Journal of Alzheimer's Disease最新文献

Background: The cost-effectiveness of interventions is a key issue owing to the limited resources of healthcare services.

Objective: To conduct a systematic review of economic evaluations of technology-based healthcare interventions in care support for people with dementia or mild cognitive impairment (MCI) and their caregivers, and of the tools used to assess effectiveness and costs.

Methods: The following databases were used: PubMed, National Health Service Economic Evaluation Database, and Health Technology Assessment. A total of 207 articles from 2012 to 2024 were identified and then screened.

Results: Seventeen studies were included, of which nine were study protocols. Almost half (n = 8) the interventions were multicomponent. The most common components used in the interventions were cognitive stimulation, physical functioning and continuing support. Regarding the efficiency results of these interventions, only three studies provided a full economic evaluation. The most frequent tools in the economic evaluations used to measure effectiveness (measured in quality-adjusted life years) and costs were the European Quality of Life-5 Dimensions and Resource Utilization in Dementia instruments, respectively.

Conclusions: Most of the interventions evaluated were cost-effective. However, these results should be interpreted with caution, given the scarcity of the literature, and further economic evaluations of technology-based healthcare interventions for people with mild dementia or MCI care support and their caregivers are therefore needed. Additionally, a meta-analysis could not be performed due to the heterogeneity of the data.

Background: Mild cognitive impairment (MCI) and mild behavioral impairment (MBI) are both considered potential prodromal stages of dementia, especially Alzheimer's disease. Previous literature has lacked specific information about MBI in individuals with MCI and associations of several aspects of both, MBI and MCI.

Objective: Our aim was to investigate whether associations exist between aspects of MBI and aspects of cognitive performance in certain dimensions of the Montreal Cognitive Assessment (MoCA).

Methods: We used baseline data from the double-blind randomized controlled intervention MCI-CCT-study. Current cognitive performance of individuals with MCI was measured with the MoCA. MBI was assessed with the MBI Shortscale (MBI short), which was administered through a self-report interview. Associations were assessed with Pearson correlations. Sensitivity analyses were conducted for gender and cognition. Group differences were examined with independent samples t-tests or Welch test. Significant correlations were considered in binary logistic regressions under control of covariates.

Results: There was no significant correlation between the current MoCA and MBI short scores in the total sample or in the gender-related analysis. Using dichotomized cognitive performance, significant correlations between MCI and MBI were revealed for individuals with lower MoCA scores. On the task level, several significant associations were identified between MoCA dimensions and MBI dimensions in the total sample and in the sensitivity analyses, also under control of covariates.

Conclusions: Our findings support the hypothesis that with increasing cognitive decline, the association between MCI and MBI becomes stronger. Furthermore, a certain cut-off on the MoCA must be reached to identify a correlation.

Research has shown that up to 40% of dementia incidence can be accounted for by 12 modifiable lifestyle risk factors. However, the predictive value of these risks factors at an individual level remains uncertain. Ethical considerations that are typically invoked with respect to the disclosure of individual research results-beneficence and non-maleficence, respect for autonomy, and justice-do not provide conclusive justification for, or against, disclosing modifiable risk factors for future dementia to cognitively unimpaired research participants. We argue for a different approach to evaluating the disclosure of individual-level modifiable risk factors for dementia. Rather than focusing on individual-level disease prediction and prevention, we suggest that disclosure should be evaluated based on the impact of behavioral and lifestyle changes on current brain health.

In this cross-sectional study, we assessed palliative care (PC) needs in older adults with dementia. Using the NECPAL CCOMS-ICO^© 3.1 tool and comprehensive geriatric assessment, 16.25% of the 554 evaluated patients required PC, which had clinical frailty and a moderate stage of dementia. Advanced frailty was associated with the poorest prognosis, according to the PC-based stratification. Our findings support the use of PC assessment in dementia care, which focuses on a person-centered approach while minimizing unnecessary or ineffective treatments and meeting the real-world patient's needs. PC care may fulfill the multidimensional nature of dementia, shifting towards personalized palliative approaches.

The study of neurodegenerative diseases, such as Alzheimer's disease (AD), has long been a complex and challenging task. One of the major hurdles in understanding these diseases is the difficulty in recapitulating the complex interactions between neurons, astrocytes, and microglia in a laboratory setting. In recent years, researchers have made significant progress in developing triculture models that combine these three cell types, allowing for a more accurate representation of the cellular context of the human brain. This commentary discusses the recent advancements and importance of using tri-culture model systems in clarifying the pathophysiology of AD and discusses the recent article by Kim et al. (2024) published in the Journal of Alzheimer's Disease.

Effective screening for communicative ability in dementia is vital to drive theoretical understanding and optimize care responsiveness globally. Communication is central to the human experience; however, routine clinical screening for progressive communication change remains limited due to a variety of resource constraints. Other challenges include the subtlety of early communication-led symptoms, heterogeneous underlying pathologies, and a lack of culturally diverse research and tools. To address the scarcity of dedicated assessment resources, future initiatives must maximize responsiveness to and representation of our global population to appropriately respond to the rising, and vastly diverse, dementia crisis.

Background: Adherence is critical in patients with Alzheimer's disease (AD) in order to achieve optimal benefit from therapy. However, patient compliance with the treatment remains a challenge.

Objective: To evaluate, in a real-world clinical setting, caregiver preference and treatment compliance with twice-weekly versus daily transdermal rivastigmine patch in mild-to-moderate AD.

Methods: 92 patients who had been treated with daily rivastigmine patch for at least six months prior to switching to twice-weekly patch were evaluated. The change in therapeutic regimen was decided by the treating physician in accordance with standard practice. Caregivers' satisfaction with daily rivastigmine patch was assessed at study entry. Caregiver's preference and satisfaction with twice-weekly patch as well as patient compliance were evaluated at weeks 12 and 24 using the Alzheimer's Disease Caregiver Preference Questionnaire.

