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Authors: Chen, Guanqun | Yang, Kun | Du, Wenying | Hu, Xiaochen | Han, Ying

Article Type: Research Article

Abstract: Background: Subjective cognitive decline (SCD) refers to the self-perception of cognitive decline among cognitively normal elderly individuals. SCD related worry confers a higher risk of developing cognitive decline. However, the clinical characteristics of SCD patients with worry are not clear. Objective: To explore the clinical characteristics of SCD patients with worry. Methods: A cross-sectional study was carried out, with 270 consecutive participants of the Sino Longitudinal Study on Cognitive Decline (SILCODE) study. Participants were classified as normal controls (n  = 36), SCD patients without worry (n  = 91), or SCD patients with worry (n  = 143) and were comprehensively compared on 1) their …self-perception of cognitive decline, 2) multiple cognitive domains, 3) neuropsychiatric symptoms, and 4) sleep status. Results: SCD patients with worry had significantly more self-perception of cognitive decline (p  < 0.001); increased depression (p  < 0.001) and anxiety (p  < 0.001); decreased sleep quality (p  < 0.001), sleep latency (p  < 0.05), sleep time (p  < 0.01), and sleep efficiency (p  < 0.05); more sleep disorders (p  < 0.05) and daytime dysfunction (p  < 0.05); and a higher global score on the Pittsburgh Sleep Quality Index (p  < 0.001) than normal controls. Although there was a significant increase only in self-perception of cognitive decline (p  < 0.001), anxiety (p  < 0.001), and Pittsburgh Sleep Quality Index scores (p  < 0.05), the severity of the increase in those without worry was between that in SCD patients with worry and normal controls. Conclusion: Our findings show that participants who had SCD with worry showed distinct clinical characteristics compared with normal controls and SCD patients without worry, which could be useful for understanding the higher risk in SCD patients with worry of subsequently developing Alzheimer’s disease. Show more

Keywords: Alzheimer’s disease, clinical characteristic, neuropsychiatric symptoms, prevention trials, sleep disorders, subjective cognitive decline, subjective cognitive decline questionnaire

DOI: 10.3233/JAD-190501

Citation: Journal of Alzheimer's Disease, vol. 72, no. 2, pp. 443-454, 2019

Authors: Du, Wenying | Ding, Changchang | Jiang, Jiehui | Han, Ying

Article Type: Research Article

Abstract: Background: Mounting evidence suggests that sex differences exist in cognitive reserve (CR) for cognitively unimpaired (CU) elderly individuals. Global left frontal connectivity (gLFC connectivity) is a reliable neural substrate of CR. Objective: The purpose of this study was to explore sex differences in gLFC connectivity among CU elderly individuals. Methods: One hundred thirteen normal controls (NCs) (women = 66) and 132 individuals with subjective cognitive decline (SCD) (women = 92) were recruited from the Sino Longitudinal Study on Cognitive Decline (SILCODE) (data 1). Among them, 88 subjects underwent amyloid-β (Aβ) imaging, including 32 Aβ+ and 56 Aβ–subjects. Forty-six subjects underwent another rs-fMRI examination (data …2) to validate the repeatability of the calculation of gLFC connectivity, which was determined through seed-based functional connectivity between the LFC and voxels throughout the whole brain. Independent-sample t -tests were used to evaluate the sex differences in gLFC connectivity across different subgroups (NC versus SCD, Aβ+ versus Aβ–). Partial correlation analysis was used to calculate the correlations between gLFC connectivity and cognitive assessments. Results: Women exhibited lower gLFC connectivity in both the NC (p  = 0.001) and SCD (p  = 0.020) subgroups than men. Women also exhibited lower gLFC connectivity in both the Aβ–(p  = 0.006) and Aβ+ (p  = 0.025) groups. However, the significant difference disappeared in the Aβ+ group when considering the covariates of age, education, total intracranial volume, and APOE4 -carrying status. In addition, gLFC connectivity values were negatively correlated with Geriatric Depression Scale scores in the SCD group (r = –0.176, p  = 0.047). Conclusion: Women showed lower gLFC connectivity among CU elderly individuals. Show more

