Clinical trial NCT06579677: PRospective Observation on CErebral microvaScular Structure and Function
Official title: PRospective Observation on CErebral microvaScular Structure and Function (PROCESS): a Population-based Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cerebral Microvascular Dysfunction
Cerebral Small Vessel Diseases
Cognitive Dysfunction
Cerebrovascular Disorders
Cardiovascular Diseases
Population
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Daxing District People Hospital
First posted: 2024-08-30
Enrollment: 3500
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The target population of the PROCESS study is community-dwelling adults aged 50-75 years based on cluster sampling from villages and communities of Daxing District, Beijing. The steering committee will attempt to ensure population representativeness of the sample. These selected villages and communities will be living communities (not occupational communities) with little population migration.

Brief summary: This is a population-based prospective cohort study, aiming to assess the prevalence, distributional characteristics, and dynamic change of cerebral small vessel dysfunction in a Chinese community population using advanced vascular imaging techniques; meanwhile to investigate the effect of vascular risk factors on cerebral small vessel dysfunction, cardiovascular and cerebrovascular diseases, cognitive dysfunction, and mortality.

Detailed description: Brain health is defined as normal brain structure, function and social adaptation and the absence of major brain diseases. Brain health is a lifespan-wide process that can be objectively measured and subjectively perceived and is determined by socio-psycho-biological factors. Currently, neurological disorders are the first cause of healthy life lost and the second leading cause of death globally, with nearly 9 million people dying each year from brain-related diseases.

Prevention of major brain diseases, including stroke and dementia, is first and foremost for brain health management. Notably, cerebral small vessel dysfunction may be an earlier pathologic change for the aforementioned major brain diseases. Cerebral small vessel dysfunction includes increased blood-brain barrier permeability, altered neurovascular coupling, decreased cerebral perfusion, decreased cerebral autoregulation, decreased cerebrovascular reactivity, and altered cerebral resting blood flow. Previous studies have shown that the prevalence of cerebral small vessel dysfunction was as high as 40% to 70% in people with illness but data from the general population remain scarce. Vascular risk factors such as aging, hypertension, diabetes, obesity, dyslipidemia, and insulin resistance have been known as important risk factors for the development of major brain diseases. Whereas, it is unclear whether vascular risk factors will cause these brain diseases through affecting cerebral small vessel function.

Thus, this prospective cohort study aims to assess the prevalence, distributional characteristics, and dynamic change of cerebral small vessel dysfunction, and to investigate the effect of vascular risk factors on cerebral small vessel dysfunction, cardiovascular and cerebrovascular diseases, cognitive dysfunction, and mortality in a Chinese community population.

In this study, a total of 3500 participants aged 50 to 75 years from villages and communities of Daxing District, Beijing will be enrolled using cluster sampling method. All the participants will be interviewed at baseline and followed up for 8 years. Baseline data will be collected through face-to-face interviews by trained interviewers using a standardized questionnaire. Baseline data include demographics, lifestyle, physical activity, medical history, cardiovascular risk factors, dietary habits, medication use, sleep status, novel coronavirus infection. Cognitive function assessment and neuropsychiatric examination will be performed based on various scales such as the Montreal Cognitive Assessment (MoCA) Scale and Mini-Mental State Examination (MMSE) Scale.

Additionally, heart function will be tested using electrocardiogram and color ultrasound. Peripheral vascular examination will be performed to measure ankle-brachial index. Fundus examination will be performed by trained ophthalmologists. Gait and eye movement examination will be performed by trained staff. The body composition will be tested using a body composition analyzer.

The samples of fasting blood, morning urine, feces, oral plaque bacteria will be collected at baseline to test genetic and metabolomic markers. An oral glucose tolerance test will be performed to measure blood glucose, insulin, and C-peptide.

Brain magnetic resonance imaging (MRI) examination will be performed to detect CSVD imaging markers, craniocarotid plaque and stenosis, neurovascular coupling, and cerebral perfusion. The sequences of brain MRI included 3D-T1, 3D-T2, 3D-FLAIR, DWI, HR-MRA, SWI, resting-state fMRI, DTI, ASL, etc. All MRI scans will be conducted on 3.0 T scanners. Imaging data will be saved in digital imaging and communications in medicine (DICOM) format on discs and be analyzed at the Imaging Research Center of Beijing Tiantan Hospital. Transcranial Doppler ultrasonography will be used to detect cerebral autoregulation and cerebral resting blood flow. Carotid ultrasound will be used to measure carotid artery diameter, carotid intramedullary thickness, carotid systolic maximal flow velocity, carotid end-diastolic velocity, pulsatility index, vascular resistance index, carotid artery plaque, carotid artery stenosis, and blood flow velocity.

Routine follow-up will be performed each year to collect cardio-/cerebrovascular diseases and death after enrollment. A further face-to-face interview will be performed at 2, 4, 6, 8 years to collect the data of brain MRI scanning, transcranial Doppler ultrasonography, and cognitive impairment. Meanwhile, standard clinical and neuropsychologic examination will be conducted using the same scale as that at baseline. Fasting blood and morning urine samples will be collected at each follow-up visit following same protocol as that at baseline.

The protocol of this study has been approved by the Ethics Committee of Beijing Tiantan Hospital. All participants will provide written informed consents before entering the study.

Eligibility criteria: Inclusion Criteria:

1. Community-dwelling adults aged 50-75 years;
2. Registered Beijing household residents or residents who can be followed up stably in their own communities for a long period;
3. Subjects with written informed consents.

Exclusion Criteria:

1. Residents with moderate to severe disabilities (MRS ≥3), mental illness, stroke, dementia, and other serious neurological disorders (e.g., encephalitis, Parkinson's disease, epilepsy, brain tumors, and rare genetic diseases of the nervous system);
2. Life expectancy of ≤4 years due to serious diseases such as end-stage cancer;
3. Contraindications to magnetic resonance imaging such as implanted devices (e.g., pacemakers, defibrillators, and others);
4. Residents who are participating in other studies.

Primary outcomes:
measure: Cerebral small vessel disease
timeFrame: 2024-09 to 2032-09
measure: Neurovascular coupling
timeFrame: 2024-09 to 2032-09
measure: Cerebral perfusion
timeFrame: 2024-09 to 2032-09
measure: Cerebral autoregulation
timeFrame: 2024-09 to 2032-09
measure: Cerebral resting blood flow
timeFrame: 2024-09 to 2032-09
Secondary outcomes:
measure: Composite vascular events
timeFrame: 2024-09 to 2032-09
measure: Cognitive impairment measured by the Montreal Cognitive Assessment (MoCA) scale
timeFrame: 2024-09 to 2032-09
measure: Cognitive impairment measured by the Mini-Mental State Examination (MMSE) scale
timeFrame: 2024-09 to 2032-09
measure: All causes of death
timeFrame: 2024-09 to 2032-09
measure: Atherosclerotic plaque in retinal arteries.
timeFrame: 2024-09 to 2032-09
measure: Atherosclerotic plaque in craniocarotid arteries.
timeFrame: 2024-09 to 2032-09
measure: Other vascular events
timeFrame: 2024-09 to 2032-09
measure: Vascular interventions
timeFrame: 2024-09 to 2032-09
measure: Mean blood flow velocity in arteries
timeFrame: 2024-09 to 2032-09
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Daxing District People Hospital
state: Beijing
Study officials:
affiliation: Beijing Tiantan Hospital
name: Yilong Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: