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Journal of Inflammation Research 2024Alzheimer's disease (AD) is the most common neurodegenerative illness, characterized by memory loss and cognitive decline, accounting for 60-80% of dementia cases. AD is... (Review)
Review
Alzheimer's disease (AD) is the most common neurodegenerative illness, characterized by memory loss and cognitive decline, accounting for 60-80% of dementia cases. AD is characterized by senile plaques made up of amyloid β (Aβ) protein, intracellular neurofibrillary tangles caused by hyperphosphorylation of tau protein linked with microtubules, and neuronal loss. Currently, therapeutic treatments and nanotechnological developments are effective in treating the symptoms of AD, but a cure for the illness has not yet been found. Recently, the increased study of extracellular vesicles (EVs) has led to a growing awareness of their significant involvement in neurodegenerative disorders, including AD. Exosomes are small extracellular vesicles that transport various components including messenger RNAs, non-coding RNAs, proteins, lipids, DNA, and other bioactive compounds from one cell to another, facilitating information transmission and material movement. There is growing evidence indicating that exosomes have complex functions in AD. Exosomes may have a dual role in Alzheimer's disease by contributing to neuronal death and also helping to alleviate the pathological progression of the disease. Therefore, the primary aim of this review is to outline the updated understandings on exosomes biogenesis and many functions of exosomes in the generation, conveyance, distribution, and elimination of hazardous proteins related to Alzheimer's disease. This review is intended to provide novel insights for understanding the development, specific treatment, and early detection of Alzheimer's disease.
PubMed: 38911990
DOI: 10.2147/JIR.S466821 -
ACS Bio & Med Chem Au Jun 2024Neurodegeneration with brain iron accumulation (NBIA) is a group of neurodegenerative diseases that are typically caused by a monogenetic mutation, leading to... (Review)
Review
Neurodegeneration with brain iron accumulation (NBIA) is a group of neurodegenerative diseases that are typically caused by a monogenetic mutation, leading to development of disordered movement symptoms such as dystonia, hyperreflexia, etc. Brain iron accumulation can be diagnosed through MRI imaging and is hypothesized to be the cause of oxidative stress, leading to the degeneration of brain tissue. There are four main types of NBIA: pantothenate kinase-associated neurodegeneration (PKAN), PLA2G6-associated neurodegeneration (PLAN), mitochondrial membrane protein-associated neurodegeneration (MKAN), and beta-propeller protein-associated neurodegeneration (BPAN). There are no causative therapies for these diseases, but iron chelators have been shown to have potential toward treating NBIA. Three chelators are investigated in this Review: deferoxamine (DFO), desferasirox (DFS), and deferiprone (DFP). DFO has been investigated to treat neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD); however, dose-related toxicity in these studies, as well as in PKAN studies, have shown that the drug still requires more development before it can be applied toward NBIA cases. Iron chelation therapies other than the ones currently in clinical use have not yet reached clinical studies, but they may possess characteristics that would allow them to access the brain in ways that current chelators cannot. Intranasal formulations are an attractive dosage form to study for chelation therapy, as this method of delivery can bypass the blood-brain barrier and access the CNS. Gene therapy differs from iron chelation therapy as it is a causal treatment of the disease, whereas iron chelators only target the disease progression of NBIA. Because the pathophysiology of NBIA diseases is still unclear, future courses of action should be focused on causative treatment; however, iron chelation therapy is the current best course of action.
PubMed: 38911909
DOI: 10.1021/acsbiomedchemau.3c00066 -
Alzheimer's & Dementia (New York, N. Y.) 2024Past Alzheimer's disease and related dementias (ADRD) research has not considered ways to ensure the representation of diverse sexual and gender minorities. This study...
INTRODUCTION
Past Alzheimer's disease and related dementias (ADRD) research has not considered ways to ensure the representation of diverse sexual and gender minorities. This study used concept mapping (CM) to identify strategies for engaging and recruiting LGBTQIA+ older adults living with memory loss and their caregivers into ADRD research.
