Vascular factors in suspected normal pressure hydrocephalus: A population-based study

Abstract

Objective: We examined clinical and imaging findings of suspected idiopathic normal pressure hydrocephalus (iNPH) in relation to vascular risk factors and white matter lesions (WMLs), using a nested case-control design in a representative, population-based sample.

Methods: From a population-based sample, 1,235 persons aged 70 years or older were examined with CT of the brain between 1986 and 2000. We identified 55 persons with hydrocephalic ventricular enlargement, i.e., radiologic findings consistent with iNPH. Among these, 26 had clinical signs that fulfilled international guideline criteria for probable iNPH. These cases were labeled suspected iNPH. Each case was matched to 5 controls from the same sample, based on age, sex, and study cohort. Data on risk factors were obtained from clinical examinations and the Swedish Hospital Discharge Register. History of hypertension, diabetes mellitus (DM), smoking, overweight, history of coronary artery disease, stroke/TIA, and WMLs on CT were examined. Risk factors associated with iNPH with a p value <0.1 in χ2 tests were included in conditional logistic regression models.

Results: In the regression analyses, suspected iNPH was related to moderate to severe WMLs (odds ratio [OR] 5.2; 95% confidence interval [CI]: 1.5-17.6), while hydrocephalic ventricular enlargement was related to hypertension (OR 2.7; 95% CI: 1.1-6.8), moderate to severe WMLs (OR 6.5; 95% CI: 2.1-20.3), and DM (OR 4.3; 95% CI: 1.1-16.3).

Conclusions: Hypertension, WMLs, and DM were related to clinical and imaging features of iNPH, suggesting that vascular mechanisms are involved in the pathophysiology. These findings might have implications for understanding disease mechanisms in iNPH and possibly prevention.

Figure 1. Gothenburg population studies: Overview of cohorts included in the present study

The sample comprised data from 4 prospective cohort studies. Pooled sample included all persons invited. H70 = Longitudinal Gerontological and Geriatric Population Studies in Gothenburg, Sweden; NORA = Nordic Research on Ageing; PPSW = Prospective Population Study of Women.

Figure 2. Overview of study sample

Of those with HVe (n = 55), 26 had suspected iNPH (i.e., had clinical signs that fulfilled guideline criteria for probable iNPH). Among those with HVe that did not fulfill guideline criteria for suspected iNPH (n = 29), 17 had gait disturbance, cognitive impairment, or urinary incontinence, and 12 persons did not have symptoms of iNPH. Both control groups were randomly selected from CT participants and comprised persons without radiologic findings consistent with iNPH. Among persons in the pooled sample, 2 were excluded because of complete lack of data. One person was found to be younger than 70 years and was therefore also excluded. HVe = hydrocephalic ventricular enlargement; iNPH = idiopathic normal pressure hydrocephalus.