Abstract P238: Cerebral Ischemia With Amyloid-Beta Infusion Deteriorates Cognitive Decline ~Possible Amelioration of Cognitive Function by AT 2 Receptor Activation~

Hypertension ◽  
2018 ◽  
Vol 72 (Suppl_1) ◽  
Author(s):  
Li-Juan Min ◽  
Masaki Mogi ◽  
Hui-Yu Bai ◽  
Bao-Shuai Shan ◽  
Akinori Higaki ◽  
...  
Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Li-Juan Min ◽  
Masaki Mogi ◽  
Kana Tsukuda ◽  
Akinori Higaki ◽  
Masanori Kukida ◽  
...  

Background and Aim: Stroke is known to be causally related with Alzheimer’s disease pathology and amyloid-β (Aβ) deposition has been suggested to induce cerebral amyloid angiopathy resulting in stroke-associated cognitive decline. Angiotensin (Ang) type 1 (AT 1 ) receptor activation impairs cognitive performance, whereas Ang II type 2 (AT 2 ) receptor stimulation has been reported to improve cognitive impairment. We examined the interaction between stroke and Aβ deposition in cognitive function, and the possible antagonist effect of AT 2 receptor in vascular smooth muscle cells (VSMC) on this cognitive decline. Methods: Adult (10-12 weeks old) male wild-type (WT) mice (C57BL/6J mice) or the mice with AT 2 receptor overexpression in VSMC (SMAT2) were used. Mice were subjected to intracerebroventricular (ICV) injection of Aβ1-40 following 15 minutes global brain ischemia operation. Three weeks after Aβ1-40 ICV injection, cognitive function of spatial learning memory was evaluated by the Morris water maze test. Brain samples were obtained after behavioral testing, and the expression of inflammatory cytokines and NADPH oxidase subunits were measured by real-time quantitative RT-PCR. Results: ICV injection of Aβ1-40 in WT mice showed impaired cognitive function. On the other hand, WT mice with transient global brain ischemia did not decline significantly cognitive function. In contrast, WT mice with Aβ1-40 ICV injection with global brain ischemia exhibited more marked cognitive impairment compared with control mice. These results suggested that transient brain ischemia and amyloid-β deposition exerted at least additive effects on cognitive impairment. This cognitive decline was accompanied with increased expressions of inflammatory cytokines such as monocyte chemoattractant protein-1 and NADPH oxidase subunits including p22 phox . On the other hand, SMAT 2 mice did not show cognitive impairment by global brain ischemia with/without Aβ1-40 ICV injection. Conclusion: Brain ischemia and amyloid-β deposition induced additive or synergistic effect on cognitive impairment. AT 2 receptor activation in VSMC could play an inhibitory role in the cognitive decline induced by brain ischemia and amyloid-β deposition.


2021 ◽  
pp. 1-8
Author(s):  
Bin Yu ◽  
Andrew Steptoe ◽  
Yongjie Chen ◽  
Xiaohua Jia

Abstract Background Social isolation and loneliness have each been associated with cognitive decline, but most previous research is limited to Western populations. This study examined the relationships of social isolation and loneliness on cognitive function among Chinese older adults. Methods This study used two waves of data (2011 and 2015) from the China Health and Retirement Longitudinal Study and analyses were restricted to those respondents aged 50 and older. Social isolation, loneliness, and cognitive function were measured at baseline. Follow-up measures on cognitive function were obtained for 7761 participants (mean age = 60.97, s.d. = 7.31; male, 50.8%). Lagged dependent variable models adjusted for confounding factors were used to evaluate the association between baseline isolation, loneliness, and cognitive function at follow-up. Results Loneliness was significantly associated with the cognitive decline at follow-up (episodic memory: β = −0.03, p < 0.01; mental status: β = −0.03, p < 0.01) in the partially adjusted models. These associations became insignificant after additional confounding variables (chronic diseases, health behaviors, disabilities, and depressive symptoms) were taken into account (all p > 0.05). By contrast, social isolation was significantly associated with decreases in all cognitive function measures at follow-up (episodic memory: β = −0.05, p < 0.001; mental status: β = −0.03, p < 0.01) even after controlling for loneliness and all confounding variables. Conclusions Social isolation is associated with cognitive decline in Chinese older adults, and the relationships are independent of loneliness. These findings expand our knowledge about the links between social relationships and the cognitive function in non-Western populations.


1994 ◽  
Vol 269 (36) ◽  
pp. 22623-22627 ◽  
Author(s):  
J. Davis-Salinas ◽  
S.M. Saporito-Irwin ◽  
F.M. Donovan ◽  
D.D. Cunningham ◽  
W.E. Van Nostrand

2021 ◽  
Vol 80 (2) ◽  
pp. 567-576
Author(s):  
Fei Han ◽  
Fei-Fei Zhai ◽  
Ming-Li Li ◽  
Li-Xin Zhou ◽  
Jun Ni ◽  
...  