METHODS
CM, involving brainstorming, thematic analysis, and rating of strategies, was conducted with 46 members from one national and three local community advisory boards. Data was analyzed using The Concept Systems Global MAX™ web platform.
RESULTS
One hundred twenty-two solutions were identified from June through December 2022, and represented five key themes: aging focused, LGBTQIA+ specific, memory loss and caregiving support focused, physical advertisements, and other media. Promising strategies included partnering with LGBTQIA+ health centers, attending social groups for older adults, and increasing community representation in marketing.
DISCUSSION
Tailored strategies, building trust, and community involvement are essential for engaging LGBTQIA+ individuals living with memory loss or ADRD and their caregivers in ADRD-focused research.
HIGHLIGHTS
Innovative ways to ensure the inclusion of LGBTQIA+ older adults in Alzheimer's disease and related dementias (ADRD) research can be bolstered through collaboration with key community stakeholders.Promising strategies for recruitment and engagement include partnering with LGBTQIA+ centers, attending social groups for older adults, and ensuring diverse representation in marketing.Tailored recruitment and engagement strategies are crucial for building trust with LGBTQIA+ populations to increase participation in ADRD research.
PubMed: 38911875
DOI: 10.1002/trc2.12477 -
Alzheimer's & Dementia (New York, N. Y.) 2024Alzheimer's disease and related dementias (ADRDs) and age-related hearing loss are the intersection of two major public health challenges. With age as the primary risk...
Alzheimer's disease and related dementias (ADRDs) and age-related hearing loss are the intersection of two major public health challenges. With age as the primary risk factor for both disease processes, the burden of ADRDs and age-related hearing loss is growing, and each field maintains significant barriers to broadscale identification and management that is affordable and accessible. With the disproportionate burden of ADRDs among racial and ethnic minority older adults and existing disparities within hearing care, both areas face challenges in achieving equitable access and outcomes across diverse populations. The publication of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) trial in July 2023 marked a significant moment in the fields of brain and hearing health. The ACHIEVE trial was the first randomized controlled trial to examine whether providing hearing intervention, specifically provision of hearing aids, compared to an education control, would reduce cognitive changes over 3 years. The participants most at risk for cognitive decline, with lower education, lower income, more likely to identify as Black, and have more cardiovascular risk factors, were the participants who benefited most from the hearing intervention and are also the least likely to be represented in research and the least likely to obtain hearing care. With growing evidence of the interconnection between cognitive and sensory health, we have an opportunity to prioritize equity, from purposeful inclusion of diverse participants in trials to influencing the emerging market of over-the-counter hearing aids to supporting expanded models of hearing care that reach those who have traditionally gone unserved. No longer can hearing go unrecognized by clinicians, researchers, and advocates for brain health. At the same time, the fields of brain and hearing health must center equity if we are going to meet the needs of diverse older adults in a world in which hearing health matters.
PubMed: 38911874
DOI: 10.1002/trc2.12484 -
Addiction Neuroscience Jun 2024While the majority of people with cocaine use disorders (CUD) also co-use tobacco/nicotine, most preclinical cocaine research does not include nicotine. The present...
While the majority of people with cocaine use disorders (CUD) also co-use tobacco/nicotine, most preclinical cocaine research does not include nicotine. The present study examined nicotine and cocaine co-use under several conditions of intravenous drug self-administration in monkeys, as well as potential peripheral biomarkers associated with co-use. In Experiment 1, male rhesus monkeys ( = 3) self-administered cocaine (0.001-0.1 mg/kg/injection) alone and with nicotine (0.01-0.03 mg/kg/injection) under a progressive-ratio schedule of reinforcement. When nicotine was added to cocaine, there was a significant leftward/upward shift in the number of injections received. In Experiment 2, socially housed female and male cynomolgus monkeys ( = 14) self-administered cocaine under a concurrent drug-vs-food choice schedule of reinforcement. Adding nicotine to the cocaine solution shifted the cocaine dose-response curves to the left, with more robust shifts noted in the female animals. There was no evidence of social rank differences. To assess reinforcing strength, delays were added to the presentation of drug; the co-use of nicotine and cocaine required significantly longer delays to decrease drug choice, compared with cocaine alone. Blood samples obtained post-session were used to analyze concentrations of neuronally derived small extracellular vesicles (NDE); significant differences in NDE profile were observed for kappa-opioid receptors when nicotine and cocaine were co-used compared with each drug alone and controls. These results suggest that drug interactions involving the co-use of nicotine and cocaine are not simply changing potency, but rather resulting in changes in reinforcing strength that should be utilized to better understand the neuropharmacology of CUD and the evaluation of potential treatments.
