Structural and cognitive correlates of body mass index in healthy older adults

Background: Obesity, commonly measured with body mass index (BMI), is associated with numerous deleterious health conditions and has been identified as a potential modifier of alterations in brain integrity related to old age. Prior research has suggested that white matter integrity observed using diffusion tensor imaging (DTI) is altered in relation to high BMI, but the integrity of specific white matter tracts remains poorly understood. Additionally, no studies have examined fractional anisotropy (FA) of white matter tract integrity in conjunction with neuropsychological evaluation associated with elevated BMI among older adults. The purpose of the present study was to examine white matter tract integrity and cognitive performance associated with elevated BMI in advanced age. Hypotheses: Elevated BMI would be independently associated with lower white matter integrity in tracts connecting frontal and temporal brain regions, and would be associated with poorer cognitive performance in tests of executive function, processing speed, and memory. Second, there would be evidence for a BMI by age interaction relating to measures of white matter integrity and cognitive performance. Methods: Sixty two healthy older adults aged 51 to 81 were evaluated with magnetic resonance imaging (MRI) and neuropsychological evaluation. Associations were examined between BMI, tract-based FA, and cognitive ability in domains of executive function, processing speed, and memory. Hierarchical linear regression analyses were utilized to determine the impact of BMI on FA and cognitive function after accounting for the influence of demographic variables, followed by a test for the interaction of BMI and age on FA and cognitive indices. Secondary analyses were conducted to assess the Bolzenius, Jacob, 2014, UMSL, p. 3 sensitivity of DTI diffusivity metrics to elevated BMI, and to relate tract FA to cognitive performance. Results: Initial analyses showed that increased age was related more strongly to cognitive performance than FA by tract. After controlling for these initial relationships, elevated BMI was associated with lower FA in the uncinate fasciculus (p = .01), though there was no evidence of an age by BMI interaction relating to FA in this tract. No relationships between cognition and BMI were observed after controlling for demographic variables. Secondary analyses did not suggest that DTI diffusivity metrics provide unique information about microstructural tract integrity related to high BMI. Conclusions: Elevated BMI is associated with altered integrity of the uncinate fasciculus. This white matter tract connects frontal and temporal lobes and is involved in memory function. There was no evidence of an age by BMI interaction on FA of the UF, and BMI did not relate to cognitive performance in this study. Future studies should examine measures of cardiovascular health and systemic inflammation to identify factors influencing relationships between BMI and white matter tract integrity. Bolzenius, Jacob, 2014, UMSL, p. 4 Structural and Cognitive Correlates of Body Mass Index in Healthy Older Adults The purpose of this study was to examine the impact of body mass index (BMI) on the integrity of white matter tracts using diffusion tensor imaging (DTI) and neuropsychological function in a sample of healthy older adults. It was hypothesized that elevated BMI would be independently associated with decreased white matter integrity in tracts connecting to frontal and temporal brain regions. It was also hypothesized that individuals with elevated BMI would exhibit poorer cognitive performance in tests of executive function, processing speed, and memory. Finally, it was hypothesized that age and BMI would interact to exhibit an additive association with white matter integrity and cognitive function in metrics shown to be altered in relation to high BMI. Obesity has become an increasingly prevalent health concern in recent decades, especially in the United States and other Western cultures (Baskin, Ard, Franklin, & Allison, 2005; Flegal, Carroll, Ogden, & Curtin, 2010). Recent estimates indicate that nearly a third of adults in the United States are classified as obese (Flegal et al., 2010). As a result, a high percentage of individuals are at increased risk for chronic obesityrelated health conditions, including diabetes, cardiovascular disease, and high cholesterol (Malnick & Knobler, 2006). If uncorrected, these obesity-related consequences can contribute to decreased quality of life, increased cost of health care, and increased mortality (Sturm, 2002). One of the most common methods to quantify body composition is BMI. BMI (defined as weight in kilograms divided by height in meters squared) provides a quick but relatively accurate standardized assessment of body weight, and is highly correlated with body fat percentage (Flegal et al., 2009). Research has shown that individuals in the Bolzenius, Jacob, 2014, UMSL, p. 5 overweight (25.0 – 29.9 kg/m) and obese (≥ 30.0 kg/m) BMI ranges experience significantly more health problems than normal-weight individuals, and individuals at the extreme ends of the BMI spectrum (i.e. underweight and obese) experience the highest number of adverse health consequences (Grundy, Brewer, Cleeman, Smith, & Lenfant, 2004; Malnick & Knobler, 2006). In addition to its utility as an epidemiological index of obesity, BMI has been widely used to examine alterations in brain integrity related to obesity. Several studies have described significant relationships between BMI, neuroimaging metrics, and measures of cognitive performance (Gunstad et al., 2007; Gunstad et al., 2008; van den Berg, Kloppenborg, Kessels, Kappelle, & Biessels, 2009). Evidence suggests that high BMI is related to poor cognitive performance. A recent meta-analysis described a negative association between BMI and executive function, processing speed, and memory performance (van den Berg et al., 2009). In addition, several studies have demonstrated poor cognitive performance in relation to high BMI independent of age (Cournot et al., 2006; Gunstad, Paul, Cohen, Tate, & Gordon, 2006; Gunstad et al., 2007; Sabia, Kivimaki, Shipley, Marmot, & SinghManoux, 2009). Some studies have demonstrated better cognitive performance with high BMI (Gunstad, Lhotsky, Wendell, Ferucci, & Zonderman, 2010; Kuo et al., 2006; Ward, Carlsson, Trivedi, Sager, & Johnson, 2005), though these include population-based designs and liberal inclusion criteria that limit application of findings to a sample of healthy older adults. Overall, while research suggests elevated BMI is associated with cognitive difficulties in adulthood, few studies have examined this relationship in healthy