Ultra-high Field Multimodal and Multinuclear Neuroimaging Cohort Study of Alzheimer's Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 750
- 试验地点
- 1
- 主要终点
- Change from Baseline in Regional Brain Sodium Concentration (mmol/L) Measured by 7 T ²³Na-MRI
研究概览
简要总结
This single-center prospective cohort study will enroll 750 participants (250 cognitively Normal (CN) individuals, 250 with mild cognitive impairment (MCI), and 250 with Alzheimer's disease (AD)). At baseline and at annual follow-ups, participants will undergo 3 Tesla (3 T) and 7 Tesla (7 T) multimodal magnetic resonance imaging (MRI) scans, blood biomarker testing, genotyping, and cognitive assessments to identify early imaging biomarkers and construct models of disease progression.
详细描述
This prospective, single-center cohort will enroll 750 participants (normal controls, MCI, and AD) for at least four years of follow-up. Using ultra-high field 7T multimodal and multinuclear (hydrogen-1 [¹H], sodium-23 [²³Na]) MRI, combined with plasma biomarkers and genetic data, the study aims to identify early neuroimaging biomarkers and clarify the clinical significance of sodium metabolic abnormalities in AD. Structural, functional, and sodium imaging data will be integrated with neuropsychological and blood-based markers, using artificial intelligence for early diagnosis and risk prediction. The study will address technical gaps in early detection and provide the first standardized 7T AD neuroimaging database for the Chinese population.
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
- 55 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 55-90 years (inclusive).
- •Willing and able to participate in baseline assessment and longitudinal follow-up; voluntary provision of biospecimens and personal information, and commitment to complete all follow-up visits.
- •Able to undergo MRI scanning (no contraindications to MRI).
- •Group-specific cognitive criteria:
- •CN: No subjective memory complaints beyond age expectation (confirmed by study partner); MMSE score 26-30 (inclusive; exceptions permitted for participants with <8 years of education with principal investigator approval; CDR = 0, memory box = 0; Normal cognitive and daily functioning, no significant impairment.
- •MCI: Subject, partner, or physician reports subjective memory concerns; MMSE criteria same as CN group; CDR = 0.5 (memory box ≥0.5); General cognition and function relatively preserved; does not meet criteria for AD.
- •AD: Subject, partner, or physician reports subjective memory concerns; MMSE score <26 (inclusive; exceptions as above); CDR = 0.5 or 1.0; Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) probable AD diagnostic criteria or 2024 National Institute on Aging-Alzheimer's Association (NIA-AA) criteria (e.g., positive Pittsburgh compound B (PIB) and tau).
排除标准
- •Self-reported or MRI-detected major neurological diseases other than AD: including but not limited to stroke (cerebral hemorrhage, infarction), congenital intellectual disability, intracranial tumors, epilepsy, Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, progressive supranuclear palsy, multiple sclerosis, severe head trauma with persistent deficits, etc.
- •Severe psychiatric disorders (e.g., schizophrenia requiring medication control) or other known brain structural abnormalities.
- •Significant organ failure (heart, liver, kidney, etc.), malignant tumors, or short life expectancy making completion of follow-up unlikely.
- •Contraindications to MRI (e.g., claustrophobia, incompatible pacemaker, aneurysm clip, artificial heart valve, cochlear implant, or other metallic implants).
- •Other clinical history or examination findings judged by investigators as potentially unsafe for MRI or follow-up.
- •Use of investigational drugs within one month prior to enrollment or during the study.
结局指标
主要结局
Change from Baseline in Regional Brain Sodium Concentration (mmol/L) Measured by 7 T ²³Na-MRI
时间窗: Baseline to 1 year
Quantitative regional brain sodium concentration measured by 7 T sodium (²³Na) MRI; units mmol/L; higher values indicate increased sodium concentration.
Change from Baseline in Resting-State Fractional Amplitude of Low-Frequency Fluctuations（fALFF, unitless) Measured by 7 T fMRI
时间窗: baseline to 1year
Fractional Amplitude of fALFF averaged within gray-matter mask (unitless; higher = greater spontaneous activity).
Change from Baseline in Mean Apparent Diffusion Coefficient (ADC) (×10-³ mm²/s) Derived from Dynamic Diffusion-Weighted Imaging (DynDWI)
时间窗: Baseline to 1 year
Mean ADC (×10-³ mm²/s) derived from DynDWI; higher values indicate increased diffusivity.
Change From Baseline in Fractional Anisotropy (FA, unitless)
时间窗: Baseline to 1 year
Change from baseline in DTI-derived FA values in major white matter tracts; higher FA indicates greater microstructural integrity.
Change From Baseline in Mean Diffusivity (MD, ×10-³ mm²/s)
时间窗: Baseline to 1 year
Change from baseline in DTI-derived MD values in major white-matter tracts; higher MD indicates increased water diffusivity (×10-³ mm²/s).
次要结局
- Change from Baseline in Montreal Cognitive Assessment (MoCA) Total Score (0-30, points)(Baseline to 1 year)
- Change from Baseline in Clinical Dementia Rating (CDR) Global Score (0-3, points)(Baseline to 1 year)
- Change from Baseline in Mini-Mental State Examination (MMSE) Total Score (0-30, points)(Baseline to 1 year)
- Change From Baseline of the Auditory Verbal Learning Test (AVLT) Total Learning Score(baseline to 1year)
- Change from Baseline in Rey-Osterrieth Complex Figure Test (ROCF) Combined Recall Score (0-72, points)(baseline to 1year)
- Change From Baseline of the Clock Drawing Test (CDT) Score (0-5, points)(Baseline to 1 year)
- Change From Baseline of the Boston Naming Test (BNT) Total Score (0-60, points)(Baseline to 1 year)
- Change from Baseline in Digit Span Test (DST) Total Score (0-15, points)(Baseline to 1 year)
- Change from Baseline in Symbol Digit Modalities Test (SDMT) Total Score (correct matches per 90 s)(Baseline to 1 year)
- Change from Baseline in Stroop Color-Word Test (SCWT) Incongruent Condition Completion Time (seconds)(Baseline to 1 year)
- Change from Baseline in Neuropsychiatric Inventory (NPI) Total Score (0-144, points)(Baseline to 1 year)
- Change from Baseline in Hamilton Anxiety Rating Scale (HAMA) Total Score (0-56, points)(Baseline to 1 year)
- Change from Baseline in Symptom Checklist-90 (SCL-90) Total Score (90-450, points)(Baseline to 1 year)
- Change from Baseline in Hamilton Depression Rating Scale (HAMD) Total Score (0-52, points)(Baseline to 1 year)
- Change from Baseline in Activities of Daily Living (ADL) Scale Score (0-100, points)(Baseline to 1 year)
- Change from Baseline in Pittsburgh Sleep Quality Index (PSQI) Total Score (0-21, points)(Baseline to 1 year)
- Change from Baseline in Trail Making Test (TMT) B-A Difference Score (seconds)(Baseline to 1 year)
- Change from Baseline in Hippocampal Volume (mm³) by FreeSurfer(Baseline to 1 year)
- Number of participants with new cerebral microbleeds detected by susceptibility-weighted imaging (SWI)(Baseline to 1 year)
- Plasma Biomarkers of AD(Baseline to 1 year)
- Change from Baseline in Brain Perivascular Spaces (PVS) Burden (semi-quantitative score)(Baseline to 1 year)
研究者
Xin Lou
Director and Clinical Professor
Chinese PLA General Hospital