Cerebrospinal fluid amyloid beta and response of cognition to a tap test in idiopathic normal pressure hydrocephalus: a case-control study

Abstract

Objectives: 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).

Design: Case-control study.

Setting: Osaka University Hospital.

Participants: Patients with possible iNPH underwent a CSF tap test.

Measurements: 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 (Aβ_42/40 ratio) and total tau concentration was compared between tap test-negative (iNPH-nTT) and -positive (iNPH-pTT) patients.

Results: We identified 27 patients as iNPH-nTT and 81 as iNPH-pTT. Aβ_42/40 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 Aβ_42/40 ratio was significantly associated with the negativity of the tap test. The response of cognition was significantly related to Aβ_42/40 ratio. The association between Aβ_42/40 ratio and tap test response, especially in cognition, remained after adjusting for disease duration and severity at baseline.

Conclusions: A low CSF Aβ_42/40 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.

Keywords: Alzheimer’s disease; Idiopathic normal-pressure hydrocephalus; amyloid beta; tap test; total tau.