Study on Clinical Characteristics of Patients With Probable Alzheimer's Dementia Stratified by Blood Biomarkers

This is a prospective observational study conducted at Tianjin Anding Hospital. A total of patients with probable Alzheimer's disease will be enrolled over a 3-year recruitment period. Participants will be stratified into p-Tau217-negative, p-Tau217-positive and grey-zone groups according to validated plasma p-Tau217 cut-off values. Baseline assessments include demographic data, physical examination, neuropsychological scales such as MMSE, MoCA, NPI, CDR, ADL, CBI and CGI, as well as brain MRI and Aβ-PET imaging. Peripheral blood samples will be collected for detection of Aβ42, Aβ40, Aβ42/40 ratio, p-Tau217, NfL, GFAP and ApoE genotyping. Subjects will receive routine clinical management without restricted study-specific medications, and follow-up evaluations will be performed at 6-, 12- and 18-month time-points. The primary objective is to compare differences across all 12 dimensions of the Neuropsychiatric Inventory (NPI) between p-Tau217-negative and p-Tau217-positive groups, and to compare the incidence of cognitive decline, new-onset severe behavioral and psychological symptoms of dementia (BPSD), cerebrovascular events and hospitalizations during follow-up. The exploratory objective is to develop a simple prognostic risk stratification model combining baseline BPSD profiles, white-matter hyperintensity burden on imaging and blood biomarkers including NfL, IL-6 and GFAP among p-Tau217-negative participants, with subsequent validation required for this exploratory analysis. Eligible participants are aged 50-90 years, meeting 2011 NIA-AA criteria for probable Alzheimer's disease dementia, with MMSE score <24, CDR>0.5 and Hachinski Ischemic Scale ≤4. Subjects with other definite neurocognitive disorders, severe unstable systemic or neurological diseases will be excluded. This study has been approved by the Ethics Committee of Tianjin Anding Hospital. All participants or their legal guardians will provide written informed consent prior to any study-related procedures. All analyses will be performed based on collected longitudinal clinical, imaging and laboratory data.