China Longitudinal Aging and Cognitive Impairment Study (CLACIS)

This is a multi-center longitudinal study that consists of five cohorts: cognitive normal aging (CN), Subjective cognitive impairment (SCI), mild cognitive impairment (MCI), Alzheimer's disease (AD) and vascular cognitive impairment (VCI). The goals of this study are as follow: 1.To establish longitudinal cohort study database containing comprehensive epidemiological data, neuropsychological test data, laboratory parameters, image data and biological samples. 2. To determine the risk factors of AD and other dementias. 3. To explore the conversion rates from CN to SCI, MCI or AD and the risk factors as well as biomarkers for the progression from CN to SCI, MCI or AD. 4. To explore and validate blood, CSF, urine, imaging and other biomarkers for the early detection and progression of AD.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease; Aging; Mild Cognitive Impairment; Neurodegeneration
• Intervention / Treatment: Other: None of intervention

Detailed Description

As the population ages in China, the number of patients with neurocognitive disorders such as Alzheimer's disease (AD) and vascular cognitive impairment (VCI) is steadily increasing. The burden of cognitive impairment in China has been an important public health problem. Cohort study on aging and cognitive impairment is urgent to better understand and address this issue. Early prevention, diagnosis and treatment are critical for reduction the burden of cognitive impairment. In this prospective study, subjects will be recruited into one of the five groups based on inclusion and exclusion criteria: 1) CN, 2) MCI 3) AD and 4) VCI. Each of the subjects will be followed up at designated time points up to 5 years. Epidemiological data, medical, imaging (MRI and PET scans), genetic information and various biological samples will be collected during the baseline and follow-up period.

• Study Type: Observational
• Enrollment (Anticipated): 4000

Contacts and Locations

• Study Contact: Name: Qing-Qing Tao, M.D.; Phone Number: 13777820430; Email: qingqingtao@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • Second Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Qing-Qing Tao, M.D.&Ph.D; Phone Number: 13777820430; Email: qingqingtao@zju.edu.cn
      • Principal Investigator: Zhi-Ying Wu, M.D.&Ph.D
    • Lishui, Zhejiang, China, 323000
      • Recruiting
      • Zhejiang Lishui central Hospital
      • Contact: Hui-Fen Huang, M.D.; Phone Number: 13666564106; Email: wuyumomo@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Male or female participants ages 40 to 99 years

Description

Inclusion Criteria:

Inclusion Criteria:

1. Cognitive normal aging (CN) 1. 40 years and older , without cognitive impairment, MMSE≥22 2. Informed consent is signed by the participant
2. Subjective cognitive impairment (SCI) Participants aged 40 and older, with absence of dementia (by DSM IV and DSM V) criteria. Normal age-, sex-, and education-adjusted performance on standardized cognitive tests, which are used to classify mild cognitive impairment (MCI) or prodromal AD. Self-experienced persistent decline in cognitive capacity in comparison with a previously normal status and unrelated to an acute event. Answering "yes" to both of the following questions: "Do you feel like your memory or thinking is becoming worse?" and "Does this concern you?"

3. Mild cognitive impairment (MCI) 1. 40 years and older 2. Diagnosis according to 2004 Peterson's MCI criteria. 3. Clinical Dementia Rating (CDR) = 0.5. 4. Memory loss is prominent, and may also be with other cognitive domain impairment.

   5. Insidious onset, slow progress.

4. Alzheimer's disease (AD)

   1. 50 years and older
   2. Dementia is diagnosed according to the criteria described by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-R). The diagnosis of AD according to the National Institute of Neurologic and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS- ADRDA) or National Institute on Aging and the Alzheimer's Assocation (NIA-AA) criteria.
   3. Subjects and their informed persons can complete relevant and follow-up examinations.
   4. Subjects or their authorized legal guardians sign the informed consent. Vascular cognitive impairment (VCI)

   1. 40 years and older 2. Diagnosis according to the criteria for small vessel VCI, with the following three core elements:

   1) Cognitive impairment: memory decline can be highlighted 2) Vascular factors 3) Causal relationship between cognitive impairment and vascular factors 3.Cognitive impairment lasts for 3 months or more, and the CDR global score ≥0.5 point.

