The Impact of Amyloid-β or Tau on Cognitive Change in the Presence of Severe Cerebrovascular Disease

Article type: Research Article

Authors: Jang, Hyemin^{a; b; c; 1; *} | Kim, Hee Jin^{a; b; c} | Choe, Yeong Sim^{a; c} | Kim, Soo-Jong^{a; c} | Park, Seongbeom^a | Kim, Yeshin^d | Kim, Ko Woon^e | Lyoo, Chul Hyoung^f | Cho, Hanna^f | Ryu, Young Hoon^g | Choi, Jae Yong^g | DeCarli, Charles^h | Na, Duk L.^{a; b; c} | Seo, Sang Won^{a; b; c; i; j; 1; *} | for the Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea | [b] Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea | [c] Samsung Alzheimer Research Center, Samsung Medical Center, Seoul, Republic of Korea | [d] Department of Neurology, Kangwon National University Hospital, Chuncheon, Republic of Korea | [e] Department of Neurology, Jeonbuk National University Medical School, Jeonju, Republic of Korea | [f] Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea | [g] Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea | [h] Department of Neurology and Center for Neuroscience, University of California, Davis, Davis, CA, USA | [i] Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea | [j] Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Correspondence: [*] Sang Won Seo, MD, PhD, Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Ilwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea. Tel.: +82 2 3410 6147; Fax: +82 2 3410 0052; E-mail: sangwonseo@empal.com and Hyemin Jang, MD, PhD, Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Ilwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea. Tel.: +82 2 2148 7338; Fax: +82 2 3410 0052; E-mail: hmjang57@gmail.com.

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

Note: [2] Some of data used in preparation of 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 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:As Alzheimer’s disease (AD) and cerebral small vessel disease (CSVD) commonly coexist, the interaction between two has been of the considerable interest. Objective:We determined whether the association of Aβ and tau with cognitive decline differs by the presence of significant CSVD. Methods:We included 60 subcortical vascular cognitive impairment (SVCI) from Samsung Medical Center and 82 Alzheimer’s disease-related cognitive impairment (ADCI) from ADNI, who underwent Aβ (florbetaben or florbetapir) and tau (flortaucipir, FTP) PET imaging. They were retrospectively assessed for 5.0±3.9 and 5.6±1.9 years with Clinical Dementia Rating-sum of boxes (CDR-SB)/Mini-Mental State Examination (MMSE). Mixed effects models were used to investigate the interaction between Aβ/tau and group on CDR-SB/MMSE changes. Results:The frequency of Aβ positivity (45% versus 54.9%, p = 0.556) and mean global FTP SUVR (1.17±0.21 versus 1.16±0.17, p = 0.702) were not different between the two groups. We found a significant interaction effect of Aβ positivity and SVCI group on CDR-SB increase/MMSE decrease (p = 0.013/p < 0.001), and a significant interaction effect of global FTP uptake and SVCI group on CDR-SB increase/MMSE decrease (p < 0.001 and p = 0.030). Finally, the interaction effects of regional tau and group were prominent in the Braak III/IV (p = 0.001) and V/VI (p = 0.003) not in Braak I/II region (p = 0.398). Conclusion:The association between Aβ/tau and cognitive decline is stronger in SVCI than in ADCI. Therefore, our findings suggested that Aβ positivity or tau burden (particularly in the Braak III/IV or V/VI regions) and CSVD might synergistically affect cognitive decline.

Keywords: Alzheimer’s disease, amyloid, cerebral small vessel diseases, cognitive dysfunction, positron emission tomography, tau, vascular dementia

DOI: 10.3233/JAD-200680

Journal: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 573-585, 2020