Study on Early Brain Injury Mechanism and Comprehensive Intervention of VCI

NCT04999813 | Unknown

• 1 other identifier: Junjian Zhang
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

Alzheimer's disease (AD) and vascular dementia (VaD) are the most common forms of senile dementia. Although the animal research of dementia has made remarkable progress, clinical trials of drugs for AD pathology have failed in recent years. The study of dementia based on cell and animal model generally aims at a single mechanism and target, and its results are quite different from the real clinical environment. More and more studies suggest that investigators should shift the focus of research to the early stage of cognitive impairment before dementia. Prevention is more important than cure, and intervention against multi-factors and multi-targets has become an important consensus. A large number of studies have shown that the mechanism of vascular brain injury plays an important role in the pathogenesis of AD and VaD, and many vascular risk factors are interventionable to some extent. Therefore, based on the clinical cohort, in-depth study of vascular cognitive impairment (Vascular cognitive impairment, VCI) has important clinical significance for the effective prevention and treatment of AD and VaD. The leading team of the project has focused on VCI research for a long time. After nearly 20 years of experimental research and preliminary clinical observation, it is proposed that chronic cerebral ischemia can not only be a clinical disease entity, but also an important pathological basis for the early onset of VCI. This view has recently been supported by a number of authoritative international research evidence. Big data's study of 1171 patients with AD reported by Nature Commun in 2016 shows that the early pathological changes of AD may not be a cascade of amyloid protein (Aβ), but a decrease in cerebral blood flow. Therefore, this project intends to establish an early clinical research cohort of VCI to focus on three key issues in VCI research and clinical practice: (1) the theory that cerebral hypoperfusion may be an important pathological basis for the occurrence and development of VCI needs direct evidence support from clinical studies, and its mechanism needs further elucidation. (2) Based on the fusion of multimodal MRI of VCI vascular brain injury pathology and PET imaging markers of Aβ molecular pathology, a multivariate VCI cognitive evaluation model is constructed, and its sensitivity and specificity may be better than the existing VCI diagnostic standards. (3) the protective effect of early comprehensive intervention of vascular risk factors on cognitive decline in VCI may be more effective than that of single risk factor. The first part of this project is to establish a study cohort of non-demented vascular cognitive impairment(VCIND). Neurocognitive function assessment combined with multimodal MRI including ASL, DCE, DTI and BOLD techniques were used to observe the role of cerebral hypoperfusion in the early stage and progression of VCI. At the same time, the relationship between the changes of blood-brain barrier and neural network and cognitive decline was dynamically observed to verify and explore the effect and mechanism of cognitive impairment caused by cerebral hypoperfusion. The second part studies the pathology of vascular brain injury based on MRI and the molecular pathology of A β based on PET and the relationship between Aβ molecular pathology and cognitive impairment, including the main factors affecting cognitive function, and uses artificial intelligence (AI) algorithm to develop a multiple quantitative evaluation system of VCI cognitive function, which is mainly based on the fusion of MRI and PET image markers. In the third part, a multicenter randomized controlled clinical cohort study was conducted to observe the cognitive protective effect of comprehensive intensive intervention of vascular risk factors on early VCI, so as to provide direct clinical evidence and intervention model for the prevention and treatment of VCI. The topics of the above three aspects covered by this project are closely related, which is not only a key scientific problem, but also an important clinical problem to be solved in the diagnosis and treatment of VCI. The study of this project is expected to further clarify the role and mechanism of cerebral hypoperfusion in VCI, provide a new theoretical basis for the prevention and treatment of dementia, and develop a quantitative evaluation system of VCI cognitive function mainly based on imaging technology and AI algorithm, so as to provide a more accurate and convenient diagnostic tool for early clinical identification and scientific research of VCI. Draw up the early comprehensive intervention paradigm of VCI based on vascular risk factors and popularize it in clinic, gradually form an expert consensus, enrich and update the guidelines for diagnosis and treatment of dementia, and effectively improve the level of prevention and treatment of dementia related to VCI.

Conditions

Vascular Cognitive Impairment

Outcome Measures

Primary Outcomes (8)

• Montreal Cognitive Assessment (MoCA)

  The scores of the MoCA tests are used to evaluate the cognitive function of the subjects. MoCA is a brief, 30-question test that helps healthcare professionals detect cognitive impairments very early on, allowing for faster diagnosis and patient care. MoCA is the most sensitive test available for measuring multiple cognitive domains which are important components not measured by the MMSE. The minimum value of Montreal Cognitive Assessment measurement is 0 and the maximum value is 30. Overall, a worse Moca score represents a worse cognitive function of the participants.

  Baseline

• Montreal Cognitive Assessment (MoCA)

  The scores of the MoCA tests are used to evaluate the cognitive function of the subjects. MoCA is a brief, 30-question test that helps healthcare professionals detect cognitive impairments very early on, allowing for faster diagnosis and patient care. MoCA is the most sensitive test available for measuring multiple cognitive domains which are important components not measured by the MMSE. The minimum value of Montreal Cognitive Assessment measurement is 0 and the maximum value is 30. Overall, a worse Moca score represents a worse cognitive function of the participants.

  One-year follow-up

• Montreal Cognitive Assessment (MoCA)

  The scores of the MoCA tests are used to evaluate the cognitive function of the subjects. MoCA is a brief, 30-question test that helps healthcare professionals detect cognitive impairments very early on, allowing for faster diagnosis and patient care. MoCA is the most sensitive test available for measuring multiple cognitive domains which are important components not measured by the MMSE. The minimum value of Moca measurement is 0 and the maximum value is 30. Overall, a worse Montreal Cognitive Assessment score represents a worse cognitive function of the participants.