PubMed: 38911873
DOI: 10.1016/j.addicn.2024.100151 -
ACS Omega Jun 2024Epidemiological studies predict that chicken eggs contain constituents other than proteins that prevent Alzheimer's disease. This study screened for constituents that...
Epidemiological studies predict that chicken eggs contain constituents other than proteins that prevent Alzheimer's disease. This study screened for constituents that inhibit the aggregation of amyloid β peptide (Aβ) and elucidated their mechanisms to explore the active components of chicken eggs. Thioflavin T assays and transmission electron microscopy observations showed that arachidonic acid (ARA), lysophosphatidylcholine, lutein (LTN), palmitoleic acid, and zeaxanthin inhibited Aβ aggregation. Among these, ARA and LTN showed the highest activity. Photoinduced cross-linking of unmodified protein assays and infrared absorption spectrometry measurements showed that LTN strongly inhibited highly toxic Aβ protofibril formation. Furthermore, LTN suppressed Aβ-induced and expression in human macrophage-like cells. In summary, LTN plays a crucial role in the AD-preventive effect of chicken eggs by suppressing Aβ aggregation and Aβ-induced inflammation.
PubMed: 38911805
DOI: 10.1021/acsomega.4c03353 -
Nature and Science of Sleep 2024Bedtime procrastination (BP) has become an important factor affecting individual well-being. This study aimed to assess the stability and changes in BP and examine risk...
Latent Profiles and Transitions of Bedtime Procrastination Among Chinese College Students: The Predictive Roles of Anxiety, Depression, Problematic Smartphone Use and Self-Control.
BACKGROUND
Bedtime procrastination (BP) has become an important factor affecting individual well-being. This study aimed to assess the stability and changes in BP and examine risk and protective factors.
METHODS
The study recruited 1423 respondents. Latent profile analysis was used to identify subgroups of BP and latent transition analysis to determine transition probabilities for each subgroup. Logistic regression examined associations between identified classes and related factors.
RESULTS
Three subgroups of BP were identified. In terms of stability and changes, the moderate bedtime procrastination group showed the highest stability (66%), followed by the severe bedtime procrastination group (62.4%), and the mild bedtime procrastination group had a 52% probability of switching to moderate bedtime procrastination. In terms of influencing factors, more problematic phone use (PSU) (OR: 1.08; 95% CI = 1.05-1.12), more depression (OR: 1.17; 95% CI = 1.06-1.29) and anxiety (OR: 1.16; 95% CI = 1.05-1.28) are all factors that aggravate the transition from mild to moderate sleep procrastination. Similarly, PSU (OR: 1.15; 95% CI = 1.12-1.19), anxiety (OR: 1.10; 95% CI = 1.06-1.14), and depression (OR: 1.10; 95% CI = 1.06-1.14) increased the risk of severe bedtime procrastination. Self-control emerged as a protective factor against BP.
CONCLUSION
This study identified three subgroups of BP at two time points and the rule of transition for each subgroup. Our findings indicate that BP were relatively stable, with some changes over time. The results also highlight the important function that PSU, depression, anxiety, and self-control can play in preventing and intervening in BP.
PubMed: 38911318
DOI: 10.2147/NSS.S462055 -
The Lancet Regional Health. Western... Jun 2024The Australian population aged 70 and above is increasing and imposing new challenges for policy makers and providers to deliver accessible, appropriate and affordable...
Pre-COVID life expectancy, mortality, and burden of diseases for adults 70 years and older in Australia: a systematic analysis for the Global Burden of Disease 2019 Study.
