Clinical trial: Alzheimer's Disease Neuroimaging Initiative 2 (NCT01231971)

Eligibility criteria:
Inclusion Criteria:

        Participants will be classified as either normal controls, SMC, EMCI, LMCI or AD
        participants. General Inclusion Criteria will apply to all groups, with specific criteria
        for each group as described below:

        General (applies to each category):

          -  Geriatric Depression Scale less than 6.

          -  Age between *55-90 (inclusive). *For normal controls and SMC participants, age must be
             between 65-90.

          -  Study partner is available who has frequent contact with the participant (e.g. an
             average of 10 hours per week or more), and can accompany the participant to all clinic
             visits for the duration of the protocol.

          -  Visual and auditory acuity adequate for neuropsychological testing.

          -  Good general health with no diseases expected to interfere with the study.

          -  Participant is not pregnant, lactating, or of childbearing potential (i.e. women must
             be two years post-menopausal or surgically sterile).

          -  Willing and able to participate in a longitudinal imaging study.

          -  Hachinski less than or equal to 4.

          -  Completed six grades of education or has a good work history (sufficient to exclude
             mental retardation).

          -  Must speak English or Spanish fluently.

          -  Willing to undergo repeated MRIs (3Tesla) and at least two PET scans (one FDG and one
             Amyloid imaging) and no medical contraindications to MRI.

          -  Agrees to collection of blood for Genome Wide Association Studies (GWAS), APOE testing
             and DNA and RNA banking.

          -  Agrees to collection of blood for biomarker testing.

          -  Agrees to at least one lumbar puncture for the collection of CSF.

        Specific Inclusion Criteria for normal controls:

          -  Participant must be free of memory complaints, verified by a study partner.

          -  Normal memory function score on Wechsler Memory Scale (adjusted for education)

          -  Mini-Mental State Exam (MMSE) score between 24 and 30 (inclusive)

          -  Clinical Dementia Rating (CDR) = 0; Memory Box score must be 0

          -  Cognitively normal, based on an absence of significant impairment in cognitive
             functions or activities of daily living

          -  Stability of Permitted Medications for 4 weeks. In particular, participants may take:

               -  Antidepressants lacking significant anticholinergic side effects

               -  Estrogen replacement therapy is permissible

               -  Gingko biloba is permissible, but discouraged

               -  Washout from psychoactive medication (e.g., excluded antidepressants,
                  neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4
                  weeks prior to screening

        Specific Inclusion Criteria for SMC participants:

          -  Subjects that are "self-referrals" that have a significant subjective memory concern

          -  Significant memory concern confirmed by a Cognitive Change Index score of more than or
             equal to 16

          -  Normal memory function score on Wechsler Memory Scale (adjusted for education)

          -  Mini-Mental State Exam (MMSE) score between 24 and 30 (inclusive)

          -  Clinical Dementia Rating (CDR) = 0; Memory Box score must be 0

          -  Cognitively normal, based on the absence of significant memory impairment in cognitive
             function or activities of daily living

          -  Stability of Permitted Medications for 4 weeks. In particular, subjects may take:

               -  Antidepressants lacking significant anticholinergic side effects

               -  Estrogen replacement therapy is permissible

               -  Gingko biloba is permissible, but discouraged

               -  Washout from psychoactive medication (e.g., excluded antidepressants,
                  neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4
                  weeks prior to screening

        Specific Inclusion Criteria for EMCI and LMCI participants:

          -  Participant must have a subjective memory concern as reported by participant, study
             partner, or clinician

          -  Abnormal memory function score on Wechsler Memory Scale (adjusted for education)

          -  Mini-Mental State Exam (MMSE) score between 24 and 30 (inclusive)

          -  Clinical Dementia Rating (CDR) = 0.5; Memory Box score must be at least 0.5

          -  General cognition and functional performance sufficiently preserved such that a
             diagnosis of AD cannot be made by the site physician at the time of the screening
             visit

          -  Stability of Permitted Medications for 4 weeks. In particular, participants may take:

               -  Antidepressants lacking significant anticholinergic side effects

               -  Estrogen replacement therapy

               -  Gingko biloba is permissible, but discouraged

               -  Washout from psychoactive medication (e.g., excluded antidepressants,
                  neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4
                  weeks prior to screening

               -  Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks
                  prior to screening

        Specific Inclusion Criteria for AD participants:

          -  Participant must have a subjective memory concern as reported by participant, study
             partner, or clinician

          -  Abnormal memory function score on Wechsler Memory Scale (adjusted for education)

          -  Mini-Mental State Exam (MMSE) score between 20 and 26 (inclusive)

          -  Clinical Dementia Rating (CDR) = 0.5 or 1.0

          -  National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's
             Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD

          -  Stability of Permitted Medications for 4 weeks. In particular, participants may take:

               -  Antidepressants lacking significant anticholinergic side effects

               -  Estrogen replacement therapy

               -  Gingko biloba is permissible, but discouraged

               -  Washout from psychoactive medication (e.g., excluded antidepressants,
                  neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4
                  weeks prior to screening

               -  Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks
                  prior to screening

        Specific Inclusion Criteria for follow-up participants from ADNI1 and ADNI GO:

          -  Must have been enrolled and followed in ADNI1 for at least one year or enrolled in
             ADNI-GO with original diagnosis of Cognitively Normal (CN), Mild Cognitive Impairment
             (MCI), or Early Mild Cognitive Impairment (EMCI) regardless of whether a diagnostic
             conversion has occurred since initial enrollment in ADNI.

          -  Willing and able to continue to participate in an ongoing longitudinal study. A
             reduced battery of tests is allowable if the participant is not able/willing to
             complete the full battery.

          -  Study partner is available who has frequent contact with the participant (e.g. an
             average of 10 hours per week or more), and can accompany the participant to all clinic
             visits for the duration of the protocol.

        Exclusion Criteria:

        General (applies to each category):

          -  Screening/baseline MRI scan with evidence of infection, infarction, or other focal
             lesions; Participants with multiple lacunes or lacunes in a critical memory structure
             are excluded

          -  Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal
             fragments or foreign objects in the eyes, skin or body

          -  Major depression, bipolar disorder as described in Diagnostic and Statistical Manual
             of Mental Disorders, Fourth Edition (DSM-IV) within the past 1 year

          -  Currently treated with medication for obsessive-compulsive disorder or attention
             deficit disorder

          -  History of schizophrenia

          -  History of alcohol or substance abuse or dependence within the past 2 years

          -  Any significant systemic illness or unstable medical condition which could lead to
             difficulty complying with the protocol

          -  Clinically significant abnormalities in B12, or TFTs that might interfere with the
             study

          -  Residence in skilled nursing facility

          -  Current use of specific psychoactive medications (e.g.,certain antidepressants,
             neuroleptics, chronic anxiolytics or sedative hypnotics, etc.); Current use of
             warfarin or dabigatran (exclusionary for lumbar puncture).

          -  Use of investigational agents one month prior to entry and for the duration of the
             trial

          -  Participation in clinical studies involving neuropsychological measures being
             collected more than one time per year

          -  Exclusion for FDG PET scan and amyloid imaging with Florbetapir F 18: Current or
             recent participation in any procedures involving radioactive agents such that the
             total radiation dose exposure to the participant in any given year would exceed the
             limits of annual and total dose commitment set forth in the US Code of Federal
             Regulations (CFR) Title 21 Section 361.1.

          -  Exceptions to these guidelines may be considered on a case-by-case basis at the
             discretion of the protocol director

        Specific Exclusion Criteria for normal controls and SMC participants:

          -  Any significant neurologic disease, such as Parkinson's disease, multi-infarct
             dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor,
             progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple
             sclerosis, or history of significant head trauma followed by persistent neurologic
             defaults or known structural brain abnormalities

        Specific Exclusion Criteria for EMCI and LMCI participants:

          -  Any significant neurologic disease other than suspected incipient Alzheimer's disease,
             such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal
             pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder,
             subdural hematoma, multiple sclerosis, or history of significant head trauma followed
             by persistent neurologic defaults or known structural brain abnormalities.

        Specific Exclusion Criteria for AD participants:

          -  Any significant neurologic disease other than Alzheimer's disease, such as Parkinson's
             disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus,
             brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma,
             multiple sclerosis, or history of significant head trauma followed by persistent
             neurologic defaults or known structural brain abnormalities.

        Specific Exclusion Criteria for follow-up participants from ADNI1 and ADNI GO:

          -  Participants will not be able to participate in FDG PET scan and amyloid imaging with
             Florbetapir F 18 if the following is true: Current or recent participation in any
             procedures involving radioactive agents such that the total radiation dose exposure to
             the participant in any given year would exceed the limits of annual and total dose
             commitment set forth in the US Code of Federal Regulations (CFR) Title 21 Section
             361.1.
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 55 Years old.
Subject must be at most 90 Years

Patient description (medical language): 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 description (patient's own words): 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.

Does the patient match the trial criteria? Entailment