Synergistic Effect of Serum Homocysteine and Diabetes Mellitus on Brain Alterations

Article type: Research Article

Authors: Byeon, Gihwan^a | Byun, Min Soo^b | Yi, Dahyun^c | Lee, Jun Ho^d | Jeon, So Yeon^e | Ko, Kang^d | Jung, Gijung^f | Lee, Jun-Young^{g; h} | Kim, Yu Kyeongⁱ | Lee, Yun-Sang^j | Kang, Koung Mi^k | Sohn, Chul-Ho^k | Lee, Dong Young^{c; f; h; *} | for the KBASE research group¹

Affiliations: [a] Department of Neuropsychiatry, Kangwon National University Hospital, Chuncheon, Republic of Korea | [b] Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea | [c] Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, Republic of Korea | [d] Department of Psychiatry, National Center for Mental Health, Seoul, Republic of Korea | [e] Department of Neuropsychiatry, Chungnam National University Hospital, Daejeon, Republic of Korea | [f] Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea | [g] Department of Neuropsychiatry, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea | [h] Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea | [i] Department of Nuclear Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea | [j] Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Republic of Korea | [k] Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea

Correspondence: [*] Correspondence to: Dong Young Lee, MD, PhD, Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea. E-mail: [email protected].

Note: [1] The co-investigators of the KBASE Research Group are listed elsewhere (http://kbase.kr).

Abstract: Background:Both elevated blood homocysteine and diabetes mellitus (DM) are related to cognitive impairments or dementia. A previous study also demonstrated that the association between homocysteine and cognitive decline was much stronger in individuals with DM than in those without DM. Objective:This study aimed to examine the interactive effect of blood homocysteine and DM on brain pathological changes including brain atrophy, amyloid-β and tau deposition, and small vessel disease (SVD) related to cognitive impairments. Methods:A total of 430 non-demented older adults underwent comprehensive clinical assessment, measurement of serum homocysteine level, [11C] Pittsburgh Compound B (PiB) PET, [18F] AV-1451 PET, and brain MRI. Results:The interactive effect of homocysteine with the presence of DM on brain atrophy, especially in aging-related brain regions, was significant. Higher homocysteine concentration was associated with more prominent brain atrophy in individuals with DM, but not in those without DM. In contrast, interaction effect of homocysteine and DM was found neither on Alzheimer’s disease (AD) pathologies, including amyloid-β and tau deposition, nor white matter hyperintensity volume as a measure of SVD. Conclusion:The present findings suggest that high blood homocysteine level and DM synergistically aggravate brain damage independently of AD and cerebrovascular disease. With regard to preventing dementia or cognitive decline in older adults, these results support the importance of strictly controlling blood glucose in individuals with hyperhomocysteinemia and lowering blood homocysteine level in those with DM.

Keywords: Brain atrophy, diabetes mellitus, homocysteine, magnetic resonance imaging, positron emission tomography

DOI: 10.3233/JAD-210036

Journal: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 287-295, 2021