New AUC for Lumbar Puncture, CSF Testing in Diagnosis of Alzheimer Disease

James Hendrix, PhD, Director, Global Science Initiatives, Alzheimers Association

James Hendrix, PhD

The Alzheimer’s Association convened a multidisciplinary workgroup to develop and publish new appropriate use criteria (AUC) guiding safe use of lumbar puncture and spinal fluid analysis for Alzheimer disease pathology detection in the diagnostic process, finalizing 14 indications, rating 6 appropriate and 8 inappropriate.¹

The AUC were developed to aid health care practitioners on the appropriate and inappropriate use of lumbar puncture to optimize patient safety and care. While developing the criteria, the workgroup evaluated the appropriateness of a wide range of clinical indications based on a review of current evidence, experience of members with cerebrospinal fluid (CSF) testing and ethical standards of patient care. These efforts complement the recently published AUC for amyloid positron emission technology (PET) and CSF recommendations.^2,3

“I think the AUC builds off of other guidelines and criteria for Alzheimer disease, one particularly that was published several years ago for amyloid PET imaging,” James Hendrix, PhD, Director, Global Science Initiatives, Alzheimer’s Association, told NeurologyLive in an interview. “This one is a little bit more expansive and not only does it include people that are difficult to diagnose, but it also adds for people that have subjective cognitive decline and have an additional risk factor maybe family history or something else.”

The discussion of the appropriateness or inappropriateness of these indications is intended to aid dementia experts in making decisions regarding tests and help primary care and other clinicians in determining when to refer to a dementia expert for specialized testing.

While this AUC recommends the use of CSF biomarker testing for 6 clinical indications considered appropriate, the decision to use CSF testing is also based on the clinical judgment of the provider and the patient’s situation. The use of advanced biomarker testing may not be needed where the clinician’s diagnostic confidence is high.

“Clinicians should understand that this is not a screening test or a first line test, this is something that really should be done by a dementia expert or a neurologist or gerontologist, somebody who has a pretty strong knowledge of Alzheimer and dementia and can diagnose and interpret the results when they come,” Hendrix added. “It could be that a primary care physician has a patient they are trying to diagnose or trying to obtain a more precise diagnosis, but they’re going to have to refer them to a specialist and the specialist would then determine if a CSF test is appropriate for that type of patient.”

The lumbar puncture AUC recommend clinicians consider the following patient populations as appropriate and inappropriate:

Appropriate uses of lumbar puncture:

• Those with subjective cognitive decline (SCD) and are considered to be at an increased risk for Alzheimer disease
• Those with mild cognitive impairment (MCI) that is persistent, progressive and unexplained.
• Symptoms suggesting possible Alzheimer disease.
• Those with MCI or dementia with onset at an early age (<65).
• Meeting core clinical criteria for probable Alzheimer disease with typical age of onset.
• Those with a dominant symptom of an unexplained change in behavior, such as delusions and delirium where an Alzheimer disease diagnosis is being considered.

Inappropriate uses of lumbar puncture:

• Cognitively unimpaired and within the normal range of functioning for age and lacks significant risk factors for Alzheimer disease.
• Cognitively unimpaired but is considered to be at risk for Alzheimer disease based on family history.
• Those with SCD that have been evaluated and found by a clinician not to be at high risk for Alzheimer disease.
• Symptoms of rapid eye movement (REM) sleep behavior disorder.
• Apolipoprotein E-e4 (ApoE-e4) carriers with no cognitive impairment.
• The test is being used to determine the severity of a previously diagnosed patient with Alzheimer.
• The test is being used in lieu of genotyping for suspected carriers autosomal dominant Alzheimer disease (ADAD).
• ADAD mutation carriers with or without symptoms.

“This AUC says that people with subjective cognitive decline are experiencing some memory problems or some other symptoms that are concerning to them, but they might actually test normally on a traditional cognitive test and what this says is that if they have other risk factors physicians should take that seriously and do further follow up,” Hendrix mentioned. “And that’s new, and that’s something that is important. Physicians should take the concerns of their patients seriously when it comes to their brain health and memory loss. They shouldn’t just say “That’s normal aging” or “Don’t worry about it, come back and see me in 6 months or a year and we’ll see how you’re doing,” those sorts of strategies can lead to really bad outcomes and we should take the concerns that people have seriously.”

The workgroup emphasizes that while CSF testing can provide important information, it doesn’t substitute for a careful history and clinical examination. Informed consent for CSF biomarker testing should include a careful discussion about the potential results and impact on clinical and nonclinical decisions.

“Sometimes people ask why I should get an earlier/accurate diagnosis of Alzheimer disease when there’s no good drugs out there,” Hendrix noted. “If people don’t get diagnosed, they can have problems later and there’s a lot of bad things that can happen if people don’t get the proper care and support. The Alzheimer field as a whole is interested in trying to test drugs on people at the earlier stage of disease and the problem has been finding those people, because they have few or no symptoms, but if we can have a test like this become more widely available, then maybe those who get the test, one of the actions they might take is to sign-up for clinical trials and then they’d have access to the most cutting-edge, exciting drug candidates that are available, and not only might that help the patient in their fight against Alzheimer, but it would also help the scientific community in better evaluating these candidates and learning if the strategy of early intervention would work.”

Photo credit: Alzheimer's Association

REFERENCES

1. Shaw L, Arias J, Blennow K, et al. Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer’s disease. Alzheimer’s and Dementia. 2018;1—17.

doi

: 10.1016/j.jalz.2018.07.220.

2. Simonsen AH, Herukka SK, Andreasen N, et al. Recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia. Alzheimer’s and Dementia. 2016; 13:274—84. Doi: 10.1016/j.jalz.2016.09.008.

3. Herukka SK, Simonsen AH, Andreasen N, et al. Recommendations for cerebrospinal fluid Alzheimer’s disease biomarkers in the diagnostic evaluation of mild cognitive impairment. Alzheimer’s and Dementia. 2016;13(3):285—95.

doi

: 10.1016/j.jalz.2016.09.009.