Temporal dynamic changes of intrinsic brain activity in Alzheimer's disease and mild cognitive impairment patients: a resting-state functional magnetic resonance imaging study.

Original Article Page 1 of 12 Temporal dynamic changes of intrinsic brain activity in Alzheimer’s disease and mild cognitive impairment patients: a resting-state functional magnetic resonance imaging study Ting Li1#, Zhengluan Liao2#, Yanping Mao3, Jiaojiao Hu3, Dansheng Le4, Yangliu Pei5, Wangdi Sun4, Jixin Lin6, Yaju Qiu2, Junpeng Zhu2, Yan Chen2, Chang Qi2, Xiangming Ye7, Heng Su2, Enyan Yu3 1 Zhejiang Provincial People’s Hospital, Qingdao University, Qingdao, China; 2Department of Psychiatry, Zhejiang Provincial People’s Hospital, Hangzhou, China; 3Department of Psychological Medicine, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China; 4The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China; 5Graduate faculty, Bengbu Medical College, Bengbu, China; 6Department of Internal Medicine, Shengsi County People’s Hospital, Zhoushan, China; 7Department of Rehabilitation Medicine, Zhejiang Provincial People’s Hospital, Hangzhou, China Contributions: (I) Conception and design: T Li, Z Liao, E Yu; (II) Administrative support: E Yu; (III) Provision of study materials or patients: T Li, Z Liao, Y Mao, Y Qiu, J Zhu, Y Chen, C Qi, Y Tan, X Ye, H Su; (IV) Collection and assembly of data: T Li, Z Liao, Y Mao, J Hu, D Le, Y Pei, W Sun, J Lin; (V) Data analysis and interpretation: T Li, Z Liao; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. # These authors contributed equally to this work. Correspondence to: Dr. Enyan Yu. Department of Psychological Medicine, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, 1# East Banshan Rd., Hangzhou, China. Email: . Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory impairment. Previous studies have largely focused on alterations of static brain activity occurring in patients with AD. Few studies to date have explored the characteristics of dynamic brain activity in cognitive impairment, and their predictive ability in AD patients. Methods: One hundred and eleven AD patients, 29 MCI patients, and 73 healthy controls (HC) were recruited. The dynamic amplitude of low-frequency fluctuation (dALFF) and the dynamic fraction amplitude of low-frequency fluctuation (dfALFF) were used to assess the temporal variability of local brain activity in patients with AD or mild cognitive impairment (MCI). Pearson’s correlation coefficients were calculated between the metrics and subjects’ behavioral scores. Results: The results of analysis of variance indicated that the AD, MCI, and HC groups showed significant variability of dALFF in the cerebellar posterior and middle temporal lobes. In AD patients, these brain regions had high dALFF variability. Significant dfALFF variability was found between the three groups in the left calcarine cortex and white matter. The AD group showed lower dfALFF than the MCI group in the left calcarine cortex. Conclusions: Compared to HC, AD patients were found to have increased dALFF variability in the cerebellar posterior and temporal lobes. This abnormal pattern may diminish the capacity of the cerebellum and temporal lobes to participate in the cerebrocerebellar circuits and default mode network (DMN), which regulate cognition and emotion in AD. The findings above indicate that the analysis of dALFF and dfALFF based on functional magnetic resonance imaging data may give a new insight into the neurophysiological mechanisms of AD. Keywords: Alzheimer’s disease (AD); mild cognitive impairment (MCI); resting-state functional magnetic resonance imaging (rs-fMRI); the dynamic amplitude of low-frequency fluctuation (dALFF); dynamic fraction amplitude of low-frequency fluctuation (dfALFF) Submitted Jul 31, 2020. Accepted for publication Dec 23, 2020. doi: 10.21037/atm-20-7214 View this article at: http://dx.doi.org/10.21037/atm-20-7214 © Annals of Translational Medicine. All rights reserved. Ann Transl Med 2021;9(1):63 | http://dx.doi.org/10.21037/atm-20-7214 Page 2 of 12 Li et al. Changes of dALFF and dfALFF value in Alzheimer’s disease and mild cognitive impairment Introduction Alzheimer’s disease (AD) is the most common form of dementia worldwide as well as the fifth leading cause of disability in people over the age of 65 (1). Clinically, AD manifests as memory impairment, cognitive degradation, and the deterioration of the individual’s ability to carry out daily living activities (2). Although some drugs can slow the progression of AD, this disease cannot currently be prevented or cured. Mild cognitive impairment (MCI) is considered to be a precursor for AD. Its onset is followed by progressive cognitive decline, but the basic everyday abilities of patients can largely be preserved (3). Many MCI patients eventually progress to AD, with an annual conversion rate of 10–15% (4). Therefore, it is essential that the pathological mechanisms of AD and MCI are illuminated and that individuals in the precursor stage of AD can be identified. Noninvasive methods based on positron emission tomography (PET), structural magnetic resonance imaging (sMRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), task functional MRI(t-fMRI), and resting-state functional MRI (rs-fMRI) have provided diversified imaging tools for discriminating MCI from AD. PET has high sensitivity and specificity in the diagnosis of AD, but it is expensive. sMRI can provide an accurate index to evaluate the brain atrophy of patients, but the ability to accurately assess the severity of dementia is limited, the associations between clinical disease stages and brain tissue loss are not linear (5). While t-fMRI and rs-fMRI studied two completely different states of the brain, rs-fMRI has no request for subjects except to stay still, so it's especially suitable for older people who can't cooperate with task. Restingstate functional magnetic resonance imaging (rs-fMRI) is a widely recognized method for investigating intrinsic brain activity (IBA) and functional connectivity networks in AD (6). Rs-fMRI internal brain activity analysis can help diagnose early stages of diseases before brain atrophy occurs. By analyzing the correlation between brain activity changes and cognitive behavior (7), it helps to clarify the pathophysiological mechanism of AD. The amplitude of low-frequency fluctuation (ALFF) measures the gross power of oscillations within a certain frequency range to detect changes of spontaneous activity of regional signals (8). Fractional ALFF (fALFF) is the ratio of the power spectrum of low-frequency (0.01–0.08 Hz), which can reduce or eliminate the effects of physiological noise (9). ALFF and fALFF have been widely used to explore IBA in AD (10-12). Ren et al. reported that MCI patients showed lower ALFF than healthy individuals in the anterior cingulate cortex, superior frontal gyrus, and medial prefrontal c (...truncated)