The Role of Cerebrovascular Disease in Amyloid Deposition

Article type: Research Article

Authors: Noh, Young^{a; b} | Seo, Sang Won^{c; d; e; f} | Jeon, Seun^g | Lee, Jong Min^h | Kim, Jae Seungⁱ | Lee, Jae-Hong^j | Kim, Jung-Hyun^c | Kim, Geon Ha^k | Ye, Byoung Seok^l | Cho, Hanna^m | Kim, Hee Jin^{c; d} | Yoon, Cindy Wⁿ | Choe, Yearn Seong^o | Lee, Kyung-Han^o | Weiner, Michael W.^{p; q} | Na, Duk L.^{c; d; e; r; *}

Affiliations: [a] Department of Neurology, Gachon University Gil Medical Center, Incheon, Republic of Korea | [b] Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, Republic of Korea | [c] Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea | [d] Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea | [e] Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea | [f] Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea | [g] McGill Center for Integrative Neuroscience, Montreal Neurological Institute, McGill University, Montreal, Canada | [h] Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea | [i] Department of Nuclear Medicine, University of Ulsan College of Medicine, >Asan Medical Center, Seoul, Republic of Korea | [j] Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea | [k] Department of Neurology, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea | [l] Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea | [m] Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea | [n] Department of Neurology, Inha University Hospital, Inha University School of Medicine, Incheon, Republic of Korea | [o] Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea | [p] University of California, San Francisco, San Francisco, CA, USA | [q] Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA | [r] Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea

Correspondence: [*] Correspondence to: Duk L. Na, MD, PhD, Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea. Tel.: +82 2 3410 3591; Fax: +82 2 3410 0052; E-mail: [email protected]

Abstract: Background: Some patients clinically diagnosed with subcortical vascular cognitive impairment (SVCI) have co-morbidity with AD pathology. Objective: We investigated topographical differences in amyloid burden between SVCI and Alzheimer’s disease type cognitive impairment (ADCI) using [11C] Pittsburgh compound B (PiB) positron emission tomography (PET). The purpose of this study was to investigate the role of cerebrovascular disease (CVD) in amyloid deposition. Methods: We recruited 44 patients with SVCI and 44 patients with ADCI (amnestic mild cognitive impairment or Alzheimer’s disease) with absent or minimal white matter hyperintensities, all with PiB-positive PET scans [PiB+]. As controls, we included 13 participants with normal cognition and PiB-negative scans. We divided the SVCI and ADCI patients into three groups according to global PiB retention ratio of SVCI, and then compared the tertiles in terms of the distribution of PiB retention using statistical parametric mapping analyses. Lobar to global PiB retention ratio and asymmetry indices were also compared between SVCI and ADCI groups Results: Compared to PiB+ ADCI patients, PiB+ SVCI patients exhibited: 1) increased left-right asymmetry, and increased anterior-posterior difference; and 2) increased PiB retention in the parietal cortex, the occipital cortex and the precuneus-posterior cingulate cortex. In contrast, ADCI patients showed increased PiB retention in the striatum. When stratified by level of PiB retention, each group showed different characteristics. Conclusion: Our results showed that the distribution of amyloid deposition differed between patients with PiB+ SVCI and ADCI. These suggest that CVD contribute to and alter the known progression pattern in amyloid deposition in Alzheimer’s disease.

Keywords: Alzheimer’s disease, cerebrovascular disease, magnetic resonance imaging, positron emission tomography, vascular dementia ∥

DOI: 10.3233/JAD-150832

Journal: Journal of Alzheimer's Disease, vol. 54, no. 3, pp. 1015-1026, 2016