NPH and Early AD Group 

Normal pressure hydrocephalus (NPH)

NPH is a poorly understood neurological disorder presenting with impaired cognitive, gait and continency functions in various combinations as well as enlarged I-IV ventricles.

NPH patients may significantly benefit of shunt surgery. The most frequent differential diagnosis is Alzheimer's disease (AD).




Neurosurgery of Kuopio University Hospital (KUH) solely serves Eastern Finnish population (see map above: green area).

Since 1991 until 2010, our NPH protocol has included 24-hour intraventricular pressure monitoring together with a small right frontal cortical biopsy to exclude other neurodegenerative  processes. Since 2010 the protocol has included systematic CSF sampling and brain biopsy is included in the shunt surgery.









Selected patients undergo advanced AD imaging at Turku PET Centre.

Kuopio NPH and AD Registry and Tissue Bank  contains clinical and long-term follow up data as well as cortical biopsy samples of over 700 patients investigated for possible NPH.

Kuopio NPH Research Group has a unique research window to NPH and AD through the cortical biopsy and CSF samples and long-term outcome data. This project is multidisciplinary approach, in which expertise from several fields of neuroscience at KUH and UEF campus area as well as national and international level are combined.

Aims of Research

  1. Genomic factors predisposing sporadic and familial idiopathic NPH.
  2. Novel biomarkers of iNPH and neurodegenerative diseases diagnostics and prognosis.
  3. Validation of CSF and PET diagnostics against brain biopsy in iNPH and AD.
  4. Personalized treatment of iNPH.


Director of Group






Ville Leinonen
MD PhD Adjunct Prof
ville.leinonen (at)
+358 44 717 2303

Ossi Nerg / MD PhD Student
Anne Koivisto / MD PhD Adjunct prof
Mikko Hiltunen / Prof
Seppo Helisalmi / PhD Adjunct Prof
Sanna-Kaisa Herukka / MD PhD Adjunct prof
Hilkka Soininen / Prof
Anne Remes / Prof

Tuomas Rauramaa / MD PhD Post Doc
Jaana Rummukainen / MD PhD Post Doc
Irina Alafuzoff / Prof (Uppsala)


Joel Huovinen / PhD Student
Antti Junkkari / PhD Student
Maria Kojoukhova / PhD Student
Ville Korhonen / PhD Student
Tiina Laiterä / MD PhD Post Doc
Antti Luikku / PhD Student
Okko Pyykkö / MD PhD Post Doc
Marita Voutilainen / RN
Sakari Savolainen / MD PhD Adjunct Prof
Juha E Jääskeläinen / Prof
Ville Leinonen / MD PhD Adjunct Prof

Cognitive Neuroscience
Jouni Ihalainen / PhD Post Doc
Heikki Tanila / Prof

Anna Sutela / MD PhD Post Doc
Ritva Vanninen / Prof

Turku Neurosurgery
Jaakko Rinne / Prof Chairman

Turku PET Centre
Juha O Rinne / Prof

 Selected Publications

  • Huovinen J, et al. Familial idiopathic normal pressure hydrocephalus. J Neurol Sci 2016

  • Kojoukhova M, et al. Associations of intracranial pressure with brain biopsy, radiological findings, and shunt surgery outcome in patients with suspected idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien) 2016

  • Laiterä T, et al. Effects of Alzheimer's Disease-Associated Risk Loci on Amyloid-β Accumulation in the Brain of Idiopathic Normal Pressure Hydrocephalus Patients. J Alzheimers Dis 2016

  • Luikku AJ, et al. Multimodal analysis to predict shunt surgery outcome of 284 patients with suspected idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien) 2016

  • Junkkari A, et al. Health-related quality-of-life outcome in patients with idiopathic normal-pressure. Eur J Neurol 2016

  • Koivisto, et al. High Risk of Dementia in Ventricular Enlargement with Normal Pressure Hydrocephalus Related Symptoms. J Alzheimers Dis 2016

  • Laiterä T, et al. The Expression of Transthyretin and Amyloid-β Protein Precursor is Altered in the Brain of Idiopathic Normal Pressure Hydrocephalus Patients. J Alzheimers Dis 2015

  • Kojoukhova M, et al. Feasibility of radiological markers in idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien) 2015

  • Junkkari A, et al. Health-related quality of life in patients with idiopathic normal pressure hydrocephalus. Eur J Neurol 2015

  • Herukka SK, et al. Amyloid-β and Tau Dynamics in Human Brain Interstitial Fluid in Patients with Suspected Normal Pressure Hydrocephalus. J Alzheimers Dis 2015

  • Laiterä T, et al. Increased γ-secretase activity in idiopathic normal pressure hydrocephalus patients with β-amyloid pathology. PLoS One 2014

  • Pyykkö OT,  et al. Cerebrospinal fluid biomarker and brain biopsy findings in idiopathic normal pressure hydrocephalus. PLoS One 2014

  • Leinonen V, et al. Positron emission tomography with [18F]flutemetamol and [11C]PiB for in vivo detection of cerebral cortical amyloid in normal pressure hydrocephalus patients. Eur J Neurol 2013

  • Koivisto, et al. Poor cognitive outcome in shunt-responsive idiopathic normal pressure hydrocephalus. Neurosurgery 2013

  • Rinne JO, Wong DF, Wolk DA, Leinonen V, et al. [(18)F]Flutemetamol PET imaging and cortical biopsy histopathology for fibrillar amyloid β detection in living subjects with normal pressure hydrocephalus: pooled analysis of four studies. Acta Neuropathol 2012

  • Pyykkö OT, et al. APOE4 predicts amyloid-β in cortical brain biopsy but not idiopathic normal pressure hydrocephalus. J Neurol Neurosurg Psychiatry 2012

  • Seppälä TT, et al. CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings. Neurology 2012

  • Leinonen V et al. Post-mortem findings in 10 patients with presumed normal-pressure hydrocephalus and review of the literature. Neuropathol Appl Neurobiol 2012

  • Leinonen V, et al. Amyloid and tau proteins in cortical brain biopsy and Alzheimer's disease. Ann Neurol 2010

  • Hansson Petersen CA, et al. The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci USA 2008

  • Leinonen V, et al. Assessment of β-Amyloid in a frontal cortical brain biopsy specimen and by positron emission tomography with carbon 11-labeled Pittsburgh compound B. Arch Neurol 2008

  • Bertram L, Hiltunen M, et al. Family-based association between Alzheimer's disease and variants in UBQLN1. N Engl J Med 2005

  • Holm A, Savolainen S, Alafuzoff I. Brain biopsy prior to treatment of Alzheimer's disease. Minim Invasive Neurosurg 2003

  • Savolainen S, et al. Five-year outcome of normal pressure hydrocephalus with or without a shunt: predictive value of the clinical signs, neuropsychological evaluation and infusion test. Acta Neurochir (Wien) 2002

  • Savolainen S, et al. MR imaging of the hippocampus in normal pressure hydrocephalus: correlations with cortical Alzheimer's disease confirmed by pathologic analysis. AJNR Am J Neuroradiol 2000