Abstract
ObjectivesThe purpose of this systematic review and meta-analysis was to evaluate the performance of cerebrospinal fluid (CSF) beta amyloid 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) as potential diagnostic biomarkers for idiopathic normal-pressure hydrocephalus (iNPH) and to assess their utility indistinguishing patients with iNPH from those with Alzheimer disease (AD) and healthy normal controls.MethodsStudies were identified by searching PubMed, Embase, the Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical Database, VIP Chinese database, and Chinese Bio-medicine Database (CBM) before August 2016. The standardized mean difference (SMD) and 95% confidence interval (CI), comparing CSF Aβ42, t-tau, and p-tau levels between iNPH, AD and healthy controls, were calculated using random-effects models. Subgroup analyses were created according to ethnicity (Caucasian or Asian) and CSF type (lumbar or ventricular), and the publication bias was estimated using Egger’s test and the Begg’s test.ResultsA total of 10 studies including 413 patients with iNPH, 186 patients with AD and 147 healthy controls were included in this systematic review and meta-analysis. The concentrations of CSF t-tau, and p-tau were significantly lower in iNPH patients compared to AD (SMD = −1.26, 95% CI −1.95 to −0.57, P = 0.0004; SMD = −1.54, 95% CI −2.34 to −0.74, P = 0.0002, respectively) and lower than healthy controls (SMD = −0.80, 95% CI −1.50 to −0.09, P = 0.03; SMD = −1.12, 95% CI −1.38 to −0.86, P < 0.00001, respectively). Patients with iNPH had significantly lower Aβ42 levels compared with controls (SMD = −1.14, 95% CI −1.74 to −0.55, P = 0.0002), and slightly higher Aβ42 levels compared with AD patients (SMD = 0.32, 95% CI 0.00–0.63, P = 0.05). Subgroup analyses showed that the outcomes may have been influenced by ethnicity and CSF source. Compared to AD, overall sensitivity in differentiating iNPH was 0.813 (95% CI 0.636–0.928) for Aβ42, 0.828 (95% CI 0.732–0.900) for t-tau, 0.943 (95% CI 0.871–0.981) for p-tau. Relative to AD, overall specificity in differentiating iNPH was 0.506 (95% CI 0.393–0.619) for Aβ42, 0.842 (95% CI 0.756–0.907) for t-tau, 0.851 (95% CI 0.767–0.914) for p-tau.ConclusionThe results of our meta-analysis suggest that iNPH may be associated with significantly reduced levels of CSF Aβ42, t-tau and p-tau compared to the healthy normal state. Compared to AD, both t-tau and p-tau were significantly decreased in iNPH, but CSF Aβ42 was slightly increased. Prospective studies are needed to further assess the clinical utility of these and other CSF biomarkers in assisting in the diagnosis of iNPH and differentiating it from AD and other neurodegenerative disorders.
Highlights
Normal pressure hydrocephalus (NPH) was first described in 1965 by Hakim, Adams and colleagues [1] as a syndrome of cerebral ventricular enlargement occurring in adults without elevated cerebrospinal fluid (CSF) pressure or macroscopic obstruction to CSF flow
A total of 413 patients with idiopathic NPH (iNPH), 186 patients with Alzheimer disease (AD), and 147 healthy controls were included in this meta-analysis. 2 studies were performed in the United States [21, 22], 2 in Japan [23, 24], 2 in Sweden [12, 25], 1 in Greece [13], 1 in Finland [26], 1 in South Korea [27] and 1 in Italy [28]
In this systematic review and meta-analysis, we explored whether concentrations of CSF Aβ42, t-tau, and p-tau are of potential value in differentiating iNPH from AD and from healthy normal controls
Summary
Normal pressure hydrocephalus (NPH) was first described in 1965 by Hakim, Adams and colleagues [1] as a syndrome of cerebral ventricular enlargement occurring in adults without elevated cerebrospinal fluid (CSF) pressure or macroscopic obstruction to CSF flow. Studies identified NPH as a progressive but treatable disorder that often presents with the classical symptom triad of gait disturbance, dementia, and urinary incontinence. This condition is considered idiopathic NPH (iNPH) when there is no identifiable antecedent cause and secondary NPH (sNPH) when events such as severe head trauma, subarachnoid hemorrhage or meningitis precede its onset. Recent studies have reported prevalence rates of iNPH ranging from 0.51 to 5.9% in the elderly population that increase with advancing age This suggests that iNPH is much more common than previously recognized [2,3,4]. This is unfortunate because iNPH and sNPH can be effectively treated by neurosurgical placement of a shunt, which leads to improvement or stabilization of symptoms in upwards of 80% of accurately diagnosed patients [8]
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