Twelve Weeks of Intermittent Caloric Restriction Diet Mitigates Neuroinflammation in Midlife Individuals with Multiple Sclerosis: A Pilot Study with Implications for Prevention of Alzheimer’s Disease

Article type: Research Article

Authors: Rahmani, Farzaneh^a | Ghezzi, Laura^b | Tosti, Valeria^b | Liu, Jingxia^{a; c} | Song, Sheng-Kwei^{d; e} | Wu, Anthony T.^{d; e} | Rajamanickam, Jayashree^a | Obert, Kathleen A.^b | Benzinger, Tammie L.S.^{a; g} | Mittendorfer, Bettina^h | Piccio, Laura^{b; e; f; i; 1} | Raji, Cyrus A.^{a; g; 1; *}

Affiliations: [a] Mallinckrodt Institute of Radiology, Division of Neuroradiology, Washington University in St. Louis, St. Louis, MO, USA | [b] Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA | [c] Department of Surgery, Division of Public Health Sciences, Washington University in St. Louis, St. Louis, MO, USA | [d] Department of Physics, Washington University in St. Louis, St. Louis, MO, USA | [e] Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO, USA | [f] Brain and Mind Centre, School of Medical Sciences, The University of Sydney, NSW, Australia | [g] Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St Louis, St. Louis, MO, USA | [h] Department of Medicine, Division of Geriatrics and Nutritional Science, Washington University in St. Louis, St. Louis, MO, USA | [i] Charles Perkin Centre, The University of Sydney NSW, Australia

Correspondence: [*] Correspondence to: Cyrus A. Raji, MD, PhD, Assistant Professor of Radiology and Neurology, Director, Neuromagnetic Resonance Imaging, Co-Director, Imaging, Knight Alzheimer Disease Research Center (ADRC), Washington University School of Medicine, Mallinckrodt Institute of Radiology, 4525 Scott Ave., Campus Box 8131, St. Louis, MO 63110, USA. Tel.: +1 314 273 0334; E-mail: craji@wustl.edu.

Note: [1] These co-authors contributed equal senior authorship to this work.

Abstract: Background:Multiple sclerosis (MS) is a prototype neuroinflammatory disorder with increasingly recognized role for neurodegeneration. Most first-line treatments cannot prevent the progression of neurodegeneration and the resultant disability. Interventions can improve symptoms of MS and might provide insights into the underlying pathology. Objective:To investigate the effect of intermittent caloric restriction on neuroimaging markers of MS. Methods:We randomized ten participants with relapsing remitting MS to either a 12-week intermittent calorie restriction (iCR) diet (n = 5) or control (n = 5). Cortical thickness and volumes were measured through FreeSurfer, cortical perfusion was measured by arterial spin labeling and neuroinflammation through diffusion basis spectrum imaging. Results:After 12 weeks of iCR, brain volume increased in the left superior and inferior parietal gyri (p: 0.050 and 0.049, respectively) and the banks of the superior temporal sulcus (p: 0.01). Similarly in the iCR group, cortical thickness improved in the bilateral medial orbitofrontal gyri (p: 0.04 and 0.05 in right and left, respectively), the left superior temporal gyrus (p: 0.03), and the frontal pole (p: 0.008) among others. Cerebral perfusion decreased in the bilateral fusiform gyri (p: 0.047 and 0.02 in right and left, respectively) and increased in the bilateral deep anterior white matter (p: 0.03 and 0.013 in right and left, respectively). Neuroinflammation, demonstrated through hindered and restricted water fractions (HF and RF), decreased in the left optic tract (HF p: 0.02), and the right extreme capsule (RF p: 0.007 and HF p: 0.003). Conclusion:These pilot data suggest therapeutic effects of iCR in improving cortical volume and thickness and mitigating neuroinflammation in midlife adults with MS.

Keywords: Alzheimer’s disease, arterial spin labeling, caloric restriction, diffusion basis spectrum imaging, multiple sclerosis, neuroinflammation, prevention, relative cerebral blood flow

DOI: 10.3233/JAD-221007

Journal: Journal of Alzheimer's Disease, vol. 93, no. 1, pp. 263-273, 2023