Elevated cerebrospinal fluid pressure in patients with Alzheimer's disease

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.

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).

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).

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 These subjects were presumed to have the AD-NPH syndrome and were withdrawn from the remainder of the study.