Association of Cerebral Microbleeds with Cognitive Decline: A Longitudinal Study

Article type: Research Article

Authors: Li, Lin^{a; 1} | Wu, Dan-Hong^{b; 1} | Li, Hong-Qi^c | Tan, Lin^a | Xu, Wei^a | Dong, Qiang^c | Tan, Lan^{a; *} | Yu, Jin-Tai^{c; *} | Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China | [b] Department of Neurology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China | [c] Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

Correspondence: [*] Correspondence to: Jin-Tai Yu, MD, PhD, Department of Neurology, Huashan Hospital, Fudan University, No. 12 Wulumuqi Road, Shanghai, China. E-mail: yu-jintai@163.com (J.T. Yu); Lan Tan, MD, PhD, Department of Neurology, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghai Middle Road, Qingdao, China. E-mail: dr.tanlan@163.com (L. Tan).

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

Note: [2] Data used in preparation for 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 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/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: Background:The role of cerebral microbleeds (CMBs) in cognitive impairment remains controversial. Objective:To investigate the possible links between the presence, progression, number, and location of CMBs and cognition. Methods:We assessed 792 subjects from the Alzheimer’s Disease Neuroimaging Initiative who underwent both brain 3 Tesla MRI scans and cognitive testing. The association between CMBs and cognitive change was explored using linear mixed-effects models (LME). Results:Presence and number of CMBs were associated with memory (β= –0.03, p = 0.015; β= –0.01, p = 0.003), executive function (β= –0.04, p = 0.010; β= –0.01, p = 0.014), and global cognitive function (β= –0.06, p = 0.025; β= –0.03, p < 0.001). Progression of CMBs showed significant negative associations with executive function (β= –0.05, p = 0.025) and global cognitive function (β= –0.12, p = 0.015). The relations with cognitive performance (memory, executive function and global cognitive function) were mainly driven by lobar CMBs (β= –0.03, p = 0.041; β= –0.04, p = 0.010; β= –0.07, p = 0.029, respectively), especially those located in temporal lobe (β= –0.08, p = 0.027; β= –0.13, p = 0.001; β= –0.26, p < 0.001, respectively). Furthermore, white matter hyperintensities may mediate the association between CMBs and cognition. Conclusion:The presence, progression, number, and location of CMBs, especially those located in temporal lobe, are associated with cognitive decline. These findings suggest CMBs play a role in cognitive impairment.

Keywords: Alzheimer’s disease, cerebral amyloid angiopathy, cerebral microbleeds, cognitive function

DOI: 10.3233/JAD-191257

Journal: Journal of Alzheimer's Disease, vol. 75, no. 2, pp. 571-579, 2020