   4. All patients need to meet the following MRI criteria:

   1. Multiple (≥3) small infarcts (3-20 mm in diameter) with or without any degree of white matter lesions (WML); or moderate to severe WML (Fazekas score ≥ 2) , with or without small infarction; or ≥ 1 small infarct in key parts of the cortex, such as: caudate nucleus, globus pallidus, thalamus et al.
   2. No WML caused by cortical infarction, watershed infarction, hemorrhage, hydrocephalus, or other causes (such as multiple sclerosis).
   3. No hippocampus or entorhinal cortex atrophy, Medial Temporal Lobe Atrophy (MTA)≤ 1 point.

   5. Subjects and their informed persons can complete relevant and follow-up examinations.

   6. Subjects or their authorized legal guardians sign the informed consent.

   Exclusion Criteria:

   Cognitive normal aging (CN)

   1. any disease that can cause cognitive impairment (such as Alzheimer's disease, dementia with Lewy bodies (DLB), frontotemporal dementia (FTLD), Parkinson's disease dementia (PDD), intracranial masses that impair cognition, history of severe brain trauma, normal pressure hydrocephalus, cerebrovascular disease with obvious clinical symptoms, etc.
   2. sequelae after previous history of severe central nervous system infection, multiple sclerosis, autoimmune encephalitis, Hashimoto's encephalopathy, etc.
   3. previous history of instable epilepsy
   4. systemic diseases affect the central nervous system, for abnormal liver and kidney functions (abdominal dialysis, hemodialysis, AST≥3× upper limit of normal value (ULN), ALT≥3× upper limit of normal value (ULN) or total bilirubin ≥2×ULN
   5. history of hereditary diseases that affect cognitive function (such as Huntington's disease, down syndrome, CADASIL, adrenal leukodystrophy, mitochondrial encephalopathy, etc.)
   6. long-term heavy drinking history (alcohol content more than 42 degree liquor, more than 150g/day, alcohol consumption more than 12 months)
   7. history of severe pulmonary diseases (COPD, pulmonary encephalopathy)
   8. history of serious cardiovascular disease (heart failure, severe hypertension)
   9. infection and immune-related diseases affecting the central nervous system (systemic lupus erythematosus, undertreated HIV infection or a history of CNS syphilis infection, etc.)
   10. metabolic and endocrine disorders (requiring new treatment or adjustment of current treatment for thyroid dysfunction, folate or vitamin B12 deficiency)
   11. unstable psychosis or long-term use of antipsychotic drugs (more than 6 months)
   12. history of malignant tumors (tumors of nervous system and other sites) active for nearly 1 year
   13. contraindications for MRI (e.g. pacemakers, stents, claustrophobia, etc.) or do not cooperate or cannot carry out PET examination
   14. uneducated illiterates
   15. hearing impairment, visual impairment and poor coordination
   16. withdraw or reject the study Subjective cognitive impairment (SCI) and Mild cognitive impairment (MCI)
   1. With history of stroke and a neurological focal sign, the imaging findings are consistent with cerebral vascular disease (Fazekas score ≥ 2 points).
   2. Other neurological diseases that can cause brain dysfunction (such as depression, brain tumor, Parkinson's disease, metabolic encephalopathy, encephalitis, multiple sclerosis, epilepsy, brain trauma, normal intracranial pressure hydrocephalus, etc.).
   3. Other systemic diseases that can cause cognitive impairment（such as liver, renal and thyroid insufficiency, severe anemia, folic acid or vitamin B12 deficiency, syphilis, HIV infection, alcohol and drug abuse, etc.）.
   4. Mental and neurodevelopmental retardation.
   5. Other diseases known to cause cognitive impairment.
   6. Contraindications to nuclear magnetics.
   7. Suffering from a disease that cannot be combined with cognitive examination.
   8. Refuse to draw blood.
   9. Refuse to sign the informed consent at baseline Alzheimer's disease (AD)
   1. Other neurological diseases that can cause brain dysfunction (such as depression, brain tumor, Parkinson's disease, metabolic encephalopathy, encephalitis, multiple sclerosis, epilepsy, brain trauma, normal intracranial pressure hydrocephalus, etc.).
   2. Other systemic diseases that can cause cognitive impairment（such as liver, renal and thyroid insufficiency, severe anemia, folic acid or vitamin B12 deficiency, syphilis, HIV infection, alcohol and drug abuse, etc.）.
   3. Mental and neurodevelopmental retardation.
   4. Other diseases known to cause cognitive impairment.
   5. Contraindications to nuclear magnetics.
   6. Suffering from a disease that cannot be combined with cognitive examination.
   7. Refuse to draw blood.
   8. Refuse to sign the informed consent at baseline Vascular cognitive impairment (VCI)
   1. Other neurological diseases that can cause brain dysfunction (such as depression, brain tumor, Parkinson's disease, metabolic encephalopathy, encephalitis, multiple sclerosis, epilepsy, brain trauma, normal intracranial pressure hydrocephalus, etc.).
   2. Other systemic diseases that can cause cognitive impairment（such as liver, renal, and thyroid insufficiency, severe anemia, folic acid or vitamin B12 deficiency, syphilis, HIV infection, alcohol and drug abuse, etc.）.
   3. Other diseases known to cause cognitive impairment.
   4. Hereditary or inflammatory small vessel disease, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
   5. Contraindications to nuclear magnetics.
   6. Refuse to draw blood.
   7. Refuse to sign the informed consent at baseline

