Current Alzheimer research最新文献

Background/objective: Alzheimer's disease (AD) is mainly characterized by amnesia that affects millions of people worldwide. This study aims to explore the effectiveness capacities of bee venom (BV) for the enhancement of the memory process in a rat model with amnesia-like AD.

Methods: The study protocol contains two successive phases, nootropic and therapeutic, in which two BV doses (D1; 0.25 and D2: 0.5 mg/kg i.p.) were used. In the nootropic phase, treatment groups were compared statistically with a normal group. Meanwhile, in the therapeutic phase, BV was administered to scopolamine (1mg/kg) to induce amnesia-like AD in a rat model in which therapeutic groups were compared with a positive group (donepezil; 1mg/kg i.p.). Behavioral analysis was performed after each phase by Working Memory (WM) and Long-Term Memory (LTM) assessments using radial arm maze (RAM) and passive avoidance tests (PAT). Neurogenic factors; Brain-derived neurotrophic factor (BDNF), and Doublecortin (DCX) were measured in plasma using ELISA and Immunohistochemistry analysis of hippocampal tissues, respectively.

Results: During the nootropic phase, treatment groups demonstrated a significant (P < 0.05) reduction in RAM latency times, spatial WM errors, and spatial reference errors compared with the normal group. In addition, the PA test revealed a significant (P < 0.05) enhancement of LTM after 72 hours in both treatment groups; D1 and D2. In the therapeutic phase, treatment groups reflected a significant (P < 0.05) potent enhancement in the memory process compared with the positive group; less spatial WM errors, spatial reference errors, and latency time during the RAM test, and more latency time after 72 hours in the light room. Moreover, results presented a marked increase in the plasma level of BDNF, as well as increased hippocampal DCX-positive data in the sub-granular zone within the D1 and D2 groups compared with the negative group (P < 0.05) in a dose-dependent manner.

Conclusion: This study revealed that injecting BV enhances and increases the performance of both WM and LTM. Conclusively, BV has a potential nootropic and therapeutic activity that enhances hippocampal growth and plasticity, which in turn improves WM and LTM. Given that this research was conducted using scopolamine-induced amnesia-like AD in rats, it suggests that BV has a potential therapeutic activity for the enhancement of memory in AD patients in a dose-dependent manner but further investigations are needed.

Alzheimer's disease (AD) is the most common cause of neurodegenerative cognitive impairment. Brain stimulation techniques based on the delivery of transcranial shockwaves are currently being studied for their increasing popularity as an approach to modulate the human brain in a focal and targeted manner making this therapy a promising line of action against AD. In the present manuscript, we review for further understanding whether transcranial pulse stimulation (TPS) is a beneficial treatment for AD patients. PubMed, Google Scholar, and Cochrane databases were accessed with the search criteria set from year 2001 to 2022 and the following keywords were used: "transcranial pulse stimulation", "focused ultrasound", "noninvasive treatment and Alzheimer" and "TPS". The search was focused on papers that provide evidence on the biological bases of the method, as well as its safety and tolerability. Even though more studies are needed with greater scientific rigor, such as a doubleblind and randomized study versus a placebo, TPS is an excellent and safe therapeutic option for AD. This novel approach accompanies currently available treatments and complements them, helping to maintain greater stability of the disease and slowing its progression. The biological effects and potential mechanisms of action of TPS for the improvement of cognitive function are further discussed.

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.

Design and 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.

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 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.

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 (AD) develops through a complex pathological process, in which many genes play a synergistic or antagonistic role. LncRNAs represent a kind of non-coding RNA, which can regulate gene expression at the epigenetic, transcriptional and post-transcriptional 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.

Alzheimer's disease (AD) is an age-related neurodegenerative disease, seriously influencing the quality of life and is a global health problem. Many factors affect the onset and development of AD, but specific mechanisms underlying the disease are unclear. Most studies investigating AD have focused on neurons and the gray matter in the central nervous system (CNS) but have not led to effective treatments. Recently, an increasing number of studies have focused on the white matter (WM). Magnetic resonance imaging and pathology studies have shown different degrees of WM abnormality during the progression of AD. Myelin sheaths, the main component of WM in the CNS, wrap and insulate axons to ensure conduction of the rapid action potential and axonal integrity. WM damage is characterized by progressive degeneration of axons, oligodendrocytes (OLs), and myelin in one or more areas of the CNS. The contributions of OLs to AD progression have, until recently, been largely overlooked. OLs are integral to myelin production, and the proliferation and differentiation of OLs, an early characteristic of AD, provide a promising target for preclinical diagnosis and treatment. However, despite some progress, the key mechanisms underlying the contributions of OLs to AD remain unclear. Given the heavy burden of medical treatment, a better understanding of the pathophysiological mechanisms underlying AD is vital. This review comprehensively summarize the results on WM abnormalities in AD and explores the relationship between OL progenitor cells and the pathogenesis of AD. Finally, the underlying molecular mechanisms and potential future research directions are discussed.