Keywords: Amyloid deposition, cognitive reserve, global left frontal cortex connectivity, sex differences, subjective cognitive decline

DOI: 10.3233/JAD-210376

Citation: Journal of Alzheimer's Disease, vol. 83, no. 2, pp. 653-663, 2021

Authors: Zhao, Xing | Du, Wenying | Jiang, Jiehui | Han, Ying

Article Type: Research Article

Abstract: Background: Sleep appears to be a sensitive biomarker that facilitates early detection and effective intervention for Alzheimer’s disease, while subjective cognitive decline (SCD) is a risk factor for Alzheimer’s disease. Prefrontal cortex atrophy is associated with both sleep disruption and cognitive decline. Transcranial brain photobiomodulation (PBM) therapy can enhance frontal cortex oxygen consumption, increasing frontal cortex mediated memory function. Objective: This study aimed to test whether PBM therapy targeting the frontal cortex could improve sleep and cognitive function in SCD. Methods: Fifty-eight SCDs were divided into the PBM group (N  = 32) in which real light therapy was administered and a …sham light therapy group (N  = 26). All the participants received either real light or sham light therapy for 6 days consecutively, while the sleep data were recorded. The n-back task was employed to measure each participant’s working memory. Results: We found no differences in sleep efficiency change (F  = 211, p  = 0.279), REM stage percent change (F  = 420, p  = 0.91), and wake-up time (F  = 212, p  = 0.277) between the two groups. The sleep efficiency and REM were improved within the true light group on the fifth day. The true light group perform better than the control group in the n-back test, the accuracy was higher in the 2-back test (88.6% versus 79.6%, p  = 0.001), and the reaction time in 1-back was shorter (544.80±202.00 versus 592.87±222.05, p  = 0.003). Conclusion: After five days of PBM therapy targeting the prefrontal cortex, sleep efficiency and N-back cognitive performance were improved on the fifth day. Show more

Keywords: Alzheimer’s disease, photobiomodulation, sleep, subjective cognitive decline

DOI: 10.3233/JAD-215715

Citation: Journal of Alzheimer's Disease, vol. 87, no. 4, pp. 1581-1589, 2022

Authors: Liu, Yi | Li, Zhuoyuan | Jiang, Xueyan | Du, Wenying | Wang, Xiaoqi | Sheng, Can | Jiang, Jiehui | Han, Ying

Article Type: Research Article

Abstract: Background: Evidence suggests that subjective cognitive decline (SCD) individuals with worry have a higher risk of cognitive decline. However, how SCD-related worry influences the functional brain network is still unknown. Objective: In this study, we aimed to explore the differences in functional brain networks between SCD subjects with and without worry. Methods: A total of 228 participants were enrolled from the Sino Longitudinal Study on Cognitive Decline (SILCODE), including 39 normal control (NC) subjects, 117 SCD subjects with worry, and 72 SCD subjects without worry. All subjects completed neuropsychological assessments, APOE genotyping, and resting-state functional magnetic resonance imaging (rs-fMRI). Graph …theory was applied for functional brain network analysis based on both the whole brain and default mode network (DMN). Parameters including the clustering coefficient, shortest path length, local efficiency, and global efficiency were calculated. Two-sample T -tests and chi-square tests were used to analyze differences between two groups. In addition, a false discovery rate-corrected post hoc test was applied. Results: Our analysis showed that compared to the SCD without worry group, SCD with worry group had significantly increased functional connectivity and shortest path length (p  = 0.002) and a decreased clustering coefficient (p  = 0.013), global efficiency (p  = 0.001), and local efficiency (p  < 0.001). The above results appeared in both the whole brain and DMN. Conclusion: There were significant differences in functional brain networks between SCD individuals with and without worry. We speculated that worry might result in alterations of the functional brain network for SCD individuals and then result in a higher risk of cognitive decline. Show more

Keywords: Functional connectivity, functional MRI, graph theory, subjective cognitive decline, worry

