Comparative Study of Risk Factors Associated with Normal Cognition and Cognitive Impairment in Rural West Elderly Texans.

Background: Alzheimer's disease (AD) is related to one or more chronic illnesses, which may develop cognitive decline and dementia. Cognitive impairment is increasing, and public health officials must address risk factors for AD to improve the health of rural West Texas communities. Objective: The purpose of this study was to explore the sociodemographic and chronic disease risk factors related to cognitive impairment among elderly adults living in Cochran, Parmer, and Bailey counties in rural West Texas. Methods: Statistical methods such as Pearson's chi-squared, proportion tests, univariate binary logistic regression, and a multivariable logistic regression were utilized to analyze data. SPSS software was used to detect the significant relationship between cognitive impairment and risk factors. Results: Summary statistics were obtained for sociodemographic and chronic diseases by using cross-tabulation analysis and comparing the county respondents with proportion tests. A univariate binary logistic regression method was utilized and found that age group 60-69, anxiety, depression, diabetes, hypertension, and cardiovascular disease were significantly associated with cognitive impairment. Using a multivariable logistic regression approach, it was found that Bailey County (age group 60-69) had a higher likelihood (p = 0.002) of cognitive impairment than Parmer (p = 0.067) and Cochran counties (p = 0.064). The risk of females (p = 0.033) in Parmer County was 78.3% lower compared to males in developing AD. Conclusions: Identifying significant risk factors for cognitive impairment are important in addressing issues of geographic variations and integrating such factors may guide relevant policy interventions to reduce cognitive impairment incidence in rural communities within West Texas.

Use and Reuse of Animal Behavioral, Molecular, and Biochemical Data in Alzheimer's Disease Research: Focus on 3Rs and Saving People's Tax Dollars.

Several decades of research on cell and animal models contributed tremendously to understanding human diseases. Particularly, research on rodents and non-human primates revealed that animal research is a major and important component in biomedical research in learning complex pathophysiological processes. Further, animal research helped us to understand human diseases, such as Alzheimer's disease. In addition, animal research has also helped us to test hundreds of drugs and develop treatments for human use. Researchers can gain a better understanding of key biological and physiological processes in humans by comparing them to laboratory animals. Based on their relevance and resemblance to people, or even usual living conditions, scientists rationalize the use of particular animal models in their studies. It is suggested that in the National Institutes of Health and other agencies-funded research, animal models should be carefully selected to study the biology and pathophysiology of human health and diseases such as Alzheimer's disease and other dementias. However, it is critical to use a minimum number of animals for human research. Further, it is also noted that the use and reuse of behavioral,  molecular, and biochemical data from wild-type (WT) control mice with mutant lines of disease models, as long as the genetic background is the same in both WT and disease mice. On the other hand, anonymous readers have challenged the use and reuse of WT mice data for comparison. In the current article, we discuss the minimum utility of animals, covering the 3Rs, Replacement, Reduction, and Refinement, and also discuss the use and reuse of behavioral, molecular, and biochemical data.

Mechanisms, consequences and role of interventions for sleep deprivation: Focus on mild cognitive impairment and Alzheimer's disease in elderly.

Sleep is established as an essential physiological need that impacts physical, emotional, and cognitive functions profoundly. Physiologically, inadequate sleep weakens immune function, heightening susceptibility to infections and chronic illnesses such as obesity, diabetes, and cardiovascular diseases. Hormonal disruptions due to sleep loss further exacerbate metabolic dysregulation, contributing to weight gain and other health complications. Emotionally, sleep deprivation leads to mood disturbances, including increased irritability, heightened stress responses, and a greater likelihood of mood disorders like depression and anxiety. These effects are compounded by cognitive impairments such as reduced alertness, impaired memory consolidation, and compromised decision-making abilities, akin to the impairments caused by alcohol consumption. Motor skills and coordination also suffer, elevating the risk of accidents, particularly in high-stress environments. For older adults, sleep quality is closely linked to cognitive function and overall longevity. Optimal sleep patterns are associated with slower brain aging and improved health outcomes. However, sleep disorders exacerbate existing conditions such as epilepsy and asthma, necessitating interventions like cognitive behavioral therapy (CBT) and medications such as melatonin to mitigate their impact. Education emerges as a crucial tool in promoting healthier sleep habits across all age groups. Addressing misconceptions about sleep and integrating sleep health into public health policies are essential steps toward improving overall well-being. Additionally, lifestyle factors such as diet and physical activity play significant roles in regulating sleep patterns, further emphasizing the interconnectedness of sleep with broader health outcomes. In summary, the articles underscore the intricate mechanisms through which sleep influences physiological functions and advocate for comprehensive approaches to enhance sleep hygiene and mitigate the adverse effects of sleep deprivation on human health.

