Regional Amyloid Accumulation and White Matter Integrity in Cognitively Normal Individuals

Article type: Research Article

Authors: Wang, Ya-Juan^a | Hu, Hao^b | Yang, Yu-Xiang^c | Zuo, Chuan-Tao^d | Tan, Lan^{a; b; *} | Yu, Jin-Tai^{c; *} | Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, China | [b] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, China | [c] Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China | [d] PET Center, Huashan Hospital, Fudan University, Shanghai, China

Correspondence: [*] Correspondence to: Prof. Jin-Tai Yu, MD, PhD, Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai 200040, China. Tel.: +86 21 52888160; Fax: +86 21 62483421; E-mail: jintai_yu@fudan.edu.cn; Prof. Lan Tan, MD, PhD, Qingdao Municipal Hospital, Qingdao University, China. E-mail: dr.tanlan@163.com.

Note: [1] 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:Recent studies have shown that amyloid-β (Aβ) burden influenced white matter (WM) integrity before the onset of dementia. Objective:To assess whether the effects of Aβ burden on WM integrity in cognitively normal (CN) individuals were regionally specific. Methods:Our cohort consisted of 71 CNs from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database who underwent both AV45 amyloid-PET and diffusion tensor imaging. Standardized uptake value ratio (SUVR) was computed across four bilateral regions of interest (ROIs) corresponding to four stages of in vivo amyloid staging model (Amyloid stages I–IV). Linear regression models were conducted in entire CN group and between APOE ɛ4 carriers and non-carriers. Results:Our results indicated that higher global Aβ-SUVR was associated with higher mean diffusivity (MD) in the entire CN group (p = 0.023), and with both higher MD (p = 0.015) and lower fractional anisotropy (FA) (p = 0.026) in APOE ɛ4 carriers. Subregion analysis showed that higher Amyloid stage I-II Aβ-SUVRs were associated with higher MD (Stage-1: p = 0.030; Stage-2: p = 0.016) in the entire CN group, and with both higher MD (Stage-1: p = 0.004; Stage-2: p = 0.010) and lower FA (Stage-1: p = 0.022; Stage-2: p = 0.014) in APOE ɛ4 carriers. No associations were found in APOE ɛ4 non-carriers and in Amyloid stage III-IV ROIs. Conclusions:Our results indicated that the effects of Aβ burden on WM integrity in CNs might be regionally specific, particularly in Amyloid stage I-II ROIs, and modulated by APOE ɛ4 status.

Keywords: Amyloid PET, cognitively normal elders, diffusion tensor imaging, in vivo amyloid staging model, white matter integrity

DOI: 10.3233/JAD-191350

Journal: Journal of Alzheimer's Disease, vol. 74, no. 4, pp. 1261-1270, 2020