Authors: Qiao, Yanan | Sun, Yu | Guo, Jing | Chen, Yaojing | Hou, Wenjie | Zhang, Junying | Peng, Dantao
Article Type: Research Article
Abstract: Background: Lobar cerebral microbleeds (CMBs), which can impair white matter (WM), are often concomitant with definite Alzheimer’s disease (AD). Objective: To explore the features of cognitive impairments and WM disruptions due to lobar CMBs in patients with AD. Methods: There were 310 participants who underwent Florbetapir F18 (AV45) amyloid PET and susceptibility-weighted imaging. Participants with cognitive impairment and amyloid-β positive (ADCI) were included into three groups: ADCI without CMBs, with strictly lobar CMBs (SL-CMBs), and with mixed CMBs (M-CMBs). Tract-based spatial statistics were performed to detect the group differences in WM integrity. Results: There were 82 patients and 29 healthy …controls finally included. A decreasing tendency in memory and executive performance can be found among HCs > no CMBs (n = 16) >SL-CMBs (n = 41) >M-CMBs (n = 25) group. Compared to no CMBs, M-CMBs group had significantly decreased fractional anisotropy in left anterior thalamic radiation (ATR), forceps major, forceps minor and inferior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus (IFOF), and superior longitudinal fasciculus. M-CMBs group also had lower fractional anisotropy in left ATR, IFOF, uncinate fasciculus, and forceps minor compared with SL-CMBs. Furthermore, analysis of Pearson correlation indicated damages in discrepant WMs were positively associated with impairment of memory, executive function, and attention. Conclusion: This study showed lobar CMBs had intensively aggravated cognitive impairments associated with extensive WM damages in definite AD. These findings highlight that lobar CMBs play an important role in AD progression and need to be taken into consideration for the early detection of AD. Show more
Keywords: Alzheimer’s disease, cerebral microbleeds, cognitive impairment, diffusion tensor imaging, Florbetapir F18 amyloid PET
DOI: 10.3233/JAD-215251
Citation: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 369-380, 2022
Authors: Zhang, Shujuan | Wei, Dongfeng | Lv, Shuang | Wang, Lei | An, Haiting | Shao, Wen | Wang, Yun | Huang, Yaping | Peng, Dantao | Zhang, Zhanjun
Article Type: Research Article
Abstract: Background: Scutellarin, a flavonoid purified from the Chinese herb Erigeron breviscapus , has been reported to prevent Alzheimer’s disease (AD) by affecting Aβ assembly. Given the low brain uptake rate of scutellarin, we hypothesize that the microbiota-gut-brain axis may be a potential route by which scutellarin prevents AD. Objective: This study aimed to explore the microbiota-gut-brain mechanism by which scutellarin prevented AD. Methods: Scutellarin was administrated to APP/PS1 mouse model of AD for two months, and the behaviors, pathological changes as well as gut microbial changes in APP/PS1 mice were evaluated after scutellarin treatment. Results: This study found that scutellarin …improved Aβ pathology, neuroinflammation, and cognitive deficits in APP/PS1 mice. It elucidated the effects of scutellarin on the diversity and activity of gut microbiota in APP/PS1 mice and these findings promoted us to focus on inflammation-related bacteria and short-chain fatty acids (SCFAs). Cognitive behaviors were significantly associated with inflammatory cytokines and inflammation-related bacteria, suggesting that microbiota-gut-brain axis was involved in this model and that inflammatory pathway played a crucial role in this axis. Moreover, we observed that cAMP-PKA-CREB-HDAC3 pathway downstream of SCFAs was activated in microglia of AD and inactivated by scutellarin. Furthermore, by chromatin immunoprecipitation (ChIP) assays, we found that the increased association between acetylated histone 3 and interleukin-1β (IL-1β) promoter in AD mice was reversed by scutellarin, leading to a decreased level of IL-1β in scutellarin-treated AD mice. Conclusion: Scutellarin reverses neuroinflammation and cognitive impairment in APP/PS1 mice via beneficial regulation of gut microbiota and cAMP-PKA-CREB-HDAC3 signaling in microglia. Show more
Keywords: Alzheimer’s disease, cAMP-response element binding protein (CREB), cyclic adenosine monophosphate (cAMP), gut microbiota, histone deacetylase, interleukin, protein kinase, scutellarin
DOI: 10.3233/JAD-220532
Citation: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 955-975, 2022
Authors: Jia, Jianping | Ji, Yong | Feng, Tao | Ye, Qinyong | Peng, Dantao | Kuang, Weihong | Ning, Yuping | Liang, Zhihou | Fan, Dongsheng | Wei, Wenshi | Li, Yansheng | Xiao, Shifu
Article Type: Research Article
Abstract: Background: Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer’s type. Objective: To explore the efficacy and safety of the maximal tolerated dose of rivastigmine capsules in Chinese patients with mild-to-moderate Alzheimer’s disease (AD). Methods: The study was a multicenter, open-label, single-arm, phase IV clinical study in mild-to-moderate drug-naïve AD patients treated with rivastigmine capsules. The primary endpoint was the changes in the total scores of Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) from baseline to week 16. Secondary endpoints included changes in the scores of the following assessment scales and safety: Alzheimer’s Disease Cooperative Study; …Activities of Daily Living; Mini-Mental Status Examination (MMSE); Neuropsychiatry Index (NPI), and Caregiver Burden Inventory. Results: 222 patients were enrolled. Of these, 136 (75.1%) patients received and maintained the effective dose (≥6 mg/d) of rivastigmine for at least 4 weeks. The ADAS-Cog scale score improved in rivastigmine-treated patients at week 16 compared with baseline (p < 0.001) by 2.0 (95% CI: –3.0 to –1.1) points, which met the pre-defined superiority criteria. NPI-10 and NPI-12 scores improved by 3.6 and 4.0 points at week 16 (p = 0.001, p < 0.001), respectively. A total of 107 patients (59.1%) experienced adverse effects (AEs) during the study; common AEs included nausea (20.5%), vomiting (16.6%), anorexia (7.8%), dizziness (7.7%), and diarrhea (7.2%). Conclusion: This was the first phase IV study on rivastigmine in mainland China. The study preliminarily demonstrated that rivastigmine capsules showed good tolerability and efficacy in mild-to-moderate AD patients with the maximal tolerated dose. Show more
Keywords: Alzheimer’s disease, capsule, Chinese population, rivastigmine
DOI: 10.3233/JAD-190791
Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1313-1322, 2019