Cognitive Decline and Underlying Mechanisms in Symptomatic Intracranial Artery Stenosis Patients: A Cohort Study

Cognitive Impairment Clinical Trial

Official title:

Cognitive Decline and Underlying Mechanisms in Symptomatic Intracranial Atherosclerotic Stenosis Patients: A Multicenter Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06336174
• Other study ID #: Anhui-SIA-cohort
• Status: Recruiting
• Start date: November 1, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2024
• Source: Anhui Medical University
• Contact: Kai Wang, PhD
• Phone: +86-0551-62922263
• Email: wangkai1964[@]126.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to explore the mechanism of cognitive impairment in patients with symptomatic intracranial atherosclerotic stenosis (ICAS), and further plans to explore the impact of different treatment options on cognitive function in symptomatic ICAS patients.

Description:

All participants underwent a medical evaluation that included routine laboratory studies before and after 3-month and 1-year follow-up. Upon meeting the inclusion criteria and providing informed consent, each participant will complete a battery measure of neuropsychological tests, blood sample collection, and magnetic resonance imaging scan after enrollment and after 3-month and 1-year follow-up.

About 100 participants were included in this study. A series of neuropsychological tests were obtained by a trained investigator to assess. The tests include the evaluation of global cognitive function and multiple individual cognitive domains. The various tasks and questionnaires to measure cognition function including Montreal Cognitive Assessment (MoCA), Mini Mental State Examination (MMSE), Chinese Auditory Verbal Learning Test (CAVLT), Digital Span Test (DST), , Stroop color test (Stroop test), Color trail test (CTT), Clock Drawing Test (CDT), Verbal Fluency Test (VFT), etc., at the same time, the investigators also pay attention to the evaluation of participants' emotions by Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD). Furthermore, the memory and the occurrence of cerebrovascular events as the primary outcome measure, this study focused on the multidimensional cognitive function and cerebrovascular events of patients with symptomatic ICAS. Blood sample will be collected for biological multiomics research. The patients will receive a magnetic resonance imaging scan in multi-modalities.

After 3-month and 1-year follow-up, the participants will be interviewed to obtain the same assessments, blood sample and magnetic resonance imaging scan in multi-modalities as before.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Non-illiterates, no symptoms and signs of central nervous system dysfunction, head CT or head MRI showed normal cerebral parenchyma or old lacunar cerebral infarction, and non-thalamus, frontal lobe, temporal lobe and other cognitively related infarction;

2. TCD\CTA\MRA\DSA present intracranial artery stenosis (50% or more) or occlusion;

3. History of vascular-related TIA and acute cerebral infarction (more than 2 weeks after lastest), and NIHSS score was less than or equivalent to 4 points at the time of enrollment;

Exclusion Criteria:

1. History of stroke,transient ischemic attack,seizures or unexplained loss of consciousness.

2. Organic brain defects on T1 or T2 images.

3. Any history or clinical signs of other severe psychiatric illnesses (like major depression,psychosis or obsessive compulsive disorder).

4. Implanted pacemaker,medication pump,vagal stimulator,deep brain stimulator. History of substance abuse within the last 6 months

Related Conditions & MeSH terms

• Atherosclerosis
• Cognitive Dysfunction
• Cognitive Impairment
• Constriction, Pathologic
• Intracranial Arteriosclerosis
• Intracranial Atherosclerosis

Intervention

Drug:
• Aspirin Tablet, Clopidogrel Bisulfate Tablets and Atorvastatin
All patients received standard medical management, including dual antiplatelet therapy (aspirin and clopidogrel) for three months with aspirin or clopidogrel monotherapy thereafter and high-dose statin, and treatment of hypertension to guideline targets.

Procedure:
• Endovascular therapy,Aspirin Tablet, Clopidogrel Bisulfate Tablets and Atorvastatin
All patients underwent endovascular therapy and received standard medical management after surgery, including dual antiplatelet therapy (aspirin and clopidogrel) for three months with aspirin or clopidogrel monotherapy thereafter and high-dose statin, and treatment of hypertension to guideline targets.

