China Longitudinal Aging and Cognitive Impairment Study

Brief Title

China Longitudinal Aging and Cognitive Impairment Study

Official Title

China Longitudinal Aging and Cognitive Impairment Study

Brief Summary

      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.
    

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


Primary Outcome

Prevalence, incidence of cognitive impairment caused by neurological disease such as AD, VCI and other types of dementia


Condition

Aging

Intervention

None of intervention

Study Arms / Comparison Groups

 Cognitive normal Aging (CN)
Description:  Normal aging subjects with normal cognitive function

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Other

Estimated Enrollment

4000

Start Date

January 10, 2021

Completion Date

December 2026

Primary Completion Date

December 2025

Eligibility Criteria

        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
      

Gender

All

Ages

40 Years - 99 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Zhi-Ying Wu, M.D&Ph.D, 13777820430, [email protected]

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT05468905

Organization ID

wulab-CLACIS


Responsible Party

Sponsor

Study Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Collaborators

 The Central Hospital of Lishui City

Study Sponsor

Zhi-Ying Wu, M.D&Ph.D, Study Chair, Second Affiliated Hospital of Zhejiang University School of Medicine


Verification Date

July 2022