Lumbar Puncture May Help Diagnose Alzheimer`s Disease
By Marilynn Larkin
NEW YORKâIn "appropriate" patients, lumbar puncture and analysis of cerebral spinal fluid (CSF) may be used to confirm or rule out Alzheimer's disease, according to recommendations from an Alzheimer's Association workgroup.
"The (workgroup's) vision is to have lumbar puncture and CSF analysis appropriately incorporated into diagnosis and care for Alzheimer's disease and other dementias, but the test is not widely available at the moment," Dr. James Hendrix, Director of Global Science Initiatives for the Alzheimer's Association told Reuters Health by email.
"We anticipate the procedure becoming standard practice in the coming years as more approved tests enter the market," he said.
"There will definitely be a learning curve with this test and interpretation of its results," Dr. Hendrix acknowledged. "This is one of the main reasons for publication of the appropriate use criteria - to help physicians understand the best use of the test."
As reported online October 10 in Alzheimer's and Dementia, the workgroup did a systematic review of the evidence and developed clinical indications for lumbar puncture and CSF analysis for "key patient groups." Six indications were rated "appropriate" by the group, and eight, "inappropriate."
According to the workgroup, "appropriate use" includes situations in which a patient:
- Has subjective cognitive decline and is considered to be at an increased risk for AD based on indicators such as a persistent decline in memory, symptom onset after age 60, onset in the last five years and others.
- Has mild cognitive impairment (MCI) that is persistent, progressive and unexplained.
- Has symptoms that suggest possible AD, meaning the dementia could be due to another cause.
- Has MCI or dementia with onset at an early age (<65).
- Meets core clinical criteria for probable AD with typical age of onset.
- Dominant symptom is an unexplained change in behavior, such as delusions and delirium, and an AD diagnosis is being considered.
Inappropriate use includes various situations in which a patient is not cognitively impaired; has subjective cognitive decline but is not at high risk for AD; has symptoms that suggest Parkinson's disease or Lewy body dementia; to determine disease severity in someone already diagnosed with AD; in lieu of genotyping for early-onset disease.
The workgroup could not recommend use of specific analytes, but when discussing the diagnostic value of biomarkers, they focus on CSF amyloid (A) b42 (sometimes normalized to a related peptide Ab40), t-tau and p-tau181.
"In anticipation of the emergence of more reliable CSF analysis platforms, the manuscript offers important guidance to health-care practitioners and suggestions for implementation and future research," the workgroup concludes.
Dr. Hendrix said, "There are many potential benefits to an early and accurate diagnosis. People may be misdiagnosed and not given the proper treatment, potentially leading to improper or inappropriate care and support."
"In addition," he noted, "the Alzheimer's research community now wants to test drugs on people who are in the early stages of the disease in order to see if progression can be stopped or slowed."
"Unfortunately, it is difficult to find people early in the course of the disease because they have few symptoms," he said. "This type of test could allow people to get into clinical trials and potentially have access to the most cutting-edge drug candidates earlier."
"There is a great deal of concern around the lumbar puncture procedure in the United States, despite it being a much more widely accepted procedure by patients and physicians in Europe," he said. "The Alzheimer's Association and workgroup members suggest that clinicians become familiar with these criteria now and anticipate using (lumbar puncture) in the near future."
Regenstrief Institute investigator Dr. Malaz Boustani, founder of the Indiana University Center for Health Innovation and Implementation Science in Indianapolis, told Reuters Health he "does not agree with the majority of the recommendations."
"The data about the accuracy of lumbar puncture-based biomarkers for AD diagnosis is not very high, with high false positives. The potential harms are not small, in addition to the cost of the procedure," he said by email.
"I will not consider using lumbar puncture for patients with subjective cognitive impairment or mild cognitive impairment," he stressed. "There are no data with high external validity to demonstrate added value for lumbar puncture in AD diagnosis on top of the current clinical practice."
With no (treatment) to reverse AD, the benefit / harms ratio of lumbar puncture is (too) close to call," he said. "The studies on the accuracy of lumbar puncture in AD have been in a very selective academic population, with low generalizability to the typical patient population."
"A validation study in a much more generalizable population capable of demonstrating added value for patients (is needed)," he concluded.
SOURCE: https://bit.ly/2ypRO41
Alzheimer's Dement 2018.
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