title: Indirect effects of elevated body mass index on memory performance through altered cerebral metabolite concentrations.
abstract: OBJECTIVE
  Elevated body mass index (BMI) at midlife is associated with increased risk of cognitive decline in later life. The goal of the current study was to assess mechanisms of early brain vulnerability by examining if higher BMI at midlife affects current cognitive performance through alterations in cerebral neurochemistry.
  
  
  METHODS
  Fifty-five participants, aged 40 to 60 years, underwent neuropsychological testing, health screen, and proton magnetic resonance spectroscopy examining N-acetylaspartate, creatine (Cr), myo-inositol (mI), choline, and glutamate concentrations in occipitoparietal gray matter. Concentrations of N-acetylaspartate, choline, mI, and glutamate were calculated as a ratio over Cr and examined in relation to BMI using multivariate regression analyses. Structural equation modeling was used to determine if BMI had an indirect effect on cognition through cerebral metabolite levels.
  
  
  RESULTS
  Higher BMI was associated with elevations in mI/Cr (F(5,45) = 3.843, p = .006, β = 0.444, p = .002), independent of age, sex, fasting glucose levels, and systolic blood pressure. Moreover, a χ(2) difference test of the direct and indirect structural equation models revealed that BMI had an indirect effect on global cognitive performance (Δχ(2) = 19.939, df = 2, p < .001). Subsequent follow-up analyses revealed that this effect was specific to memory (Δχ(2) = 22.027, df = 2, p < .001).
  
  
  CONCLUSIONS
  Higher BMI was associated with elevations in mI/Cr concentrations in the occipitoparietal gray matter and indirectly related to poorer memory performance through mI/Cr levels, potentially implicating plasma hypertonicity and neuroinflammation as mechanisms underlying obesity-related brain vulnerability.
authors: Department of Psychology, The University of Texas at Austin, 1 University Station, A8000, Austin, TX 78712, USA.
authors: Mitzi M
authors: MM
authors: Gonzales
authors: Takashi
authors: T
authors: Tarumi
authors: Danielle E
authors: DE
authors: Eagan
authors: Hirofumi
authors: H
authors: Tanaka
authors: Miral
authors: M
authors: Vaghasia
authors: Andreana P
authors: AP
authors: Haley
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015992:Body Mass Index; D001921:Brain / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D003072:Cognition Disorders / Q000150:complications / Q000378:metabolism*; D003401:Creatine / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008568:Memory; D008875:Middle Aged; D009483:Neuropsychological Tests; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D011522:Protons
chemical_list: D015415:Biomarkers; D011522:Protons; D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline