Investigating the link between obesity and Alzheimer's disease

Neuroinflammation and Alzheimer's Disease Imaging Biomarkers in Midlife Obesity

This study is trying to see how being overweight or obese affects the risk of developing Alzheimer's disease in healthy adults aged 40-60.

Quick facts

• Study type: Observational
• Enrollment: 240 (estimated)
• Ages: 40 Years to 60 Years
• Sex: All
• Sponsor: Washington University School of Medicine (other)
• Locations: 1 site (St Louis, Missouri)
• Trial ID: NCT05077579 on ClinicalTrials.gov

What this trial studies

This observational study aims to explore the relationship between obesity and Alzheimer's disease by creating a cohort of 120 cognitively normal individuals aged 40-60. Participants will be categorized based on their metabolic health status, including metabolically abnormal overweight and obese (MAOO), metabolically normal overweight and obese (MNOO), and metabolically normal lean participants (MNLP). The study will utilize metabolic tests and neuroimaging techniques to assess differences in Alzheimer's biomarkers among these groups. The goal is to better understand the underlying mechanisms connecting obesity and Alzheimer's risk.

Who should consider this trial

Good fit: Ideal candidates are cognitively normal adults aged 40-60 who are overweight or obese and willing to undergo metabolic testing and neuroimaging.

Not a fit: Patients who are already diagnosed with Alzheimer's disease or have significant cognitive impairment may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into how obesity contributes to Alzheimer's disease, potentially leading to targeted prevention strategies.

How similar studies have performed: While the connection between obesity and Alzheimer's has been explored, this specific approach of metabolic subtyping in midlife individuals is relatively novel.

Eligibility criteria

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 or abnormal 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. Fasting blood glucose: ≥100 mg/dl or blood glucose 2 h after an OGTT: ≥140 or fasting insulin: \>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. Blood glucose 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 body circumference \< 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: \< 140 mg/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 the risk to the participant, limit the participant's ability to tolerate the research procedures or interfere with the collection of the data, (e.g., currently taking a drug 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 obesity clinical trial;
7. Laboratory Evaluations exclusion: • Oral glucose tolerance test should not be performed in patients who already fulfill the criteria for diabetes mellitus. These include: - History of Type 1 or 2 diabetes mellitus - Prior documentation of a fasting plasma glucose \>7.0 mmol/L or two or more occasions or clinical symptoms of diabetes e.g. polydipsia, polyuria, ketonuria and rapid weight loss with a random plasma glucose of \>11.1 mmol/L • Other contraindications for venous access as part of OGTT or blood draws: - Venous fibrosis or shunt grafts in both upper extremities - Ongoing cellulitis or infection, particularly in the upper extremities. - Presence of a hematoma at the site of vascular access. - History of hypoglycemic encephalopathy that can occur with prolonged fasting
8. MRI exclusion: • Contraindications to MRI (e.g., certain incompatible electronic medical devices that make it potentially unsafe for the individual to participate). All participants must be willing to undergo at least two MRI screenings, supervised by Level II MRI personnel as designated by the American College of Radiology (ACR).

Where this trial is running

St Louis, Missouri

• Washington University School of Medicine — St Louis, Missouri, United States (RECRUITING)

Study contacts

• Principal investigator: Cyrus Raji, MD, PhD — Washington University School of Medicine
• Study coordinator: Cyrus Raji, MD, PhD

Conditions: Alzheimer Disease, Obesity, Metabolic Disease