CNSA White Paper Advocates for Earlier Detection of Alzheimer’s Using Biomarkers

Due to the availability of amyloid-reducing therapies, it is critical to use biomarkers to detect Alzheimer disease (AD) in its early stages, according to a new comprehensive Clinical Proceedings White Paper published by the Clinical Neurological Society of America (CNSA). The white paper titled “Alzheimer’s Disease: Understanding its Impact & Trend Toward Biological Diagnosis” was developed by an expert panel, including:

• Marissa Natelson Love, MD (Clinical Proceedings Chair)
• Ryan Darby, MD
• James Eaton, MD
• Mary Ellen Koran, MD
• R. Scott Turner, MD, PhD

The white paper provides commentary on the current state of AD in the United States, including details related to the burden of the disease on patients, families, and the healthcare system, and the importance of reducing barriers to early diagnosis to meet windows for treatment with amyloid-reducing therapies.

Details provided in the report about the burden of AD include:

• The increasing prevalence of AD in the United States, projected to double by 2060.
• AD’s devastating symptoms affecting memory, cognitive function, neuropsychiatric symptoms, and quality of life.
• The impact of the condition on caregivers and family members.
• AD’s disease course, characterized by progression through stages.
• The significant and growing economic burden of AD and other dementias in the United States, projected to reach $1.4 trillion by 2050.

In terms of barriers to earlier detection and diagnosis for AD, the authors discuss:

• Cerebrospinal fluid (CSF) testing, which patients may be reluctant to receive due to cost and invasiveness
• PET and MRI, which are expensive and time-consuming procedures that require specialized equipment and expertise to perform
• Concerns about the generalizability and validity of biomarker blood tests
• The amount of time required to provide a clinical diagnosis of AD
• A patient’s reluctance to receive care due to AD’s cogntivie and memory symptoms
• Ethical concerns associated with an early biological diagnosis of AD, including impacts on employment and insurance

Amyloid-targeting therapies, including Leqembi (lecanemab-irmb; Eisai, Tokyo, Japan; Biogen, Cambridge, MA) and Kisnula (donanemab; Eli Lilly and Company, Indianapolis, IN) are indicated for the treatment of early AD. The limited window for treatment demonstrates the importance of providing earlier diagnoses of AD before progression to moderate dementia, at which point patients would no longer qualify to receive these medications.

"The trend toward more significant use of biomarkers to detect Alzheimer's disease will help us get patients on therapy earlier in the disease before it progresses, improving their quality of life and that of their family and caregivers,” said Dr. Natelson Love, Clinical Proceedings Chair of the University of Alabama at Birmingham Heersink School of Medicine.

In a recent publication in JAMA Neurology, the International Working Group (IWG) recommended against a solely biological approach to diagnosing AD, instead suggesting that early biomarker testing for cognitively normal individuals be implemented only for the purpose of evaluating, communicating, and reducing risk.

The publication of the white paper was supported with funding from Esai (Tokyo, Japan) and Eli Lilly and Company (Indianapolis, IN).