Research reportBrain structure and cognitive correlates of body mass index in healthy older adults
Introduction
Obesity has become an increasingly prevalent health concern in recent decades, especially in the United States and other Western cultures [1], [2]. Recent estimates indicate that nearly one third of adults in the United States are classified as obese [2]. High body weight, commonly quantified by body mass index (BMI), is associated with increased risk for chronic health conditions such as diabetes, cardiovascular disease, and late life dementia [3], [4]. If uncorrected, these obesity-related consequences can contribute to decreased quality of life, increased cost of health care, and increased mortality [5].
Elevated BMI has also been associated with alterations in brain structure and function. A recent meta-analysis suggested that high BMI is related to poor cognitive performance, especially in domains of executive function, processing speed, and memory [6]. Other studies have demonstrated poor cognitive performance in relation to high BMI after controlling for demographics and cardiovascular comorbidities [7], [8], [9]. In addition, neuroimaging methodologies incorporating structural magnetic resonance imaging (MRI) have reported smaller volumes of gray and white matter in obese individuals compared to normal-weight individuals, especially in frontal and temporal structures [10], [11], [12], [13]. Though these volumetric approaches are valuable for assessing the amount of regional tissue composition in the brain, they are unable to provide information regarding the microstructural integrity of brain tissue.
Diffusion tensor imaging (DTI) provides detail regarding the integrity of neural microstructure in the brain. The advantage of DTI over other neuroimaging sequences is the opportunity to quantify microstructural characteristics of white matter not captured by standard magnetic resonance imaging [14]. Several studies have demonstrated that the integrity of white matter is adversely affected in individuals with high BMI [15], [16], [17]. White matter regions such as the corpus callosum, cingulate portion of the cingulum bundle, and fornix are shown to exhibit lower fractional anisotropy (FA) associated with high BMI, indicating that the directionality of water diffusion within these areas is reduced in individuals with elevated BMI [15], [17], [18]. Few studies, however, have examined BMI as it relates to FA in white matter tracts connecting to frontal and temporal lobes given volumetric evidence for this relationship. Assessment of these tracts may provide insight into early disruptions in white matter microstructure that lead to cortical atrophy and cognitive dysfunction associated with high BMI.
While many studies suggest that high BMI relates to lower white matter integrity and cognitive performance [19], [8], [9], [16], few studies have examined these measures in a healthy older adult sample. Evidence suggests that elevated body mass may have a compounding effect on the cascade of biological process related to aging, which may be a key factor related to aging brain variability [20]. Activation of age-related physiological processes, including oxidative stress, vascular inflammation, and endothelial cell dysfunction, may be partially modified by obesity, potentially resulting in increased risk of ischemic stroke and white matter damage [3], [21], [22]. Increased quantities of adipocytes seen in obese individuals may exacerbate the cellular inflammatory response, which have a detrimental impact on the cellular integrity of brain tissue, particularly oligodendrocytes that comprise white matter [23], [24]. Some studies have demonstrated an interactive effect of advanced age and high BMI affecting white matter integrity [16], yet many of these studies have focused exclusively on corpus callosum integrity rather than inclusion of cortical association tracts [16], [25]. Investigating the integrity of these tracts in relation to high BMI is important for identifying disruption to white matter microstructure that may contribute to later cognitive dysfunction.
In the present study we examined FA in the superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), cingulate portion of the cingulum bundle, and posterior sections of the corpus callosum associated with BMI. We also investigated the impact of high BMI on cognitive performance on tests of executive function, processing speed, and memory, which represent cognitive domains associated with the specific tracts of interest [26], [27], [28]. We hypothesized that while age would relate to DTI and cognitive measures, elevated BMI would be independently associated with lower white matter tract integrity and cognitive performance.
Section snippets
Participants
A total of 62 individuals between the ages of 51 and 81 were included in the study. Participants were recruited from the local community in addition to the Research Participant Registry of the Washington University Institute of Clinical and Translational Sciences. Demographics and health history were obtained as part of cognitive assessment procedures within one month of MRI acquisition. All participants were required to be fluent English speakers to participate in the study protocol.
Results
See Table 1 for full characterization statistics regarding demographic/health status. Preliminary demographic analyses revealed that age was strongly associated with most cognitive scores (p < .05) but not tract FA. Significant associations were observed between FA in the cingulate and sex (t(59) = 3.703, p < .001) and between FA of the pCC and years of education (r(53) = .294, p < .05).
After controlling for these associations, regression analyses revealed significant alterations in FA in the UF related
Discussion
This study provides one of the first examinations of white matter tract integrity and neuropsychological performance in relation to BMI in a healthy older adult sample. Results of initial analyses suggested that age was strongly related to cognitive performance. By contrast, age was not significantly related to tract-based FA in this sample. After controlling for these confounding influences, elevated BMI was associated with lower FA in the UF. Contrary to hypotheses, there was no evidence of
Conflict of interest
The authors declare that they have no conflict of interest.
Acknowledgements
Study Funding: Supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke grant numbers R01 NS052470 and R01 NS039538, and National Institutes of Health/National Institute of Mental Health grant R21 MH090494. Recruitment database searches were supported in part by National Institutes of Health/National Center for Research Resources grant UL1 TR000448.
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