MicroRNA-455-3P as a peripheral biomarker and therapeutic target for mild cognitive impairment and Alzheimer's disease.

MicroRNAs are small non-coding RNAs evolutionary conserved molecules. They regulate cellular processes, including RNA silencing, post-translational gene expression and neurodegeneration. MicroRNAs are involved with human diseases such as cancer, Alzheimer's disease (AD) and others. Interestingly, cerebrospinal fluids (CSF) and the blood of AD patients have altered expressions of many RNAs, which may serve as potential peripheral biomarkers. The intensive investigation from our lab revealed that microRNA-455-3 P (miR-455-3p) is a strong candidate as a potential biomarker and therapeutic target for AD. Several genes implicated in the pathogenesis of AD are directly targeted by miR-455-3p. Several years of our lab research revealed that miR-455-3p regulates important physiological processes associated with AD, such as the processing of the amyloid precursor protein (APP), TGF-ß signaling, the regulation of oxidative stress, mitochondrial biogenesis, and synaptic damages. The expression of miR-455-3p in mild cognitive impaired subjects and AD patients pointed out its involvement in AD progression. Recently, our lab generated both transgenic and knockout mice for miR-455-3p. Interestingly miR-455-3p transgenic mice showed superior cognitive learning, improved memory and extended lifespan compared to age matched wild-type mice, whereas miR-455-3-p knockout mice showed cognitive decline and reduced lifespan. Information derived from mouse models further demonstrated the advantageous impact of miR-455-3p on dendritic growth, synaptogenesis, and mitochondrial biogenesis in preventing the onset and progression of AD. The identification of miR-455-3p as a biomarker was suggested by its presence in postmortem AD brains, B-lymphocytes, and fibroblasts. Our hypothesis that miR-455-3p could be a peripheral biomarker and therapeutic target for AD.

Acetylation of Steroidogenic Acute Regulatory Protein Sensitizes 17ß-Estradiol Regulation in Hormone-Sensitive Breast Cancer Cells.

An imbalance in estrogen signaling is a critical event in breast tumorigenesis. The majority of breast cancers (BCs) are hormone-sensitive; they majorly express the estrogen receptor (ER+) and are activated by 17ß-estradiol (E2). The steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in steroid biosynthesis. The dysregulation of the epigenetic machinery, modulating E2 levels, is a primary occurrence for promoting breast tumorigenesis. StAR expression, concomitant with E2 synthesis, was reported to be aberrantly high in human and mouse hormone-dependent BC cells compared with their non-cancerous counterparts. However, the mechanism of action of StAR remains poorly understood. We discovered StAR as an acetylated protein and have identified a number of lysine (K) residues that are putatively acetylated in malignant and non-malignant breast cells, using LC-MS/MS (liquid chromatography-tandem mass spectrometry), suggesting they differently influence E2 synthesis in mammary tissue. The treatment of hormone-sensitive MCF7 cells with a variety of histone deacetylase inhibitors (HDACIs), at therapeutically and clinically relevant doses, identified a few additional StAR acetylated lysine residues. Among a total of fourteen StAR acetylomes undergoing acetylation and deacetylation, K111 and K253 were frequently recognized either endogenously or in response to HDACIs. Site-directed mutagenesis studies of these two StAR acetylomes, pertaining to K111Q and K253Q acetylation mimetic states, resulted in increases in E2 levels in ER+ MCF7 and triple negative MB-231 BC cells, compared with their values seen with human StAR. Conversely, these cells carrying K111R and K253R deacetylation mutants diminished E2 biosynthesis. These findings provide novel and mechanistic insights into intra-tumoral E2 regulation by elucidating the functional importance of this uncovered StAR post-translational modification (PTM), involving acetylation and deacetylation events, underscoring the potential of StAR as a therapeutic target for hormone-sensitive BC.

