Brittany Intzandt1,2,3, Safa Sanami4, Julia Huck4, Richard D Hoge5, Louis Bherer2,3,6,7, and Claudine J Gauthier3,4,6
1INDI Department, Concordia University, Montreal, QC, Canada, 2Centre de Recherche de l'Institut Universitaire de Geriatrie, Montreal, QC, Canada, 3Centre de Recherche, l'Institut de Cardiologie de Montréal, Montreal, QC, Canada, 4Physics Department, Concordia University, Montreal, QC, Canada, 5Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada, 6PERFORM Centre, Concordia Univeristy, Montreal, QC, Canada, 7Départment de Médicine, Université de Montréal, Montreal, QC, Canada
Synopsis
Cortical thinning occurs
during aging and has been reported to worsen with increased adiposity, although
this relationship seems dependent on sex. Increased cortical thickness is related
to greater cardiovascular fitness in aging, but previous work has not explored
if fitness moderates these conflicting relationships between overweight and cortical
thinning. Here, we investigated if fitness moderates relationships between
overweight status and cortical thickness in older women and men. Results
revealed overweight women had greater cortical thickness than overweight men,
but fitness did not moderate this. Future work should investigate sex hormones
to further understand these sex differences in overweight individuals.
Summary of main findings
Cardiovascular
fitness did not moderate the relationship between increased adiposity and cortical
thickness in overweight males and females, nor in those with normal weight.Introduction
Cortical thinning is
frequently reported in aging. These declines in cortical thickness have been
shown to be attenuated by lifestyle factors such as increased cardiovascular
fitness (CVF)1, whereas increased adiposity (i.e. greater body mass
index (BMI)) has been reported to accentuate deterioration of cortical thickness2. However, the consistency of these findings changes when
considering sex. For example, it has been observed that increased BMI was
related to greater cortical thickness in men, whereas in females there was no
relationship3. Conversely, others have shown men to have no
association between BMI and cortical thickness, but that higher BMI in women is
related to cortical thinning4. Yet, in these studies CVF was not reported, thus it
is unclear if, knowing its positive effects on the brain, it might have an
influential role and potentially aid in explaining these paradoxical findings
among sex, BMI and cortical thickness. Thus, we aimed to identify if being normal
weight versus overweight/obese had a differential effect on cerebral structure
depending on sex, and if so, whether there is a moderating role of CVF. Methods
Data from three unique study datasets were pooled,
providing a total of 82 older adults with MRI acquisitions, all on 3T Siemens
MRI scanners (n=3). An anatomical MPRAGE was acquired in all participants (see
Table 1 for the unique imaging parameters for each study).
Participants also completed a peak
oxygen consumption (VO2 peak) test, the gold standard for measuring
fitness levels, outside of the scanner, as well as demographics about height,
weight, education and age.
The MPRAGE images were used to calculate cortical parcellations using the
FreeSurfer software package (v6.0) processing pipeline (http://surfer.nmr.mgh.harvard.edu). We used standard parameter settings for this study
as reported in 5. Part of this includes registration of data to Talairach common template, and a smoothing
kernel of 15 mm was used. Differences in cortical thickness among overweight men
(OBM), women (OBW), and normal weight men (NWM) and women (NWW) (4 groups) was
the primary objective. A general linear model was defined, and these groups were
used as predictors. We then defined age, education and dataset as nuisance covariates
in the model. All statistical tests with FreeSurfer were corrected for multiple
comparisons with a Monte Carlo method. Regions of interest (ROI) that were
significant, were extracted to investigate the potential influence of VO2peak
using SPSS and SPSS PROCESS software.Results
Initial
analysis revealed that sex differences were present regardless of BMI status;
females had higher cortical thickness in the left and right hemisphere (Figure
1). Upon further investigation, it was found that OBW had significantly greater
cortical thickness than OBM in the superior parietal regions of both left and
right hemispheres (p =0.0001) (see Figure 1). This latter relationship was
investigated with VO2peak as a moderator and was not significant for
the left hemisphere (LH; p >0.05) or the right hemisphere (RH; p > 0.05).