Aims: Exploring the neurobiological mechanisms of early AD damage Background: The early diagnosis of Alzheimer's disease (AD) has a very important impact on the prognosis of AD. However, the early symptoms of AD are not obvious and difficult to diagnose. Existing studies have rarely explored the mechanism of early AD. AMPARs are early important learning memory-related receptors. However, it is not clear how the expression levels of AMPARs change in early AD.

Objective: We explored learning memory abilities and AMPAR expression changes in APP/PS1 mice at 4 months, 8 months, and 12 months.

Method: We used the classic Morris water maze to explore the learning and memory impairment of APP/PS1 mice and used western blotting to explore the changes in AMPARs in APP/PS1 mice.

Result: We found that memory impairment occurred in APP/PS1 mice as early as 4 months of age, and the impairment of learning and memory gradually became serious with age. The changes in GluA1 and p-GluA1 were most pronounced in the early stages of AD in APP/PS1 mice.

Conclusion: Our study found that memory impairment in APP/PS1 mice could be detected as early as 4 months of age, and this early injury may be related to GluA1.

Background: Recent findings suggest that both dietary protein intake and hand grip strength (HGS) were associated with cognitive function, however, few studies have been devoted specifically to the mediation effect of HGS on the association of dietary protein with cognitive function.

Objectives: To confirm the hypothesis that HGS mediated the association of dietary protein intake with cognitive function in the elderly, which was modified by triglyceride level and methylenetetrahydrofolate reductase (MTHFR) gene status.

Methods: This cross-sectional study included 3,268 participants. Dietary protein intake, HGS, and cognitive function were collected by food frequency questionnaires (FFQ), grip measurements and mini mental state examination (MMSE), respectively. In this mediation analysis, dietary protein intake was entered as independent variable, HGS was entered as mediator, and cognitive function was entered as dependent variable.

Results: HGS significantly mediated the associations of dietary protein (β = 0.0013, 95% CI: 0.0007, 0.0022), animal protein (β = 0.0024, 95% CI: 0.0012, 0.0037), and plant protein intake (β = 0.0011, 95% CI: 0.0001, 0.0023) with cognitive function in total participants, with the mediated proportion of 16.19%, 12.45% and 20.57%, respectively. Furthermore, significant mediation effects of HGS on the associations of dietary protein, animal protein, and plant protein intake with MMSE score were found in the elderly without hypertriglyceridemia or in MTHFR C677T CC/CT carriers.

Conclusion: This study suggested that HGS mediated the association of dietary protein intake with cognitive function, and this mediation effect was modified by triglyceride level and MTHFR C677T gene status.

Background: Currently available medication for Alzheimer's disease (AD) may slows cognitive decline only transitory, but has failed to bring about long term positive effects. For this slowly progressive neurodegenerative disease so far no disease modifying therapy exists.

Objective: To find out if non-pharmacologic non-ivasive neuromodulatory repetitive transcranial magnetic stimulation (rTMS) may offer a new alternative or an add on therapeutic strategy against loss of cognitive functions.

Methods: In this exploratory intervention study safety and symptom development before and after frontopolar cortex stimulation (FPC) using intermittent theta burst stimulation (iTBS) at 10 subsequent working days was monitored as add-on treatment in 28 consecutive patients with AD. Out of these, 10 randomly selected patients received sham stimulation as a control. In addition, ​serum concentrations of neurotransmitter precursor amino acids, of immune activation and inflammation markers, of brain derived neurotrophic factor (BDNF) as well as of nitrite were measured.

Results: Treatment was well tolerated, no serious adverse effects were observed. Improvement of cognition was detected by an increase of Mini Mental State Examination score (MMSE; p<0.01, paired rank test) and also by an increase in a modified repeat address phrase test, part of the 6-item cognitive ​impairment test (p < 0.01). A trend to an increase in the clock drawing test (CDT; p = 0.08) was also found in the verum treated group. Furtheron, in 10 of the AD patients with additional symptoms of depression treated with iTBS, a significant decrease in the HAMD-7 scale (p <0.01) and a trend to lower serum phenylalanine concentrations (p = 0.08) was seen. No changes of the parameters tested were found in the sham treated patients.

Conclusion: Our preliminary results may indicate that iTBS is effective in the treatment of AD. Also a slight influence of iTBS on the metabolism of phenylalanine was found after 10 iTBS sessions. An impact of iTBS to influence the enzyme phenylalanine hydroxylase (PAH), as found in previous series of treatment resistant depression, could not be seen in this our first observational trial in 10 AD patients with comorbidity of depression. Longer treatment periods for several weeks in a higher number of AD patients with depression could cause more intense and disease modifying effects visible in different neurotransmitter concentrations important in the pathogenesis of AD.