Resolving the current controversy of use and reuse of housekeeping proteins in ageing research: Focus on saving people's tax dollars.

The use of housekeeping genes and proteins to normalize mRNA and protein levels in biomedical research has faced growing scrutiny. Researchers encounter challenges in determining the optimal frequency for running housekeeping proteins such as ß-actin, Tubulin, and GAPDH for nuclear-encoded proteins, and Porin, HSP60, and TOM20 for mitochondrial proteins alongside experimental proteins. The regulation of these proteins varies with age, gender, disease progression, epitope nature, gel running conditions, and their reported sizes can differ among antibody suppliers. Additionally, anonymous readers have raised concerns about peer-reviewed and published articles, creating confusion and concern within the research and academic institutions. To clarify these matters, this minireview discusses the role of reference housekeeping proteins in Western blot analysis and outlines key considerations for their use as normalization controls. Instead of Western blotting of housekeeping proteins, staining of total proteins, using Amido Black and Coomassie Blue can be visualized the total protein content on a membrane. The reducing repeated Western blotting analysis of housekeeping proteins, will save resources, time and efforts and in turn increase the number of competitive grants from NIH and funding agencies. We also discussed the use of dot blots over traditional Western blots, when protein levels are low in rare tissues/specimens and cell lines. We sincerely hope that the facts, figures, and discussions presented in this article will clarify the current controversy regarding housekeeping protein(s) use, reuse, and functional aspects of housekeeping proteins. The contents presented in our article will be useful to students, scholars and researchers of all levels in cell biology, protein chemistry and mitochondrial research.

Artificial intelligence in Parkinson's disease: Early detection and diagnostic advancements.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, globally affecting men and women at an exponentially growing rate, with currently no cure. Disease progression starts when dopaminergic neurons begin to die. In PD, the loss of neurotransmitter, dopamine is responsible for the overall communication of neural cells throughout the body. Clinical symptoms of PD are slowness of movement, involuntary muscular contractions, speech & writing changes, lessened automatic movement, and chronic tremors in the body. PD occurs in both familial and sporadic forms and modifiable and non-modifiable risk factors and socioeconomic conditions cause PD. Early detectable diagnostics and treatments have been developed in the last several decades. However, we still do not have precise early detectable biomarkers and therapeutic agents/drugs that prevent and/or delay the disease process. Recently, artificial intelligence (AI) science and machine learning tools have been promising in identifying early detectable markers with a greater rate of accuracy compared to past forms of treatment and diagnostic processes. Artificial intelligence refers to the intelligence exhibited by machines or software, distinct from the intelligence observed in humans that is based on neural networks in a form and can be used to diagnose the longevity and disease severity of disease. The term Machine Learning or Neural Networks is a blanket term used to identify an emerging technology that is created to work in the way of a "human brain" using many intertwined neurons to achieve the same level of raw intelligence as that of a brain. These processes have been used for neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, to assess the severity of the patient's condition. In the current article, we discuss the prevalence and incidence of PD, and currently available diagnostic biomarkers and therapeutic strategies. We also highlighted currently available artificial intelligence science and machine learning tools and their applications to detect disease and develop therapeutic interventions.

Unraveling the complexity of human brain: Structure, function in healthy and disease states.

The human brain stands as an intricate organ, embodying a nexus of structure, function, development, and diversity. This review delves into the multifaceted landscape of the brain, spanning its anatomical intricacies, diverse functional capacities, dynamic developmental trajectories, and inherent variability across individuals. The dynamic process of brain development, from early embryonic stages to adulthood, highlights the nuanced changes that occur throughout the lifespan. The brain, a remarkably complex organ, is composed of various anatomical regions, each contributing uniquely to its overall functionality. Through an exploration of neuroanatomy, neurophysiology, and electrophysiology, this review elucidates how different brain structures interact to support a wide array of cognitive processes, sensory perception, motor control, and emotional regulation. Moreover, it addresses the impact of age, sex, and ethnic background on brain structure and function, and gender differences profoundly influence the onset, progression, and manifestation of brain disorders shaped by genetic, hormonal, environmental, and social factors. Delving into the complexities of the human brain, it investigates how variations in anatomical configuration correspond to diverse functional capacities across individuals. Furthermore, it examines the impact of neurodegenerative diseases on the structural and functional integrity of the brain. Specifically, our article explores the pathological processes underlying neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's diseases, shedding light on the structural alterations and functional impairments that accompany these conditions. We will also explore the current research trends in neurodegenerative diseases and identify the existing gaps in the literature. Overall, this article deepens our understanding of the fundamental principles governing brain structure and function and paves the way for a deeper understanding of individual differences and tailored approaches in neuroscience and clinical practice-additionally, a comprehensive understanding of structural and functional changes that manifest in neurodegenerative diseases.