Results: A significantly higher proportion of caregivers expressed a preference for the twice-weekly patch over the daily patch (p < 0.001), and this preference was found to be associated with ease of use (p < 0.001), ease of following the schedule (p < 0.001), and ease of compliance (p < 0.001). Furthermore, caregivers were more satisfied with the twice-weekly patch (p < 0.0001). At 24 weeks, patient compliance was significantly better with the twice-weekly patch than with the daily patch (p = 0.002). Caregiver burden significantly improved at the end of the treatment (p = 0.003). No serious adverse events were reported.

Conclusions: The twice-weekly rivastigmine patch offers a convenient and straightforward dosing regimen for caregivers, with potential to enhance adherence with treatment in AD patients without causing serious adverse events.

Background: Microglia play a critical role in neurodegenerative disorders, such as Alzheimer's disease, where alterations in microglial function may result in pathogenic amyloid-β (Aβ) accumulation, chronic neuroinflammation, and deleterious effects on neuronal function. However, studying these complex factors in vivo, where numerous confounding processes exist, is challenging, and until recently, in vitro models have not allowed sustained culture of critical cell types in the same culture.

Objective: We employed a rat primary tri-culture (neurons, astrocytes, and microglia) model and compared it to co-culture (neurons and astrocytes) and mono-culture (microglia) to study microglial function (i.e., motility and Aβ clearance) and proteomic response to exogenous Aβ.

Methods: The cultures were exposed to fluorescently-labeled Aβ (FITC-Aβ) particles for varying durations. Epifluorescence microscopy images were analyzed to quantify the number of FITC-Aβ particles and assess cytomorphological features. Cytokine profiles from conditioned media were obtained. Live-cell imaging was employed to extract microglia motility parameters.

Results: FITC-Aβ particles were more effectively cleared in the tri-culture compared to the co-culture. This was attributed to microglia engulfing FITC-Aβ particles, as confirmed via epifluorescence and confocal microscopy. FITC-Aβ treatment significantly increased microglia size, but had no significant effect on neuronal surface coverage or astrocyte size. Upon FITC-Aβ treatment, there was a significant increase in proinflammatory cytokines in tri-culture, but not in co-culture. Aβ treatment altered microglia motility evident as a swarming-like motion.

Conclusions: The results suggest that neuron-astrocyte-microglia interactions influence microglia function and highlight the utility of the tri-culture model for studies of neuroinflammation, neurodegeneration, and cell-cell communication.

Background: Alzheimer's disease (AD) is a progressive and irreversible neurological disorder that gradually deteriorates an individual's ability to carry out even the simplest tasks.

Objective: This study was undertaken to investigate the potential therapeutic efficacy of a novel bithiophene in a rat model of aluminum-induced AD pathology.

Methods: A total of 108 adult male albino rats weighing 160 ± 20 g, were randomly assigned to six groups: (1) a control group administered DMSO, (2) group receiving a high dose of bithiophene (1 mg/kg), (3) a model group received AlCl₃ (100 mg/kg), those rats were then treated by either (4) bithiophene low dose (0.5 mg/kg), (5) high dose (1 mg/kg), or (6) memantine (20 mg/kg).

Results: Low dose bithiophene treatment was a promising strategy for mitigating oxidative stress and improving synaptic plasticity. This was demonstrated by reductions in malondialdehyde level, and increased activities of superoxide dismutase and catalase, and elevated glutathione content. Likewise, low dose bithiophene enhanced synaptic plasticity through a reduction in excitatory glutamate and norepinephrine levels, while increasing dopamine. Moreover, bithiophene significantly downregulated the expression of GSAP, GSK3-β, and p53, which are implicated in AD progression. This treatment also decreased caspase 3 and amyloid-β (Aβ_1-42) accumulation in the hippocampus. Finally, behavioral assessments revealed that low dose bithiophene significantly enhanced learning abilities, as proved by Morris water maze.

Conclusions: Low dose bithiophene mitigated AD through ameliorating oxidative stress, promoting synaptic plasticity, inhibiting the Aβ accumulation, and enhancing the cognitive functions in a rat model.

Background: Alzheimer's disease (AD) is a common neurodegenerative disorder, currently lacking effective early diagnostic methods. However, natural killer (NK) cells may play a potential role in AD pathogenesis.

Objective: This study aims to identify AD-related feature genes from NK cell markers to construct a diagnostic model and explore their potential biological mechanisms in AD.

Methods: Single-cell RNA sequencing data was used to identify NK cell markers. A novel feature selection algorithm, adaptive dynamic graph convolutional network (ADGCN), was proposed to extract AD-related feature genes and construct a diagnostic model. Differential, correlation and enrichment analyses were performed to understand the biological mechanisms of these genes. Immune infiltration analysis compared the immune microenvironment between AD and controls. Two regulatory networks explored interactions between feature genes, transcription factors and microRNAs. The association between SNPs and feature genes' expression was examined through expression quantitative trait loci analysis. Differential CpG sites were identified to analyze their association with the NK cell markers' expression.

Results: We developed an optimal diagnostic model (ADGCN-XGBoost) with 17 feature genes, demonstrating high diagnostic effectiveness across datasets. These genes were primarily related to macromolecule biosynthesis, cytoplasmic translation biological processes and ribosome pathway, and potentially modulated immune infiltration of AD patients. We predicted 27 target miRNAs and 21 transcription factors influencing these genes. Multimodal analysis identified 57 significant SNP-gene associations and seven CpG-gene pairs.

Conclusions: This study proposed a novel feature selection algorithm and developed a diagnostic model based on 17 feature genes, providing new potential biomarkers for AD diagnosis.