Contributed Commentary by Stephen Salloway and José Luis Molinuevo
December 10, 2018 | Growing evidence suggests biological markers of Alzheimer’s disease may begin forming decades before an individual begins experiencing symptoms. Because of this, researchers are finding ways to detect the disease earlier and with more accuracy than standard diagnostic methods. Analysis of cerebrospinal fluid (CSF), a colorless liquid that circulates in the brain and spinal cord, is one way researchers can accurately identify biological markers of Alzheimer’s - specifically, beta-amyloid and tau proteins.
To raise awareness of the usefulness and accuracy of CSF analysis in Alzheimer’s, a workgroup of experts convened by the Alzheimer’s Association developed appropriate use criteria (AUC) to guide clinicians in deciding the right patient candidates for this procedure. Two of the co-authors of this AUC, Stephen Salloway, M.D., Director of Neurology and the Memory and Aging Program at Butler Hospital in Rhode Island, and José Luis Molinuevo, M.D., Ph.D., Scientific Director of the Alzheimer Prevention Program at Barcelona Beta Brain Research Center in Spain, answer some anticipated frequently asked questions about the stigma of lumbar puncture in their respective countries, the new criteria, and the importance of early Alzheimer’s diagnosis.
What is the current standard method of diagnosing Alzheimer’s disease?
Salloway: If a person is experiencing some cognitive decline or memory changes, they’d typically visit their doctor to have some standard tests done. This would include a medical history, physical examination and tests of memory, thinking and reasoning followed by an MRI or CT scan of the brain. Plus, the doctor often seeks valuable input from a spouse, partner or other appropriate proxy. But these tests don’t definitively diagnose Alzheimer’s.
Molinuevo: We are noticing that patients are coming in earlier and earlier. Fifteen years ago, we were seeing people in the moderate stages of dementia. But now, we’re seeing more people with perceived cognitive decline, and these patients may be within normal range on their cognitive tests. Our task as clinicians and researchers is to find alternate, more accurate ways to detect the early biological signs of Alzheimer’s so we can answer as many of our patient’s questions as we can.
What alternate diagnostic tools are available to patients today?
Salloway: Positron emission tomography (PET) scans have been in the market for a few years and can provide an image of the amyloid buildup in the brain. But, it’s an optional diagnostic—and it’s expensive. Obtaining CSF through a lumbar puncture is another method, but there’s only one test approved in the U.S. and it isn’t reimbursed by most private insurance or Medicare in many states. The hope is more CSF tests will be approved in the near future.
Molinuevo: The problem is many clinicians aren’t aware of the accuracy of this CSF analysis. Thanks to the Alzheimer’s Association and the expert workgroup who created the AUC, there will be more education and awareness in the field so everyone knows that these are really good tests that are letting us see the pathology earlier.
Salloway: That’s right. The goal of the AUC is to increase the use of lumbar puncture and CSF analysis for Alzheimer’s, and make sure it’s done appropriately.
What is the fear behind lumbar punctures?
Molinuevo: In Europe in general, lumbar puncture is well accepted for diagnostic purposes by specialists. There are countries that have lumbar puncture completely integrated as part of the neurospecialist and general practitioner routine. From a diagnostic perspective, in general, in the specialist setting, it is very well accepted and is performed with high frequency in Europe.
Salloway: The overall use of lumbar puncture is lower in the U.S. than in Europe, and that’s an interesting distinction. There’s a perception that it’s a risky procedure—that it’s associated with paralysis. I think it has to do with the polio epidemic. People had a spinal tap as part of their evaluation and ended up paralyzed, not due to the spinal tap but due to the virus. The nomenclature is important, too: “lumbar puncture” sounds like a hole is being put in the spine. Because of this pervasive fear about the procedure, the clinician plays an important role in reassuring and educating the patient that the procedure is safe and simple in most cases.
How is lumbar puncture and CSF analysis reimbursed in the U.S. and in Europe?
Molinuevo: In Europe, reimbursement varies country to country. It is generally not reimbursed in Spain. As soon as something is approved by the European Medicines Agency (EMA), things get complex. Let’s take the example of amyloid imaging. In Spain, amyloid PET reimbursement is deferred to different regions’ medical budgets and then further divided to each hospital budget. Based on that, the hospital decides the amount of tests they can cover per year.
Salloway: For the U.S., that’s a big issue: the coverage. Amyloid PET is not covered either. We have this FDA-approved procedure, but physicians are not ordering the test because it’s not covered by insurance. Hopefully, both CSF analysis and amyloid PET will be covered—they’re really great in improving diagnostic accuracy and influencing treatment decisions.
What should clinicians know about CSF analysis and the importance of an early and accurate diagnosis?
Salloway: We want to diagnose Alzheimer’s and intervene early before dementia to hopefully delay the disease. A concern for people is why would you want to find out you have a fatal disease earlier, but there are advantages. An early diagnosis of Alzheimer's provides a range of benefits for patients and families, including making important decisions about work, financial planning, driving safety, and taking advantage of medications that are approved or in clinical trials.
Molinuevo: All European societies are perceiving Alzheimer’s as a major threat. People are concerned and worried about it. And we can clearly tell this because patients are coming in earlier and earlier with concerns.
Salloway: MRI and CT tests are standard of care in this field, but they are non-specific tests for Alzheimer’s disease. Amyloid PET and CSF analysis are much more specific in diagnosing Alzheimer’s and they’re not standard of care. We want to change that. As more CSF analysis tests for Alzheimer’s and other dementias enter the market and are covered by insurance, healthcare professionals - no matter where they are located - will need to balance both disclosing the minor risks of lumbar puncture and reassuring their patient that the test is generally safe and easily administered.
Stephen Salloway, M.D., is Director of Neurology and the Memory and Aging Program at Butler Hospital in Rhode Island, and the Martin M. Zucker Professor of Psychiatry and Human Behavior and Professor of Neurology at the Warren Alpert Medical School of Brown University. He can be reached at SSalloway@Butler.org.
José Luis Molinuevo, M.D., Ph.D., Scientific Director of the Alzheimer Prevention Program at Barcelona Beta Brain Research Center in Spain. He can be reached at jlmolinuevo@barcelonabeta.org.
Drs. Salloway and Molinuevo are members of the Alzheimer’s Association work group and co-authors of the paper, “Appropriate Use Criteria for Lumbar Puncture and Cerebrospinal Fluid Testing in the Diagnosis of Alzheimer’s Disease,” available online at Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.