Vascular risk factors for idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis.

Objective: Idiopathic normal-pressure hydrocephalus (iNPH) is a treatable cause of dementia; however, its etiology and pathogenesis remain poorly understood. The objective of this study was to investigate the prevalence and impact of vascular risk factors in patients with iNPH compared to a control cohort to better understand the potential mechanisms and preventive measures. Methods: We systematically searched PubMed, Web of Science, Embase, and the Cochrane Library (from inception to December 20, 2022) for studies reporting vascular risk factors for the development of iNPH. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects models. Results: After screening 1,462 articles, 11 case-control studies comprising 1,048 patients with iNPH and 79,668 cognitively unimpaired controls were included in the meta-analysis. Our data showed that hypertension (N = 991, OR = 2.30, 95% CI 1.64 to 3.23, I2= 64.0%), diabetes mellitus (DM) (N = 985, OR = 3.12, 95% CI 2.29 to 4.27, I2= 44.0%), coronary heart disease (CHD; N = 880, OR = 2.34, 95% CI 1.33 to 4.12, I2= 83.1%), and peripheral vascular disease (N = 172, OR = 2.77, 95% CI 1.50 to 5.13, I2= 0.0%) increased the risk for iNPH, while overweight was a possible factor (N = 225, OR = 2.01, 95% CI 1.34 to 3.04, I2= 0.0%) based on the sensitivity analysis. Smoking and alcohol consumption were not associated with iNPH. Conclusions: Our study suggested that hypertension, DM, CHD, peripheral vascular disease, and overweight were associated with iNPH. These factors might be involved in the pathophysiological mechanisms promoting iNPH. These findings require further investigation in future studies. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, CRD42022383004.

Association between vascular risk factors and idiopathic normal pressure hydrocephalus: a Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Patients with idiopathic normal pressure hydrocephalus (iNPH) have a higher prevalence of hypertension and diabetes. However, the causal effects of these vascular risk factors on iNPH remain unclear. This study aimed to explore the causal relationship between vascular risk factors (VRFs) and iNPH. METHODS: We conducted the Mendelian randomization (MR) analysis of iNPH. We included nineteen vascular risk factors related to hypertension, diabetes, lipids, obesity, smoking, alcohol consumption, exercise, sleep, and cardiovascular events as exposure factors. We used the inverse-variance weighted method for causal effect estimation and weighted median, maximum likelihood, and MR Egger regression methods for sensitivity analyses. RESULTS: We found that genetically predicting essential hypertension (OR = 1.608 (1.330-1.944), p = 0.013) and increased sleep duration (OR = 16.395 (5.624-47.799), p = 0.009) were associated with higher odds of iNPH. Type 1 diabetes (OR = 0.869 (0.828-0.913), p = 0.004) was associated with lower odds of iNPH. For the other 16 VRFs, there was no evidence that they were significantly associated with iNPH. Sensitivity analyses showed that essential hypertension and type 1 diabetes were significantly associated with iNPH. CONCLUSION: In our MR study on VRFs and iNPH, we found essential hypertension to be a causal risk factor for iNPH. This suggests that hypertension may be involved in the pathophysiological mechanism of iNPH.

Necrostatin-1 decreases necroptosis and inflammatory markers after intraventricular hemorrhage in mice.

Necrostatin-1, an inhibitor of necroptosis, can effectively inhibit necrotic apoptosis in neurological diseases, which results in the inhibition of inflammation, endoplasmic reticulum stress, and reactive oxygen species production and substantial improvement of neurological function. However, the effects of necrostatin-1 on intraventricular hemorrhage (IVH) remain unknown. In this study, we established a mouse model of IVH by injecting autologous blood into the lateral ventricle of the brain. We also injected necrostatin-1 into the lateral ventricle one hour prior to IVH induction. We found that necrostatin-1 effectively reduced the expression levels of the necroptosis markers receptor-interacting protein kinase (RIP)1, RIP3, mixed lineage kinase domain-like protein (MLKL), phosphorylated (p)-RIP3, and p-MLKL and the levels of interleukin-1ß , interleukin-6, and tumor necrosis factor-α in the surrounding areas of the lateral ventricle. However, necrostatin-1 did not reduce ependymal ciliary injury or brain water content. These findings suggest that necrostatin-1 can prevent local inflammation and microglial activation induced by IVH but does not greatly improve prognosis.

Radiological biomarkers of idiopathic normal pressure hydrocephalus: new approaches for detecting concomitant Alzheimer's disease and predicting prognosis.

Idiopathic normal pressure hydrocephalus (iNPH) is a clinical syndrome characterized by cognitive decline, gait disturbance, and urinary incontinence. As iNPH often occurs in elderly individuals prone to many types of comorbidity, a differential diagnosis with other neurodegenerative diseases is crucial, especially Alzheimer's disease (AD). A growing body of published work provides evidence of radiological methods, including multimodal magnetic resonance imaging and positron emission tomography, which may help noninvasively differentiate iNPH from AD or reveal concurrent AD pathology in vivo. Imaging methods detecting morphological changes, white matter microstructural changes, cerebrospinal fluid circulation, and molecular imaging have been widely applied in iNPH patients. Here, we review radiological biomarkers using different methods in evaluating iNPH pathophysiology and differentiating or detecting concomitant AD, to noninvasively predict the possible outcome postshunt and select candidates for shunt surgery.