No statistical differences were observed between NW and OB individuals, or
between NWM and NWW (p > 0.05). Discussion
OBW
demonstrated significantly greater cortical thickness in superior parietal
regions as compared to OBM. These findings contrast other work3,6 which reported OBW had decreased or no difference in cortical
thickness, although these previous studies compared OBW to NWW and OBM to NWM,
they did not compare OBW to OBM. Further, Neth et al., found this relationship between
higher BMI and decreased cortical thickness in regions associated with cortical
decline in Alzheimer’s disease6. Whereas here, a whole brain analysis was completed without a priori
regions defined. Interestingly, previous studies from our group also observed
sex differences in the relationship between overweight status and brain
function, such that only in men, better body composition was associated with
greater cognitive performance7. Notably,
VO2peak was not found to moderate the relationship among sex and
cortical thickness in OB individuals in the LH or RH. This is the first time
that CVF has been reported to be investigated as an influential factor in
relationships among sex, cortical thickness and overweight in aging. Given the
positive effect that greater CVF has demonstrated on cortical thickness during
aging1, it was surprising to observe no influence of CVF on these
relationships3,8. However, with the small sample here, it is possible that we had insufficient
power to detect a significant effect. Conclusions
Results
reported here show that OBW had greater cortical thickness than OBM. These
results should be interpreted with caution due to the small sample size of OBM.
Future work should attempt to investigate the influence of CVF on BMI in a
larger and more balanced cohort, and cortical thickness in ROIs known to
decline in Alzheimer’s disease. Moreover, other cerebral structural outcomes should
be examined, such as grey matter volume and white matter hyperintensities.
Furthermore, work should focus on identifying what other physiological
mechanisms are influencing these contradictory results that are being reported
on the effects of sex and overweight on cortical thickness.
Acknowledgements
No acknowledgement found.References
1. Williams
VJ, Hayes, J, Forman D, et al. Cardiorespiratory fitness is differentially
associated with cortical thickness in young and older adults. NeuroImage.
2017;146:1084-1092. doi:10.1016/j.neuroimage.2016.10.033
2. Isaac V, Sim S, Zheng H, Zagorodnov V,
Tai E-S, Chee M. Adverse Associations between Visceral Adiposity, Brain
Structure, and Cognitive Performance in Healthy Elderly. Front Aging
Neurosci. 2011;3. doi:10.3389/fnagi.2011.00012
3. Kim H, Kim C, Seo SW, et al. Association
between body mass index and cortical thickness: among elderly cognitively
normal men and women. Int Psychogeriatr. 2015;27(1):121-130.
doi:10.1017/S1041610214001744
4. Kim SE, Lee JS, Woo S, et al.
Sex-specific relationship of cardiometabolic syndrome with lower cortical
thickness. Neurology. 2019;93(11):e1045-e1057. doi:10.1212/WNL.0000000000008084
5. Fischl B, Salat DH, Busa E,
et al. Whole Brain Segmentation:
Automated Labeling of Neuroanatomical Structures in the Human Brain. Neuron.
2002;33(3):341-355. doi:10.1016/S0896-6273(02)00569-X
6. Neth BJ, Graff-Radford J, Mielke MM, et
al. Relationship Between Risk Factors and Brain Reserve in Late Middle Age:
Implications for Cognitive Aging. Front Aging Neurosci. 2020;11. doi:10.3389/fnagi.2019.00355
7. Langeard A, Fakrahnak Z,
Vrinceanu T, et al. Sex-moderated
association between body composition and cognition in older adults. Experimental
Gerontology. 2020;138:111002. doi:10.1016/j.exger.2020.111002
8. Veit R, Kullmann S, Heni M,
et al. Reduced cortical
thickness associated with visceral fat and BMI. Neuroimage Clin.
2014;6:307-311. doi:10.1016/j.nicl.2014.09.013