Discussion

The objective of this study was to provide a description of the demographic, vascular, cognitive and gait/balance profiles of patients diagnosed with probable iNPH in Eastern Quebec. The sample consisted of 53% men, with a mean age of 73.9 years and mean education level of 11.9 years. Hypertension was the most common vascular risk factor, followed by hyperlipidemia. The cognitive and gait/balance assessments exhibited substantial heterogeneity, as evidenced by large standard deviations and wide score ranges, reflecting marked inter-individual variability in the severity of impairment among iNPH patients. A secondary objective was to examine demographic predictors of cognitive and gait/balance outcomes. Biological sex had no significant impact, while age predicted most outcomes. Education influenced cognitive performance but not gait/balance measures.

The demographic, vascular, cognitive and gait/balance profiles of the patients with probable iNPH in this study were generally in line with those reported in the literature, with a few exceptions. In the sample, males constituted 53% of the patients compared to 47% females, representing only a modest male predominance. This contrasts with other studies that have reported a more pronounced overrepresentation of males. For instance, a recent Swedish prevalence study found that 2.1% of men had iNPH, compared to 0.96% of women, ^{Reference Constantinescu, Wikkelsø and Westman59} and a study in Hawaii reported that men are 1.96 times more likely to develop iNPH than women. ^{Reference Ghaffari-Rafi, Gorenflo, Hu, Viereck and Liow12} Regardless of geographic location, these findings consistently indicate a higher risk for iNPH in men, suggesting that sex-related differences, such as the higher aqueductal CSF stroke volumes and average flow rates observed in men, ^{Reference Schmid Daners, Knobloch and Soellinger60,Reference Sartoretti, Wyss and Sartoretti61} may provide valuable insights into the underlying pathophysiology. Although the degree of male predominance observed in our study was less marked, the overall trend remains present.

This study evidenced that hypertension was the most common vascular risk factor in patients with iNPH in Quebec, as observed in previous studies. ^{Reference Cai, Yang and Gao7,Reference Israelsson, Carlberg and Wikkelsö8,Reference Eide and Pripp62,Reference Graff-Radford and Godersky63} Hypertension has been widely studied for its potential involvement in the pathogenesis of iNPH, with proposed mechanisms including arterial stiffening and increased pulse pressure, which may exert greater mechanical force on brain tissue and contribute to ventricular dilation, a phenomenon known as the Windkessel effect. ^{Reference Jaraj, Agerskov and Rabiei10,Reference Deng, Wang and Huang64–Reference Greitz69} In the literature, diabetes is the second most commonly reported vascular risk factor, with a prevalence of 25% in a recent meta-analysis. ^{Reference Cai, Yang and Gao7} In this study, 26% of iNPH patients had diabetes. However, diabetes was not the second most common vascular comorbidity in the current sample. Hyperlipidemia, smoking and coronary artery disease were more common than diabetes. These findings suggest that the prevalence of vascular risk factors differs accross geographic areas, which may influence their association with iNPH. It is also possible that risk factors beyond hypertension and diabetes have been less frequently studied, leading to an underestimation of their relevance in iNPH. Notably, previous studies have reported inconsistencies across different populations. For instance, while European and Asian cohorts typically show an association between vascular comorbidities and iNPH, ^{Reference Cai, Yang and Gao7,Reference Deng, Wang and Huang64,Reference Kuriyama, Miyajima and Nakajima70} a study conducted in Hawaii found no significant association. ^{Reference Ghaffari-Rafi, Gorenflo, Hu, Viereck and Liow12} Such discrepancies may reflect differences in genetic susceptibility, lifestyle or environmental exposures. Similarly, the higher prevalence of certain vascular risk factors in the present cohort may be influenced by population-specific characteristics, such as socioeconomic status, gender and educational levels. ^{Reference Adhikary, Barman, Ranjan and Stone71,Reference Di Cesare, Perel and Taylor72} The role of these factors in iNPH remains underexplored. To clarify their contribution, future studies should compare vascular risk profiles in iNPH patients and matched controls within Quebec, where demographic and lifestyle factors may differ from those studied in European and Asian cohorts.

The significant heterogeneity observed in cognitive and gait/balance profiles suggests substantial inter-individual variability in iNPH, which may reflect differences in disease stage. While the presence of the full triad (gait, cognitive, and urinary symptoms) is associated with more advanced stages of the disease, ^{Reference Nakajima, Yamada and Miyajima1,Reference Kiefer and Unterberg5} there is currently no standardized framework for staging iNPH from early symptoms to severe impairment. Patients may be at different points along this continuum, ranging from subtle cognitive or gait/balance impairments to more pronounced dysfunction, contributing to the heterogeneity observed. This variability not only makes it challenging to identify iNPH patients based solely on baseline assessments but also likely reflects the complex clinical profiles and presence of comorbidities commonly seen in hospital-based cohorts referred to specialized neurological settings, as opposed to more narrowly selected research cohorts. This clinical complexity underscores the ecological validity of studying patients in real-world contexts and highlights the inherent challenges in diagnosing iNPH in such heterogeneous populations. Additionally, prior studies have reported similar variability in iNPH cohorts. ^{Reference Nimni, Weiss, Cohen and Laviv16,Reference Laidet, Herrmann, Momjian, Assal and Allali20,Reference Bluett, Ash and Farheen73} Future research should aim to stratify patients based on symptom severity and identify clinical or biomarker-based predictors of disease progression. Given the diagnostic challenges posed by this heterogeneity, post-CSF tap test improvement remains an important element to support the diagnosis and predict surgical outcomes.

