Wake Forest Alzheimer's Disease Clinical Core

NCT03140865 | Recruiting

• 2 other identifiers: IRB0002554040010560
• Study Type: observational
• Target: 850
• Locations: 1 country
• Sites: 1

Brief Summary

Efforts to find treatments for AD have yielded only modest benefits, likely because longstanding AD pathological processes induce irreversible neurological compromise. These processes begin years before the onset of clinical symptoms. This possibility has been incorporated into a model describing stages of AD development, articulated by the NIA/Alzheimer's Association preclinical workgroup of which the Co-Director of the Kulynych Alzheimer's Research Center, Dr. Suzanne Craft, was a member. According to this model, the best hope for countermanding the effects of AD lies in intervening at the earliest possible point in the pathological cascade. There are several important ongoing efforts in adults with preclinical AD that directly target amyloid aggregation. Although this strategy addresses an important aspect of the AD pathological cascade, we believe that addressing metabolic dysfunction affecting glucose and insulin regulation offers a complementary approach, in that it may reduce amyloid burden and toxicity, while also directly enhancing synaptic health, brain metabolism, tau regulation and neurovascular function. The purpose of the ADCC is to identify and characterize early risk factors that predict cognitive decline and dementia in asymptomatic adults and adults with early signs of cognitive impairment. The data obtained from this study, collected at enrollment and follow-up will allow us to examine disease trajectory in individuals with and without prediabetes and other measures of glucoregulatory dysfunction in this process. The enrollees, who will be well-characterized with regard to cognitive and metabolic status through ADCC assessments, will provide an important resource for other local (institution) and national investigations. Data collected from participants enrolled in the ADCC will be stored indefinitely for future investigations.

Conditions

Alzheimer's Disease; Mild Cognitive Impairment; Prediabetic State

Keywords

Alzheimer's; observational; prediabetes; mild cognitive impairment

Outcome Measures

Primary Outcomes (1)

• Change in performance on cognitive measures.

  Cognitive measure such as memory, verbal fluency and executive function will be assessed annually, either by phone or in person depending on group.

  5 years

Secondary Outcomes (2)

• Change in biomarker levels in cerebrospinal fluid (CSF).

  5 years

• Change in brain volumes on magnetic resonance imaging (MRI).

  5 years

Study Arms (3)

Cognitively Normal

This group will include 300 healthy volunteers with no apparent memory problems. Participants will complete an assessment at enrollment and once per year for the following 5 years. In addition to memory assessments at baseline and year 4, participants will have a brain MRI, OGTT A reliable study partner will need to attend the visits or be available via telephone to complete study interviews.

Mild Cognitive Impairment

This group will include 400 volunteers who have mild memory problems that are observed during cognitive testing. Participants will complete an assessment at enrollment and once per year for the following 5 years. In addition to memory assessments at baseline and year 4, participants will have a brain MRI, OGTT A reliable study partner will need to attend the visits or be available via telephone to complete study interviews.

Alzheimer's disease

This group will include 150 volunteers with mild stage Alzheimer's disease dementia. Participants will complete an assessment at enrollment and once per year for the following 5 years. In addition to memory assessments at baseline and year 4, participants will have a brain MRI, OGTT A reliable study partner will need to attend visits to complete study interviews.

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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.

You may qualify if:

• Group 1: Cognitively Normal (CN)
• No subjective complaints of cognitive impairment
• No cognitive impairment evident on formal testing interpreted by expert adjudication committee (typically, performance not worse than 1 SD below demographically relevant norms)
• Clinical Dementia Rating (CDR) = 0 or 0.5
• 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).
• Reliable collateral or study partner available to attend Visit 1 at a minimum
• Group 2: Mild Cognitive Impairment (MCI)
• Objective evidence of memory and/or executive function deficits on neuropsychological testing (typically 1.5 SD below demographically relevant norms)
• CDR = 0 or 0.5
• Reliable collateral or study partner
• Group 3: Alzheimer's Disease (AD)
• 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.
• Mini-Mental Status Exam (MMSE) score ≥ 10; CDR = ≥0.5
• Normal glycemic control or prediabetes
• Reliable collateral or study partner available to attend all visits

You may not qualify if:

• Clinically significant abnormal labs
• 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
• 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
• 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
• Current poorly controlled depression or other psychiatric illness as determined by clinical judgement of study clinicians or neuropsychologists
• 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
• 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.)
• Current use of insulin
• 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
• For participants completing any brain imaging protocol, inability to lie on the scanner bed for 40 minutes, or claustrophobia
• 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
• Other significant medical conditions at the investigators' discretion

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood collection for routine laboratory tests (hemoglobin A1c, CBC, BMP 8, lipid panel, TSH, Vitamin B12, insulin, and coagulation). Blood will also be drawn for genotyping and determining ApoE status as well as stored for future assays. CSF will be collected on a subset of participants and used to analyze amyloid beta, t-tau, p-tau, and stored for future assays.

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Prediabetic State

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Jeff Williamson, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lauren Latham

CONTACT

(336) 716-6317; lauren.latham@advocatehealth.org

Karen Gagnon

CONTACT

(336) 713-8010; Karen.Gagnon@Advocatehealth.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2014
• First Posted: May 4, 2017
• Study Start: January 1, 2014
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2031
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)