Harnessing Artificial Intelligence for the detection and management of Colorectal Cancer Treatment.

Currently, eight million people in the United States suffer from cancer, and is a major global health concern. Early detection and interventions are urgently needed for all cancers, including colorectal cancer (CRC). CRC is the third most common type of cancer worldwide; From diagnostic efforts to general awareness and lifestyle choices, it is understandable why CRC is so prevalent today. There is a notable lack of awareness concerning the impact of this cancer and its connection to lifestyle elements, as well as people sometimes mistaking symptoms for a different gastrointestinal condition. Artificial Intelligence (AI) may assist in the early detection of all cancers, including CRC. The usage of AI has exponentially grown within healthcare through extensive research and since clinical implementation, has succeeded in improving patient lifestyles, modernizing diagnostic processes, and innovating current treatment strategies. Numerous challenges arise for CRC patients and Oncologists alike during treatment. For initial screening phases, conventional methods oftentimes result in misdiagnosis. Moreover, after detection, determining the course of which CRC can sometimes contribute to treatment delays. This article touches on recent advancements in AI and its clinical application while shedding light on why this disease is so common today.

Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching.

ABSTRACT: The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration. Axons and dendrites, sometimes referred to as neurites, are extensions of a neuron's cellular body that are used to start networks. Here we explored the effects of diethyl (3,4-dihydroxyphenethylamino)(quinolin-4-yl) methylphosphonate (DDQ) on neurite developmental features in HT22 neuronal cells. In this work, we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22 cells expressing mutant Tau (mTau) cDNA. To investigate DDQ characteristics, cell viability, biochemical, molecular, western blotting, and immunocytochemistry were used. Neurite outgrowth is evaluated through the segmentation and measurement of neural processes. These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth. These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22. DDQ-treated mTau-HT22 cells (HT22 cells transfected with cDNA mutant Tau) were seen to display increased levels of synaptophysin, MAP-2, and ß-tubulin. Additionally, we confirmed and noted reduced levels of both total and p-Tau, as well as elevated levels of microtubule-associated protein 2, ß-tubulin, synaptophysin, vesicular acetylcholine transporter, and the mitochondrial biogenesis protein-peroxisome proliferator-activated receptor-gamma coactivator-1α. In mTau-expressed HT22 neurons, we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth. Our findings conclude that mTau-HT22 (Alzheimer's disease) cells treated with DDQ have functional neurite developmental characteristics. The key finding is that, in mTau-HT22 cells, DDQ preserves neuronal structure and may even enhance nerve development function with mTau inhibition.

Effects of sleep deprivation on brain atrophy in individuals with mild cognitive impairment and Alzheimer's disease.

Dementia, a prevalent condition in the United States, affecting millions of individuals and their families, underscores the importance of healthy cognitive ageing, which involves maintaining cognitive function and mental wellness as individuals grow older, promoting overall well-being and quality of life. Our original research study investigates the correlation between lifestyle factors and brain atrophy in individuals with mild cognitive impairment (MCI) or Alzheimer's disease (AD), as well as healthy older adults. Conducted over six months in West Texas, the research involved 20 participants aged 62-87. Findings reveal that sleep deprivation in MCI subjects and AD patients correlate with posterior cingulate cortex, hippocampal atrophy and total brain volume, while both groups exhibit age-related hippocampal volume reduction. Notably, fruit/vegetable intake negatively correlates with certain brain regions' volume, emphasizing the importance of diet. Lack of exercise is associated with reduced brain volume and hippocampal atrophy, underlining the cognitive benefits of physical activity. The study underscores lifestyle's significant impact on cognitive health, advocating interventions to promote brain health and disease prevention, particularly in MCI/AD cases. While blood profile data showed no significant results regarding cognitive decline, the study underscores the importance of lifestyle modifications in preserving cognitive function.

