The Diagnostic and Prognostic Role of Plasma Biomarkers in Alzheimer's Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 2,000
- 试验地点
- 1
- 主要终点
- Time to progression to all-cause dementia in MCI patients (primary prognostic endpoint)
研究概览
简要总结
BLAD is a prospective, monocentric, observational epidemiological study with an additional procedure (annual blood draw) evaluating the diagnostic and prognostic performance of plasma biomarkers for Alzheimer's disease (AD) in a large cohort of patients attending the Cognitive Disorders and Dementia Center (CDCD) at IRCCS San Raffaele Hospital, Milan, Italy.
2000 patients will be enrolled and followed annually for 5 years. A validation sub-study (150 patients) will compare plasma biomarkers against CSF biomarkers as the gold standard.
The study aims to establish plasma biomarkers as a less invasive and more cost-effective alternative to CSF analysis and amyloid-PET for the diagnosis and prognosis of AD.
详细描述
In light of the possible advent of disease-modifying drugs for Alzheimer's disease (AD), reliable biomarkers have been developed in recent years to define the presence of AD pathology at the brain level. The current biological gold standards are cerebrospinal fluid (CSF) biomarkers (CSF-Abeta40, CSF-Abeta42, CSF-pTau, CSF-NfL) and amyloid-PET. Both methods have excellent diagnostic properties but are costly and invasive, limiting their use outside of highly specialized centers.
Plasma biomarkers (plasma-Abeta40, plasma-Abeta42, plasma-pTau-181, plasma-NfL, plasma-ApoE, plasma-ApoE4, plasma-GFAP, plasma-sTREM2, and other plasma neurodegeneration biomarkers) represent a potentially less invasive and more economically accessible alternative. Recent studies have shown that plasma biomarkers can differentiate AD from other neurodegenerative disorders with accuracy comparable to CSF and PET, detect AD pathology in MCI patients, and predict future development of AD dementia in patients with SCD or MCI. However, more research is needed before their widespread use in clinical practice.
The BLAD study is designed as a monocentric, prospective, observational epidemiological study with an additional procedure (annual blood draw for 5 years) and a diagnostic accuracy sub-study (not device-based).
Patients will be recruited among those attending the Cognitive Disorders and Dementia Center (CDCD) at IRCCS San Raffaele Hospital during routine clinical practice. All enrolled patients will undergo annual blood sampling for 5 years in addition to standard clinical assessments.
A sub-population of 150 patients who undergo lumbar puncture as part of their routine diagnostic workup will enter the validation sub-study. Only those whose CSF biomarkers confirm a biological diagnosis of Alzheimer's disease will continue follow-up; others will exit the sub-study.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(main study and sub-study):
- •Age greater than or equal to 40 years (patients of childbearing age are admitted).
- •Subjective or objective cognitive complaints, progressive in nature and of suspected neurodegenerative origin.
- •Mini-Mental State Examination (MMSE) score greater than or equal to
- •Additional inclusion criterion for the validation sub-study:
- •Availability of CSF biomarkers for Alzheimer's disease within 6 months of the blood draw.
排除标准
- •(main study):
- •Secondary forms of cognitive impairment based on medical history, neurological examination, and neuroimaging findings.
- •Pregnancy or breastfeeding.
- •Rapidly progressive cognitive decline occurring over weeks or months, typically indicative of prion disease, neoplasia, or metabolic disorders.
- •Subjects who require a legal guardian or tutor.
- •Exclusion Criteria (validation sub-study):
- •Secondary forms of cognitive impairment based on medical history, neurological examination, and neuroimaging findings.
- •Rapidly progressive cognitive decline occurring over weeks or months, typically indicative of prion disease, neoplasia, or metabolic disorders.
- •Subjects who are unable to give informed consent and require a legal guardian or tutor.
结局指标
主要结局
Time to progression to all-cause dementia in MCI patients (primary prognostic endpoint)
时间窗: Annually from baseline up to 5 years
Time to clinical progression to all-cause dementia in patients with Mild Cognitive Impairment (MCI) at baseline, assessed using multivariable Cox proportional hazards models. For each plasma biomarker, patients are divided into two groups (above/below the median) and compared using the log-rank test (cause-specific hazard). The study has greater than 95% power to detect a Hazard Ratio of 2 and approximately 75-80% power for HR of 1.5.
次要结局
- Change in MMSE score over time(Annually from baseline up to 5 years)
- Conversion from MCI to Alzheimer's disease dementia(Annually from baseline up to 5 years)
- Longitudinal change in plasma Abeta42/Abeta40 ratio(Annually from baseline up to 5 years)
- Longitudinal change in plasma pTau-181 levels(Annually from baseline up to 5 years)
- Longitudinal change in plasma NfL levels(Annually from baseline up to 5 years)
- Longitudinal change in plasma GFAP levels(Annually from baseline up to 5 years)
- Longitudinal change in plasma sTREM2 levels(Annually from baseline up to 5 years)
- Longitudinal change in plasma Abeta40 levels(Annually from baseline up to 5 years)
- Longitudinal change in plasma Abeta42 levels(Annually from baseline up to 5 years)
研究者
Prof. Massimo Filippi
Prof, MD
IRCCS San Raffaele