Wake Forestin Alzheimerin taudin kliininen ydin (ADCC)

Adults, 55 years old and older, who have normal memory, mild memory impairment or AD. All subjects will be in reasonably good health with no significant medical illness that may contribute to memory decline other than MCI or probable AD.

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 adjudication committee (typically, performance not worse than 1 SD below demographically relevant norms)
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 (< 140 mg/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 on neuropsychological 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 and vascular 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 as stroke, Parkinson's disease, multiple sclerosis, or recent severe head injury with loss of consciousness for more than 30 minutes within the last year, or with permanent neurologic sequelae
3. Clinically significant medical illness or organ failure as determined by study clinicians, including severe, uncontrolled cardiovascular disease, oxygen-treated chronic obstructive pulmonary disease, severe liver disease, Stage 4 chronic kidney disease or impending dialysis, active cancer, or other life-limiting condition with life expectancy less than 3 years
4. Current substance abuse or heavy alcohol consumption defined as >14 alcoholic drinks per week; or history of alcoholism or substance abuse within previous 10 years
5. Current poorly controlled depression or other psychiatric illness as determined by clinical judgement of study clinicians or neuropsychologists
6. Current use of anti-psychotic, benzodiazepines (PRN use <3 times per week is acceptable), 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 other illnesses will be reviewed by the study MD and eligibility will be determined on a case by case basis.)
8. Current use of insulin
9. Brain MRI contraindications; including use of pacemakers, aneurysm clips, artificial heart valves, ear implants or metal/foreign objects in the eyes will be excluded from MRI
10. For participants completing any brain imaging protocol, inability to lie on the scanner bed for 40 minutes, or claustrophobia
11. For ADCC-BIG, significant obesity or a lower back condition that is likely to impede successful collection of CSF, as determined by study physician judgment
12. Other significant medical conditions at the investigators' discretion