Caring for Individuals with Alzheimer's Disease: A Spotlight on Hispanic Caregivers.

 A caregiver is a constantly evolving role that an individual most likely undertakes at some point in their lifetime. With discoveries and research in increasing life expectancy, the prevalence of neurological-related diseases, such as Alzheimer's disease (AD) and dementia, is certainly likely to require more caregivers. The demand for AD caregivers is escalating as the prevalence of the disease continues to rise. The projected rise in AD within the Hispanic population in the United States over the next few decades is expected to be the most significant among all ethnic groups. The Hispanic population faces unique dementia risks due to cultural factors like language barriers, lower education, and limited healthcare access. Higher rates of conditions such as diabetes and cardiovascular disease further elevate dementia risk. Family dynamics and caregiving responsibilities also differ, affecting dementia management within Hispanic households. Addressing these distinct challenges requires culturally sensitive approaches to diagnosis, treatment, and support for Hispanic individuals and their family's facing dementia. With AD and other dementia becoming more prevalent, this article will attempt to expand upon the status of caregivers concerning their economic, health, and cultural statuses. We will attempt to focus on the Hispanic caregivers that live in Texas and more specifically, West Texas due to the lack of current literature that applies to this area of Texas. Lastly, we discuss the ramifications of a multitude of factors that affect caregivers in Texas and attempt to provide tools that can be readily available for Hispanics and others alike.

Circulating Cell Free DNA and DNA Double-Strand Breakage in Alzheimer's Disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disease that is characterized by memory loss and multiple cognitive impairments. AD is pathologically characterized by age-dependent accumulation of amyloid-ß protein and the phosphorylation of tau protein in the brains of patients with AD. Clinically, manifestations of AD include cognitive decline, dementia, alterations of high-order brain functions, and movement disorders. Double-stranded DNA breaks are a lethal form of DNA damage and are typically repaired via non-homologous end joining and homologous recombination. However, in AD brain, repair mechanism is disrupted, leading to a cascade of events, cognitive dysfunction, organ failure and reduced lifespan. Increased circulating cell-free DNA in the blood, cerebrospinal fluid, and urine in patients with AD, can be used as early detectable biomarkers for AD. The purpose of our article is to explore the potential uses of cell-free DNA and double-stranded DNA breaks as prognostic markers for AD and examine the recent research on the application of these markers in studies.

Creating Cultural and Lifestyle Awareness About Dementia and Co-morbidities.

Dementia is a major health concern in society, particularly in the aging population. It is alarmingly increasing in ethnic minorities such as Native Americans, African Americans, Hispanics/Latinos, and to some extent Asians. With increasing comorbidities of dementia such as diabetes, obesity, and hypertension, dementia rates are expected to increase in the next decade and beyond. Understanding and treating dementia, as well as determining how to prevent it, has become a healthcare priority across the globe for all races and genders. Awareness about dementia and its consequences such as healthcare costs, and caregiver burden are immediate needs to be addressed. Therefore, it is high time for all of us to create awareness about dementia in society, particularly among Hispanics/Latinos, Native Americans, and African Americans. In the current article, we discuss the status of dementia, cultural, and racial impacts on dementia diagnosis and care, particularly in Hispanic populations, and possible steps to increase dementia awareness. We also discussed factors that need to be paid attention to, including, cultural & language barriers, low socioeconomic status, limited knowledge/education, religious/spiritual beliefs and not accepting modern medicine/healthcare facilities. Our article also covers both mental & physical health issues of caregivers who are living with patients with dementia, Alzheimer's disease, and Alzheimer's disease-related dementias. Most importantly, we discussed possible measures to create awareness about dementia, including empowering community advocacy, promoting healthy lifestyle choices, education on the impact of nutrition, encouraging community participation, and continued collaboration and evaluation of the success of dementia awareness.

Amyloid-ß and Phosphorylated Tau are the Key Biomarkers and Predictors of Alzheimer's Disease.