Locations

Country	Name	City	State
China	Anhui Medical University	Hefei	Anhui

Sponsors (1)

Lead Sponsor	Collaborator
Anhui Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The changes in Memory	The changes in Memory function will constitute one of the main indicators of research results, which will be used to evaluate the follow-up results of the standard treatment regimen. The investigators will use the Chinese Auditory Verbal Learning Test (CAVLT) to evaluate the immediate, delayed and recognition memory of patients with symptomatic ICAS to evaluate the immediate, delayed and recognition memory of patients with ICAS.	baseline, 3-month and 1-year follow-up
Primary	Occurrence of ischemic cerebrovascular events	The changes in occurrence of ischemic cerebrovascular events constitute another major indicator of research result. The new responsible cerebrovascular events during the follow-up period are also the clinical information the investigators pay attention to, including transient ischemic attack (TIA) and stroke.	baseline, 3-month and 1-year follow-up
Secondary	MoCA (Montreal Cognitive Assessment)	The changes in MoCA will constitute the secondary research outcome. MoCA was based on clinical experience and reference to the MMSE cognitive items and scores, and the final version was finalized in November 2004. The investigators adopted a localized version (Mandarin-8.1 version) in line with the Chinese cultural background. It includes 11 inspection items in 8 cognitive fields, including visual structure skills, executive function, naming, attention and calculation, language, abstract thinking, memory, and orientation. With a total score of 30 or more than 26, it is normal. Anyone who has been education for less than 12 years will need to add one point to his final score. The final score of the higher the better.	baseline, 3-month and 1-year follow-up
Secondary	MMSE (Mini Mental State Examination)	The changes in MMSE will also constitute the secondary research outcome. The full name of MMSE is mini-mental state examination, and the scale consists of 30 subjects, include the following seven aspects: time orientation, place orientation, immediate memory, attention and calculation, delay memory, language, visual space. One point is awarded for each question correctly answered during MMSE evaluation. If subject give the wrong answer or don't know answer he/she awarded 0 score, scope of scale score of 0 to 30 points. The higher the score, the better. In this study, the investigators suspect that scores would decrease after follow-up.	baseline, 3-month and 1-year follow-up
Secondary	DST (Digital Span Test; Forward and Backward)	The changes in DST will constitute the secondary research outcome. Digital span test (DST) was commonly used to evaluate attention ability and instantaneous memory ability. There are two types of test: forward (0-14) and backward (0-13). In the forward test, the subjects were asked to retell the the digits immediately after hearing it until they could not be repeated correctly. In backward test, the subjects were asked to repeat a set of numbers in reverse order until they could not be repeated correctly. The length of the last set of Numbers correctly repeated by the subjects was the final score, forward and backward are counted separately. The higher the score, the better. In this study, the investigators suspect that scores would decrease after follow-up.	baseline, 3-month and 1-year follow-up
Secondary	The Stroop Color Test	The changes in The Stroop color test will constitute the secondary research outcome measure. The Stroop color word test was developed by Stroop in 1935 and is used to evaluate the attention function of the subject. The subject is required to correctly read the target color on the stimulus card and record the completion time. The final completion time is the score of the participant. The shorter the time used, the better the performance of the subjects	baseline, 3-month and 1-year follow-up
Secondary	CTT (Color Trail Test)	The changes in CTT will constitute the secondary research outcome. The Color Trail Test (CTT) is divided into two parts, part A and part B. Part A requires the subject to connect 25 Numbers on the paper in sequence, and part B requires the subject to connect 25 Numbers of different colors alternately in sequence. The time it takes for the subject to complete all the Numbers is the subject's final score.In this study, the investigators suspect that scores would decrease after follow-up.	baseline, 3-month and 1-year follow-up