DOI: 10.3233/JAD-215156

Citation: Journal of Alzheimer's Disease, vol. 84, no. 3, pp. 1279-1289, 2021

Authors: Yan, Tianyi | Wang, Yonghao | Weng, Zizheng | Du, Wenying | Liu, Tiantian | Chen, Duanduan | Li, Xuesong | Wu, Jinglong | Han, Ying

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is one of the most common progressive and irreversible neurodegenerative diseases. The study of the pathological mechanism of AD and early-stage diagnosis is essential and important. Subjective cognitive decline (SCD), the first at-risk stage of AD occurring prior to amnestic mild cognitive impairment (aMCI), is of great research value and has gained our interest. To investigate the entire pathological development of AD pathology efficiently, we proposed a machine learning classification method based on a multimodal support vector machine (SVM) to investigate the structural and functional connectivity patterns of the three stages of AD (SCD, aMCI, and AD). …Our experiments achieved an accuracy of 98.58% in the AD group, 97.76% in the aMCI group, and 80.24% in the SCD group. Moreover, in our experiments, we identified the most discriminating brain regions, which were mainly located in the default mode network and subcortical structures (SCS). Notably, with the development of AD pathology, SCS regions have become increasingly important, and structural connectivity has shown more discriminative power than functional connectivity. The current study may shed new light on the pathological mechanism of AD and suggests that whole-brain connectivity may provide potential effective biomarkers for the early-stage diagnosis of AD. Show more

Keywords: Alzheimer’s disease, diffusion tensor imaging, machine learning, multimodal MRI, resting-state fMRI

DOI: 10.3233/JAD-181049

Citation: Journal of Alzheimer's Disease, vol. 68, no. 3, pp. 1013-1027, 2019

Authors: Sheng, Can | Yang, Kun | He, Beiqi | Li, Taoran | Wang, Xiaoqi | Du, Wenying | Hu, Xiaochen | Jiang, Jiehui | Jiang, Xueyan | Jessen, Frank | Han, Ying

Article Type: Research Article

Abstract: Background: Subjective cognitive decline (SCD) is considered as the first symptomatic manifestation of Alzheimer’s disease (AD), which is also affected by different cultural backgrounds. Establishing cross-cultural prediction models of SCD is challenging. Objective: To establish prediction models of SCD available for both the Chinese and European populations. Methods: In this project, 330 SCD from China and 380 SCD from Germany are intended to be recruited. For all participants, standardized assessments, including clinical, neuropsychological, apolipoprotein E (APOE ) genotype, blood, and multi-parameter magnetic resonance imaging (MRI) at baseline will be conducted. Participants will voluntarily undergo amyloid positron emission tomography (PET) and …are classified into amyloid-β (Aβ) positive SCD (SCD+) and Aβ negative SCD (SCD-). First, baseline data of all SCD individuals between the two cohorts will be compared. Then, key features associated with brain amyloidosis will be extracted in SCD+ individuals, and the diagnosis model will be established using the radiomics method. Finally, the follow-up visits will be conducted every 12 months and the primary outcome is the conversion to mild cognitive impairment or dementia. After a 4-year follow-up, we will extract factors associated with the conversion risk of SCD using Cox regression analysis. Results: At present, 141 SCD from China and 338 SCD from Germany have been recruited. Initial analysis showed significant differences in demographic information, neuropsychological tests, and regional brain atrophy in SCD compared with controls in both cohorts. Conclusion: This project may be of great value for future implications of SCD studies in different cultural backgrounds. Trial registration: ClinicalTrials.gov, NCT04696315. Registered 3 January 2021. Show more

Keywords: Alzheimer’s disease, amyloid, cross-cultural, magnetic resonance imaging, radiomics, subjective cognitive decline

DOI: 10.3233/JAD-215452

Citation: Journal of Alzheimer's Disease, vol. 87, no. 3, pp. 1319-1333, 2022

Authors: Sheng, Can | Sun, Yu | Wang, Min | Wang, Xiaoni | Liu, Yi | Pang, Dongqing | Liu, Jiaqi | Bi, Xiaoxia | Du, Wenying | Zhao, Mingyan | Li, Yuxia | Li, Xiaobo | Jiang, Jiehui | Han, Ying

