Drug Development.

Area of Science:

• Neurology
• Biomarker Research
• Geriatric Medicine

Background:

• Biomarkers of Alzheimer's pathology (BAP) enable new diagnostic considerations for at-risk, asymptomatic individuals.
• International Working Group (IWG) updated recommendations emphasize a patient-centered approach, integrating clinical evaluation with risk factors, biomarkers, and genetics.
• Risk stratification and tailored patient journeys are key components of the updated IWG guidelines.

Purpose of the Study:

• To review and update recommendations for diagnosing and managing individuals at risk for Alzheimer's disease (AD) based on biomarkers.
• To establish a risk stratification framework for cognitively unimpaired individuals with BAP.
• To guide clinical management and research priorities for different risk groups.

Main Methods:

• An evidence review of literature published between July 2020 and March 2024 was conducted.
• The review focused on various biomarker search terms related to Alzheimer's disease (AD) and cognitively unimpaired individuals.
• Papers examining near-term and lifetime risks of AD dementia progression in relation to BAP patterns were analyzed.

Main Results:

• A risk stratification framework was developed, classifying individuals as "Asymptomatic At-Risk" or "Presymptomatic".
• Most cognitively unimpaired individuals with BAP, including amyloid positivity, will not develop clinical AD.
• The "Presymptomatic" group includes those with genetic mutations, Down syndrome, or specific tau PET biomarker patterns indicating a high likelihood of clinical AD expression.

Conclusions:

• Diagnosis of Alzheimer's disease (AD) should not be based solely on biomarkers without clinical expression.
• The IWG risk stratification classification supports tailored management approaches and individualized patient journeys.
• Urgent prioritization of preventive disease-modifying treatments is recommended for the "Presymptomatic" group.