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. 2021;79(4):1801-1811.
doi: 10.3233/JAD-201242.

Obesity and White Matter Neuroinflammation Related Edema in Alzheimer's Disease Dementia Biomarker Negative Cognitively Normal Individuals

Maria Ly  1 , Cyrus A Raji  2   3 , Gary Z Yu  1 , Qing Wang  2 , Yong Wang  2 , Suzanne E Schindler  3 , Hongyu An  2 , Amjad Samara  4 , Sarah A Eisenstein  2   4 , Tamara Hershey  2   3   4   5 , Gordon Smith  6 , Samuel Klein  6 , Jingxia Liu  7 , Chengjie Xiong  7 , Beau M Ances  3 , John C Morris  3 , Tammie L S Benzinger  2
Affiliations

Obesity and White Matter Neuroinflammation Related Edema in Alzheimer's Disease Dementia Biomarker Negative Cognitively Normal Individuals

Maria Ly et al. J Alzheimers Dis. 2021.

Abstract

Background: Obesity is related to quantitative neuroimaging abnormalities including reduced gray matter volumes and impaired white matter microstructural integrity, although the underlying mechanisms are not well understood.

Objective: We assessed influence of obesity on neuroinflammation imaging that may mediate brain morphometric changes. Establishing the role of neuroinflammation in obesity will enhance understanding of this modifiable disorder as a risk factor for Alzheimer's disease (AD) dementia.

Methods: We analyzed brain MRIs from 104 cognitively normal participants (CDR = 0) and biomarker negativity for CSF amyloid or tau. We classified body mass index (BMI) as normal (BMI <25, N = 62) or overweight and obese (BMI ≥25, N = 42). Blood pressure was measured. BMI and blood pressure classifications were related to neuroinflammation imaging (NII) derived edema fraction in 17 white matter tracts. This metric was also correlated to hippocampal volumes and CSF biomarkers of inflammation and neurodegeneration: YKL-40, SNAP25, VILIP, tau, and NFL.

Results: Participants with BMI <25 had lower NII-derived edema fraction, with protective effects of normal blood pressure. Statistically significant white matter tracts included the internal capsule, external capsule, and corona radiata, FDR correc-ted for multiple comparisons to alpha = 0.05. Higher NII-derived edema fractions in the internal capsule, corpus callosum, gyrus, and superior fronto-occipital fasciculus were related with smaller hippocampal volumes only in individuals with BMI ≥25. There were no statistically significant correlations between NII-derived edema fraction and CSF biomarkers.

Conclusion: We demonstrate statistically significant relationships between neuroinflammation, elevated BMI, and hippocampal volume, raising implications for neuroinflammation mechanisms of obesity-related brain dysfunction in cognitively normal elderly.

Keywords: Alzheimer’s disease; neuroinflammation imaging; obesity.

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Figures

Figure 1:
Figure 1:. Partial Correlation Matrix of age, sex, blood pressure, and BMI against NII Edema Fraction.
This figure is a matrix of partial correlations between age, sex, healthy blood pressure (BP, defined as systolic blood pressure<120 and diastolic blood pressure<80), BMI<25, and the interaction between BMI<25 and healthy BP against NII-derived edema fraction. Male sex was correlated with a lower level of NII edema fraction. There was no statistically significant relationship between BP alone and edema fraction. BMI<25 related to lower levels of NII edema fraction. The interaction between healthy BP and BMI<25 also showed a similar relationship with lower NII edema fraction. ** indicates significance after FDR correction with alpha = 0.05. * indicates significance after FDR correction with alpha = 0.10.
Figure 2:
Figure 2:. Scatterplots of Statistically Significant Relationships between Total Hippocampal Volume and Regional NII Edema Fraction.
Scatterplots of significant associations between NII-derived edema fraction for different white matter tracts and hippocampal volumes are shown for individuals with BMI≥25. Linear regression lines are plotted as well in red.
See this image and copyright information in PMC

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