Secondary	CDT (Clock drawing test)	The clock drawing test is currently widely used in the evaluation of cognitive impairment, requiring a free hand drawing of a clock within 10 minutes with the pointer pointing towards 11:10, which can be well used to evaluate the visual spatial ability of participants. The commonly used scoring methods include the 3-point method, the 4-point method, and the 10-point method.	baseline, 3-month and 1-year follow-up
Secondary	VFT (Verbal Fluency Test)	The changes in The Verbal Fluency Test (VFT) will constitute the secondary research outcome measure. The VFT can be used to evaluate the frontal lobe fluency of patients, mainly including semantic verbal fluency and phonemic verbal fluency.	baseline, 3-month and 1-year follow-up
Secondary	HAMD (Hamilton Depression Scale)	The changes in HAMD will constitute the secondary research outcome. Hamilton Depression Scale (HAMD) compiled by Hamilton in 1960, is the most common clinical to assess Depression Scale. In this study, 17 versions were selected, and there were 17 questions. The subjects were assessed for their depression in the past week. Each question scored between 0 and 4 points.Higher scores indicate more depressive symptoms.	baseline, 3-month and 1-year follow-up
Secondary	HAMA (Hamilton Anxiety Scale)	The changes in HAMA will constitute the secondary research outcome. Hamilton Anxiety Scale (HAMA) was compiled by Hamilton in 1959.It was one of the most commonly used scales in psychiatric clinic, including 14 items. It is often used in clinical diagnosis and degree classification of anxiety disorder. The subjects were assessed for their anxiety in the past week. Each question scored between 0 and 4 points. The higher the score, the more symptoms of anxiety.	baseline, 3-month and 1-year follow-up
Secondary	MRI measure- resting state MRI images	The resting state magnetic resonance data were collected to compare the neuroimaging differences between the patients and healthy control groups.	baseline, 3-month and 1-year follow-up
Secondary	MRI measures-structural phase MRI images	The structural phase magnetic resonance data were collected to compare the neuroimaging differences between the patients and healthy control groups.	baseline, 3-month and 1-year follow-up
Secondary	MRI measures-3D pCASL images	The three-dimensional pseudo continuous Arterial Spin Labeling (3D pCASL) data were collected to compare the differences in cerebral perfusion between the patients and healthy control groups.	baseline, 3-month and 1-year follow-up
Secondary	Ultrasound measures-MCA-PI (middle cerebral artery-pulsatility index)	Pulsatility index (PI) in the middle cerebral artery (MCA) is considered a measure of peripheral vascular resistance. The investigators want to explore the peripheral vascular resistance by MCA-PI.	baseline, 3-month and 1-year follow-up
Secondary	Ultrasound measures-IMT (intima-media thickness)	The carotid intima-media thickness (IMT) is a widely used surrogate marker for atherosclerosis worldwide. The investigators want to explore the risk of recurrence of cerebrovascular events by IMT.	baseline, 3-month and 1-year follow-up
Secondary	Blood Metabolomics measures-CRP (C-reactive protiein)	CRP is a plasma protein synthesized by the liver and is often used as a nonspecific biomarker of inflammation. Elevated CRP levels are associated with increased risk of cerebrovascular disease and dementia. The investigators intend to use CRP to explore the relationship between inflammatory response and cognitive impairment.	baseline, 3-month and 1-year follow-up
Secondary	Blood Metabolomics measures-oxLDL(Oxidized low-density lipoprotein)	Oxidized low-density lipoprotein (oxLDL) is a biomarker that is a key factor for the occurrence and development of atherosclerosis and the formation of unstable plaque. Atherosclerosis has been associated with the onset, severity and progression of cognitive dysfunction. The investigators intend to further explore the relationship between LDL level and cognitive impairment.	baseline, 3-month and 1-year follow-up
Secondary	Blood Metabolomics measures-miRNA/microRNA	microRNA (miRNA) is a type of non-coding single-stranded small RNA that plays a role in biological functions by regulating post-transcriptional gene expression. miRNA is involved in the regulation of synaptic plasticity and is related to learning and memory. The investigators intend to reserve serum samples for the study of miRNA and cognitive impairment.	baseline, 3-month and 1-year follow-up