University of Oulu

Räsänen, J., Huovinen, J., Korhonen, V.E. et al. Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case–control comparison with family members. Fluids Barriers CNS 17, 57 (2020).

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

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Author: Räsänen, Joel1,2; Huovinen, Joel1,2; Korhonen, Ville E.1,2;
Organizations: 1Department of Neurosurgery, Kuopio University Hospital, P.O.Box 100, 70029, Kuopio, KYS, Finland
2Institute of Clinical Medicine-Neurosurgery, University of Eastern Finland, Kuopio, Finland
3Department of Neurosurgery, University of Helsinki, Helsinki, Finland
4Department of Neurosurgery, Helsinki University Hospital, Helsinki, Finland
5Clinical Neurosciences, Department of Neurosurgery, University of Turku, Turku, Finland
6Department of Neurosurgery, Turku University Hospital, Turku, Finland
7Department of Neurosurgery, Tampere University Hospital, Tampere, Finland
8Unit of Clinical Neuroscience, Neurosurgery, University of Oulu and Medical Research Center, Oulu University Hospital, Oulu, Finland
9National Institute for Health and Welfare, Helsinki, Finland
10University of Helsinki, Helsinki, Finland
11Institute of Clinical Medicine–Neurology, University of Eastern Finland, Kuopio, Finland
12Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
13Medical Research Center, Oulu University Hospital, Oulu, Finland
14Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
15Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, USA
16Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA
17Stanley Center for Psychiatric Research, Broad Institute for Harvard and MIT, Cambridge, USA
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
Persistent link:
Language: English
Published: Springer Nature, 2020
Publish Date: 2020-12-04


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.

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Series: Fluids and barriers of the CNS
ISSN: 2045-8118
ISSN-E: 2045-8118
ISSN-L: 2045-8118
Volume: 17
Issue: 1
Article number: 57
DOI: 10.1186/s12987-020-00217-0
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
3112 Neurosciences
Funding: This study was funded by the Finnish Medical Foundation, Academy of Finland (307866), EVO/VTR Grants 5252614 and 5772708 of Kuopio University Hospital, Sigrid Juselius Foundation, the Strategic Funding of the University of Eastern Finland (UEF-Brain), FP7, Grant Agreement No. 601055, VPH Dementia Research Enabled by IT VPH-DARE@IT and BIOMARKAPD project in the JPND Program. The funding sources had no involvement in the study design; the collection, the analysis and the interpretation of the data; in the writing of the report; and in the decision to submit the article for publication.
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