Overview
This prospective, longitudinal observational cohort study will examine clinical, cognitive, blood-based, and neuroimaging features across the cognitive continuum. It will also assess whether these measures can distinguish disease stages and predict progression from mild cognitive impairment (MCI) to dementia.
The study will enroll 600 participants. These will include 200 individuals without cognitive impairment, 200 with MCI, and 200 with dementia. The MCI group will comprise participants with Alzheimer disease-related MCI and non-Alzheimer disease-related MCI. The dementia group will be further characterized by clinical subtype (Alzheimer disease-related versus non-Alzheimer disease-related).
At baseline, participants will undergo clinical evaluation, neuropsychological assessment, blood collection, and multimodal magnetic resonance imaging. Neuropsychological assessment, blood collection, and magnetic resonance imaging will be repeated at 12 months. No treatment will be assigned.
The analyses will compare biomarker profiles across the study groups and examine relationships among blood biomarkers, neuroimaging findings, and cognitive performance. Clinical, cognitive, genetic, blood-based, and neuroimaging measures will then be integrated to develop diagnostic and risk-prediction models.
Description
This prospective, longitudinal observational cohort study will characterize multidimensional biomarker profiles across the cognitive continuum. Its principal aim is to develop integrated approaches for disease classification and prediction of progression from mild cognitive impairment (MCI) to dementia.
The study will enroll 600 participants in three cohorts: approximately 200 cognitively unimpaired participants, 200 participants with mild cognitive impairment, and 200 participants with dementia. The mild cognitive impairment and dementia cohorts may include Alzheimer disease-related and non-Alzheimer disease-related clinical subtypes, without fixed enrollment quotas for these subtypes. No therapeutic intervention will be assigned.
Baseline evaluations will include demographic and clinical characterization, comprehensive neuropsychological testing, and blood collection. Participants will also undergo multimodal neuroimaging.
Blood-based analyses will assess established and exploratory biomarkers. Established measures will include amyloid beta 42 and phosphorylated tau 217. These biomarkers will be evaluated using chemiluminescent enzyme immunoassay, electrochemiluminescence immunoassay, immunoprecipitation-mass spectrometry, and single-molecule array platforms. Exploratory analyses will examine protein biomarkers, microRNA expression profiles, and lipid-metabolomic markers. Apolipoprotein E genotype will also be determined.
Blood collection, neuropsychological testing, and neuroimaging will be repeated at 12 months. Cross-sectional analyses will compare biomarker profiles across the study groups. Longitudinal analyses will characterize changes in cognition, circulating biomarkers, and neuroimaging measures.
Associations among blood biomarkers, neuroimaging measures, and clinical phenotypes will be examined using prespecified statistical methods. Multivariable statistical and machine-learning approaches will then be used to identify informative combinations of clinical, cognitive, genetic, blood-based, and neuroimaging features. These features will be incorporated into diagnostic and risk-prediction models for MCI, dementia, and progression from MCI to dementia.
Eligibility
Inclusion Criteria:
General criteria:
- Age 50 years or older.
- Male or female.
- Able and willing to comply with the study assessments and follow-up procedures.
- Able to provide written informed consent, or written informed consent is provided by a legally authorized representative when applicable.
Dementia cohort:
- Diagnosis of dementia established by consensus among three senior neurologists with experience in cognitive disorders.
- Clinical Dementia Rating score of 1 or higher.
- Availability of a Chinese-speaking caregiver who can provide information about the participant's clinical condition and who lives with or has contact with the participant for at least 4 days per week.
Mild cognitive impairment cohort:
- Diagnosis of mild cognitive impairment established by consensus among three senior neurologists with experience in cognitive disorders.
- Clinical Dementia Rating score of 0.5.
- Availability of a Chinese-speaking caregiver who can provide information about the participant's clinical condition and who lives with or has contact with the participant for at least 4 days per week.
Cognitively unimpaired cohort:
- No history of a major neurological or psychiatric disorder.
- Clinical Dementia Rating score of 0.
Exclusion Criteria:
- An acute neurological disorder, including acute stroke, or another medical or neurological condition that would prevent valid assessment of cognitive status.
- A severe psychiatric disorder that would interfere with cognitive assessment or study participation.
- Terminal malignant disease or another severe medical condition that would prevent completion of the study procedures.
- Severe visual or hearing impairment that would interfere with neuropsychological assessment.
- Inability or unwillingness to complete the planned 12-month follow-up.
