A Phase II Trial of Florbetapir (18F) Positron Emission Tomography (PET) Imaging in Japan of Healthy Volunteers, Patients With Mild Cognitive Impairment (MCI) and Patients With Alzheimer's Disease (AD)

Inclusion Criteria: Subjects who meet all of the following criteria are eligible to enroll in the arm of thistrial reserved for subjects with AD:

1. Japanese males or females at least 50 years of age, with probable AD according to theNINCDS-ADRDA criteria (McKhann et al., 1984);

2. Subjects with mild/moderate dementia as evidenced by a MMSE score ranging from 10 to 24, boundaries included, at screening;

3. Subjects whose history of cognitive decline has been gradual in onset and progressiveover a period of at least 6 months. Evidence should be present indicating sustainedmemory deterioration in an otherwise cognitively normal subject, plus additionalimpairment in another cognitive function such as: orientation, judgment and problemsolving, or functioning in personal care;

4. Subjects who live with or have regular visits from a responsible caregiver willing toprovide information about the subject's cognitive status; and

5. Subjects who signed an Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved informed consent prior to any study procedures. If the subject isincapable of giving informed consent, the caregiver may consent on behalf of thesubject (the subject must still confirm assent). Subjects who meet all of the following criteria are eligible to enroll in the arm of thistrial reserved for subjects with mild cognitive impairment:

6. Japanese males or females at least 50 years of age;

7. Subjects with complaint of memory or cognitive decline corroborated by an informant;

8. Subjects with a Clinical Dementia Rating (CDR) of 0.5;

9. Subjects with objective cognitive impairment or marginally normal cognition with adocumented history of high cognitive performance;

10. Have no obvious causes for their cognitive impairment (e.g., onset coincides withrecent head trauma or stroke);

11. Have sufficiently preserved general cognition and functional performance such that adiagnosis of AD cannot be made at the time of the screening visit;

12. Subjects with essentially normal ADL;

13. Subjects who are not demented;

14. Subjects with an MMSE score > 24;

15. Subjects who are presenting for initial diagnosis of cognitive impairment or who havepresented for initial diagnosis of cognitive impairment within the past year;

16. Subjects who live with or have regular visits from a responsible caregiver willing toprovide information about the subject's cognitive status; and

17. Subjects who signed an IRB/IEC approved informed consent prior to any studyprocedures. Subjects who meet all of the following criteria are eligible to enroll in the arm of thistrial reserved for cognitively normal volunteers:

18. Japanese males or females at least 50 years of age;

19. Subjects with an MMSE score >= 29, and are cognitively normal based on history andpsychometric test battery at screening;

20. Subjects who live with or have a reliable person who can verify their cognitivestatus; and

21. Subjects who signed an IRB/IEC approved informed consent prior to any studyprocedures.

Exclusion Criteria: Subjects with any of the following are ineligible to enroll in this trial:

1. A documented diagnosis of MCI for greater than 1 year (for subjects considered for theMCI group);

2. Neurodegenerative disorders other than AD, including, but not limited to Parkinson'sdisease, Pick's disease, frontotemporal dementia, Huntington's chorea, Down'ssyndrome, Creutzfeldt-Jacob disease, normal pressure hydrocephalus, and progressivesupranuclear palsy;

3. Have had or currently have a diagnosis of other dementing / neurodegenerative disease (e.g. Parkinson's disease, dementia with Lewy bodies, Lewy body variant AD, etc.);

4. Have had or currently have a diagnosis of mixed dementia;

5. Cognitive impairment resulting from:

• Acute cerebral trauma or post-traumatic brain injury, subdural hematoma, orinjuries secondary to chronic trauma (e.g. sequela from boxing);

• Hypoxic cerebral damage regardless of etiology; e.g. cognitive or neurologicaldeficits resulting from cardiac arrest or cardiac surgery, anesthesia, or severeself-poisoning episode, secondary to severe hypovolemia (orthostatic hypotensionshould not lead to exclusion);

• Vitamin deficiency states documented by medical history such as folate, vitamin B 12 and other B complex deficiencies; e.g. thiamin deficiency in Korsakoff'ssyndrome. (Note: subjects taking regular B12 and folate are not necessarilyexcluded);

• Cerebral infection including abscess, syphilis, meningitis, encephalitis or AIDS;

• Primary or metastatic cerebral neoplasia;

• Significant endocrine or metabolic disease; e.g., thyroid, parathyroid, orpituitary disease, Cushing's syndrome, or severe renal failure; or

• Mental retardation. Before enrolling a subject with past or current history ofany of the above conditions, the investigator must contact the sponsor to discusswhether the condition could have contributed to the cognitive impairment.