Alzheimer's disease (AD) is a age-related neurodegenerative disease and is a major public health concern both in Texas, US and Worldwide. This neurodegenerative disease is mainly characterized by amyloid-beta (Aß) and phosphorylated Tau (p-Tau) accumulation in the brains of patients with AD and increasing evidence suggests that these are key biomarkers in AD. Both Aß and p-tau can be detected through various imaging techniques (such as positron emission tomography, PET) and cerebrospinal fluid (CSF) analysis. The presence of these biomarkers in individuals, who are asymptomatic or have mild cognitive impairment can indicate an increased risk of developing AD in the future. Furthermore, the combination of Aß and p-tau biomarkers is often used for more accurate diagnosis and prediction of AD progression. Along with AD being a neurodegenerative disease, it is associated with other chronic conditions such as cardiovascular disease, obesity, depression, and diabetes because studies have shown that these comorbid conditions make people more vulnerable to AD. In the first part of this review, we discuss that biofluid-based biomarkers such as Aß, p-Tau in cerebrospinal fluid (CSF) and Aß & p-Tau in plasma could be used as an alternative sensitive technique to diagnose AD. In the second part, we discuss the underlying molecular mechanisms of chronic conditions linked with AD and how they affect the patients in clinical care.

Unraveling the NRF2 confusion: Distinguishing nuclear respiratory factor 2 from nuclear erythroid factor 2.

In recent years, the acronym NRF2 has garnered significant attention in scientific discourse. However, this attention has occasionally led to confusion due to the existence of two distinct proteins sharing the same acronym: Nuclear Respiratory Factor 2 (NRF2), also known as GA-binding protein transcription factor subunit alpha (GABPA), and Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2 or NRF2). This confusion has been highlighted in various scientific forums, including PubPeer and anonymous reader comments, where the confusion between the two proteins has been expressed. In this article, we aim to elucidate the disparities between these two proteins. Both are transcription factors that play pivotal roles in cellular homeostasis and response to stress, with some overlapping functional aspects. Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2) is a key regulator of the antioxidant response element (ARE) pathway. It functions by binding to antioxidant response elements in the promoters of target genes, thereby orchestrating the expression of various cytoprotective enzymes and proteins involved in detoxification, redox balance, and cellular defense against oxidative stress. Conversely, Nuclear Respiratory Factor 2 (GABPA) is primarily associated with the regulation of mitochondrial biogenesis, in relation to PGC1α, and maintaining cellular energy metabolism. It is important to recognize and differentiate between these two proteins to avoid misconceptions and misinterpretations in scientific literature and discussions. Our laboratories (Arubala P Reddy and P. Hemachandra Reddy) focued on Nuclear Respiratory Factor 2 (NRF2), but not on Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2). We hope that the facts, figures, and discussions presented in this article will clarify the current controversy regarding the sizes, structural features, and functional aspects of these proteins.

Overlooked cases of mild cognitive impairment: Implications to early Alzheimer's disease.

Mild cognitive impairment (MCI) marks the initial phase of memory decline or other cognitive functions like language or spatial perception, while individuals typically retain the capacity to carry out everyday tasks independently. Our comprehensive article investigates the intricate landscape of cognitive disorders, focusing on MCI and Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRD). The study aims to understand the signs of MCI, early Alzheimer's disease, and healthy brain aging while assessing factors influencing disease progression, pathology development and susceptibility. A systematic literature review of over 100 articles was conducted, emphasizing MCI, AD and ADRD within the elderly populations. The synthesis of results reveals significant findings regarding ethnicity, gender, lifestyle, comorbidities, and diagnostic tools. Ethnicity was found to influence MCI prevalence, with disparities observed across diverse populations. Gender differences were evident in cognitive performance and decline, highlighting the need for personalized management strategies. Lifestyle factors and comorbidities were identified as crucial influencers of cognitive health. Regarding diagnostic tools, the Montreal Cognitive Assessment (MoCA) emerged as superior to the Mini-Mental State Examination (MMSE) in early MCI detection. Overall, our article provides insights into the multifaceted nature of cognitive disorders, emphasizing the importance of tailored interventions and comprehensive assessment strategies for effective cognitive health management.

SuperAgers and centenarians, dynamics of healthy ageing with cognitive resilience.

