Clinical Evaluation of the Revised Biological and Clinical Staging Criteria for Alzheimer Disease in China.

Abstract (English)

BACKGROUND AND OBJECTIVES: The 2024 revised criteria introduced an integrated framework for staging Alzheimer disease (AD) across biological and clinical dimensions. However, how this criterion characterizes clinical and biological features in populations outside the original development setting, particularly in non-Western and specialized clinic settings, remains insufficiently described. METHODS: We consecutively enrolled 1,214 memory clinic participants who underwent both amyloid-PET and tau-PET imaging. Among amyloid-positive (A+) individuals, clinical stages (0-6) and biological stages (A-D) were assigned according to the 2024 criteria. Participants were classified as typical (concordant stages), susceptible (clinical > biological), or resilient (clinical < biological). Plasma p-tau217 was measured in 379 A+ participants. Associations were examined using generalized linear models adjusted for relevant covariates, with false discovery rate correction for multiple comparisons. RESULTS: Among the 1,214 participants, 818 were amyloid positive, comprising 412 (50.4%) typical, 330 (40.3%) susceptible, and 76 (9.3%) resilient individuals. Plasma p-tau217 increased progressively across advancing tau PET stages (<i>p</i> for trend <0.001), with significantly higher levels in stage D (1.31 pg/mL) compared with stage A (0.56 pg/mL, <i>q</i> = 0.029) and stage C (0.95 pg/mL, <i>q</i> = 0.013). Compared with the typical group, resilient individuals demonstrated superior cognitive performance (e.g., Mini-Mental State Examination [MMSE]: &#x3b2; = 8.56, <i>q</i> < 0.001), higher educational attainment (>9 years: 74.1% vs 45.1%, <i>q</i> = 0.020), and greater AD-signature regional cortical thickness (<i>t</i> = 3.033, <i>q</i> = 0.005) and volume (<i>t</i> = 3.209, <i>q</i> = 0.003). Conversely, susceptible individuals exhibited inferior cognitive scores (e.g., MMSE: &#x3b2; = -8.29, <i>q</i> < 0.001), reduced cortical thickness (<i>t</i> = -2.872, <i>q</i> = 0.005), and volume (<i>t</i> = -2.751, <i>q</i> = 0.007) in AD-signature regions and a numerically higher burden of vascular risk factors. DISCUSSION: In a large cohort from a specialized tertiary memory clinic, clinical-biological stage discordance under the 2024 AD criteria was common among amyloid-positive individuals. Distinct cognitive, educational, biomarker, and neuroanatomic profiles characterized susceptible, typical, and resilient subgroups. In addition, plasma p-tau217 showed a stepwise increase across tau PET stages, supporting its utility as a blood-based marker of tau pathology severity. These findings support the clinical relevance of the revised staging framework and may inform future refinements of AD diagnostic guidelines. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the 2024 revised biological and clinical criteria for AD demonstrate clinical utility in a Chinese cohort from a specialized tertiary memory clinic.