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

Article type: Research Article

Authors: Ly, Maria^{a; 1} | Raji, Cyrus A.^{b; c; 1; *} | Yu, Gary Z.^a | Wang, Qing^b | Wang, Yong^b | Schindler, Suzanne E.^c | An, Hongyu^b | Samara, Amjad^d | Eisenstein, Sarah A.^{b; d} | Hershey, Tamara^{b; c; d; e} | Smith, Gordon^f | Klein, Samuel^f | Liu, Jingxia^g | Xiong, Chengjie^g | Ances, Beau M.^c | Morris, John C.^c | Benzinger, Tammie L.S.^b

Affiliations: [a] University of Pittsburgh Medical Scientist Training Program, Pittsburgh, PA, USA | [b] Mallinckrodt Institute of Radiology, Division of Neuroradiology, Washington University in St. Louis, St. Louis, MO, USA | [c] Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA | [d] Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA | [e] Department of Psychological & Brain Sciences, Washington University School of Medicine, St. Louis, MO, USA | [f] Center for Human Nutrition, Washington University in St. Louis, St. Louis, MO, USA | [g] Department of Biostatistics, Washington University in St. Louis, St. Louis, MO, USA

Correspondence: [*] Correspondence to: Cyrus A. Raji, MD, PhD, Mallinckrodt Institute of Radiology, Division of Neuroradiology, Washington University in St. Louis, St. Louis, MO 63130, USA. E-mail: [email protected].

Note: [1 ] These authors contributed equally to this work.

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

DOI: 10.3233/JAD-201242

Journal: Journal of Alzheimer's Disease, vol. 79, no. 4, pp. 1801-1811, 2021