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.
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: Xiaoping Zhu; Norbert Schuff; John Kornak; Brian Soher; Kristine Yaffe; Joel H Kramer; Frank Ezekiel; Bruce L Miller; William J Jagust; Michael W Weiner Journal: Alzheimer Dis Assoc Disord Date: 2006 Apr-Jun Impact factor: 2.703
Authors: J C Morris; A Heyman; R C Mohs; J P Hughes; G van Belle; G Fillenbaum; E D Mellits; C Clark Journal: Neurology Date: 1989-09 Impact factor: 9.910
Authors: H Randall Griffith; Jan A den Hollander; Ozioma Okonkwo; William T Evanochko; Lindy E Harrell; Edward Y Zamrini; John C Brockington; Daniel C Marson Journal: J Clin Exp Neuropsychol Date: 2007-08 Impact factor: 2.475