Alzheimer's Disease Neuroimaging Initiative 2

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.