Insulin Resistance and Accelerated Cognitive Aging
Condition: Insulin Resistance
MeSH terms: Insulin Resistance
Study type: Observational

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.
    

Detailed description: 
      Premature and accelerated brain aging trajectories started to be recognized in cognitive and
      neural responses, but specific mechanisms for the course of cognitive aging remain to be
      elucidated. Insulin resistance (IR) is known to change with age, affect cognition in older
      and elderly adults as well as in patients with affective disorders. It is unknown whether IR
      can predict cognitive decline in individuals younger than age 50 without overt mental
      illness. Studies in younger adults afford a unique opportunity to assess whether IR mediates
      cognitive and correlating neural processes decades before the manifestation of cognitive
      decline. The investigators propose to use an innovative accelerated longitudinal design (ALD)
      to characterize trajectories of cognitive and neural biomarkers and to: 1) describe baseline
      cognitive and neural biomarkers of brain function across the spectrum of IR in persons ages
      25-50; 2) assess how the baseline IR and change in IR at a younger age affects the pattern of
      decline in cognitive and neural biomarkers and 3) explore the effects of baseline IR on
      changes in cognitive and neural variables of interest as moderated by non-modifiable risk
      factors for cognitive decline (gender, and APOE4/family history of AD). The current proposal
      aims 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.
      Utilizing an accelerated longitudinal design (ALD) we will recruit overweight/obese
      individuals (total N=160) aged 25-50. Based on semi-longitudinal data, this design will allow
      us to examine outcome development over 25 years between ages 25-50 after 3-year follow-up.
      All subjects will undergo baseline qualitative measure of IR, cognitive assessments and
      multimodal magnetic resonance imaging (MMRI). Neuropsychological evaluation will focus on
      cognitive flexibility/set shifting tests reflecting hippocampal connectivity to the medial
      prefrontal region. MMRI will include memory-related hippocampal function and connectivity
      (measured with task- and resting-state fMRI) and hippocampal volumes. The ALD design will
      allow investigation of the relation between cognitive performance and a corresponding neural
      response across the IR spectrum over a long period of time and the predictive value of IR of
      long-term trajectories of change in cognitive and neural biomarkers over span of 25 years.
    

Observational model: Cohort
Time perspective: Prospective
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.