Amnestic mild cognitive impairment in Parkinson’s disease: White matter structural changes and mechanisms

RESEARCH ARTICLE Amnestic mild cognitive impairment in Parkinson’s disease: White matter structural changes and mechanisms Fuyong Chen ID1,2,3, Tao Wu4,5, Yuejia Luo6,7, Zhihao Li6,7, Qing Guan6,7, Xianghong Meng1,2, Wei Tao1,2, Haobo Zhang ID6,7,8* a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Department of Neurosurgery, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong Province, China, 2 Shenzhen University Clinical Research Center for Neurological Diseases, Shenzhen, Guangdong Province, China, 3 Department of Neurosurgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China, 4 Department of Neurology, National Clinical Research Center for Geriatric Disorders, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China, 5 Beijing Key Laboratory on Parkinson’s Disease, Parkinson Disease Center of Beijing Institute for Brain Disorders, Beijing, China, 6 School of Psychology, Shenzhen University, Shenzhen, Guangdong Province, China, 7 Shenzhen Key Laboratory of Affective and Social Cognitive Science, Shenzhen, Guangdong Province, China, 8 Center for Emotion and Brain, Shenzhen Institute of Neuroscience, Shenzhen, Guangdong Province, China * OPEN ACCESS Citation: Chen F, Wu T, Luo Y, Li Z, Guan Q, Meng X, et al. (2019) Amnestic mild cognitive impairment in Parkinson’s disease: White matter structural changes and mechanisms. PLoS ONE 14(12): e0226175. https://doi.org/10.1371/journal. pone.0226175 Editor: Kai Wang, Anhui Medical University, CHINA Received: August 26, 2019 Accepted: November 21, 2019 Published: December 12, 2019 Copyright: © 2019 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Data contain potentially identifying patient information. Due to the requirement of protecting patient privacy that has been imposed by the ethics committee of Fujian Medical University, data cannot be publicly deposited. The data underlying the results presented in the study are available upon request from the Neurological Clinics of the First Affiliated Hospital of Fujian Medical University (contact via the Department of Scientific Research of the First Affiliated Hospital of Fujian Medical University, E-mail: ). Abstract Mild cognitive impairment (MCI) is a heterogeneous cognitive disorder that is often comorbid with Parkinson’s diseases (PD). The amnestic subtype of PD-MCI (PD-aMCI) has a higher risk to develop dementia. However, there is a lack of studies on the white matter (WM) structural changes of PD-aMCI. We characterized the WM structural changes of PD-aMCI (n = 17) with cognitively normal PD (PD-CN, n = 19) and normal controls (n = 20), using voxelbased and tract-based spatial statistics (TBSS) analyses on fractional anisotropy (FA) axial diffusivity (AD), and radial diffusivity (RD). By excluding and then including the motor performance as a covariate in the comparison analysis between PD-aMCI and PD-CN, we attempted to discern the influences of two neuropathological mechanisms on the WM structural changes of PD-aMCI. The correlation analyses between memory and voxel-based WM measures in all PD patients were also performed (n = 36). The results showed that PDaMCI had smaller FA values than PD-CN in the diffuse WM areas, and PD-CN had higher AD and RD values than normal controls in the right caudate. Most FA difference between PD-aMCI and PD-CN could be weakened by the motor adjustment. The FA differences between PD-aMCI and PD-CN were largely spatially overlapped with the memory-correlated FA values. Our findings demonstrated that the WM structural differences between PDaMCI and PD-CN were mainly memory-related, and the influence of motor adjustment might indicate a common mechanism underlying both motor and memory impairment in PDaMCI, possibly reflecting a predominant influence of dopaminergic neuropathology. PLOS ONE | https://doi.org/10.1371/journal.pone.0226175 December 12, 2019 1 / 15 White matter changes of amnestic mild cognitive impairment in Parkinson’s disease Funding: This study was supported by the National Natural Science Foundation of China (No. 31700960, 31571129, 31500922), the Natural Science Foundation of Guangdong Province of China (No. 2017A030310336), the Discipline Layout of Fundamental Research of Shenzhen Science and Technology Innovation Commission (No. JCYJ 20160428164548896), the Ministry of Science and Technology of the People’s Republic of China (2016YFC1306503), the Natural Science Foundation of Shenzhen University General Hospital (No. SUGH2018QD067), and Beijing Municipal Commission of Health (No. PXM2017_026283_000002). These grants provided financial support to the following investigators: Zhang: 31700960, 2017A030310336; Chen: JCYJ 20160428164548896, SUGH2018QD067; Wu: 2016YFC1306503, PXM2017_026283_000002; Guan: 31571129, 31500922. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. 1 Introduction Parkinson’s disease (PD) is often comorbid with mild cognitive impairment (MCI), a heterogeneous cognitive disorder characterized as mild deficits in various cognitive functions, with the prevalence varying between 25% and over 80% at different stages of PD [1]. According to the impaired cognitive functions, MCI can be classified into different subtypes with disparate neuroanatomical abnormalities [2, 3]. Similarly, PD-MCI can be classified into different cognitive impairment subtypes; among them, the amnestic subtype of PD-MCI (PD-aMCI) shows a higher progression rate to develop dementia [4, 5]. Several studies have investigated the neuroanatomical changes of PD-MCI [6–8]; however, few studies focused on any specific subtypes of PD-MCI [9]. To our knowledge, no study has examined the white matter (WM) changes of any specific PD-MCI subtype. Without specifying the subtypes of PD-MCI, several studies investigated the WM structural changes in PD-MCI, and the findings were inconsistent, possibly owing to the heterogeneous nature of PD-MCI [10–13]. Compared to cognitively normal PD patients, Agosta and colleagues found that PD-MCI showed a diffuse pattern of WM abnormalities [10], while two studies showed a localized WM decrease pattern for PD-MCI in the frontal, temporal and anterior cingulate WM bundles [11, 13]. There was also a report of no significant WM structural difference between PD-MCI and cognitively normal PD patients [12]. Our first aim would be to characterize the WM structural changes of PD-aMCI with cognitively normal PD patients (PD-CN) and normal controls on three diffusion tensor imaging (DTI) metrics, including fractional (...truncated)