Oct. 22, 2002 ST. PAUL, MN – In a first study of its kind, researchers tested the hypothesis that improving cerebrospinal fluid (CSF) turnover will slow or stop the progression of dementia in people with Alzheimer's disease. Researchers from Stanford University, University of Washington (Seattle), and the Barrow Neurological Institute in Phoenix, have published the conclusions of their study in the October 22 issue of Neurology, the scientific journal of the American Academy of Neurology. CSF shunting for dementia was first described in 1969 and, despite early optimism, was largely abandoned due to mixed clinical results and an unacceptably high incidence of adverse events related to the shunts. Recent clinical studies in which CSF shunting was used to treat patients with symptomatic hydrocephalus demonstrated a coincidental lack of cognitive decline in patients who also had Alzheimer's dementia.
"We speculated that, although the subjects described in these recent studies may have had two unrelated diseases, both Alzheimer's and normal pressure hydrocephalus may be part of a disease spectrum whose primary determinant is CSF circulatory failure," says study author Gerald Silverberg, MD, of Stanford University.
Silverberg and colleagues conducted a prospective, randomized, controlled clinical trial in which an investigational low-flow ventriculoperitoneal (VP) shunt was evaluated in Alzheimer's patients. The surgically implanted shunts drained CSF at a constant rate much lower than in the hydrocephalus studies to minimize the potential for overdrainage and optimize constant CSF flow.
Subjects were screened and randomized into test and control groups, with 12 completing the shunt testing, and 11 patients tested as a comparison group. Both control and shunted patients were tested at baseline and every three months using the National Adult Reading Test, the Mattis Dementia Rating Scale and the Mini Mental Status Examination.
There were no substantial differences in age or severity of dementia between the shunted patients and the control group at baseline. However, the shunted patients experienced relative stability while the control group demonstrated a fairly robust decline in cognitive function over the 12 months of the study. The number of shunted patients in this study was too small to make broad claims about the safety of the shunt device, though the outcomes are encouraging.
"Our preliminary safety and efficacy data, including the outstanding questions they present, suggest that more definitive testing is appropriate," concludes Silverberg. A larger, multi-center, controlled clinical trial is now underway.
The study was funded by Eunroe Inc. and the Ray Richter Alzheimer's Disease Research Fund at Stanford.
The American Academy of Neurology, an association of more than 18,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research.
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