Journal of Dementia and Alzheimer's Disease

Introduction: Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia, sleep fragmentation, daytime sleepiness, cognitive impairment, and brain cell damage due to brain blood flow reduction, with ischemic damage, increased microvascular reactivity, and brain tissue damage. OSAS is strongly linked to chronic, neurodegenerative, and inflammatory cerebrovascular disease and cognitive impairment. Continuous positive airway pressure (CPAP) is the first-line treatment for OSAS. Objective: This article aims to evaluate the effect of CPAP treatment on neurocognitive performance in OSAS patients with mild cognitive impairment or dementia by reviewing the literature. Methods: We performed a comprehensive review of the Portuguese and English languages without a time limit using the following Mesh terms: dementia, mild cognitive impairment, obstructive sleep apnea, and CPAP. We included randomized controlled trials (RCTs), meta-analyses, and systematic reviews (SRs) where the impact of CPAP on neurocognitive performance was addressed. Results: Five SRs and three RCTs reported significant improvements in neurocognitive performance, especially in verbal, visuospatial, and working memory. Conclusion: CPAP treatment seems to improve cognitive defects associated with OSA. Full article

Alzheimer’s disease (AD) is the most common cause of dementia, and no cure is currently available. The β-amyloid cascade of AD and neurofibrillary tangles are the basis of the current understanding of AD pathogenesis, driving drug investigation and other discoveries. Up until now, no AD models have entirely validated the β-amyloid cascade hypothesis. AD models must be capable of recapitulating the critical events of this pathology, including β-amyloid plaques and neurofibrillary tangles. The development of plaques is probably derived from the amyloid precursor protein (APP) and presenilin 1 (PS1) familial Alzheimer’s disease (FAD) mutations, while the tangle-like pathology is determined by tau mutations. Transgenic mouse models struggle to replicate the entire spectrum of AD, particularly neuronal death stemming from β-amyloid and tau pathologies. Furthermore, the success of these transgenic mice often relies on the overexpression of APP transgenes enclosing FAD-associated mutations at levels beyond physiological. Ultimate species-specific discrepancies in genome and protein composition between the human and the mouse may hinder the accurate recapitulation of AD pathological events in mouse models. Although none of the AD models fully mirrors human pathology, these experimental in vivo animal models have provided valuable insights into β-amyloid toxicity and the overall pathophysiological basis of AD. Therefore, these experimental models have been widely used in the preclinical evaluation of therapeutic strategies and have played a pivotal role in the development of immunotherapies for AD. In this review, we sum up the main transgenic mouse models used for AD research, whether they are APP mutation-based mice, APP plus presenilin mutation-based mice, or tau mutation-based mice. The specific characteristics of each mouse model and the significance of their use for AD research, focusing on their current advantages and disadvantages, as well as on the progress made and the forthcoming challenges in replicating this neurodegenerative disease, are also highlighted. Full article

Context: The systematic evaluation of a practitioner’s adherence to and competence in delivering psychotherapeutic interventions can be complex. This study describes the development of a fidelity assessment tool for the Reitman Centre CARERS Program (RCCP), a carer group-psychotherapy intervention with multiple didactic and clinical components. The tool’s value in informing psychotherapy training and best practices for practitioners from diverse professional settings is examined. Methods: The RCCP Fidelity Assessment Tool (RCCP-FAT) was developed following an iterative process of item writing and checking. Seven components of the RCCP—Group Structure, Dementia Education, Problem-Solving Techniques, Therapeutic Simulation, Vertical Cohesion, Horizontal Cohesion, and Overall Global Rating—were assessed, with three to eight items, and a “global score” assigned to each. Fifteen trained raters were paired up to rate 36 RCCP sessions using the RCCP-FAT. Rater agreement, correlation between itemized and global scores, and correlation between global ratings and RCCP participants’ satisfaction were calculated. Results: A total of 1188 RCCP-FAT items were rated by each of the two rater groups. Rater agreement was calculated to be 54.3% (κ = 0.32; 95% CI, 0.02681–0.3729). A positive correlation was found between the itemized and global scoring for four RCCP components evaluated (R = 0.833 to 0.929; p < 0.01). The global score and the participants’ satisfaction with “Simulation” was also positively correlated (R = 0.626, p < 0.01). Conclusions: The study provided evidence for fair rater agreement for all RCCP-FAT assessment items. More importantly, the process of developing the tool systematically crystallized the clinical elements of the RCCP and helped to standardize the training methods by creating a framework for providing feedback to learners that matches the items on the RCCP-FAT. The use of the RCCP-FAT to guide the training and mentoring of incoming group leaders is essential in the scaling and dissemination of a complex training method like the RCCP to ensure fidelity to the original evidence-based intervention. Full article

