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Continuous CSF drainage in AD: results of a double-blind, randomized, placebo-controlled study
G D Silverberg1, M Mayo, T Saul
1Warren Alpert School of Medicine, Brown University, Providence, RI, USA. geralds@stanford.edu
Background:
Alzheimer disease (AD) has been associated with abnormal cerebral clearance of macromolecules, such as amyloid and microtubule-associated-protein tau (MAP-tau). We hypothesized that improving clearance of macromolecules from the CNS might slow the progression of dementia.
Objective:
This prospective, randomized, double-blinded, placebo-controlled trial evaluated the safety and effectiveness of a surgically implanted shunt in subjects with probable AD.
Methods:
A total of 215 subjects with probable AD by National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria received either a low-flow ventriculoperitoneal shunt or a sham (occluded) shunt for 9 months. Longitudinal CSF sampling was performed in both active and control subjects. Primary outcome measures were the Mattis Dementia Rating Scale and the Global Deterioration Scale. CSF Abeta((1-42)) and MAP-tau also were assayed.
Results:
After a planned interim analysis, the study was halted for futility. Using the intent-to-treat population, no between-group differences were observed in the primary outcome measures. The surgical procedure and device were associated with 12 CNS infections, some temporally associated with CSF sampling. All were treated successfully.
Conclusions:
We found no benefit to low-flow CSF shunting in subjects with mild to severe Alzheimer disease. CSF infections, while treatable, occurred more frequently than expected, in some cases likely related to CSF sampling.
