Predicting Development of Alzheimer’s Disease in Patients with Shunted Idiopathic Normal Pressure Hydrocephalus

Article type: Research Article

Authors: Luikku, Antti J.^{a; b; c} | Hall, Anette^a | Nerg, Ossi^{a; d} | Koivisto, Anne M.^{a; d} | Hiltunen, Mikko^{a; d; e} | Helisalmi, Seppo^a | Herukka, Sanna-Kaisa^{a; d} | Junkkari, Antti^{b; c} | Sutela, Anna^f | Kojoukhova, Maria^{c; f} | Korhonen, Ville^c | Mattila, Jussi^g | Lötjönen, Jyrki^g | Rummukainen, Jaana^{h; i} | Alafuzoff, Irina^j | Jääskeläinen, Juha E.^{b; c} | Remes, Anne M.^{k; l} | Solomon, Alina^{a; m} | Kivipelto, Miia^{a; m; n} | Soininen, Hilkka^{a; d} | Rauramaa, Tuomas^{h; i; 1} | Leinonen, Ville^{b; c; l; o; 1}

Affiliations: [a] Institute of Clinical Medicine – Neurology, University of Eastern Finland, Kuopio, Finland | [b] Institute of Clinical Medicine – Neurosurgery, University of Eastern Finland, Kuopio, Finland | [c] Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland | [d] Neurology of NeuroCenter Kuopio University Hospital, Kuopio, Finland | [e] Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland | [f] Department of Radiology, Kuopio University Hospital, Kuopio, Finland | [g] Combinostics Ltd, Tampere, Finland | [h] Department of Pathology, Kuopio University Hospital, Kuopio, Finland | [i] Department of Pathology, University of Eastern Finland, Kuopio, Finland | [j] Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University and Departmentof Pathology and Cytology, Uppsala University Hospital, Uppsala, Sweden | [k] Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland | [l] Medical Research Center, Oulu University Hospital, Oulu, Finland | [m] Division of Clinical Geriatrics, NVS, Karolinska Institutet, Stockholm, Sweden | [n] Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland | [o] Research Unit of Clinical Neuroscience, Neurosurgery, University of Oulu, Oulu, Finland

Correspondence: [*] Correspondence to: Antti J. Luikku, Neurosurgery of NeuroCenter, Kuopio University Hospital, PO Box 100, FIN-70029 KYS Kuopio, Finland. Tel.: +358 44 2909918; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Idiopathic normal pressure hydrocephalus (iNPH) patients often develop Alzheimer’s disease (AD) related brain pathology. Disease State Index (DSI) is a method to combine data from various sources for differential diagnosis and progression of neurodegenerative disorders. Objective:To apply DSI to predict clinical AD in shunted iNPH-patients in a defined population. Methods:335 shunted iNPH-patients (median 74 years) were followed until death (n = 185) or 6/2015 (n = 150). DSI model (including symptom profile, onset age of NPH symptoms, atrophy of medial temporal lobe in CT/MRI, cortical brain biopsy finding, and APOE genotype) was applied. Performance of DSI model was evaluated with receiver operating characteristic (ROC) curve analysis. Results:A total of 70 (21%) patients developed clinical AD during median follow-up of 5.3 years. DSI-model predicted clinical AD with moderate effectiveness (AUC = 0.75). Significant factors were cortical biopsy (0.69), clinical symptoms (0.66), and medial temporal lobe atrophy (0.66). Conclusion:We found increased occurrence of clinical AD in previously shunted iNPH patients as compared with general population. DSI supported the prediction of AD. Cortical biopsy during shunt insertion seems indicated for earlier diagnosis of comorbid AD.

Keywords: Alzheimer’s disease, computer-assisted diagnosis, normal pressure hydrocephalus

Keywords: Data and results has been partly presented as an abstract at Hydrocephalus 2017, Kobe, Japan

DOI: 10.3233/JAD-190334

Journal: Journal of Alzheimer's Disease, vol. 71, no. 4, pp. 1233-1243, 2019