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Background: Superradiance is the phenomenon of many identical quantum systems absorbing and/or emitting photons collectively at a higher rate than any one system can individually. This phenomenon has been studied analytically in idealized distributions of electronic two-level systems (TLSs), each with a ground and excited state, as well as numerically in realistic photosynthetic nanotubes and cytoskeletal architectures. Methods: Superradiant effects are studied here in idealized toy model systems and realistic biological mega-networks of tryptophan (Trp) molecules, which are strongly fluorescent amino acids found in many proteins. Each Trp molecule acts as a chromophore absorbing in the ultraviolet spectrum and can be treated approximately as a TLS, with its 1La excited singlet state; thus, organized Trp networks can exhibit superradiance. Such networks are found, for example, in microtubules, actin filaments, and amyloid fibrils. Microtubules and actin filaments are spiral-cylindrical protein polymers that play significant biological roles as primary constituents of the eukaryotic cytoskeleton, while amyloid fibrils have been targeted in a variety of neurodegenerative diseases. We treat these proteinaceous Trp networks as open quantum systems, using a non-Hermitian Hamiltonian to describe interactions of the chromophore network with the electromagnetic field. We numerically diagonalize the Hamiltonian to obtain its complex eigenvalues, where the real part is the energy and the imaginary part is its associated enhancement rate. We also consider multiple realizations of increasing static disorder in either the site energies or the decay rates. Results: We obtained the energies and enhancement rates for realistic microtubules, actin filament bundles, and amyloid fibrils of differing lengths, and we use these values to calculate the quantum yield, which is the ratio of the number of photons emitted to the number of photons absorbed. We find that all three of these structures exhibit highly superradiant states near the low-energy portion of the spectrum, which enhances the magnitude and robustness of the quantum yield to static disorder and thermal noise. Conclusion: The high quantum yield and stable superradiant states in these biological architectures may play a photoprotective role in vivo, downconverting energetic ultraviolet photons -- absorbed from those emitted by reactive free radical species -- to longer, safer wavelengths and thereby mitigating biochemical stress and photophysical damage. Contrary to conventional assumptions that quantum effects cannot survive in large biosystems at high temperatures, our results suggest that macropolymeric collectives of TLSs in microtubules, actin filaments, and amyloid fibrils exhibit increasingly observable and robust effects with increasing length, up to the micron scale, due to quantum coherent interactions in the single-photon limit. Superradiant enhancement and high quantum yield exhibited in neuroprotein polymers could thus play a crucial role in information processing in the brain, the development of neurodegenerative diseases such as Alzheimer's and related dementias, and a wide array of other pathologies characterized by anomalous protein aggregates. [ABSTRACT FROM AUTHOR]

Clearance of amyloid-beta (Ab) from the brain is impaired in both early-onset and late-onset Alzheimer's disease (AD). Mechanisms for clearing cerebral Ab include proteolytic degradation, antibody-mediated clearance, blood brain barrier and blood cerebrospinal fluid barrier efflux, glymphatic drainage, and perivascular drainage. ATP-binding cassette (ABC) transporters are membrane efflux pumps driven by ATP hydrolysis. Their functions include maintenance of brain homeostasis by removing toxic peptides and compounds, and transport of bioactive molecules including cholesterol. Some ABC transporters contribute to lowering of cerebral Ab. Mechanisms suggested for ABC transportermediated lowering of brain Ab, in addition to exporting of Ab across the blood brain and blood cerebrospinal fluid barriers, include apolipoprotein E lipidation, microglial activation, decreased amyloidogenic processing of amyloid precursor protein, and restricting the entrance of Ab into the brain. The ABC transporter superfamily in humans includes 49 proteins, eight of which have been suggested to reduce cerebral Ab levels. This review discusses experimental approaches for increasing the expression of these ABC transporters, clinical applications of these approaches, changes in the expression and/or activity of these transporters in AD and transgenic mouse models of AD, and findings in the few clinical trials which have examined the effects of these approaches in patients with AD or mild cognitive impairment. The possibility that therapeutic upregulation of ABC transporters which promote clearance of cerebral Ab may slow the clinical progression of AD merits further consideration. [ABSTRACT FROM AUTHOR]

