Elevated cerebrospinal fluid pressure in patients with Alzheimer's disease

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 These subjects were presumed to have the AD-NPH syndrome and were withdrawn from the remainder of the study.Alzheimer's disease (AD) and adult-onset, idiopathic chronic hydrocephalus, or normal pressure hydrocephalus (NPH), are age-related disorders involving various degrees of dementia. Patients with both diseases have reduced cerebrospinal fluid (CSF) production and decreased CSF turnover that may be associated with a decreased ability to clear potentially toxic metabolites, such as amyloid beta-peptides (Aβ) [1]. Several clinical series have documented the surprisingly high frequency of pathologically confirmed AD in patients meeting clinical criteria for NPH. In one series, seven of 21 NPH patients (33%) who underwent cortical biopsy at the time of ventriculo-peritoneal shunt implantation, had neuropathological changes consistent with AD [2]. In two other series, one-quarter to one-half of NPH patients had AD-type neuropathology [3,4]. In a more recent series, 23 of 55 patients (42%) biopsied at the time of shunt placement for NPH met CERAD (Consortium to establish a registry for Alzheimer's disease) criteria for AD [5], including 75% of those with severe dementia