Are Alzheimer Biomarkers Clinically Relevant?

There’s been much ado about Alzheimer disease (AD) biomarkers for more than 2 decades, but can these biological indicators really aid clinical diagnosis and treatment?

Patients with AD have distinct cerebrospinal fluid (CSF) amyloid, total tau, and phosphorylated tau.¹ Correspondingly, guidelines include assessment of these biomarkers.^2-4

“CSF biomarkers have been included in the diagnostic criteria for AD, without any specific guideline on how to use them,” according to Dr Flora Duits of the Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. “This impreciseness brings along a risk of erroneous decision making by clinicians, based on incorrect interpretation of CSF biomarkers.”

In a recent study published in Alzheimer’s & Dementia, Duits and colleagues⁵ found that 23 of 351 diagnoses (7%) changed when assessment of CSF biomarkers was included. Diagnoses changed to no dementia, myocardial infarction, Alzheimer disease, other dementia, or unclear diagnosis.

Based on the CSF results, clinicians altered their AD management decisions in 13% of the patients. In addition, diagnostic confidence increased from 84% to 89%, a statistically significant effect. Diagnostic confidence was based on the neurologists’ self-rating, on a scale of 0% to 100%, of how sure they were of their diagnosis.

The study included patients who visited the VU University Medical Center Alzheimer’s disease clinic for cognitive screening within a period of 1 year. The average age was 63 years; 39% of the participants were women. The neurologists who examined the patients completed questionnaires both before and after receiving information about CSF biomarkers.

The study is unique in that it assesses biomarker use in an actual clinical setting. Dr Duits remarked on the pros and cons of this approach: “As we included all patients presenting at our clinic during 1 year, clinical impact may not be as large as suggested by previous studies, but our study probably gives a more realistic overview of the daily practice in a memory clinic.”

Dr Duits continued, “Our study suggests that CSF biomarkers have additional value on top of the standard diagnostic work-up of cognitive disorders and influence patient management in a subset of patients. Moreover, appropriate use criteria should be developed for CSF biomarkers, next to those of amyloid-PET imaging, which have already been published last year.”

Now that AD CSF biomarkers are established and recommended, more specific criteria for clinical use may follow. CSF biomarker assessment in AD could conceivably become a part of routine clinical practice.

Take-aways:

• AD guidelines include assessment of biomarkers.

• In 1 study, CSF biomarker assessment changed diagnosis in 7% of patients and management decisions in 13% of patients.

• This study demonstrates AD biomarker use in real clinical practice.

References:

1. Blennow K, Hampel H. CSF markers for incipient Alzheimer’s disease. Lancet Neurol. 2003;2:605-613.

2. Dubois B, Feldman HH, Jacova C, et al. Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol. 2010;9:1118-1127.

3. Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6:734-746.

4. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263-269.

5. Duits FH, Prins ND, Lemstra AW, et al. Diagnostic impact of CSF biomarkers for Alzheimer’s disease in a tertiary memory clinic. Alzheimers Dement. 2014 Aug 21. pii: S1552-5260(14)02461-3. doi: 10.1016/j.jalz.2014.05.1753. [Epub ahead of print]