Overview
This is a prospective, observational cohort study. The primary objective is to characterize the clinical features and mechanisms of behavioral and psychological symptoms of dementia (BPSD) in patients with probable Alzheimer's disease (AD) who are plasma p-Tau217 negative, and to compare them with p-Tau217-positive patients. After grouping participants by an authoritative p-Tau217 cutoff value, the negative and positive groups will be systematically compared across all 12 domains of the Neuropsychiatric Inventory (NPI). Participants will be followed up at 6, 12, and 18 months to compare the incidence of cognitive decline, new-onset severe BPSD (hallucinations, agitation/aggression, depression, etc.), cerebrovascular events, and hospitalization between the two groups. As an exploratory objective, baseline BPSD domains combined with imaging (white matter hyperintensity burden) and blood biomarkers (NfL, IL-6, GFAP, etc.) will be used to construct a simple prognostic risk-stratification model within the negative group and to validate its predictive performance. The study aims to improve the recognition of non-AD-driven dementia with overlapping clinical presentations, thereby informing clinical management and care planning in the era of biology-based AD diagnosis.
Description
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.
Eligibility
Inclusion Criteria:
- Aged between 50 and 90 years, without gender restriction;
- Meet the diagnostic criteria for probable Alzheimer's disease dementia (probable AD) proposed by the National Institute on Aging and Alzheimer's Association (2011 NIA-AA);
- Mini-Mental State Examination (MMSE) score \< 24;
- Clinical Dementia Rating (CDR) score \> 0.5;
- Hachinski Ischemic Scale score ≤ 4 (to exclude prominent vascular contributions);
- Understand the entire study procedure; written informed consent is obtained from participants or their legal guardians.
Exclusion Criteria:
- Established diagnosis of vascular dementia, frontotemporal dementia, dementia with Lewy bodies, or neurocognitive disorders attributable to other etiologies;
- Concomitant definite neurological diseases;
- Presence of severe and unstable somatic diseases involving the respiratory, circulatory, immune, endocrine or other systems.
