TY - JOUR
T1 - Cerebrospinal Fluid Biomarkers to Differentiate Idiopathic Normal Pressure Hydrocephalus from Subcortical Ischemic Vascular Disease
AU - Manniche, Christina
AU - Simonsen, Anja Hviid
AU - Hasselbalch, Steen Gregers
AU - Andreasson, Ulf
AU - Zetterberg, Henrik
AU - Blennow, Kaj
AU - Høgh, Peter
AU - Juhler, Marianne
AU - Hejl, Anne-Mette
PY - 2020
Y1 - 2020
N2 - BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) remains a challenge to differentiate from subcortical ischemic vascular disease (SIVD). Despite major research efforts, the cerebrospinal fluid (CSF) biomarker profiles of the two diseases are still not known in detail.OBJECTIVE: To determine if novel CSF biomarkers, neurofilament light (NFL) reflecting axonal damage, the synaptic protein neurogranin (NG), and the astroglial marker chitinase-3-like protein 1 (YKL-40), and the core Alzheimer's disease (AD) biomarkers, amyloid-β 42 (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), can differentiate iNPH from SIVD. Patients with AD and healthy controls (HC) were included for comparison purposes.METHODS: Patients with iNPH (n = 28), SIVD (n = 30), AD (n = 57), and HC (n = 33) were retrospectively included from the Danish Dementia Biobank. All patients with iNPH had effect of shunt surgery with a follow-up period of 4 to 69 months. CSF biomarkers were measured using immunoassays.RESULTS: Lower levels of NFL, NG, Aβ42, and t-tau were found in patients with iNPH versus SIVD, while YKL-40 and p-tau were similar in the two diseases. NFL and Aβ42 were the most reliable biomarkers to differentiate iNPH from SIVD with an area under the curve (AUC) on 0.82 and 0.80, respectively. Combining NFL with Aβ42, t-tau, and p-tau resulted in an AUC of 0.90, which was equivalent to the diagnostic accuracy of all six biomarkers combined.CONCLUSION: An addition of NFL to the CSF panel of Aβ42, t-tau, and p-tau may improve the differentiation of iNPH from SIVD.
AB - BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) remains a challenge to differentiate from subcortical ischemic vascular disease (SIVD). Despite major research efforts, the cerebrospinal fluid (CSF) biomarker profiles of the two diseases are still not known in detail.OBJECTIVE: To determine if novel CSF biomarkers, neurofilament light (NFL) reflecting axonal damage, the synaptic protein neurogranin (NG), and the astroglial marker chitinase-3-like protein 1 (YKL-40), and the core Alzheimer's disease (AD) biomarkers, amyloid-β 42 (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), can differentiate iNPH from SIVD. Patients with AD and healthy controls (HC) were included for comparison purposes.METHODS: Patients with iNPH (n = 28), SIVD (n = 30), AD (n = 57), and HC (n = 33) were retrospectively included from the Danish Dementia Biobank. All patients with iNPH had effect of shunt surgery with a follow-up period of 4 to 69 months. CSF biomarkers were measured using immunoassays.RESULTS: Lower levels of NFL, NG, Aβ42, and t-tau were found in patients with iNPH versus SIVD, while YKL-40 and p-tau were similar in the two diseases. NFL and Aβ42 were the most reliable biomarkers to differentiate iNPH from SIVD with an area under the curve (AUC) on 0.82 and 0.80, respectively. Combining NFL with Aβ42, t-tau, and p-tau resulted in an AUC of 0.90, which was equivalent to the diagnostic accuracy of all six biomarkers combined.CONCLUSION: An addition of NFL to the CSF panel of Aβ42, t-tau, and p-tau may improve the differentiation of iNPH from SIVD.
KW - Biomarkers
KW - cerebrospinal fluid
KW - normal pressure hydrocephalus
KW - vascular dementia
UR - http://www.scopus.com/inward/record.url?scp=85086052021&partnerID=8YFLogxK
U2 - 10.3233/JAD-200036
DO - 10.3233/JAD-200036
M3 - Journal article
C2 - 32390628
SN - 1387-2877
VL - 75
SP - 937
EP - 947
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 3
ER -