Abstract
To examine the relationship between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and tap test response to elucidate the effects of comorbidity of AD in idiopathic normal-pressure hydrocephalus (iNPH). Case-control study. Osaka University Hospital. Patients with possible iNPH underwent a CSF tap test. Concentrations of amyloid beta (Aβ) 1-40, 1-42, and total tau in CSF were measured. The response of tap test was judged using Timed Up and Go test (TUG), 10-m reciprocation walking test (10MWT), Mini-Mental State Examination (MMSE), and iNPH grading scale. The ratio of Aβ1-42 to Aβ1-40 (Aβ42/40 ratio) and total tau concentration was compared between tap test-negative (iNPH-nTT) and -positive (iNPH-pTT) patients. We identified 27 patients as iNPH-nTT and 81 as iNPH-pTT. Aβ42/40 ratio was significantly lower (mean [SD] = 0.063 [0.026] vs. 0.083 [0.036], p = 0.008), and total tau in CSF was significantly higher (mean [SD] = 385.6 [237.2] vs. 293.6 [165.0], p = 0.028) in iNPH-nTT than in iNPH-pTT. Stepwise logistic regression analysis revealed that low Aβ42/40 ratio was significantly associated with the negativity of the tap test. The response of cognition was significantly related to Aβ42/40 ratio. The association between Aβ42/40 ratio and tap test response, especially in cognition, remained after adjusting for disease duration and severity at baseline. A low CSF Aβ42/40 ratio is associated with a poorer cognitive response, but not gait and urinary response, to a tap test in iNPH. Even if CSF biomarkers suggest AD comorbidity, treatment with iNPH may be effective for gait and urinary dysfunction.
Highlights
Normal-pressure hydrocephalus (NPH) is a treatable disorder characterized by a triad of symptoms including gait disturbance, cognitive impairment, and urinary dysfunction resulting from an accumulation of cerebrospinal fluid (CSF) (Adams et al, 1965)
Stepwise logistic regression analysis revealed that low Aβ42/40 ratio was significantly associated with the negativity of the tap test
108 patients participated in this study; 27 patients responded negatively while 81 responded positively to the tap test
Summary
Normal-pressure hydrocephalus (NPH) is a treatable disorder characterized by a triad of symptoms including gait disturbance, cognitive impairment, and urinary dysfunction resulting from an accumulation of cerebrospinal fluid (CSF) (Adams et al, 1965). NPH is classified into idiopathic NPH (iNPH), in which there is no apparent antecedent cause of hydrocephalus, and secondary NPH. INPH is a common disease with a prevalence rate of 2.1–2.8% (Jaraj et al, 2014; Nakashita et al, 2016). Due to its high prevalence rate and treatable nature, iNPH is clinically important for older people. The symptoms of iNPH are typically relieved following CSF shunt surgery.
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