Obesity is linked with lower brain volume in 700 AD and MCI patients

Abstract

Obesity is associated with lower brain volumes in cognitively normal elderly subjects, but no study has yet investigated the effects of obesity on brain structure in patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD). To determine if higher body mass index (BMI) is associated with brain volume deficits in cognitively impaired elderly subjects, we analyzed brain magnetic resonance imaging (MRI) scans of 700 MCI or AD patients from 2 different cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Cardiovascular Health Study-Cognition Study (CHS-CS). Tensor-based morphometry (TBM) was used to create 3-dimensional maps of regional tissue excess or deficits in subjects with MCI (ADNI, n = 399; CHS-CS, n = 77) and AD (ADNI, n = 188; CHS, n = 36). In both AD and MCI groups, higher body mass index was associated with brain volume deficits in frontal, temporal, parietal, and occipital lobes; the atrophic pattern was consistent in both ADNI and CHS populations. Cardiovascular risk factors, especially obesity, should be considered as influencing brain structure in those already afflicted by cognitive impairment and dementia.

Figure 1

Histogram of body mass index (BMI) values from (a) ADNI and (b) CHS cohorts.

Figure 2

Box plot of body mass index (BMI) values from ADNI and CHS cohorts. In this type of plot, the bottom and top of the boxes show the 25th and 75th percentiles of the data (lower and upper quartiles); the band near the middle of each box shows the median (50th percentile). From the plot, the outliers are shown as observations that extend beyond the whiskers.

Figure 3

3D maps show areas where regional brain tissue volumes were significantly associated with BMI in AD and MCI subjects (pooled together) from the CHS and ADNI cohorts (N=700). In the significant areas, the regression coefficients (unstandardized beta values) are shown at each voxel for the CHS subjects (top row; N=113, critical uncorrected P-value: 0.0062) and ADNI subjects (bottom row; N=587, critical uncorrected P-value: 0.025). These represent the estimated degree of tissue excess or deficit at each voxel, as a percentage, for every unit increase in BMI, after statistically controlling for effects age, sex, and education on brain structure. They can be considered as the slope of best fitting line relating tissue deficits to BMI. Images are in radiological convention (left side of the brain shown on the right) and are displayed on a specially constructed average brain template created from the subjects within each cohort (mean deformation template, MDT).

Figure 4

3D maps show areas where regional brain tissue volumes were significantly associated with BMI in MCI subjects in the CHS cohort (top row; N=77; critical uncorrected P-value: 0.0093) and ADNI cohort (bottom row; N=400, critical uncorrected P-value: 0.018). These represent the estimated degree of tissue excess or deficit at each voxel, as a percentage, for every unit increase in BMI, after statistically controlling for effects age, sex, and education on brain structure. Images are in radiological convention (left side of the brain shown on the right) and are displayed on a specially constructed average brain template created from the subjects within each cohort (mean deformation template, or MDT).

Figure 5

3D maps show areas where regional brain tissue volumes were significantly associated with BMI in AD subjects only in the ADNI cohort (N=188, critical uncorrected P-value: 0.012). 3D maps for the CHS cohort did not pass FDR and are therefore not displayed. These represent the estimated degree of tissue excess or deficit at each voxel, as a percentage, for every unit increase in BMI, after statistically controlling for effects age, sex, and education on brain structure. Images are in radiological convention (left side of the brain shown on the right) and are displayed on a specially constructed average brain template created from the subjects within each cohort (mean deformation template, or MDT).