Role of White Matter Abnormalities in the Relationship Between Microbleed Burden and Cognitive Impairment in Cerebral Amyloid Angiopathy

Article type: Research Article

Authors: Jo, Sungyang^{a; 1} | Cheong, E-Nae^{b; 1} | Kim, Nayoung^c | Oh, Jungsu S.^d | Shim, Woo Hyun^b | Kim, Hyung-Ji^a | Lee, Sun Ju^a | Lee, Yoojin^a | Oh, Minyoung^d | Kim, Jae Seung^d | Kim, Bum Joon^a | Roh, Jee Hoon^e | Kim, Sang Joon^f | Lee, Jae-Hong^{a; *}

Affiliations: [a] Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea | [b] Department of Medical Science and Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea | [c] Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea | [d] Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea | [e] Department of Physiology, Neuroscience Research Institute, Korea University College of Medicine, Seoul, Republic of Korea | [f] Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

Correspondence: [*] Correspondence to: Jae-Hong Lee, MD, PhD, Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea. Tel.: +82 2 3010 3446; Fax: +82 2 474 4691; E-mail: [email protected].

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

Abstract: Background:Cerebral amyloid angiopathy (CAA) often presents as cognitive impairment, but the mechanism of cognitive decline is unclear. Recent studies showed that number of microbleeds were associated with cognitive decline. Objective:We aimed to investigate how microbleeds contribute to cognitive impairment in association with white matter tract abnormalities or cortical thickness in CAA. Methods:This retrospective comparative study involved patients with probable CAA according to the Boston criteria (Aβ+ CAA) and patients with Alzheimer’s disease (Aβ+ AD), all of whom showed severe amyloid deposition on amyloid PET. Using mediation analysis, we investigated how FA or cortical thickness mediates the correlation between the number of lobar microbleeds and cognition. Results:We analyzed 30 patients with Aβ+ CAA (age 72.2±7.6, female 53.3%) and 30 patients with Aβ+ AD (age 71.5±7.6, female 53.3%). The two groups showed similar degrees of cortical amyloid deposition in AD-related regions. The Aβ+ CAA group had significantly lower FA values in the clusters of the posterior area than did the Aβ+ AD group(family-wise error-corrected p < 0.05). The correlation between the number of lobar microbleeds and visuospatial function was indirectly mediated by white matter tract abnormality of right posterior thalamic radiation (PTR) and tapetum, while lobar microbleeds and language function was indirectly mediated by the abnormality of left PTR and sagittal stratum. Cortical thickness did not mediate the association between lobar microbleeds and cognition. Conclusion:This result supports the hypothesis that microbleeds burden leads to white matter tract damage and subsequent cognitive decline in CAA.

Keywords: Amyloid PET, cerebral amyloid angiopathy, cognition, microbleeds

DOI: 10.3233/JAD-215094

Journal: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 667-678, 2022