Wake Forest Alzheimer's Disease Clinical Core

The data and specimen repository of the ADCC study will provide a unified mechanism for
cataloging and storing data that can be efficiently shared across studies. This repository
will also allow for important collaborations with other Alzheimer's Disease Centers across
the US that are performing similar investigations of adults at increased risk of dementia.
Data sharing across multiple institutions and investigators will be critical to optimize
speed of acquisition and standardization of outcomes that may ultimately lead to the
development of innovative tools for early detection and new treatment strategies. The
repository will include cognitive data, human specimen samples (blood, cerebrospinal fluid),
medical and family history information, and neuroimaging data. Data collected from
participants enrolled in the ADCC will be stored indefinitely for future investigations.

Participants will include adults at least 55 years old, with or without a cognitive deficit,
who meet criteria for inclusion into one of the groups described below. Males and females
will be equal to distribution in the Triad area population. Additional recruitment efforts
targeting underserved communities will be used to increase representation of these adults in
the study cohort beyond what is typical in other local and national studies of AD.

Eligible participants will have the option to participate in the core ADCC study and also in
a biomarker-intensive substudy that will collect additional measurements of brain function
and chemical markers of AD pathology. While all participants enrolled in the core ADCC study
will receive brain magnetic resonance imaging (MRI) and a DEXA scan to measure fat and bone
densities within the body, those enrolled in the substudy will complete a lumbar puncture
(LP) to permit quantification of AD biomarkers in cerebrospinal fluid (CSF). Participants
enrolled in the substudy will be referred to as the Biomarker-Intensive Group, or ADCC-BIG.

At study entry, participants will meet inclusion criteria for membership in one of the groups
that differ according to cognitive status and metabolic health (described below). Once
enrolled, a change in cognitive or metabolic status will not affect eligibility to receive
follow-up assessments as part of this study, although frequency of assessment may change
(i.e., enrollees who progress to late-stage AD or type 2 diabetes will not be dis-enrolled).
Eligible participants who choose to also enroll in ADCC-BIG must agree to complete the LP. If
participants have screened or participated in another Kulynych Center study within the last 3
months, some data may be reused to avoid redundant data collection and reduce participant
burden. This data may include specimen samples such as blood or CSF, cognitive testing data
and MRI imaging data.

Inclusion Criteria:

Group 1: Cognitively Normal/Normoglycemic (CN-N)

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

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: Cognitively Normal/Prediabetic (CN-P)

1. 1) No cognitive impairment evident on formal testing (as defined above), though
subjective complaints are allowed

2. CDR = 0

3. Prediabetes as indicated by 2-hour OGTT ADA glycemic criteria (blood glucose levels ≥
140 mg/dL and < 200 at the 2-h timepoint). Participants with glucose levels ≥200 mg/dL
will be asked to provide written assurance that their PCP does not recommend drug
treatment, and if this is the case, they will be eligible to enroll.

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

Group 3: Mild Cognitive Impairment/Normoglycemic (MCI-N)

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 4: Mild Cognitive Impairment/Prediabetic (MCI-P)

Participants in this group will have impaired glucose metabolism.

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 5: 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 ≥ 18; CDR = 0.5 or 1

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 or past use (within the last 5 years) of hypoglycemic agents or 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