The Alzheimer's Association has released revised criteria for the diagnosis and staging of Alzheimer's disease, incorporating the latest scientific advancements in biomarkers and reflecting a shift towards a biological definition of the disease.
The revised criteria published in the Association's journal Alzheimer's & Dementia, emphasize that Alzheimer's Disease (AD) should be defined biologically rather than based on clinical symptoms alone. The disease is now considered a continuum that begins with changes in the brain associated with AD pathology in asymptomatic individuals, progressing through stages of increasing disease-related brain changes, and eventually leading to the appearance and progression of clinical symptoms.
Under the new criteria, AD is diagnosed in patients by abnormalities in core biomarkers, which are categorized as either early-changing (Core 1) or later-changing (Core 2). Core 1 biomarkers, such as amyloid positron-emission tomography (PET), approved cerebrospinal fluid biomarkers, and accurate plasma biomarkers, are considered sufficient to establish an AD diagnosis. Core 2 biomarkers, including biofluid and tau PET, provide prognostic information and increase confidence that AD is contributing to symptoms when abnormal.
The criteria also introduce an integrated biological and clinical staging scheme that accounts for the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages. Importantly, the criteria do not currently support the evaluation of AD-related brain changes in asymptomatic individuals for clinical care purposes outside of research studies.
The integrated staging scheme uses a combination of amyloid PET and tau PET or Core 1 fluid biomarkers plus tau PET. It defines four biological stages: A (initial stage), B (early-stage), C (intermediate-stage), and D (advanced-stage). These biological stages are then integrated with the previously established numeric clinical staging, ranging from Stage 0 (asymptomatic, deterministic gene) to Stage 6 (severe dementia).
Furthermore, the revised criteria acknowledge the importance of identifying comorbid pathologies, such as cerebrovascular disease, neuronal synuclein disease, and limbic-associated TAR DNA-binding protein 43 encephalopathy. Multimodal biomarker profiles, using a combination of core AD and noncore biomarkers, can help characterize individuals with comorbid pathologies, which may have implications for prognosis and treatment decisions.
The Alzheimer's Association convened a workgroup of experts, chaired by Clifford Jack, M.D. of the Mayo Clinic, to translate the 2011 diagnostic guidance and the 2018 research framework into the newly proposed diagnostic criteria. The workgroup presented their work at several scientific conferences and incorporated public feedback before finalizing the criteria.
The Association plans to collaborate with clinical experts, methodologists, external organizations, and patient representatives to develop guidelines for the clinical implementation of the new AD staging criteria and treatment. This work is set to begin later in 2024.
