Cerebrospinal Fluid Diagnostics of Alzheimer's Disease in Patients with Idiopathic Normal Pressure Hydrocephalus.


Journal

Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863

Informations de publication

Date de publication:
2023
Historique:
medline: 25 7 2023
pubmed: 19 6 2023
entrez: 19 6 2023
Statut: ppublish

Résumé

Alzheimer's disease (AD) is the most common cause of dementia worldwide and a frequent comorbidity in idiopathic normal pressure hydrocephalus (iNPH). The presence of AD pathology is associated with worse outcomes after a shunt procedure in iNPH. Preoperative diagnosis of AD is challenging in patients with iNPH, which involves reduced concentrations of the cerebrospinal fluid (CSF) AD biomarkers. Our aim was to estimate the effect size of iNPH as a factor in CSF levels of AD biomarkers and to test if correction could be used to improve diagnostic value. Our cohort included 222 iNPH patients with data in the Kuopio NPH registry and brain biopsy and CSF samples available. We divided the patients into groups according to AD pathology per brain biopsy. For control cohorts, we had CSF samples from cognitively healthy individuals (n = 33) and patients with diagnosed AD and no iNPH (n = 39).*-31ptResults:Levels of all investigated biomarkers differed significantly between groups, with the exception of t-Tau levels between healthy individuals and iNPH patients with AD pathology. Applying a correction factor for each biomarker (0.842*Aβ1 - 42, 0.779*t-Tau, and 0.610*P-Tau181) for the effect of iNPH yielded a sensitivity of 2.4% and specificity of 100%. The ratio of P-Tau181 to Aβ1 - 42 was moderately effective in aiding recognition of AD pathology in iNPH patients (sensitivity 0.79, specificity 0.76, area under the curve 0.824). Correcting for iNPH as a factor failed to improve diagnostic effectiveness, but the P-Tau181/Aβ1 - 42 ratio showed some utility in the diagnosis of AD in iNPH patients.

Sections du résumé

BACKGROUND
Alzheimer's disease (AD) is the most common cause of dementia worldwide and a frequent comorbidity in idiopathic normal pressure hydrocephalus (iNPH). The presence of AD pathology is associated with worse outcomes after a shunt procedure in iNPH. Preoperative diagnosis of AD is challenging in patients with iNPH, which involves reduced concentrations of the cerebrospinal fluid (CSF) AD biomarkers.
OBJECTIVE
Our aim was to estimate the effect size of iNPH as a factor in CSF levels of AD biomarkers and to test if correction could be used to improve diagnostic value.
METHODS
Our cohort included 222 iNPH patients with data in the Kuopio NPH registry and brain biopsy and CSF samples available. We divided the patients into groups according to AD pathology per brain biopsy. For control cohorts, we had CSF samples from cognitively healthy individuals (n = 33) and patients with diagnosed AD and no iNPH (n = 39).*-31ptResults:Levels of all investigated biomarkers differed significantly between groups, with the exception of t-Tau levels between healthy individuals and iNPH patients with AD pathology. Applying a correction factor for each biomarker (0.842*Aβ1 - 42, 0.779*t-Tau, and 0.610*P-Tau181) for the effect of iNPH yielded a sensitivity of 2.4% and specificity of 100%. The ratio of P-Tau181 to Aβ1 - 42 was moderately effective in aiding recognition of AD pathology in iNPH patients (sensitivity 0.79, specificity 0.76, area under the curve 0.824).
CONCLUSION
Correcting for iNPH as a factor failed to improve diagnostic effectiveness, but the P-Tau181/Aβ1 - 42 ratio showed some utility in the diagnosis of AD in iNPH patients.

Identifiants

pubmed: 37334597
pii: JAD230144
doi: 10.3233/JAD-230144
pmc: PMC10357203
doi:

Substances chimiques

Amyloid beta-Peptides 0
tau Proteins 0
Biomarkers 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

727-736

Auteurs

Aleksi Vanninen (A)

Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland.
Neurosurgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Heikki Lukkarinen (H)

Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland.
Neurosurgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Tarja Kokkola (T)

Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Anne M Koivisto (AM)

Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
Department of Neurosciences, University of Helsinki, Helsinki, Finland.
Department of Geriatrics, Helsinki University Hospital, Helsinki, Finland.

Merja Kokki (M)

School of Medicine, University of Eastern Finland, Kuopio, Finland.
Department of Anaesthesia and Intensive Care Medicine, Kuopio University Hospital, Kuopio, Finland.

Tadeusz Musialowicz (T)

Department of Anaesthesia and Intensive Care Medicine, Kuopio University Hospital, Kuopio, Finland.

Mikko Hiltunen (M)

Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.

Henrik Zetterberg (H)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
UK Dementia Research Institute at UCL, London, UK.
Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.

Ville Leinonen (V)

Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland.
Neurosurgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Sanna-Kaisa Herukka (SK)

Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Department of Neurology, Kuopio University Hospital, Kuopio, Finland.

Tuomas Rauramaa (T)

Department of Pathology, Kuopio University Hospital, Kuopio, Finland.
Pathology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

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Classifications MeSH