Concurrent Alzheimer's pathology in patients with clinical normal pressure hydrocephalus.

Abstract

Patients with normal pressure hydrocephalus (NPH) and Alzheimer's dementia (AD) can often present with similar symptoms. NPH remains a clinical diagnosis and there are reported shared underlying dynamics of cerebrospinal fluid (CSF) flow and histopathology with patients with biopsy-proven AD. This is a review on the histopathology and cerebrospinal fluid dynamics of both NPH and AD. In a prior study at the University of Virginia, the authors reviewed patients over a 15 year period who were shunted for a preoperative diagnosis of NPH. Of these patients, 74% received high volume lumbar puncture and at the time of surgery, 159 total biopsies were performed on 113 patients with 46 repeat biopsies. The results of high-volume lumbar punctures, cortical brain biopsies, and clinical outcomes were compared between patients with NPH and those found to have Alzheimer's pathology. As many as 24% of patients with clinical diagnosis of NPH may demonstrate concomitant Alzheimer's dementia based on histopathological biopsy performed at the time of shunt placement. In patients in whom a CSF shunt was placed and biopsy obtained, 19% of patients demonstrated histopathologiy consistent with CERAD diagnosis of AD. However, more than half (53%) of all patients demonstrated some degree of neuritic plaque development, while 14% and 9% demonstrated evidence of neurofibrillary tangles and amyloid angiopathy, respectively. The improved clinical response seen with HVLP was not sustained following shunt insertion; 45% of NPH patients with positive response to HVLP improved following shunt placement compared to just 18% of concurrent NPH and AD patients (p = 0.0136). There is a high prevalence of AD in patients who are shunted for a clinical diagnosis of NPH. The presenting symptoms of NPH and AD may be very similar and the significant difference in histopathology is what separates the two disease processes. There may be temporary relief with restoring cerebrospinal fluid flow but the presence of underlying neurodegenerative changes more directly correlates with long-term outcomes. There may also be a direct correlation between altered CSF dynamics in both the metabolic clearance and the development of dementia.