Article Type: Research Article

Abstract: Background: Visual rating scales for medial temporal lobe atrophy (MTA) and posterior atrophy (PA) have been reported to be useful for Alzheimer’s disease diagnosis in routine clinical practice. Objective: To investigate the efficacy of combined MTA and PA visual rating scales to discriminate amnestic mild cognitive impairment (aMCI) patients from healthy controls. Methods: This study included T1-weighted MRI images from two different cohorts. In the first cohort, we recruited 73 patients with aMCI and 48 group-matched cognitively normal controls for training and validation. Visual assessments of MTA and PA were carried out for each participant. Global gray matter volume and …density were estimated using voxel-based morphometry analysis as the objective reference. We investigated the discriminative power of a single visual rating scale and the combination of the MTA and PA rating scales for identifying aMCI. The second cohort, consisting of 33 aMCI patients and 45 controls, was used to verify the reliability of the visual assessments. Results: Compared with the single visual rating scale, the combination of the MTA and PA exhibited the best discriminative power, with an AUC of 0.818±0.041, which was similar to the diagnostic accuracy of the gray matter volumetric measures. The discriminative power of the combined MTA and PA was verified in the second cohort (AUC 0.824±0.058). Conclusion: The combined MTA and PA rating scales demonstrated practical diagnostic value for distinguishing aMCI patients from controls, suggesting its potential to serve as a convenient and reproducible method to assess the degree of atrophy in clinical settings. Show more

Keywords: Magnetic resonance imaging, medial temporal lobe atrophy, mild cognitive impairment, posterior atrophy, visual rating scales

DOI: 10.3233/JAD-200016

Citation: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 323-337, 2020

Authors: Hao, Lixiao | Wang, Xiaoni | Zhang, Ling | Xing, Yue | Guo, Qihao | Hu, Xiaochen | Mu, Bin | Chen, Yili | Chen, Guanqun | Cao, Jing | Zhi, Xiaodong | Liu, Jiaojiao | Li, Xuanyu | Yang, Liu | Li, Jiachen | Du, Wenying | Sun, Yu | Wang, Ting | Liu, Zhen | Liu, Zheng | Zhao, Xuexue | Li, Hongyan | Yu, Yang | Wang, Xue | Jia, Jianguo | Han, Ying

Article Type: Research Article

Abstract: Background: Substantial studies have reported the prevalence and the affecting factors of subjective cognitive decline (SCD). The complaints screening scale has also been used for probing. However, little is known in China. Objective: To investigate the prevalence and risk factors of SCD, and explore an SCD complaints screening scale in China. Methods: Stratified cluster random sampling was conducted. 2,689 residents aged 60–80 years completed questionnaire 1. 814 residents were included for clinical and neuropsychological evaluations. Two standards were used to make the diagnosis of mild cognitive impairment (MCI) and SCD, and a preliminary screening rate comparison was carried out. Finally, …we assessed the risk factors of SCD and the correlation between the SCD-questionnaire 9 (SCD-Q9) and the Auditory Verbal Learning Test-Long Delay Free Recall (AVLT-LR). Results: 1) Standard 1 (ADNI2): the prevalence of SCD was 18.8% (95% CI = 14.7–22.9%) and zero conformed to six criteria (SCD plus). 2) Standard 2 (Jak/Bondi): the prevalence of SCD was 14.4% (95% CI = 10.7–18.1%). 3) Standard 1 had a relatively higher “false” positive rate, whereas Standard 2 had higher “false” negative rate. 4) Age, low education, fewer close friends, and daily drinking were independent risk factors for SCD progressing to MCI. 5) Total points of SCD-Q9 were negatively correlated to the value of AVLT-LR. Conclusions: The prevalence of SCD is high in the ShunYi District in Beijing, China. Age, low education, less social support, and daily drinking are independent risk factors. The brief SCD-Q9 can be used as a reference. Show more

Keywords: Alzheimer’s disease, prevalence, risk factors, SCD-Q9, subjective cognitive decline

DOI: 10.3233/JAD-170347

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 371-388, 2017