Background: Mechanisms through which arterial stiffness impacts cognitive function are crucial for devising better strategies to prevent cognitive decline. Objective: To examine the associations of arterial stiffness with white matter integrity and cognition in community dwellings, and to investigate whether white matter injury was the intermediate of the associations between arterial stiffness and cognition. Methods: This study was a cross-sectional analysis on 952 subjects (aged 55.5±9.1 years) who underwent diffusion tensor imaging and measurement of brachial-ankle pulse wave velocity (baPWV). Both linear regression and tract-based spatial statistics were used to investigate the association between baPWV and white matter integrity. The association between baPWV and global cognitive function, measured as the mini-mental state examination (MMSE) was evaluated. Mediation analysis was performed to assess the influence of white matter integrity on the association of baPWV with MMSE. Results: Increased baPWV was significantly associated with lower mean global fractional anisotropy (β= –0.118, p < 0.001), higher mean diffusivity (β= 0.161, p < 0.001), axial diffusivity (β= 0.160, p < 0.001), and radial diffusivity (β= 0.147, p < 0.001) after adjustment of age, sex, and hypertension, which were measures having a direct effect on arterial stiffness and white matter integrity. After adjustment of age, sex, education, apolipoprotein E ɛ4, cardiovascular risk factors, and brain atrophy, we found an association of increased baPWV with worse performance on MMSE (β= –0.093, p = 0.011). White matter disruption partially mediated the effect of baPWV on MMSE. Conclusion: Arterial stiffness is associated with white matter disruption and cognitive decline. Reduced white matter integrity partially explained the effect of arterial stiffness on cognition.


2021 ◽  
pp. 1-5
Author(s):  
Hesam Khodadadi ◽  
Évila Lopes Salles ◽  
Abbas Jarrahi ◽  
Vincenzo Costigliola ◽  
MB Khan ◽  
...  

There is a dire need for due innovative therapeutic modalities to improve outcomes of AD patients. In this study, we tested whether cannabidiol (CBD) improves outcomes in a translational model of familial AD and to investigate if CBD regulates interleukin (IL)-33 and triggering receptor expressed on myeloid cells 2 (TREM2), which are associated with improved cognitive function. CBD was administered to 5xFAD mice, which recapitulate early onset, familial AD. Behavioral tests and immunoassays were used to evaluate cognitive and motor outcomes. Our findings suggest that CBD treatment enhanced IL-33 and TREM2 expression, ameliorated the symptoms of AD, and retarded cognitive decline.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dan Song ◽  
Yaohua Chen ◽  
Cheng Chen ◽  
Lili Chen ◽  
Oumei Cheng

Abstract Purpose and background Previous studies have suggested that promoting endogenous neurogenesis has great significance for the recovery of cognitive dysfunction caused by cerebral ischemia (CI). Pharmacological inhibition of GABAB receptor can enhance neurogenesis in adult healthy and depressed mice. In the study, we intended to investigate the effects of GABAB receptor antagonists on cognitive function and hippocampal neurogenesis in mice following CI. Methods Adult mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 20 min to induce CI and treated with CGP52432 (antagonist of GABAB receptor, CGP, 10 mg/kg intraperitoneal injection) starting 24 h after CI. The Morris water maze test was performed to test spatial learning and memory at day 28. Immunofluorescence was applied to detect neurogenesis in the DG region at day 14 and 28. In in vitro experiments, cell proliferation was detected by CCK8 and immunofluorescence, and the expression of cAMP/CREB signaling pathway-related proteins was detected by ELISA assay and Western blot. Results CGP significantly improved spatial learning and memory disorders caused by CI, and it enhanced the proliferation of neural stem cells (NSCs), the number of immature neurons, and the differentiation from newborn cells to neurons. In vitro experiments further confirmed that CGP dose-dependently enhanced the cell viability of NSCs, and immunofluorescence staining showed that CGP promoted the proliferation of NSCs. In addition, treatment with CGP increased the expression of cAMP, PKA, and pCREB in cultured NSCs. Conclusion Inhibition of GABAB receptor can effectively promote hippocampal neurogenesis and improve spatial learning and memory in adult mice following CI.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 439-439
Author(s):  
Changmin Peng ◽  
Sae Hwang Han ◽  
Jeffrey Burr

Abstract Neighborhood environments shape the availability of resources for social engagement and social interaction, which are associated with better health outcomes. However, these contextual factors are also considered sources of potential social distress and tension, increasing the risk of subsequent health deficits, including cognitive decline. Our understanding of the linkage between childhood neighborhood environments and cognitive functioning in later life is limited. This study employed three waves of nationally representative data from the China Health and Retirement Longitudinal Study (2011-2015; N = 11,105) to investigate the relationship between self-reported neighborhood social cohesion during childhood (i.e., neighborhood safety, neighbors willing to help, and close-knit neighborhood) and cognitive functioning (Chinese version of TICS). We employed latent growth curve modeling to test hypotheses relating to life course models of childhood conditions and later life cognitive functioning (the long arm of childhood). The results showed that perceptions regarding the willingness of neighbors to help and close-knit neighborhood characteristics during childhood were positively associated with levels of later life cognitive function. Further, growing up in a neighborhood characterized by the willingness of neighbors to help others was negatively associated with the rate of cognitive decline, net of childhood and adulthood covariates. Self-report of neighborhood safety during childhood was unrelated to cognitive function (level and change). These findings underscored the long-term ramifications of childhood conditions as potential risk factors for later-life cognitive health. Social cohesion at the neighborhood level as experienced during childhood may be a protective factor for healthy cognitive aging among older Chinese adults.


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