6. Clinically significant infarct or possible multi-infarct dementia as defined by theNINCDS criteria, including:

• A history of a significant cerebrovascular event resulting in a physical orneurologic deficit that may confound the assessment of the subject's intellectualfunction;

• Multiple focal signs on neurologic examination indicative of multiple ischemicepisodes;

• One or more of the following findings on a MRI scan:

• Multiple (two or more) infarcts or white matter lacunes;

• A single large infarct or a strategically placed infarct in the angulargyrus, the thalamus, the basal forebrain, the posterior cerebral artery (PCA) or anterior cerebral artery (ACA) territory;

• Extensive periventricular white matter disease. Leukoaraiosis (periventricularwhite matter, low attenuation) should be distinguished from multiple infarctions.Leukoaraiosis is common in normal individuals and patients with AD. White matterdeterioration should not result in exclusion unless it is abnormal andwidespread, e.g., Binswanger's disease;

7. Any evidence on screening MRI, computed tomography (CT), or other biomarker studiesthat suggests an alternate etiology (other than probable AD in subjects with AD) forcognitive deficit; or in the case of cognitively normal controls any evidence onscreening MRI, CT, or other biomarker studies that suggests the presence of ADpathology;

8. Current clinically significant psychiatric disease, as judged by Diagnostic andStatistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria, particularlycurrent major depression or schizophrenia. Subjects with dementia who are experiencingbehavioral disturbances that may require treatment with psychotropic medications maybe entered only after discussion and with the approval of the sponsor. Theinvestigator and sponsor should carefully consider whether subjects with behavioraldysfunction will be able to complete the imaging session;

9. History of epilepsy or convulsions, except for febrile convulsions during childhood;

10. Clinically significant hepatic, renal, pulmonary, metabolic, or endocrinedisturbances;

11. Current clinically significant cardiovascular disease. Clinically significantcardiovascular disease usually includes one or more of the following:

• cardiac surgery or myocardial infarction within the last 6 months;

• unstable angina;

• coronary artery disease that required an increase in medication within the last 3months;

• decompensated congestive heart failure;

• significant cardiac arrhythmia or conduction disturbance, particularly thoseresulting in atrial or ventricular fibrillation, or causing syncope, nearsyncope, or other alterations in mental status;

• severe mitral or aortic valvular disease;

• uncontrolled high blood pressure;

• congenital heart disease;

• clinically significant abnormal result on ECG, including but not limited to QTc > 450 msec. Before enrolling a subject with any of the above conditions, theinvestigator must contact the sponsor.

12. History of drug or alcohol abuse within the last year, or prior prolonged history ofabuse;

13. Clinically significant infectious disease, including Acquired Immune DeficiencySyndrome (AIDS) or Human Immunodeficiency Virus (HIV) infection or previous positivetest for hepatitis;

14. Females of childbearing potential who are not surgically sterile, not refraining fromsexual activity or not using reliable methods of contraception. Females ofchildbearing potential must not be pregnant (negative serum beta-hCG at the time ofscreening and negative urine beta-hCG on the day of imaging) or breastfeeding atscreening. Females must agree to avoid becoming pregnant, and must agree to refrainfrom sexual activity or to use reliable contraceptive methods such as prescribed birthcontrol or IUD for 24 hours following administration of florbetapir (18F);

15. Subjects who, in the opinion of the investigator, are otherwise unsuitable for a studyof this type;

16. History of relevant severe drug allergy or hypersensitivity;

17. Subjects who have received an investigational medication within the last 30 days. Additionally, the time between the last dose of the previous experimental medicationand enrollment (completion of screening assessments) must be at least equal to 5 timesthe terminal half-life of the previous experimental medication. Subjects who have everparticipated in an experimental study with an amyloid targeting therapy (e.g.,immunotherapy, secretase inhibitor) may not be enrolled unless it can be demonstratedthat the subject received only placebo in the course of the trial;

18. Subjects with current clinically significant medical comorbidities, as indicated byhistory, physical exam, ECG (including but not limited to QTc>450 msec) or laboratoryevaluations, that might pose a potential safety risk, interfere with the absorption ormetabolism of the study medication or limit interpretation of the trial results. Theseinclude but are not limited to clinically significant hepatic, renal, pulmonary,metabolic or endocrine disease, cancer, HIV infection and AIDS;

19. Subjects who have known hypersensitivity to alcohol; and

20. Subjects who received a radiopharmaceutical for imaging or therapy within the past 7days prior to the imaging session for this study.