The findings of this study indicate that demographic factors significantly influence cognitive and gait/balance performance in iNPH patients, particularly age and education level. In a cognitively healthy population, it is well established in both neuropsychology and physiotherapy that individual performance declines with advancing age. ^{Reference Murman74–Reference Salthouse77} However, in the context of cognitive pathology, the influence of age appears to differ. For instance, one study found that while advancing age was associated with decreased performance on a balance test and the MoCA in cognitively healthy individuals, these associations were not observed in patients with Parkinson’s disease. ^{Reference Gallagher, Farella-Accurso and Johnson78} Similar findings have been reported in individuals with advanced-stage Alzheimer’s disease. ^{Reference Rubin, Storandt and Miller46} However, the present results support the hypothesis that age exerts an influence on performance in iNPH patients, particularly in attentional, processing speed, executive functioning, gait and balance tasks.

Furthermore, education level was found to be associated with certain aspects of cognitive performance in iNPH patients. Higher education levels are known to enhance cognitive reserve and may delay the onset of cognitive decline. ^{Reference Clouston, Smith and Mukherjee79–Reference Valenzuela and Sachdev82} However, this protective effect appears to diminish as cognitive impairment progresses. ^{Reference Amieva, Mokri and Le Goff83} In the context of iNPH, cognitive deficits are rarely the first presenting symptoms of the triad. ^{Reference Nakajima, Yamada and Miyajima1,Reference Isaacs, Williams and Hamilton84} Thus, it is plausible that some iNPH patients, particularly those in the early stages of cognitive decline, may continue to benefit from the protective effects of education. Additionally, higher education levels have been linked to a slower decline in executive functions. ^{Reference Hindle, Martyr and Clare85} Given that several studies have established a connection between executive function and gait and balance performance ^{Reference Iersel, Kessels, Bloem, Verbeek and Olde Rikkert86–Reference Hirota, Watanabe, Tanimoto, Kono, Higuchi and Kono88} one might expect education to similarly influence motor abilities. The present study found an association between education level and executive functioning in iNPH, specifically on TMT condition 4 and alphabetic verbal fluency tasks. However, no significant association was found between education level and gait or balance in iNPH patients. This contrasts with findings in other clinical populations, such as patients with Parkinson’s disease, where lower education levels have been associated with both poorer executive functioning (as measured by the Trail Making Test Part B, p = 0.018) and reduced balance (as measured by the BBS, p < 0.001). ^{Reference Souza, Voos, Francato, Chien and Barbosa89} In summary, while education may modulate cognitive and motor interactions in some neurological conditions, its influence on gait and balance in iNPH remains ambiguous and warrants further investigation.

Interestingly, sex was not a significant predictor of cognitive or gait/balance outcomes, which contrasts with findings in non-iNPH older adults. For example, in cognitive testing, females have been reported to perform better than males on tasks assessing information processing speed, ^{Reference Munro, Winicki and Schretlen90} such as Coding and Symbol Search subtests of the WAIS, ^{Reference Roivainen, Suokas and Saari91} and psychomotor speed, such as the Grooved Pegboard test. ^{Reference Ruff and Parker92} In the context of physiotherapy, the evidence is mixed. One study found no significant differences between males and females on the BBS, ^{Reference Nakagawa, Ferraresi, Prata and Scheicher93} whereas another reported that females had lower scores than males. ^{Reference Avdić and Skrbo94} The absence of sex-related differences in cognitive and gait/balance performance in iNPH patients observed in the present study may reflect the overriding impact of the disorder itself, which could mask the typical sex-based differences seen in healthy aging populations.

Overall, these findings support the notion that the impact of demographic factors differs in the iNPH population compared to other clinical populations and cognitively healthy individuals. Currently, the CSF tap test method is used to predict surgical response, with raw scores typically employed in the interpretation of outcomes. The results highlight the importance of thoroughly documenting demographic influences at baseline, as this foundational knowledge is essential for future research to evaluate their role in repeated assessments such as the CSF tap test. Understanding how demographic factors affect pre- and post-test performance could ultimately inform the integration of these factors into diagnostic and prognostic models, thereby refining assessment accuracy and supporting more individualized patient management.