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cognitive normal Aging (CN); Normal aging subjects with normal cognitive function	Other: None of intervention; None of intervention
Subjective cognitive impairment (SCI); Self-experienced persistent decline in cognitive capacity in comparison with a previously normal status and unrelated to an acute event. Answering "yes" to both of the following questions: "Do you feel like your memory or thinking is becoming worse?" and "Does this concern you?"	Other: None of intervention; None of intervention
Mild cognitive impairment (MCI); Mild cognitive impairment subjects with memory loss as predominant symptom	Other: None of intervention; None of intervention
Alzheimer's disease (AD); Mild to moderate sporadic and familial Alzheimer disease subjects	Other: None of intervention; None of intervention
Vascular cognitive impairment (VCI); Cognitive impairment subjects caused by cerebral vessel disease	Other: None of intervention; None of intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence, incidence of cognitive impairment caused by neurological disease such as AD, VCI and other types of dementia	All of the participants will be evaluated by cognitive assessment scale annually.	5 years
The conversion rate of normal aging to SCI, MCI and AD	All of the participants will be evaluated by cognitive assessment scale annually.	5 years
The fluid biomarkers for normal aging, SCI, MCI and AD diagnosis	Cerebrospinal fluid, plasma, saliva and urine biomarkers included Aβ42, Aβ40, phosphated tau and total tau, and other novel biomarkers.	5 years
The imaging biomarkers for normal aging, MCI and AD diagnosis	Imaging biomarkers included cerebral atrophy, amyloid and tau deposition of whole brain or hippocampus, glucose metabolism and other novel biomarkers.	5 years
Gut microbiota	Fecal microbiome will be analyzed by 16S rRNA gene sequencing and metagenome sequencing.	5 years
Gait	Gait characteristics such as stride-to-stride variability of stride time, and gait speed were evaluated by 3D gait detection.	5 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: The Central Hospital of Lishui City; Zhejiang Rehabilitation Center
• Investigators: Study Chair: Zhi-Ying Wu, M.D&Ph.D, Second Affiliated Hospital of Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2021
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: July 18, 2022
• First Submitted That Met QC Criteria: July 18, 2022
• First Posted (Actual): July 21, 2022

Study Record Updates

• Last Update Posted (Actual): July 21, 2022
• Last Update Submitted That Met QC Criteria: July 18, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction; Nerve Degeneration
• Other Study ID Numbers: wulab-CLACIS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No