Research

Elevated cerebrospinal fluid pressure in patients with Alzheimer's disease

Gerald Silverberg¹ , Martha Mayo² , Thomas Saul³ , Jere Fellmann⁴ and Dawn McGuire⁵

¹  Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA

²  Genitope Corp, 525 Penobscot Drive, Redwood City, CA,94063, USA

³  Turning Point Engineering, PO box 372 Moss Beach CA, 94038, USA

⁴  Acologix Inc, 3960 Point Eden Way, Hayward, CA 94545, USA

⁵  Avigen Inc, 1301 Harbor Bay Parkway, Alameda CA 94502, USA

author email corresponding author email

Cerebrospinal Fluid Research 2006, 3:7doi:10.1186/1743-8454-3-7

Published:	31 May 2006

Abstract

Background

Abnormalities in cerebrospinal fluid (CSF) production and turnover, seen in normal pressure hydrocephalus (NPH) and in Alzheimer's disease (AD), may be an important cause of amyloid retention in the brain and may relate the two diseases. There is a high incidence of AD pathology in patients being shunted for NPH, the AD-NPH syndrome. We now report elevated CSF pressure (CSFP), consistent with very early hydrocephalus, in a subset of AD patients enrolled in a clinical trial of chronic low-flow CSF drainage. Our objective was to determine the frequency of elevated CSFP in subjects meeting National Institutes of Neurological and Communicative Diseases and Stroke – Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for AD, excluding those with signs of concomitant NPH.

Methods

AD subjects by NINCDS-ADRDA criteria (n = 222), were screened by history, neurological examination, and radiographic imaging to exclude those with clinical or radiographic signs of NPH. As part of this exclusion process, opening CSFP was measured supine under general anesthesia during device implantation surgery at a controlled pCO₂ of 40 Torr (40 mmHg).

Results

Of the 222 AD subjects 181 had pressure measurements recorded. Seven subjects (3.9%) enrolled in the study had CSFP of 220 mmH₂0 or greater, mean 249 ± 20 mmH₂0 which was significantly higher than 103 ± 47 mmH₂O for the AD-only group. AD-NPH patients were significantly younger and significantly less demented on the Mattis Dementia Rating Scale (MDRS).

Conclusion

Of the AD subjects who were carefully screened to exclude those with clinical NPH, 4% had elevated CSFP. These subjects were presumed to have the AD-NPH syndrome and were withdrawn from the remainder of the study.