Alzheimer"s Imaging Biomarkers in Obesity

Inclusion Criteria:

1. Male and female, 40-60 years of age and any race;

2. MMSE = or greater than 25 or a Clinical Dementia Rating Scale (CDR)=0;

3. Willing and able to undergo MRI

4. Willing to complete PET scans, including [11C]PiB and 18F-AV-1451 (Flortaucipir)radioactive tracer injection under protocols IRB #201409014 & 201906028

5. Willing to participate in the metabolic subtyping of metabolically normal orabnormal overweight or obese status for the following three groups: a. Group 1: MAOO criteria: i. BMI ≥25 but <45 kg/m2; ii. Maximum body circumference < 165 cm to ensure participants fit into the PET/CT and MR scanners; iii. Fastingblood glucose: ≥100 mg/dl or blood glucose 2 h after an OGTT: ≥140 or fastinginsulin: >20 µu/ml; b. Group 2: MNOO criteria: i. BMI ≥ 25 but <45 kg/m2; ii. Maximum body circumference < 165 cm to ensure participants fit into the PET/CT and MR scanners; iii. Bloodglucose 2 h after an OGTT: iv. HbA1c < 5.7% v. Fasting insulin: < 20 µu/ml; c. Group 3: MNLP criteria: i. BMI ≥18.5 but < 25.0 kg/m2; ii. Maximum bodycircumference < 165 cm to ensure subjects fit into the PET/CT and MR scanners; iii.Fasting blood glucose: < 100 mg/dl; iv. Blood glucose 2 h after an OGTT: < 140mg/dl; v. HbA1c < 5.7% vi. Fasting insulin: < 20 µu/ml;

Exclusion Criteria:

1. Any condition that in the opinion of the Investigator or designee could increase therisk to the participant, limit the participant's ability to tolerate the researchprocedures or interfere with the collection of the data, (e.g., currently taking adrug for treatment of obesity);

2. Intend to have bariatric surgery;

3. Inability to tolerate to lie still during the scanning procedures (e.g., severe,chronic back pain);

4. Severe claustrophobia;

5. Women who are currently pregnant or breast-feeding;

6. Currently receiving an active obesity study drug (or placebo) or in an obesityclinical trial;

7. Laboratory Evaluations exclusion: • Oral glucose tolerance test should not beperformed in patients who already fulfill the criteria for diabetes mellitus. Theseinclude: - History of Type 1 or 2 diabetes mellitus - Prior documentation of afasting plasma glucose >7.0 mmol/L or two or more occasions or clinical symptoms ofdiabetes e.g. polydipsia, polyuria, ketonuria and rapid weight loss with a randomplasma glucose of >11.1 mmol/L • Other contraindications for venous access as partof OGTT or blood draws: - Venous fibrosis or shunt grafts in both upper extremities

• Ongoing cellulitis or infection, particularly in the upper extremities. - Presenceof a hematoma at the site of vascular access. - History of hypoglycemicencephalopathy that can occur with prolonged fasting

8. MRI exclusion: • Contraindications to MRI (e.g., certain incompatible electronicmedical devices that make it potentially unsafe for the individual to participate).All participants must be willing to undergo at least two MRI screenings, supervisedby Level II MRI personnel as designated by the American College of Radiology (ACR).