Continuous CSF drainage in AD: results of a double-blind, randomized, placebo-controlled study

Topic: Risk, prevention and care in population studies

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.

@article{silverberg2008-18525029,
  author  = {Silverberg, G. D. and Mayo, M. and Saul, T. and Fellmann, J. and Carvalho, J. and McGuire, D.},
  title   = {{Continuous CSF drainage in AD: results of a double-blind, randomized, placebo-controlled study}},
  journal = {Neurology},
  year    = {2008},
  doi     = {10.1212/01.wnl.0000316197.04157.6f},
  pmid    = {18525029},
  url     = {https://doi.org/10.1212/01.wnl.0000316197.04157.6f}
}

Key findings

• Background Alzheimer disease (AD) has been associated with abnormal cerebral clearance of macromolecules, such as amyloid and microtubule-associated-protein tau (MAP-tau).
• Results After a planned interim analysis, the study was halted for futility.
• The surgical procedure and device were associated with 12 CNS infections, some temporally associated with CSF sampling.
• Conclusions We found no benefit to low-flow CSF shunting in subjects with mild to severe Alzheimer disease.

Why it matters

In 215 people with probable Alzheimer's disease, a low-flow ventriculoperitoneal shunt showed no benefit, the study was halted for futility, and there were 12 CNS infections. This clearly found no benefit for this surgical approach.

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Study details

• Study designlongitudinal study
• Participants215
• Evidence strengthHigh

Read the original

• DOI: 10.1212/01.wnl.0000316197.04157.6f
• PubMed: 18525029
• Original source →

May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial Neurology · 2005-05-01 · usefulness score 82/100 · Treatments
• Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease Neurology · 1984-07-01 · usefulness score 58/100 · Getting a diagnosis
• Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo Nature medicine · 2006-06-25 · usefulness score 58/100 · Risk genes beyond APOE
• The Global Deterioration Scale for assessment of primary degenerative dementia The American journal of psychiatry · 1982-09-01 · usefulness score 54/100 · Getting a diagnosis
• Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease Archives of neurology · 1999-06-01 · usefulness score 51/100 · Getting a diagnosis

Later studies that cite this one

1 study in the alzhub library lists this one in its references.

• CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings Neurology · 2012-04-18 · usefulness score 52/100 · Genetics

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