Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case–control comparison with family members

Abstract

Background The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families. Methods Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their ≥ 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher’s exact test (two-tailed), the Mann–Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses. Results Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1–12.9, p = 0.030). Conclusions Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH.

Exploring mechanisms of ventricular enlargement in idiopathic normal pressure hydrocephalus: a role of cerebrospinal fluid dynamics and motile cilia

“…Patients with iNPH have a higher comorbidity rate of diabetes, which is more than double, compared with an age-adjusted general population [ 64 – 66 ]; however, the causal relationship between diabetes and iNPH has not yet been determined. Studies from patients with vestibular schwannoma have reported to have higher occurrence of communicating-type hydrocephalus, rather than non-communicating hydrocephalus due to the fourth ventricular compression [ 67 – 72 ].…”

Reduced coupling between the global blood-oxygen-level-dependent signal and cerebrospinal fluid inflow is associated with the severity of small vessel disease

“…Diabetes was associated with decreased gBOLD-CSF coupling and a faster gBOLD-CSF coupling decline rate. Indeed, previous studies found that diabetes was associated with both hydrocephalus ( Räsänen et al, 2020 ) and SVD progression ( Bernbaum et al, 2015 ). Our results further support their associations.…”

Molecular Mechanisms and Risk Factors for the Pathogenesis of Hydrocephalus

“…Alcohol consumption demonstrated a correlation with iNPH development possibly due to ethanol-induced decrease in beating frequency of motile cilia and consequent dysfunction on the ependymal cells of ventricles ( Omran et al, 2017 ; Ghaffari-Rafi et al, 2020 ). Although iNPH patients present with increased morbidity of diabetes, the causal relationship has not been concluded ( Hudson et al, 2019 ; Rasanen et al, 2020 ). The speculative pathogenesis may be attributed to high concentration of sugar and increased fluid viscosity in CSF.…”