Graceful healthy ageing and extended longevity is the most desired goal for human race. The process of ageing is inevitable and has a profound impact on the gradual deterioration of our physiology and health since it triggers the onset of many chronic conditions like dementia, osteoporosis, diabetes, arthritis, cancer, and cardiovascular disease. However, some people who lived/live more than 100 years called 'Centenarians" and how do they achieve their extended lifespans are not completely understood. Studying these unknown factors of longevity is important not only to establish a longer human lifespan but also to manage and treat people with shortened lifespans suffering from age-related morbidities. Furthermore, older adults who maintain strong cognitive function are referred to as "SuperAgers" and may be resistant to risk factors linked to cognitive decline. Investigating the mechanisms underlying their cognitive resilience may contribute to the development of therapeutic strategies that support the preservation of cognitive function as people age. The key to a long, physically, and cognitively healthy life has been a mystery to scientists for ages. Developments in the medical sciences helps us to a better understanding of human physiological function and greater access to medical care has led us to an increase in life expectancy. Moreover, inheriting favorable genetic traits and adopting a healthy lifestyle play pivotal roles in promoting longer and healthier lives. Engaging in regular physical activity, maintaining a balanced diet, and avoiding harmful habits such as smoking contribute to overall well-being. The synergy between positive lifestyle choices, access to education, socio-economic factors, environmental determinants and genetic supremacy enhances the potential for a longer and healthier life. Our article aims to examine the factors associated with healthy ageing, particularly focusing on cognitive health in centenarians. We will also be discussing different aspects of ageing including genomic instability, metabolic burden, oxidative stress and inflammation, mitochondrial dysfunction, cellular senescence, immunosenescence, and sarcopenia.

Cell-Free DNA As Peripheral Biomarker of Alzheimer's Disease.

Alzheimer's disease (AD) and Alzheimer's disease-related disorders (ADRD) are progressive neurodegenerative diseases without cure. Alzheimer's disease occurs in 2 forms, early-onset familial AD and late-onset sporadic AD. Early-onset AD is a rare (~1%), autosomal dominant, caused by mutations in presenilin-1, presenilin-2, and amyloid precursor protein genes and the other is a late-onset, prevalent and is evolved due to age-associated complex interactions between environmental and genetic factors, in addition to apolipoprotein E4 polymorphism. Cellular senescence, promoting the impairment of physical and mental functions is constituted to be the main cause of aging, the primary risk factor for AD, which results in progressive loss of cognitive function, memory, and visual-spatial skills for an individual to live or act independently. Despite significant progress in the understanding of the biology and pathophysiology of AD, we continue to lack definitive early detectable biomarkers and/or drug targets that can be used to delay the development of AD and ADRD in elderly populations. However, recent developments in the studies of DNA double-strand breaks result in the release of fragmented DNA into the bloodstream and contribute to higher levels of cell-free DNA (cf-DNA). This fragmented cf-DNA can be released into the bloodstream from various cell types, including normal cells and cells undergoing apoptosis or necrosis and elevated levels of cf-DNA in the blood have the potential to serve as blood blood-based biomarker for early detection of AD and ADRD. The overall goal of our study is to discuss the latest developments in circulating cell-free DNA into the blood in the progression of AD and ADRD. Our article summarized the status of research on double-strand breaks and circulating cell-free DNA in both healthy and disease states and how these recent developments can be used to develop early detectable biomarkers for AD and ADRD. Our article also discussed the impact of lifestyle and epigenetic factors that are involved in DNA double-strand breaks and circulating cell-free DNA in AD and ADRD.

Treating Alzheimer's disease using nanoparticle-mediated drug delivery strategies/systems.

The administration of promising medications for the treatment of neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) is significantly hampered by the blood-brain barrier (BBB). Nanotechnology has recently come to light as a viable strategy for overcoming this obstacle and improving drug delivery to the brain. With a focus on current developments and prospects, this review article examines the use of nanoparticles to overcome the BBB constraints to improve drug therapy for AD The potential for several nanoparticle-based approaches, such as those utilizing lipid-based, polymeric, and inorganic nanoparticles, to enhance drug transport across the BBB are highlighted. To shed insight on their involvement in aiding effective drug transport to the brain, methods of nanoparticle-mediated drug delivery, such as surface modifications, functionalization, and particular targeting ligands, are also investigated. The article also discusses the most recent findings on innovative medication formulations encapsulated within nanoparticles and the therapeutic effects they have shown in both preclinical and clinical testing. This sector has difficulties and restrictions, such as the need for increased safety, scalability, and translation to clinical applications. However, the major emphasis of this review aims to provide insight and contribute to the knowledge of how nanotechnology can potentially revolutionize the worldwide treatment of NDDs, particularly AD, to enhance clinical outcomes.