How Can Neurologists Use Alzheimer’s Disease Biomarkers in Clinical Practice?

LONDON—The Alzheimer’s Biomarkers in Daily Practice (ABIDE) project may help neurologists to choose diagnostic tests, select proper treatment, and effectively communicate with patients who have suspected Alzheimer’s disease, according to an overview presented at the 2017 Alzheimer’s Association International Conference. Furthermore, biomarkers may enable neurologists to predict individual progression, target underlying proteinopathy, and measure progression.

Phillip Scheltens, MD, PhD

“Ultimately, biomarkers will help us to prevent Alzheimer’s disease if we start as soon as possible,” said Phillip Scheltens, MD, PhD, Director of the Alzheimer Center at the VU University Medical Center in Amsterdam.

The advent of MRI and the discovery of CSF biomarkers and amyloid PET are among the greatest successes in Alzheimer’s disease research, allowing diagnosis at an earlier stage of the disease, Dr. Scheltens said. Established and promising biomarkers for Alzheimer’s disease include Abeta_1–42, total tau, p-tau₁₈₁, NF-L, neurogranin, and VILIP-1. Further research has characterized probable Alzheimer’s disease in its prodromal stage, defined different phenotypes of Alzheimer’s disease, and offered insights into the rate of decline based on biomarker profiles.

Despite a wealth of literature on Alzheimer’s disease biomarkers, there remains a gap between the scientific value and the actual utilization of biomarkers in daily clinical practice. “Translating research findings to individual patients in daily practice is difficult, as the prognostic value of each biomarker may vary with, for example, age, gender, and cognitive status,” said Dr. Scheltens and colleagues. “Moreover, when combining biomarkers, interpretation becomes complicated, especially when they are not clearly positive, negative, or even conflicting.” Also, little is known about patients’ preferences towards diagnostic testing and the best ways to communicate test results to patients and caregivers.

ABIDE Study and New App

To address these concerns, Dr. Scheltens and colleagues started the ABIDE study, an ongoing four-year project with a goal of determining what biomarkers mean for clinical practice, what patients think about biomarkers, and how to engage patients to determine which biomarkers to use.

In one of the ABIDE substudies, researchers are using retrospective data to develop personalized risk estimates for patients with mild cognitive impairment (MCI). In addition, investigators are using quantitative and qualitative research methods to collect MRI and CSF data from 200 patients from local memory clinics and amyloid PET from 500 patients in tertiary settings. Ultimately, the study will help to create practical tools for clinicians and improve interpretation and communication of results. The investigation also focuses on the impact of disclosing amyloid positivity or negativity with patients. For this study, the researchers used an anxiety–uncertainty questionnaire and found that anxiety level did not change after disclosure of PET results. “Even if the result is not positive, patients felt less uncertain and somewhat assured,” Dr. Scheltens said.

The researchers used what they have learned thus far to develop the Addapt app, a new tool based on statistical and predictive modeling to help clinicians determine the most useful tests and imaging to perform and which biomarkers are most informative for a given patient. “You can look at the results of the individual, and it can help you to decide, for example, if it will be helpful to do a CSF or to do another PET scan,” said Dr. Scheltens.

A Need for New Criteria

The evolution of biomarker research has resulted in new diagnostic criteria and proposed guidelines. The National Institute on Aging (NIA) and the Alzheimer’s Association (AA) have developed the 2018 NIA-AA Research Framework to Investigate the Alzheimer’s Disease Continuum. By incorporating new scientific insights and technological advances, the new guidelines aim to improve current diagnosis, strengthen autopsy reporting of Alzheimer’s brain changes, and establish a research agenda for future progress in earlier detection and greater diagnostic accuracy.

Three of the new guidelines focus on three stages of Alzheimer’s disease: dementia due to Alzheimer’s disease, MCI due to Alzheimer’s disease, and preclinical (ie, presymptomatic) Alzheimer’s disease. The fourth guideline updates criteria for documenting and reporting Alzheimer’s disease-related changes observed during an autopsy. Unlike previous guidelines, the 2018 criteria will not require clinical symptoms to diagnose Alzheimer’s disease. In addition, the new guidelines state that the presence of both amyloid and tau protein pathology is indicative of Alzheimer’s disease.

New Research and the Future of Biomarkers

Despite all the advances in biomarker research, there is still work to do, said Dr. Scheltens. Analytical issues, clinical validation, clinical utility, ethical issues, and reimbursement still need to be addressed, he added. “We have to educate not only the patients, but more importantly, the physicians, on how to work with biomarkers, how to interpret biomarkers, and when to use them and when not to use them,” said Dr. Scheltens. “Hopefully we will experience patients who survive Alzheimer’s disease if we have the right drugs at the right doses at the right moment.”

—Erica Tricarico

Suggested Reading

de Wilde A, van Maurik IS, Kunneman M, et al. Alzheimer’s biomarkers in daily practice (ABIDE) project: Rationale and design. Alzhiemers Dement (Amst). 2017;6:143-151.

Frisoni GB, Boccardi M, Barkhof F, et al. Strategic roadmap for an early diagnosis of Alzheimer’s disease based on biomarkers. Lancet Neurol. 2017;16(8):661-676.

Morbelli S, Bauckneht M, Scheltens P. Imaging biomarkers in Alzheimer’s disease: added value in the clinical setting. Q J Nucl Med Mol Imaging. 2017 Jul 17 [Epub ahead of print].

van Maurik IS, Zwan MD, Tijms BM, et al. Interpreting biomarker results in individual MCI patients - the ABIDE project. JAMA Neurol. In press.