The aim was to investigate whether neurodegenerative biomarkers in cerebrospinal fluid (CSF) differentiate patients with suspected normal pressure hydrocephalus (NPH) who respond to CSF drainage from patients who do not respond. Methods: Data from 62 consecutive patients who presented with magnetic resonance imaging changes indicative of NPH were studied with regard to cognitive and gait functions before and after drainage of 40-50ml of CSF. Additionally, S100 protein, neuron-specific enolase, β-amyloid protein, tau protein and phospho-tau were determined in CSF. Statistical analyses were carried out with ANOVA and multiple linear regression. Results: Patients with CSF constellations typical for Alzheimer's disease (n = 28) improved significantly in cognitive and gait-related functions after CSF drainage. In contrast, those patients without a CSF constellation typical for Alzheimer's disease (n = 34) did not improve in cognitive and gait-related functions after CSF drainage. In addition, positive CSF biomarkers for Alzheimer's disease predicted these improvements. Interpretation: Our data suggest an association between Alzheimer's disease and NPH changes, supporting the recently suggested dichotomy of a neurodegenerative NPH and a true idiopathic NPH, with the latter appearing to be rare.

Objective To investigate if visuomotor coordination of hand movements is impaired in patients with normal pressure hydrocephalus (NPH) identified by dedicated testing procedures. Methods Forty-seven patients admitted for diagnostic workup for suspected NPH were studied prospectively with MRI, testing of cognitive and motor functions, lumbar puncture, and visuomotor coordination of hand movements using the PABLOR-device before and after a spinal tap of 40–50 ml CSF. Statistical analyses were carried out with repeated measures ANOVA and non-parametric correlation analyses. Results Fourteen patients were found to suffer from ideopathic NPH. They were severely impaired in visuomotor control of intermittent arm movements in comparison to patients who were found not to be affected by NPH (n = 18). In the patients with NPH the deficient arm control was improved after the spinal tap in proportion to the improvement of gait. There was no improvement of cognitive and motor functions in the patients not affected by NPH, while the patients with possible NPH (n = 15) showed intermediate deficit and improvement patterns. Interpretation: Our data underline the importance of a multiparametric assessment of NPH and provide evidence for a motor control deficit in idiopathic NPH involving leg and arm movements. It is suggested that this motor control deficit resulted from an affection of the output tracts from the supplementary motor area in the periventricular vicinity.