Alzheimer’s disease (AD) is a brain disorder that is more prevalent in developed nations and remains one of most intractable conditions so far. It is characterized by a gradual onset, a prolonged progression, and an unclear pathophysiology. At the present time, there are no effective treatments available for the disease. However, human neural stem cells (hNSCs) have the capacity to substitute lost neurons in a functional manner, strengthen synaptic networks that have been compromised, and repair the damaged brain. Due to the unavailability of restorative therapeutics, there is a significant global burden on the economy. When it comes to the treatment of neurodegenerative diseases, NSCs provide a potentially game-changing approach to treating Alzheimer’s disease. Through the delivery of trophic factors that promote the viability and regeneration of lost neurons in experimental animals suffering from neurodegenerative disorders, these treatments have the potential to facilitate beneficial recuperation. Positive restorative outcomes may be achieved in a variety of ways, including the replacement of lost cells, the combining of cells, the secretion of neurotrophic factors, the formation of endogenous stem cells, and transdifferentiation. Conversely, there are obstacles that need to be overcome before NSC-based treatments can be used in clinical settings. This review article discusses current developments in the use of neural stem cells (NSCs) for the treatment of Alzheimer’s disease (AD). In addition, we highlight the difficulties and opportunities that are involved with the use of neural stem cell transplant treatment for Alzheimer’s disease. Full article

Background: The heavily right-skewed data seen in recently reported Alzheimer’s disease (AD) clinical trials influenced treatment contrasts when data were analyzed via the typical mixed-effects model for repeated measures (MMRM). Methods: An MMRM analysis similar to what is commonly used in AD clinical trials was compared versus robust regression (RR) and the non-parametric Hodges–Lehman estimator (HL). Results: Results in simulated data patterned after AD trials showed that imbalance across treatment arms in the number of patients in the extreme right tail (those with rapid disease progression) frequently occurred. Each analysis method controlled Type I error at or below the nominal level. The RR analysis yielded smaller standard errors and more power than MMRM and HL. In data sets with appreciable imbalance in the number of rapid progressing patients, MMRM results favored the treatment arm with fewer rapid progressors. Results from HL showed the same trend but to a lesser degree. Robust regression yielded similar results regardless of the ratio of rapid progressors. Conclusions: Although more research is needed over a wider range of scenarios, it should not be assumed that MMRM is the optimal approach for trials in early Alzheimer’s disease. Full article

Endoplasmic reticulum (ER) stress is a detrimental cellular phenomenon in the cells and is activated by the accumulation of unfolded or misfolded proteins in the ER. The unfolded protein accumulation activates the unfolded protein response (UPR), an adaptive mechanism designed to mitigate cellular stress by enhancing the ER’s protein-folding capacity and protecting cells from apoptotic stimuli in neuroinflammation and neurodegenerative diseases. However, chronic ER stress and prolonged activation of the UPR can have adverse effects, including the activation of pro-apoptotic and inflammatory signaling pathways, which contribute to the development and progression of neurodegenerative disorders. Neurodegenerative diseases are complex and devastating conditions with underlying pathogenesis that are not fully understood. Genetic mutations leading to the accumulation of misfolded or phosphorylated tau proteins and amyloid-beta in the ER can induce ER stress, resulting in neuroinflammation and neuronal death. Several studies have reported the involvement of increased ER stress and UPR signaling proteins in the pathogenesis and progression of neurodegenerative diseases. Thus, inhibiting ER stress and neuroinflammation and targeting their associated signaling pathways represent a significant area of research interest. This review discusses the critical signaling molecules involved in ER stress, their mechanisms in the progression of neurodegenerative diseases, and the latest developments in the available ER stress inhibitors. Despite the extensive development of ER stress inhibitors over the years, only a limited number have been approved as pharmaceutical drugs. There remains a critical need for effective ER stress inhibitors to provide efficient treatments for neurodegenerative diseases, including Alzheimer’s disease. Full article

