Elevated Homocysteine Levels and Hypertension Relate to Cognitive Impairment via Increased White Matter Hyperintensity Volume

Article type: Research Article

Authors: Gao, Yuan^{a; b; 1} | Duan, Xiaocui^{b; 1} | Li, Wanlin^a | Zhang, Xiaoyu^a | Xian, Xiaohui^c | Zhu, Yuan^{d; *} | Wang, Hualong^{a; *} | Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] Department of Neurology, The First Hospital of Hebei Medical University, Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang, Hebei, China | [b] Department of Cell Biology, Hebei Medical University, Shijiazhuang, Hebei, China | [c] Department of Pathophysiology, Hebei Medical University, Shijiazhuang, Hebei, China | [d] Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine Geriatrics Department, Shanghai, China

Correspondence: [*] Correspondence to: Hualong Wang, Department of Neurology, The First Hospital of Hebei Medical University, Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang 050000, Hebei, China. E-mail: [email protected] and Yuan Zhu, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine Geriatrics Department, Shanghai, China. E-mail: [email protected].

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

Note: [2] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of the ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at http://adni.loni.usc.edu/wpcontent/uploads/howtoapply/ADNIAcknowledgmentList.pdf

Abstract: Background:Recent studies have identified a relationship between elevated homocysteine levels and hypertension (HTN) with Alzheimer’s disease (AD), but its pathogenesis remains unclear. Objective:To evaluate elevated homocysteine levels and HTN as risk factors for cognitive impairment (CI) and determine their relationship with white matter hyperintensity (WMH) volume. Methods:A total of 521 subjects were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database and divided into two groups according to the diagnostic criteria of the ADNI database. The CI group included 370 subjects, consisting of 122 with AD and 248 with mild CI, while the cognitively normal (CN) group contained 151 subjects. The history of HTN, homocysteine levels, WMH volume and Mini-Mental State Examination (MMSE) scores were analyzed. Results:The study found that patients with CI had higher homocysteine levels than those with CN. Additionally, WMH volume was significantly correlated with homocysteine levels in CI patients, and MMSE scores decreased as WMH volume increased. Further analysis revealed that CI patients with HTN had significantly higher homocysteine levels than those without HTN. Furthermore, the correlation between WMH volume and homocysteine levels was significant only in CI patients with HTN and not in those without HTN. In CN patients, there was no correlation between WMH volume and homocysteine levels in either the HTN or non-HTN groups, and no difference was observed in homocysteine levels. Conclusions:It is indicated that elevated homocysteine levels in conjunction with HTN are associated with the increased volume of WMHs and CI.

Keywords: Alzheimer’s disease, homocysteine, hypertension, white matter hyperintensities

DOI: 10.3233/JAD-230687

Journal: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1739-1746, 2023