title: Familial idiopathic normal pressure hydrocephalus.
abstract: Idiopathic normal pressure hydrocephalus (iNPH) is a late-onset surgically alleviated, progressive disease. We characterize a potential familial subgroup of iNPH in a nation-wide Finnish cohort of 375 shunt-operated iNPH-patients. The patients were questionnaired and phone-interviewed, whether they have relatives with either diagnosed iNPH or disease-related symptomatology. Then pedigrees of all families with more than one iNPH-case were drawn. Eighteen patients (4.8%) from 12 separate pedigrees had at least one shunt-operated relative whereas 42 patients (11%) had relatives with two or more triad symptoms. According to multivariate logistic regression analysis, familial iNPH-patients had up to 3-fold risk of clinical dementia compared to sporadic iNPH patients. This risk was independent from diagnosed Alzheimer's disease and APOE ε4 genotype. This study describes a familial entity of iNPH offering a novel approach to discover the potential genetic characteristics of iNPH. Discovered pedigrees offer an intriguing opportunity to conduct longitudinal studies targeting potential preclinical signs of iNPH.
authors.affiliation: Department of Neurosurgery, Kuopio University Hospital, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. Electronic address: joel_huovinen@hotmail.com.
authors.forename: Joel
authors.initials: J
authors.lastname: Huovinen
authors.affiliation: Department of Neurosurgery, Kuopio University Hospital, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. Electronic address: samikas@student.uef.fi.
authors.forename: Sami
authors.initials: S
authors.lastname: Kastinen
authors.affiliation: Department of Neurosurgery, Kuopio University Hospital, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. Electronic address: simokom@student.uef.fi.
authors.forename: Simo
authors.initials: S
authors.lastname: Komulainen
authors.affiliation: Department of Neurosurgery, University of Helsinki, Helsinki University Hospital, Finland. Electronic address: minna.oinas@hus.fi.
authors.forename: Minna
authors.initials: M
authors.lastname: Oinas
authors.affiliation: Department of Neurosurgery, University of Helsinki, Helsinki University Hospital, Finland. Electronic address: cecilia.avellan@hus.fi.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Avellan
authors.affiliation: Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital, Turku, Finland. Electronic address: janek.frantzen@tyks.fi.
authors.forename: Janek
authors.initials: J
authors.lastname: Frantzen
authors.affiliation: Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital, Turku, Finland. Electronic address: jaakko.rinne@tyks.fi.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Rinne
authors.affiliation: Department of Neurosurgery, Tampere University Hospital, Tampere, Finland. Electronic address: antti.ronkainen@pshp.fi.
authors.forename: Antti
authors.initials: A
authors.lastname: Ronkainen
authors.affiliation: Department of Neurosurgery, Oulu University Hospital, Oulu, Finland. Electronic address: mikko.kauppinen@ppshp.fi.
authors.forename: Mikko
authors.initials: M
authors.lastname: Kauppinen
authors.affiliation: South Ostrobothnia Central Hospital, Seinäjoki, Finland. Electronic address: kimmo.lonnrot@epshp.fi.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Lönnrot
authors.affiliation: National Institute for Health and Welfare, Finland; University of Helsinki, Helsinki, Finland. Electronic address: markus.perola@thl.fi.
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.affiliation: Department of Neurosurgery, Kuopio University Hospital, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. Electronic address: okko.pyykko@gmail.com.
authors.forename: Okko T
authors.initials: OT
authors.lastname: Pyykkö
authors.affiliation: Unit of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Department of Neurology, Kuopio University Hospital, Kuopio, Finland. Electronic address: anne.koivisto@kuh.fi.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Koivisto
authors.affiliation: Unit of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Department of Neurology, Kuopio University Hospital, Kuopio, Finland. Electronic address: anne.remes@uef.fi.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Remes
authors.affiliation: Unit of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Department of Neurology, Kuopio University Hospital, Kuopio, Finland. Electronic address: hilkka.soininen@uef.fi.
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.affiliation: Unit of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Department of Neurology, Kuopio University Hospital, Kuopio, Finland; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland. Electronic address: mikko.hiltunen@uef.fi.
authors.forename: Mikko
authors.initials: M
authors.lastname: Hiltunen
authors.affiliation: Unit of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Department of Neurology, Kuopio University Hospital, Kuopio, Finland. Electronic address: seppo.helisalmi@uef.fi.
authors.forename: Seppo
authors.initials: S
authors.lastname: Helisalmi
authors.affiliation: Department of Neurosurgery, Kuopio University Hospital, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, USA; Stanley Center for Psychiatric Research, Broad Institute for Harvard and MIT, USA. Electronic address: mitja.kurki@gmail.com.
authors.forename: Mitja
authors.initials: M
authors.lastname: Kurki
authors.affiliation: Department of Neurosurgery, Kuopio University Hospital, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. Electronic address: juha.e.jaaskelainen@kuh.fi.
authors.forename: Juha E
authors.initials: JE
authors.lastname: Jääskeläinen
authors.affiliation: Department of Neurosurgery, Kuopio University Hospital, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. Electronic address: ville.leinonen@kuh.fi.
authors.forename: Ville
authors.initials: V
authors.lastname: Leinonen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D002557:Cerebrospinal Fluid Shunts; D015897:Comorbidity; D003704:Dementia / Q000134:cerebrospinal fluid / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000453:epidemiology* / Q000235:genetics / Q000601:surgery; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D015995:Prevalence
chemical_list: D001057:Apolipoproteins E
keywords: APOE; Alzheimer's disease; Complex traits; Familial aggregation; Genetics; Heritability; Idiopathic; Normal pressure hydrocephalus; Pedigree