Episodic memory is affected early and is a basic indication of neurodegeneration especially for Alzheimer’s disease. The aim of this study was to examine whether adults with vascular risk factors are differentiated in their episodic memory performance from individuals with mild cognitive impairment (MCI). The episodic memory of adults diagnosed with MCI, adults with vascular risk factors (VRF; blood pressure, diabetes mellitus, or hypercholesterolemia), and healthy controls was assessed using the Doors and People test. Statistical processing included mediation analyses which were performed separately for the VRF and healthy control groups, and the MCI and healthy control groups. ANOVA was used for the MCI and VRF groups which were matched in age and education. ANOVA showed that the MCI adults had significantly lower performance than the VRF adults in verbal recall only, F (1, 83) = 9.541, p = 0.003, and η_p² = 0.10. A direct effect of diagnosis on verbal recall was found via mediation analysis as concerns individuals with MCI and healthy controls, b = 0.506, SE = 0.128, p < 0.001, and 95%CI: 0.221–0.771, in favor of the healthy controls. Concerning the VRF and healthy groups, a tendency of diagnosis to directly affect verbal recall was shown (α = 0.005) in favor of the healthy controls, b = 0.388, SE = 0.150, p = 0.010, and 95%CI: 0.043–0.720. In conclusion, it is supported that patients with MCI present deficit performance in verbal recall; in addition, the diagnostic category affects all the groups’ performance on the same condition. These results indicated that the verbal recall aspect of episodic memory can be a sensitive indicator that can differentiate healthy adults from adults with mild cognitive impairment and vascular risk factors, as well as the two pathological groups from each other. Full article

The entrance of cells into a permanent state of cell cycle arrest with the ability to resist apoptosis is termed “cellular senescence”. The accumulation of senescent cells within the body can lead to tissue aging and the dysfunction of organs. Whether due to external stressors or the passage of time, aging is an inevitable process that afflicts every living being. Current studies that investigate aging rely on the use of cells or rodent models. Although cells present a cost-effective and quick way to analyze aging, they lack the complexity of whole-body systems and therefore require the use of an in vivo model post-in vitro assays. The zebrafish, Danio rerio, presents a cost-effective model with quick development and large numbers of offspring. These fish share 70% similarity of their genes with humans, including genes known to be associated with human diseases, such as those diseases of aging and/or senescence, like Alzheimer’s disease. Major tissues and organs of humans are also found in these fish, and therefore, zebrafish can serve as a useful model when studying diseases, aging, Alzheimer’s disease, and other disorders. In this review, we will discuss some of the major senescence biomarkers and detection methods, as well as discuss how zebrafish models can be used for the study of aging and age-related disorders. Full article

The gut microbiota (GM) communicates with the brain via biochemical signaling constituting the gut–brain axis, which significantly regulates the body’s physiological processes. The GM dysbiosis can impact the digestive system and the functioning of the central nervous system (CNS) linked to the onset of neurodegenerative diseases. In this review, the scientific data compiled from diverse sources primarily emphasize the neuropathological characteristics linked to the accumulation of modified insoluble proteins (such as β-amyloid peptides and hyperphosphorylated tau proteins) in Alzheimer’s disease (AD) and the potential impact of gut microbiota (GM) on AD susceptibility or resilience. The specific GM profile of human beings may serve as an essential tool for preventing or progressing neurodegenerative diseases like AD. This review focuses mainly on the effect of gut microfauna on the gut–brain axis in the onset and progression of AD. The GM produces various bioactive molecules that may serve as proinflammatory or anti-inflammatory signaling, contributing directly or indirectly to the repression or progression of neurodegenerative disorders by modulating the response of the brain axis. Human studies must focus on further understanding the gut–brain axis and venture to clarify microbiota-based therapeutic strategies for AD. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms due to the loss of dopamine-producing neurons and the presence of Lewy bodies in the brain. While current treatments such as dopamine replacement with levodopa and deep brain stimulation mainly manage symptoms and do not stop disease progression, recent advancements in nanomedicine provide promising new therapy options. These include drug-loaded nanocarriers that improve drug delivery to the brain, enhancing effectiveness and reducing side effects. This review explores novel nanomedical approaches like solid lipid nanocarriers (SLNs), which could improve drug profiles and decrease the adverse effects seen with traditional PD treatments. Additionally, it discusses the challenge of crossing the blood–brain barrier, which is crucial for treating central nervous system disorders, and how nanocarriers facilitate targeted brain delivery. Despite these advancements, the review emphasizes more research into the safety and long-term impacts of nanomedicine in PD, highlighting the challenge of moving these treatments from lab to clinical use. Full article