Associations of Microvascular Dysfunction with Mild Cognitive Impairment and Cognitive Function Among Rural-Dwelling Older Adults in China¹

Article type: Research Article

Authors: Jiang, Chunyan^a | Wang, Yongxiang^{a; b; c} | Dong, Yi^{a; b; c} | Liu, Rui^b | Song, Lin^{a; b; c} | Wang, Shanshan^{a; b; c} | Xu, Zhe^b | Niu, Sijie^d | Ren, Yifei^b | Han, Xiaodong^b | Zhao, Mingqing^a | Wang, Jiafeng^b | Li, Xiaohui^d | Cong, Lin^{a; b; c} | Hou, Tingting^{a; b; c} | Zhang, Qinghua^{a; b; c; *} | Du, Yifeng^{a; b; c; *} | Qiu, Chengxuan^{a; e}

Affiliations: [a] Department of Neurology, Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China | [b] Department of Neurology, Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China | [c] Shandong Provincial Clinical Research Center for Geriatric Neurological Diseases, Jinan, Shandong, P. R. China | [d] Shandong Provincial Key Laboratory of Network based Intelligent Computing, School of Information Science and Engineering, University of Jinan, Jinan, China | [e] Department of Neurobiology, Care Sciences and Society, Aging Research Center and Center for Alzheimer Research, Karolinska Institutet-17 Stockholm University, Stockholm, Sweden

Correspondence: [*] Correspondence to: Prof. Yifeng Du, Department of Neurology, Provincial Hospital affiliated to Shandong First Medical University, No. 324 Jingwuweiqi Road, Jinan, Shandong 250021, P. R. China. E-mail: [email protected] or Dr. Qinghua Zhang, E-mail: [email protected].

Note: [1] This article received a correction notice (Erratum) with the reference: 10.3233/JAD-239004, available at http://doi.org/10.3233/JAD-239004.

Abstract: Background:Microvascular dysfunction (MVD) may contribute to cognitive impairment and Alzheimer’s disease, but evidence is limited. Objective:To investigate the association of composite and organ-specific MVD burden with mild cognitive impairment (MCI) and cognition among rural-dwelling Chinese older adults. Methods:In this population-based cross-sectional study, we assessed MVD makers using optical coherence tomographic angiography for retinal microvasculature features, brain magnetic resonance imaging scans for cerebral small vessel disease (CSVD), and serum biomarkers for MVD. A composite MVD score was generated from the aforementioned organ-specific parameters. We used a neuropsychological test battery to assess memory, verbal fluency, attention, executive function, and global cognitive function. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were diagnosed following the Petersen’s criteria. Data was analyzed with the linear and logistic regression models. Results:Of the 274 dementia-free participants (age≥65 years), 56 were diagnosed with MCI, including 47 with aMCI and 9 with naMCI. A composite MVD score was statistically significantly associated with an odds ratio (OR) of 2.70 (95% confidence interval 1.12–6.53) for MCI and β-coefficient of –0.29 (–0.48, –0.10) for global cognitive score after adjustment for socio-demographics, lifestyle factors, APOE genotype, the Geriatric Depression Scale score, serum inflammatory biomarkers, and cardiovascular comorbidity. A composite score of retinal microvascular morphology was associated with a multivariable-adjusted OR of 1.72 (1.09–2.73) for MCI and multivariable-adjusted β-coefficient of –0.11 (–0.22, –0.01) for global cognitive score. A composite CSVD score was associated with a lower global cognitive score (β= –0.10; –0.17, –0.02). Conclusion:Microvascular dysfunction, especially in the brain and retina, is associated with MCI and poor cognitive function among rural-dwelling older adults.

Keywords: Alzheimer’s disease, cerebral small vessel disease, microvascular dysfunction, mild cognitive impairment, population-based study, retinal microvascular lesions

DOI: 10.3233/JAD-221242

Journal: Journal of Alzheimer's Disease, vol. 93, no. 3, pp. 1111-1124, 2023