Wake Forest Alzheimer's Disease Clinical Core

Inclusion Criteria:

Group 1: Cognitively Normal (CN)

1. No subjective complaints of cognitive impairment

2. No cognitive impairment evident on formal testing interpreted by expert adjudicationcommittee (typically, performance not worse than 1 SD below demographically relevantnorms)

3. Clinical Dementia Rating (CDR) = 0 or 0.5

4. Normal glycemic control as indicated by American Diabetes Association (ADA)guidelines for normal 2 hour glycemic response to a glucose tolerance test (< 140mg/dL).

5. Reliable collateral or study partner available to attend Visit 1 at a minimum

Group 2: Mild Cognitive Impairment (MCI)

1. Objective evidence of memory and/or executive function deficits onneuropsychological testing (typically 1.5 SD below demographically relevant norms)

2. CDR = 0 or 0.5

3. Reliable collateral or study partner

Group 3: Alzheimer's Disease (AD)

1. Diagnosis of probable mild AD, diagnosed with NIA-AA criteria, or mixed AD andvascular pathology as long as there is not a large vessel territory stroke,adjudicated by expert consensus panel.

2. Mini-Mental Status Exam (MMSE) score ≥ 10; CDR = ≥0.5

3. Normal glycemic control or prediabetes

4. Reliable collateral or study partner available to attend all visits

Exclusion Criteria:

1. Clinically significant abnormal labs

2. Significant neurologic disease that might affect cognition, other than AD, such asstroke, Parkinson's disease, multiple sclerosis, or recent severe head injury withloss of consciousness for more than 30 minutes within the last year, or withpermanent neurologic sequelae

3. Clinically significant medical illness or organ failure as determined by studyclinicians, including severe, uncontrolled cardiovascular disease, oxygen-treatedchronic obstructive pulmonary disease, severe liver disease, Stage 4 chronic kidneydisease or impending dialysis, active cancer, or other life-limiting condition withlife expectancy less than 3 years

4. Current substance abuse or heavy alcohol consumption defined as >14 alcoholic drinksper week; or history of alcoholism or substance abuse within previous 10 years

5. Current poorly controlled depression or other psychiatric illness as determined byclinical judgement of study clinicians or neuropsychologists

6. Current use of anti-psychotic, benzodiazepines (PRN use <3 times per week isacceptable), anti-coagulants (for participants who will receive a lumbar puncture),strongly anticholinergic or sedative medications

7. Use of anticonvulsant for seizure disorder. (Use of anticonvulsant to treat otherillnesses will be reviewed by the study MD and eligibility will be determined on acase by case basis.)

8. Current use of insulin

9. Brain MRI contraindications; including use of pacemakers, aneurysm clips, artificialheart valves, ear implants or metal/foreign objects in the eyes will be excludedfrom MRI

10. For participants completing any brain imaging protocol, inability to lie on thescanner bed for 40 minutes, or claustrophobia

11. For ADCC-BIG, significant obesity or a lower back condition that is likely to impedesuccessful collection of CSF, as determined by study physician judgment

12. Other significant medical conditions at the investigators' discretion