Patient case (clinical description): A 70-year-old man comes to the office accompanied by his wife.  The patient has experienced progressive memory loss over the last years.  He needs help with some of his routine activities, such as paying bills.  The patient's wife says, "He used to be such an independent person, but now he needs help with many things, even finding direction to home!"  Medical history includes hypertension, hyperlipidemia, and type 2 diabetes mellitus.  Family history includes Alzheimer disease in his father.  MRI reveals diffuse cortical and hippocampal atrophy. The diagnosis of AD is made using the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria.

Patient's own account: I am a 70-year-old man, and I paid a visit to the doctor with my wife the other day. I noticed that I tend to forget small things and that my memory has decreased over the past few years. I even ask my wife to help me out with my daily routine. I used to be the one paying the bills, but now she has to give me a hand. My wife mentioned to the doctor that I used to be independent and that I tend to forget where we live. I suffer from hypertension, high cholesterol, and type 2 diabetes. My poor dad was suffering from Alzheimer disease, so I hope I'm not going to end the same way! I did an MRI and they found out that some part of my brain was decreasing. I also did an Alzheimer test.

Clinical trial: China Cognition and Aging Study

Eligibility criteria:
Community population: age ≥ 55 years, male or female, with consent to participant the
        study.

        Hospital population: subjects are all over 18 years old. Through clinical evaluation,
        neuropsychological test, imaging examination, blood and cerebrospinal fluid examination,
        etc, we will comprehensively evaluate the cognitive function and various test measures.

        (1) MCI and its subtypes

        Inclusion criteria:

          1. Diagnosis according to 2004 Peterson's MCI criteria.

          2. CDR = 0.5.

          3. Memory loss is prominent, and may also be with other cognitive domain dysfunction.

          4. Insidious onset, slow progress.

          5. Not reaching the level of dementia.

        Exclusion criteria:

          1. With history of stroke and a neurological focal sign, the imaging findings are
             consistent with cerebral small vessal 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. Contraindications to MRI.

          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

        (2) Sporadic Alzheimer's disease (SAD)

        Inclusion criteria:

          1. 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 is made using 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 Association (NIA-AA)
             criteria.

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

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

        Exclusion criteria:

          1. With a family history of dementia.

          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. Contraindications to MRI.

          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

        (3) Familial Alzheimer's disease (FAD)

        Inclusion criteria:

          1. Written informed consent obtained from participant or legal guardian prior to any
             study-related procedures.

          2. Members in FAD pedigree (FAD is defined as at least two first- degree relatives suffer
             from AD).

          3. Aged 18 (inclusive) or older.

          4. At least two persons who can provide reliable information for the study. Note:
             Dementia is diagnosed according to the criteria described by DSM-IV-R. The diagnosis
             of AD is made using NINCDS-ADRDA or NIA-AA criteria. A diagnosis of MCI is assigned
             according to Petersen criteria.

        Exclusion criteria:

          1. Dementia caused by other factors such as depression, other psychiatric illnesses,
             thyroid dysfunction, encephalitis, multiple sclerosis, brain trauma, brain tumor,
             syphilis, acquired immunodeficiency syndrome (AIDS), Creutzfeldt-Jakob disease and
             other types of dementias such as vascular dementia (VaD), frontotemporal dementia
             (FTD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD).

          2. MRI and laboratory tests do not support or rule out a diagnosis of AD.

          3. Severe circulatory, respiratory, urinary, digestive, hematopoietic diseases (such as
             unstable angina, uncontrollable asthma, active gastric bleeding) and cancer.

          4. Participant has severe psychiatric illness or severe dementia that would interfere in
             completing initial and follow-up clinical assessments.

          5. With history of alcohol or drug abuse.

          6. Pregnant or lactating women.

          7. No reliable insiders.

          8. Refuse to sign the informed consent at baseline.

        (4) Vascular dementia (VaD)

        Inclusion criteria:

        Diagnosis for probable VaD according to NINDS-AIREN diagnostic criteria.

        MRI inclusion criteria:

        All patients who meet clinical inclusion criteria should accept MRI scans which include an
        assessment of hippocampal volume.

          1. multiple (≥3) supratentorial subcortical small infarcts (3-20 mm in diameter) with or
             without any degree of white matter lesion (WML); or moderate to severe WML (Fazekas
             score ≥ 2), with or without small infarction; or ≥ 1 subcortical small infarct in key
             regions, such as caudate nucleus, globus pallidus, or thalamus.

          2. no cortical and watershed infarction, hemorrhage, hydrocephalus, or WML with specific
             causes (such as multiple sclerosis).

          3. no hippocampus or entorhinal cortex atrophy (MTA score = 0 point).

        Exclusion criteria:

          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
             insufficiency, renal insufficiency, thyroid insufficiency, severe anemia, folic acid
             or vitamin B12 deficiency, syphilis, HIV infection, alcohol and drug abuse, etc.).

          3. With a history of mental illness or those with congenital mental retardation.

          4. Suffering from a disease that cannot be combined with a cognitive examination.

          5. Contraindications to MRI.

          6. Refuse to draw blood.

          7. Refuse to sign informed consent.

        (5) Normal control

        Inclusion criteria:

          1. Aged 18 (inclusive) or above.

          2. Normal MMSE and MoCA evaluations. MMSE>19 points for illiteracy, >24 points for those
             educated less than 7 years, >27 points for those educated equal to or more than 7
             years. MoCA>13 points for illiteracy, >19 points for those educated less than 7 years,
             >24 points for those educated equal to or more than 7 years.

        Exclusion criteria:

          1. Subjects with abnormal MMSE or MoCA scores.

          2. Subjects with a history of cerebral infarction, traumatic brain injury or related
             manifestations in MRI.

          3. 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.).

          4. 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.).

          5. Mental and neurodevelopmental retardation.

          6. Suffering from a disease that cannot be combined with a cognitive examination.

          7. Contraindications to MRI.

          8. Refuse to draw blood.

          9. Refuse to sign the informed consent at baseline.
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 18 Years old.


Eligibility (NLI label): Entailment