Topography Staging and Dual Phase Image Quantification of Tau PET in Cognitive Impairment Subjects

1.1 All subjects

1. Age between 55-80 years
2. Written informed consent must be obtained before any assessment is performed.
3. Female subjects must be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral oophorectomy, or tubal ligation) or post-menopausal for at least 1 year or, if they are of child-bearing potential, must commit to use a barrier contraception method for the duration of the study.
4. Male subjects and their partners of childbearing potential must commit to the use of two methods of contraception, one of which is a barrier method for male subjects for the study duration.
5. Male subjects must not donate sperm for the study duration.
6. Willing to undergo repeated MRIs and at least two PET scans.

1.2 Patient with Prodromal AD or AD dementia

1. Patients fulfill the criteria of prodromal AD or AD dementia based on IWG-2 criteria
2. Able to provide written informed consent with reliable carer in AD population. The participant should have reading ability OR 6/more years of formal education OR with working experiences.

1.3 Cognitive normal control

1. Cognitive unimpaired individual is defined as normal control in this study. Cognitive un-impaired normal control is defined as cognitive performance in the non-impaired range for that individual, defined as not mild cognitive impairment or demented).
2. The normal control should have their clinical dementia rating score 0
3. Cognitive Ability Screening Instrument (CASI) scores rated >50 percentile.

Exclusion Criteria:

1. Already receive outpatient clinic follow-ups with diseases that may affect the cognitive evaluation or presentation that include but not limited to Parkinsonism, Parkinson's disease dementia, schizophrenia, major depression, epilepsy, alcohol or drug abuse, major head trauma with consciousness loss
2. Severe progressive or unstable systemic disease that may interfere with the follow-up and test results. These included but not limited to cancer in the past 5 years, end stage renal or liver dysfunction, clinical significant myocardial infarction (New York Heart Association Functional Classification III-IV), Active disease that received admission in the past one year and unstable angina. Other diseases that were not listed but may interfere with the follow-up or test will be judged by the principle investigator.
3. Any treatment that suggests any of the aforementioned disease will be excluded.
4. Depression with ongoing diagnosis and treatment, suicide idea or suicide behavior in the past 6 months.
5. Contraindications or previously failure for receiving brain magnetic resonance imaging or PET scan.
6. History of risk factors for torsades de pointes (a cardiac dysrhythmia associated with sudden death) or taking medications known to prolong the QT interval.
7. Have an ECG obtained prior to the 18F-PM-PBB3 PET scan that in the opinion of the investigator is clinically significant regarding the subject's participation in the study.
8. Pregnant, lactating or breastfeeding.
9. Patients with severe liver disease (such as ALT > 3x upper limit of normal).