Total Cerebral Small Vessel Disease Burden Is Related to Worse Performance on the Mini-Mental State Examination and Incident Dementia: A Prospective 5-Year Follow-Up

Article type: Research Article

Authors: Jiang, Yanfeng^{a; b; 1} | Wang, Yingzhe^{c; 1} | Yuan, Ziyu^b | Xu, Kelin^{d; b} | Zhang, Kexun^{e; b} | Zhu, Zhen^{e; b} | Li, Peixi^c | Suo, Chen^{e; b} | Tian, Weizhong^f | Fan, Min^g | Jin, Li^{a; b; h; 2} | Ye, Weimin^{i; b; 2} | Dong, Qiang^c | Cui, Mei^{c; *} | Chen, Xingdong^{a; b; h; *}

Affiliations: [a] State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China | [b] Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China | [c] Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China | [d] School of Data Science and Institute for Big Data, and the Collaborative Innovation Center for Genetics and Development, Fudan University, Shanghai, China | [e] Department of Epidemiology, School of Public Health, and The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China | [f] Taizhou People’s Hospital, Taizhou, Jiangsu, China | [g] Taixing Disease Control and Prevention Center, Taizhou, Jiangsu, China | [h] Human Phenome Institute, Fudan University, Shanghai, China | [i] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

Correspondence: [*] Xingdong Chen PhD, School of Life Sciences, Fudan University, Songhu Road 2005, Shanghai 200438, China. Tel.: +86 21 32146602; Fax: +86 21 31246607; E-mail: [email protected] and Mei Cui MD, PhD, Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, Middle Wulumuqi Road 12, Shanghai 200040, China. Tel.: +86 21 52888164; Fax: +86 21 52887145; E-mail: [email protected]

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

Note: [2] Joint senior authors.

Abstract: Individual cerebral small vessel disease (CSVD) may cause cognitive decline. However, the association between total burden of CSVD and cognitive deterioration in the general population remains unclear. We aimed to determine whether total CSVD score is associated with cognitive performance change and incident dementia in the general population. In the longitudinal population-based Taizhou Imaging Study, 556 participants free of neurological disorders underwent brain MRI and neuropsychological testing at baseline. A total of 456 participants were followed up for cognitive performance for a mean (standard deviation) of 4.6 (0.6) years. Total CSVD score (range 0–4) was calculated by assigning 1 point for the presence of each of the following markers: lacune, white matter hyperintensity, cerebral microbleed, and perivascular space. Beta regression was used to evaluate the association between total CSVD burden and MMSE score change. The association of prevalent CSVD with incident dementia was studied using Fisher’s exact test. CSVDs were present in 262 individuals (47.1%). The total CSVD score was significantly associated with MMSE score decline (p = 0.001). Compared to those with no CSVD, participants with 4 CSVD markers had a steeper decline in MMSE score (β: –0.53, 95% CI: –0.86 to –0.21; p = 0.001). A total of 15 participants developed dementia during follow-up. The presence of more than three CSVD markers at baseline was associated with a significantly higher risk of dementia (p = 0.020). Total CSVD burden appears to be associated with MMSE score decline and incident dementia in a general population in China.

Keywords: Cerebral small vessel disease, cognitive dysfunction, dementia, magnetic resonance imaging

DOI: 10.3233/JAD-181135

Journal: Journal of Alzheimer's Disease, vol. 69, no. 1, pp. 253-262, 2019