Current Alzheimer Research - Volume 19, Issue 11, 2022

Alzheimer’s disease (AD) and dysphagia are important health and socioeconomic problems in the aging population. Currently, the medical treatment of dysphagia in AD patients remains insufficient, and there are significant gaps in the management and clinical needs to postpone tube feeding. Literatures published over the last 30 years were searched in the PubMed and Embase databases. All relevant and promising pharmacological management studies were included. Because of the heterogeneity in design and methodology, only narrative reports were mentioned. Nine studies were included with two case reports, two case series, and two observational and three randomized controlled trials. The key approaches and clinical problems related to dysphagia include onset pattern, dementia stage, review of offending drugs and polypharmacy, and comorbidities (cerebrovascular disease, hypertension, parkinsonism, depression, and anorexia). The corresponding strategies of pharmacological treatments are further proposed and discussed comprehensively, with transient receptor potential channel modulators as promising treatment. With the integration of adequate and potential pharmacomanagement, AD patients with dysphagia can achieve a good prognosis and postpone tube feeding to maintain a better quality of life. More rigorous studies are needed to verify the effectiveness of innovative strategies and develop targets for neurostimulation.

Background: Alzheimer's disease is the most common form of dementia, affecting millions of people worldwide. Methods: Here, we analyzed the effects of metformin on APP/PS1 transgenic mice by behavioral test and single-cell sequencing. Results: It showed that metformin can improve the spatial learning, memory function, and anxiety mood of APP/PS1 transgenic mice. We identified transcriptionally distinct subpopulations of nine major brain cell types. Metformin increased the differentiation of stem cells, decreased the proportion of cells in the G2 phase, enhanced the generation of neural stem cells and oligodendrocyte progenitor cells, and the tendency of neural stem cells to differentiate into astrocytes. Notably, 253 genes expressed abnormally in APP/PS1 transgenic mice and were reversed by metformin. Ttr, Uba52, and Rps21 are the top 3 genes in the cell-gene network with the highest node degree. Moreover, histochemistry showed the expressions of RPS15, Uba52, and RPL23a were consistent with the data from single-cell sequencing. Pathway and biological process enrichment analysis indicated metformin was involved in nervous system development and negative regulation of the apoptotic process. Conclusion: Overall, metformin might play an important role in the differentiation and development and apoptotic process of the central nervous system by regulating the expression of Ttr, Uba52, Rps21, and other genes to improve cognition of APP/PS1 transgenic mice. These results provided a clue for elaborating on the molecular and cellular basis of metformin on AD.

Background: Alzheimer’s disease (AD) develops through a complex pathological process, in which many genes play a synergistic or antagonistic role. LncRNAs represent a kind of noncoding RNA, which can regulate gene expression at the epigenetic, transcriptional and posttranscriptional levels. Multiple lncRNAs have been found to have important regulatory functions in AD. Thus, their expression patterns, targets and functions should be explored as therapeutic targets. Methods: We used deep RNA-seq analysis to detect the dysregulated lncRNAs in the hippocampus of APP/PS1 mice. We performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to predict the biological roles and potential signaling pathways of dysregulated lncRNAs. Finally, we constructed lncRNA-miRNA-mRNA and lncRNA-mRNA co-expression networks to reveal the potential regulator roles in AD pathogenesis. Results: Our findings revealed 110 significantly dysregulated lncRNAs. GO and KEGG annotations showed the dysregulated lncRNAs to be closely related to the functions of axon and protein digestion and absorption. The lncRNA-mRNA network showed that 19 lncRNAs regulated App, Prnp, Fgf10 and Il33, while 5 lncRNAs regulated Lfng via the lncRNA-miR-3102-3p-Lfng axis. Furthermore, we preliminarily demonstrated the important regulatory role of the Lfng/Notch1 signaling pathway through lncRNA-ceRNA networks in AD. Conclusion: We revealed the important regulatory roles of dysregulated lncRNAs in the etiopathogenesis of AD through lncRNA expression profiling. Our results showed that the mechanism involves the regulation of the Lfng/Notch1 signaling pathway.

Background: Providing quality end-of-life care to individuals with advanced dementia is crucial. To date, little attention has been paid to palliative care knowledge and attitudes toward palliative care for people with advanced dementia in Spain. Objectives: To investigate the knowledge of and attitudes toward palliative care for advanced dementia among registered nurses and physicians in Spain. Methods: A descriptive, cross-sectional survey design was used. This study included a convenience sample of 402 nurses (n = 290) and physicians (n = 112). Two instruments were administered: demographic characteristics and Spanish version of the Questionnaire of Palliative Care for Advanced Dementia (qPAD-SV). Descriptive statistics and multiple regression were used for data analysis. Results: Overall, the nurses and physicians had moderate mean scores for both knowledge of and attitudes regarding palliative care for advanced dementia. Physicians had a higher level of knowledge (p < 0.05) compared to nurses. Additionally, physicians and nursing staff who had professional experience/ education in geriatrics and those who had received palliative care and hospice training had greater (p < 0.01) knowledge of palliative care. In addition, healthcare professionals who had received dementia care training and who had worked in nursing homes had higher levels (p < 0.05) of knowledge and attitudes toward palliative care. Conclusion: This study indicates the need to provide nurses and physicians with more education for select groups of professionals who have had limited education and experience in caring for older adults with advanced dementia.