In a first study of its kind, researchers from Stanford University, the University of Washington (Seattle), and the Barrow Neurological Institute in Phoenix tested the hypothesis that improving the circulation of cerebrospinal fluid (CFS), the liquid surrounding the brain and spinal cord, will slow or stop the progression of dementia in people with Alzheimer's disease. The study is published 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, a disease in which CSF increases in the brain causing enlargement of the skull, 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 pervious studies to minimize the potential for over-drainage and to 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.