BACKGROUND
The Australian population aged 70 and above is increasing and imposing new challenges for policy makers and providers to deliver accessible, appropriate and affordable health care. We examine pre-COVID patterns of health loss between 1990 and 2019 to inform policies and practices.
METHODS
Using the standardised methodology framework and analytical strategies from GBD 2019 methodologies, we estimated mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life years (DALYs), life expectancy at age 70 and above (LE-70), and healthy life expectancy (HALE-70) in Australia comparing them globally and with high socio-demographic index (SDI) groups.
FINDINGS
DALY rates have been improving steadily over the past 30 years among Australians aged 70 and above. Decreases in DALY rates were primarily attributed to a fall in YLLs attributable to cardiovascular diseases (60%) and chronic respiratory disorders (30.2%) and transport injuries (56.9%), while the non-fatal burden remained stable from 1990 to 2019. According to the DALY rates, the top five leading causes are ischemic heart disease, Alzheimer's disease, COPD, stroke, and falls, where falls exhibited the largest increase since 1990.
INTERPRETATION
This study provides an in-depth report on the main causes of mortality and disability in Australia's population aged 70 and above. It sheds light on the shifts in burden over three decades, emphasising the need for the Australian health system to enhance its readiness in addressing the escalating demands of an ageing population. These findings establish pre-COVID baseline estimates for Australia's population aged 70 and above, informing healthcare preparedness.
FUNDING
Bill & Melinda Gates Foundation.
PubMed: 38911261
DOI: 10.1016/j.lanwpc.2024.101092 -
Open Medicine (Warsaw, Poland) 2024Mitochondria-derived reactive oxygen species production at a moderate physiological level plays a fundamental role in the anti-aging signaling, due to their action as... (Review)
Review
Mitochondria-derived reactive oxygen species production at a moderate physiological level plays a fundamental role in the anti-aging signaling, due to their action as redox-active sensors for the maintenance of optimal mitochondrial balance between intracellular energy status and hormetic nutrients. Iron regulatory protein dysregulation, systematically increased iron levels, mitochondrial dysfunction, and the consequent oxidative stress are recognized to underlie the pathogenesis of multiple neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Central to their pathogenesis, Nrf2 signaling dysfunction occurs with disruption of metabolic homeostasis. We highlight the potential therapeutic importance of nutritional polyphenols as substantive regulators of the Nrf2 pathway. Here, we discuss the common mechanisms targeting the Nrf2/vitagene pathway, as novel therapeutic strategies to minimize consequences of oxidative stress and neuroinflammation, generally associated to cognitive dysfunction, and demonstrate its key neuroprotective and anti-neuroinflammatory properties, summarizing pharmacotherapeutic aspects relevant to brain pathophysiology.
PubMed: 38911254
DOI: 10.1515/med-2024-0986 -
RSC Medicinal Chemistry Jun 2024Alzheimer's disease (AD) and cancer are among the most devastating diseases of the 21st century. Although the clinical manifestations are different and the cellular...
Alzheimer's disease (AD) and cancer are among the most devastating diseases of the 21st century. Although the clinical manifestations are different and the cellular mechanisms underlying the pathologies are opposite, there are different classes of molecules that are effective in both diseases, such as quinone-based compounds and histone deacetylase inhibitors (HDACIs). Herein, we investigate the biological effects of a series of compounds built to exploit the beneficial effects of quinones and histone deacetylase inhibition (compounds 1-8). Among the different compounds, compound 6 turned out to be a potent cytotoxic agent in SH-SY5Y cancer cell line, with a half maximal inhibitory concentration (IC) value lower than vorinostat and a pro-apoptotic activity. On the other hand, compound 8 was nontoxic up to the concentration of 100 μM and was highly effective in stimulating the proliferation of neural precursor cells (NPCs), as well as inducing differentiation into neurons, at low micromolar concentrations. In particular, it was able to induce NPC differentiation solely towards a neuronal-specific phenotype, without affecting glial cells commitment.
PubMed: 38911150
DOI: 10.1039/d4md00175c