Impaired Glymphatic Flow on Diffusion Tensor MRI as a Marker of Neurodegeneration in Alzheimer’s Disease: Correlation with Gray Matter Volume Loss and Cognitive Decline Independent of Cerebral Amyloid Deposition

Article type: Research Article

Authors: Kim, Minjae^{a; b; 1} | Song, Yoo Sung^{c; 1} | Han, Kyunghwa^d | Bae, Yun Jung^{a; *} | Han, Ji Won ^{e; f; *} | Kim, Ki Woong^{e; f; g}

Affiliations: [a] Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Bundang-gu, Seongnam, Gyeonggi, Republic of Korea | [b] Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea | [c] Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Bundang-gu, Seongnam, Gyeonggi, Republic of Korea | [d] Department of Radiology and Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Republic of Korea | [e] Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Bundang-gu, Seongnam, Gyeonggi, Republic of Korea | [f] Department of Psychiatry, College of Medicine, Seoul National University, Seoul, Republic of Korea | [g] Department of Brain & Cognitive Sciences, Seoul National University, Seoul, Republic of Korea

Correspondence: [*] Correspondence to: Yun Jung Bae, MD, PhD, Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam, Gyeonggi, 13620, Republic of Korea. Tel.: +82 31 787 7635; Fax: +82 31 787 4011; Email: [email protected] and Ji Won Han, MD, PhD, Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam, Gyeonggi, 13620, Republic of Korea. Tel.: +82 31 787 7430; Fax: +82 31 787 4058; Email: [email protected].

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

Abstract: Background:Impaired glymphatic flow on the Alzheimer’s disease (AD) spectrum may be evaluated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). Objective:We aimed to validate impaired glymphatic flow and explore its association with gray matter volume, cognitive status, and cerebral amyloid deposition on the AD spectrum. Methods:80 participants (mean age, 76.9±8.5 years; 57 women) with AD (n = 65) and cognitively normal (CN) (n = 15) who underwent 3T brain MRI including DTI and/or amyloid PET were included. After adjusting for age, sex, apolipoprotein E status, and burden of white matter hyperintensities, the ALPS-index was compared according to the AD spectrum. The association between the ALPS-index and gray matter volume, cognitive status, and quantitative amyloid from PET was assessed. Results:The ALPS-index in the AD was significantly lower (mean, 1.476; 95% CI, 1.395–1.556) than in the CN (1.784;1.615–1.952; p = 0.026). Volumes of the entorhinal cortex, hippocampus, temporal pole, and primary motor cortex showed significant associations with the ALPS-index (all, p < 0.05). There was a positive correlation between the ALPS-index and MMSE score (partial r = 0.435; p < 0.001), but there was no significant correlation between the ALPS-index and amyloid SUVRs (all, p > 0.05). Conclusions:Decreased glymphatic flow measured by DTI-ALPS in AD may serve as a marker of neurodegeneration correlating with structural atrophy and cognitive decline.

Keywords: Alzheimer’s disease, amyloid PET, diffusion tensor, glymphatic function, volumetry

DOI: 10.3233/JAD-231131

Journal: Journal of Alzheimer's Disease, vol. 99, no. 1, pp. 279-290, 2024