  Two-year follow-up

• Montreal Cognitive Assessment (MoCA)

  The scores of the MoCA tests are used to evaluate the cognitive function of the subjects. MoCA is a brief, 30-question test that helps healthcare professionals detect cognitive impairments very early on, allowing for faster diagnosis and patient care. MoCA is the most sensitive test available for measuring multiple cognitive domains which are important components not measured by the MMSE. The minimum value of Montreal Cognitive Assessment measurement is 0 and the maximum value is 30. Overall, a worse Moca score represents a worse cognitive function of the participants.

  Three-year follow-up

• Mini-Mental State Examination(MMSE)

  MMSE is used as a screening scale for cognitive impairment, can measure the participants' global cognitive function. The minimum value of the Mini-Mental State Examination measurement value is 0 and the maximum value is 30. A worse MMSE score represents a worse cognitive function of the participants.

  Baseline

• Mini-Mental State Examination(MMSE)

  MMSE is used as a screening scale for cognitive impairment, can measure the participants' global cognitive function. The minimum value of the Mini-Mental State Examination measurement value is 0 and the maximum value is 30. A worse MMSE score represents a worse cognitive function of the participants.

  One-year follow-up

• Mini-Mental State Examination(MMSE)

  MMSE is used as a screening scale for cognitive impairment, can measure the participants' global cognitive function. The minimum value of the Mini-Mental State Examination measurement value is 0 and the maximum value is 30. A worse MMSE score represents a worse cognitive function of the participants.

  Two-year follow-up

• Mini-Mental State Examination(MMSE)

  MMSE is used as a screening scale for cognitive impairment, can measure the participants' global cognitive function. The minimum value of the Mini-Mental State Examination measurement value is 0 and the maximum value is 30. A worse MMSE score represents a worse cognitive function of the participants.

  Three-year follow-up

Secondary Outcomes (16)

• Auditory Verbal Learning Test(AVLT)

  Baseline

• Auditory Verbal Learning Test(AVLT)

  One-year follow-up

• Auditory Verbal Learning Test(AVLT)

  Two-year follow-up

• Auditory Verbal Learning Test(AVLT)

  Three-year follow-up

• Verbal Fluency Test (VFT)

  Baseline

Study Arms (2)

Comprehensive intensive intervention

EXPERIMENTAL

On the basis of routine management, carry out individualized cerebrovascular risk factor assessment and comprehensive intervention in a medical-nursing cooperation model, and require corresponding control indicators to be achieved. A comprehensive intervention team is established by specialized medical staff to monitor blood pressure, heart rate, exercise and other data through smart wearable devices, and automatically upload them to the cloud platform, conduct comprehensive data analysis every week, timely feedback and online reminders, establish health management files, and improve the target population The blood-brain tube risk factor control and self-management ability.

Combination Product: Comprehensive intensive intervention

Routine management

NO INTERVENTION

Only routine management was carried out for the subjects without special intervention.

Interventions

Comprehensive intensive intervention COMBINATION_PRODUCT

* Health education ② Medication guidance: antihypertensive therapy, hypoglycemic therapy, lipid-lowering therapy * Diet guidance: A healthy diet requires low-salt, low-oil, more fruits and vegetables, more cellulose, appropriate amount of protein, restricted fat and cholesterol foods, etc. Quit smoking, drink less alcohol, and limit alcohol intake. * Exercise guidance: Do aerobic exercises of medium and low intensity at least 5 times a week, and exercise for at least 30 minutes each time. * Weight loss guidance.

Comprehensive intensive intervention

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ①Healthy volunteers or VCIND patients（Diagnostic criteria comply with the "Guidelines for the Diagnosis and Treatment of Vascular Cognitive Impairment" formulated by the Dementia and Cognitive Impairment Group of the Neurology Branch of the Chinese Medical Association）;
• ②Age between 50-70 years old;
• ③Able to accept and cooperate in completing various instrumental examinations and neuropsychological examinations Scale testing;
• ④Agree to sign an informed consent form.

You may not qualify if:

• ①Combined with other serious diseases, life expectancy is less than 3 years;
• ②Patients with vision and hearing impairment that significantly affect cognitive testing;
• ③Severe heart, brain, lung, kidney and other diseases;
• ④Have a history of psychoactive substance abuse;
• ⑤Have other serious physical diseases that affect cognitive testing, such as coma, epilepsy, hypothyroidism , Hypoxemia, etc.;
• ⑥have a history of mental illness;
• ⑦have MRI contraindications, unwilling to participate in research and unconditional follow-up.

Sponsors & Collaborators

• Zhongnan Hospital: lead

Study Sites (1)

Zhongnan Hospital

Wuhan, Hubei, 430071, China

RECRUITING

Study Officials

• Zhipeng Xu, Ph. D.

  Zhongnan Hospital

  STUDY DIRECTOR

Central Study Contacts

Junjian Zhang, Ph. D.

CONTACT

13986225751; xsssm@sina.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2021
• First Posted: August 11, 2021
• Study Start: July 1, 2020
• Primary Completion: November 1, 2023
• Study Completion: December 1, 2023
• Last Updated: August 11, 2021

Record last verified: 2021-08

Locations

CN (1)