Overview
The China HEalthy Aging and Dementia (HEAD) study is a large-scale, community-based, multi-center prospective cohort study covering eastern, northern, southern, and central-western regions of China. By integrating comprehensive clinical, neuroimaging, biospecimen, and multi-omics data, the study aims to advance the early prediction and diagnosis of Alzheimer's disease and related dementias (ADRD) and provide a foundation for future intervention studies in the Chinese population.
The primary aims of the China HEAD study are as follows:
- To establish a community-based prospective cohort by recruiting over 20,000 participants from eastern, northern, southern, western, and middle regions of China.
- To build a comprehensive biobank by collecting demographic information, disease history, cognitive function, physical measures, electrophysiologic data, multimodal imaging data, as well as biospecimens and derived multi-omics data.
- To conduct early prediction and diagnosis studies for ADRD and support future intervention studies based on the above-mentioned cohort and biobank.
Description
The China HEalthy Aging and Dementia (HEAD) study is a large prospective community study aiming to recruit 20,000 participants. The participants are recruited from 14 provinces distributed in eastern, northern, southern, western, and middle regions of China by investigators from 33 centers. The study was approved by the Ethics Committee of Huashan Hospital of Fudan University with approval number KY2022-879. Written informed consent is obtained from each participant at recruitment.
At baseline, all participants undergo questionnaires, neuropsychological assessment, physical measures, and biospecimen collection. Part of the participants further receive electrophysiologic and imaging examinations. Long-term follow-up is planned for up to 50 years, with assessments conducted approximately annually, subject to participant availability and continued participation. Biospecimen collection and imaging examinations are performed as feasible and are not necessarily repeated at every follow-up visit.
The main research contents are as follows:
- Cohort establishment and cognitive aging research. The HEAD study aims to establish a nationwide community-based prospective cohort and investigate the natural progression of cognitive aging, cognitive impairment, and Alzheimer's disease and related dementias (ADRD) in the Chinese population. The study will investigate cognitive changes and the progression from normal cognition to mild cognitive impairment (MCI) and dementia through longitudinal follow-up.
- Questionnaires and neuropsychological assessment. A standardized questionnaire administered by trained interviewers is used to collect demographic information, lifestyle and environmental factors, family history, disease history, medication intake, and the status of specific peripheral organs. The HEAD cohort evaluates cognition, emotion, living ability, and sleep quality with a battery of neuropsychological tests. Global cognitive function is assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Cognitive subdomains including memory, working memory, attention, executive function, visuospatial function, and language are assessed using standardized neuropsychological tests. Emotional status, activity of daily living, and sleep quality are also evaluated.
- Physical measures and biospecimen collection. Anthropometric and hemodynamic parameters, including height, weight, neck circumference, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, and pulse rate, are measured according to standardized protocols. All enrolled participants are consented to the collection of blood, urine, and stool. Some participants also provide mucosal secretions, including nasopharyngeal swabs, tears, and saliva, while a subset undergoes lumbar puncture for cerebrospinal fluid (CSF) collection. All biospecimens are collected, processed, transported, and stored according to standardized protocols.
- Electrophysiologic and imaging examinations. Some participants undergo electrophysiologic examinations, including electrocardiography (ECG) and electroencephalography (EEG). Participants without contraindications to magnetic resonance imaging (MRI) are offered multimodal brain MRI scans, including structural MRI, diffusion tensor imaging (DTI), resting-state functional MRI (fMRI), arterial spin labeling (ASL), and quantitative susceptibility mapping (QSM). Positron emission tomography (PET) scans are also provided to detect cerebral amyloid-β (Aβ) and tau deposition and glucose metabolism. Additional examinations include carotid artery ultrasound, echocardiography, abdominal ultrasound, lower extremity vascular ultrasound, and dual-energy X-ray absorptiometry (DXA) assessment.
- Biospecimen assays and multi-omics studies. The collected biospecimens are used for routine laboratory examinations, AD biomarker measurements, and multi-omics investigations. The detection of core AD biomarkers in plasma and CSF is performed using standardized protocols, mainly based on single molecule array (SIMOA) technology and enzyme-linked immunosorbent assay (ELISA). The biomarkers include Aβ1-42, Aβ1-40, phosphorylated tau (p-tau) 181, p-tau 217, total tau (t-tau), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Whole-genome sequencing (WGS), transcriptomics, proteomics, metabolomics, metagenomics, and epigenomics are also performed to investigate the molecular characteristics of ADRD.
- Risk factors and prediction study. The risk factors for ADRD incidence and progression will be investigated, incorporating both cross-sectional data across different stages of ADRD and longitudinal data. Genetic factors detected in genome sequencing and modifiable factors, mainly extracted from questionnaires and physical measures, are considered. Based on identified factors, the study aims to establish a generalizable risk prediction model for ADRD.
- Biomarkers and diagnosis study. Fluid and imaging biomarkers will be screened and validated for early and precise diagnosis of ADRD. Based on identified biomarkers, diagnostic criteria will be developed and compared with the well-accepted amyloid-β, tau, and neurodegeneration (ATN) framework.
Eligibility
Inclusion Criteria:
China HEAD Community Cohort:
- Resident in a Chinese community.
- Aged 50-79 years.
- Have adequate vision and hearing (with glasses or hearing aids if necessary), and be able to walk, communicate, and complete study-related assessments (including questionnaires, physical examinations, neuropsychological assessments, and biospecimen collection) independently or with assistance.
- Willing to provide written informed consent for baseline assessments, follow-up, biospecimen donation, and data collection.
China HEAD Familial Sub-cohort:
- Resident in a Chinese community.
- Aged 18 years or older.
- Have a family history of Alzheimer's disease (AD) involving at least two first-degree relatives across at least two consecutive generations, with AD diagnoses previously established at tertiary hospitals and verified through medical history.
- Meet the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) diagnostic criteria for AD.
- Have adequate vision and hearing (with glasses or hearing aids if necessary), and be able to walk, communicate, and complete study-related assessments (including questionnaires, physical examinations, neuropsychological assessments, and biospecimen collection) independently or with assistance.
- Willing to provide written informed consent for baseline assessments, follow-up, biospecimen donation, and data collection.
Exclusion Criteria:
The following exclusion criteria apply to participants in the HEAD study:
- Refusal to provide written informed consent.
- Refusal to participate in questionnaires or other data collection procedures.
- Refusal to provide blood or other biological samples.
- Self-reported stroke events (e.g., cerebral hemorrhage or cerebral infarction) within the past six months.
- Self-reported diseases potentially impairing cognition, including congenital intellectual disability, intracranial tumors, epilepsy, Parkinson's disease, or severe psychiatric disorders such as schizophrenia requiring medication.
- Self-reported major organ failure (e.g., liver or kidney failure), malignancy, or other conditions associated with a shortened life expectancy that prevent completion of follow-up assessments.
Additional exclusion criteria for participants undergoing magnetic resonance imaging (MRI):
1\. Inability to tolerate MRI examinations or contraindications to MRI, including claustrophobia; MRI-incompatible implanted pacemakers, aneurysm clips, artificial heart valves, cochlear implants, or other metallic implants; or other clinical conditions or examination findings that investigators consider potentially harmful during MRI.
