s41598-020-66154-y
Lukkarinen H, Tesseur I, Pemberton D, Van Der Ark P, Timmers M, Slemmon R, et al. Time trends of cerebrospinal fluid biomarkers of neurodegeneration in idiopathic normal pressure hydrocephalus. J Alzheimers Dis. 2021;80(4):1629–42. https://doi.org/10.3233/JAD-201361
Virhammar J, Laurell K, Ahlgren A, Larsson EM. Arterial spin-labeling perfusion MR imaging demonstrates regional CBF decrease in idiopathic normal pressure hydrocephalus. AJNR Am J Neuroradiol. 2017;38(11):2081–8. https://doi.org/10.3174/ajnr.A5347
Zhuang H, Cho J, Chiang GC, Kovanlikaya I, Heier LA, Dyke JP, et al. Cerebral oxygen extraction fraction declines with ventricular enlargement in patients with normal pressure hydrocephalus. Clin Imaging. 2023;97:22–7. https://doi.org/10.1016/j.clinimag.2023.02.001
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Ali Qudratullah Shah, Rukan Aalamuddin Shah, Erum Khatoon, Anam Ramzan, Muhammad Bilawal Chawhan, Aakash Lund, Muneeb Rehman Kalhoro, Jawad Rehman Solangi, Abdul Wasay Soomro, Iftikhar Ahmed Shaikh

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.