Insulin Resistance and Accelerated Cognitive Aging

NCT03039647 | Completed

• 1 other identifier: 38733
• Study Type: observational
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

Premature and accelerated brain aging trajectories have been observed among people with metabolic dysfunction, but mechanisms of these altered trajectories are not understood. Insulin resistance (IR) is known to change with age and affect cognition in older and elderly adults as well as in patients with mood disorders. The main purpose of the study is to describe the developmental trajectory of cognitive and neural biomarkers across the spectrum of metabolic dysfunction in overweight/obese adults younger than 50 years of age. The innovative study design will allow the investigators to examine cognitive outcome development over a 25-year span without an investment into the longitudinal observation of changes in cognition and neural function.

Conditions

Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• Change in hippocampal connectivity

  This will be assessed by MRI and cognitive assessments.

  Change in hippocampal connectivity from entry point to exit point three years later

Secondary Outcomes (2)

• Change in hippocampal volume

  Change in hippocampal volume from entry point to exit point three years later

• Change in memory-related functional activation

  Change in memory-related functional activation from entry point to exit point three years later

Study Arms (2)

Entry Point IR (SSPG, HOMA-IR)

All subjects will undergo baseline indirect (HOMA-IR) and direct (SSPG) measures of IR. The investigators hypothesize that a higher entry point IR will predict steeper decline in memory and executive function performance and hippocampal connectivity.

Change in IR (HOMA-IR)

The investigators predict that change in IR (as measured by HOMA-IR) will predict the pattern of decline in memory and executive function performance and hippocampal connectivity.

Eligibility Criteria

• Age: 25 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The investigators will consent and enroll 160 medically stable men and women in and around Stanford. Stanford will be the only study site. Subjects will be 25-50 years old, with a body mass index (BMI) of 25 to 35kg/m2, and will have at least 12 years of education.

You may qualify if:

• Between 25 and 50 years of age
• BMI of 25 to 33 kg/m\^2
• At least 12 years of education
• All subjects will be medically stable (i.e. no uncontrolled or poorly controlled medical illnesses), cognitively intact as defined by Mini Mental Status Exam (MMSE) score of \> 27, and will have adequate visual and auditory acuity to allow for cognitive testing. Glycemic history will be collected together with other pertinent medical information from primary care providers.

You may not qualify if:

• Diagnosis of possible or probably dementia, MCI, or any other dementia
• Evidence of cognitive decline by MMSE \< 27 or self-reported significant decline in memory within the past year (per the Memory Function Questionnaire)
• History of Type 1 or Type 2 Diabetes
• Fasting plasma glucose \> 126 mg/dL
• History of significant cardiovascular disease or myocardial infarction, cerebrovascular/pulmonary disease, cancer, untreated hypothyroidism, unstable or untreated hypertension, history of head trauma, MRI-contraindications (i.e. metal in body, claustrophobia), premature birth (which may affect MRI findings), history of neurological disorder (ischemic attacks, carotid bruits, or lacunes upon MRI scan), or evidence of neurological or other physical illness that could produce cognitive deterioration
• Use of any drug that may significantly affect the SSPG or cognitive testing results (specifically: centrally active beta-blockers, narcotics, clonidine, antipsychotics, benzodiazepines, systemic corticosteroids, medications with significant cholinergic or anticholinergic effects, anti-convulsants, anti-diabetics, or anti-cholesterol medications)
• Drug or alcohol abuse or dependence within the past 6 months, or positive urine toxicology screen for illicit substances at eligibility screening
• History of mental illness, with the exception of past mood disorder, or evidence of acute depression as determined by a 17-item Hamilton Depression Rating Scale (HDRS-17) score of 8 or more
• Participants with history of mood disorder must be in remission for at least 6 months prior to study entry

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford Psychiatry Building

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Natalie Rasgon, M.D., Ph.D.

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry and Behavioral Sciences

Study Record Dates

• First Submitted: January 26, 2017
• First Posted: February 1, 2017
• Study Start: January 1, 2017
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2022
• Last Updated: May 9, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)