BackgroundSuperradiance is the phenomenon of many identical quantum systems absorbing and/or emitting photons collectively at a higher rate than any one system can individually. This phenomenon has been studied analytically in idealized distributions of electronic two-level systems (TLSs), each with a ground and excited state, as well as numerically in realistic photosynthetic nanotubes and cytoskeletal architectures.MethodsSuperradiant effects are studied here in idealized toy model systems and realistic biological mega-networks of tryptophan (Trp) molecules, which are strongly fluorescent amino acids found in many proteins. Each Trp molecule acts as a chromophore absorbing in the ultraviolet spectrum and can be treated approximately as a TLS, with its 1La excited singlet state; thus, organized Trp networks can exhibit superradiance. Such networks are found, for example, in microtubules, actin filaments, and amyloid fibrils. Microtubules and actin filaments are spiral-cylindrical protein polymers that play significant biological roles as primary constituents of the eukaryotic cytoskeleton, while amyloid fibrils have been targeted in a variety of neurodegenerative diseases. We treat these proteinaceous Trp networks as open quantum systems, using a non-Hermitian Hamiltonian to describe interactions of the chromophore network with the electromagnetic field. We numerically diagonalize the Hamiltonian to obtain its complex eigenvalues, where the real part is the energy and the imaginary part is its associated enhancement rate. We also consider multiple realizations of increasing static disorder in either the site energies or the decay rates.ResultsWe obtained the energies and enhancement rates for realistic microtubules, actin filament bundles, and amyloid fibrils of differing lengths, and we use these values to calculate the quantum yield, which is the ratio of the number of photons emitted to the number of photons absorbed. We find that all three of these structures exhibit highly superradiant states near the low-energy portion of the spectrum, which enhances the magnitude and robustness of the quantum yield to static disorder and thermal noise.ConclusionThe high quantum yield and stable superradiant states in these biological architectures may play a photoprotective role in vivo, downconverting energetic ultraviolet photons—absorbed from those emitted by reactive free radical species—to longer, safer wavelengths and thereby mitigating biochemical stress and photophysical damage. Contrary to conventional assumptions that quantum effects cannot survive in large biosystems at high temperatures, our results suggest that macropolymeric collectives of TLSs in microtubules, actin filaments, and amyloid fibrils exhibit increasingly observable and robust effects with increasing length, up to the micron scale, due to quantum coherent interactions in the single-photon limit. Superradiant enhancement and high quantum yield exhibited in neuroprotein polymers could thus play a crucial role in information processing in the brain, the development of neurodegenerative diseases such as Alzheimer’s and related dementias, and a wide array of other pathologies characterized by anomalous protein aggregates.

Introduction: Caring for people with Alzheimer's disease (AD) is burdensome, especially when family members act as caregivers. This multicenter survey first aimed to investigate caregivers' mental states as well as its influencing factors in caring for people with different severities of AD in China. Methods: People with AD and their caregivers from 30 provincial regions in mainland China were enrolled from October 2020 to December 2020 to be surveyed for caregivers' mental states and living conditions, as well as caregivers' attitudes toward treatment and caring. Logistic regression was used to explore the factors that influence the positive and negative states of caregivers who care for people with different stages of AD. Results: A total of 1,966 valid questionnaires were analyzed (mild AD: 795, moderate AD: 521, severe AD: 650). A total of 73.6% of caregivers maintained normal states (mild group: 71.9%, moderate group: 73.9%, severe group: 75.2%; X2 = 2.023, p = 0.364), and the proportions of caregivers with positive and negative states were 26.3% (mild group: 38.4%, moderate group: 24.6%, severe group: 13.1%; X2 = 119.000, p < 0.001) and 36.5% (mild group: 25.2%, moderate group: 36.9%, severe group: 50.2%; X2 = 96.417, p < 0.001), respectively. The major factors that both influenced caregivers' positive and negative states were the severity of AD, perceived efficacy of treatment, safety issues after AD dementia diagnosis and perceived social support (p < 0.005), while neuropsychiatric symptoms causing stress in caregivers (p < 0.001) only affected the negative states of caregivers. The results of further analysis according to disease severity showed that safety issues after AD dementia diagnosis (p < 0.005) only made significant differences in the mild-to-moderate group. Conclusion: To reduce negative states and promote positive states among caregivers, flexible and sensitive caregiving support could be built on caregivers' demands in caring for people with different stages of AD. The support of emotion, social functioning and nursing skills is one of the significant ways for health workers to enhance caregivers' competency. [ABSTRACT FROM AUTHOR]

Clearance of amyloid-beta (Aβ) from the brain is impaired in both early-onset and late-onset Alzheimer’s disease (AD). Mechanisms for clearing cerebral Aβ include proteolytic degradation, antibody-mediated clearance, blood brain barrier and blood cerebrospinal fluid barrier efflux, glymphatic drainage, and perivascular drainage. ATP-binding cassette (ABC) transporters are membrane efflux pumps driven by ATP hydrolysis. Their functions include maintenance of brain homeostasis by removing toxic peptides and compounds, and transport of bioactive molecules including cholesterol. Some ABC transporters contribute to lowering of cerebral Aβ. Mechanisms suggested for ABC transporter-mediated lowering of brain Aβ, in addition to exporting of Aβ across the blood brain and blood cerebrospinal fluid barriers, include apolipoprotein E lipidation, microglial activation, decreased amyloidogenic processing of amyloid precursor protein, and restricting the entrance of Aβ into the brain. The ABC transporter superfamily in humans includes 49 proteins, eight of which have been suggested to reduce cerebral Aβ levels. This review discusses experimental approaches for increasing the expression of these ABC transporters, clinical applications of these approaches, changes in the expression and/or activity of these transporters in AD and transgenic mouse models of AD, and findings in the few clinical trials which have examined the effects of these approaches in patients with AD or mild cognitive impairment. The possibility that therapeutic upregulation of ABC transporters which promote clearance of cerebral Aβ may slow the clinical progression of AD merits further consideration.

Neurodegenerative diseases, such as Alzheimer's disease (AD), pose significant challenges in early diagnosis, leading to irreversible brain damage and cognitive decline. In this study, we present a novel diagnostic approach that utilizes whole molecule analysis of neuron-derived cell-free DNA (cfDNA) as a biomarker for early detection of neurodegenerative diseases. By analyzing Differential Methylation Regions (DMRs) between purified cortical neurons and blood plasma samples, we identified robust biomarkers that accurately distinguish between neuronal and non-neuronal cfDNA. The use of cfDNA offers the advantage of convenient and minimally invasive sample collection compared to traditional cerebrospinal fluid or tissue biopsies, making this approach more accessible and patient friendly. Targeted sequencing at the identified DMR locus demonstrated that a conservative cutoff of 5% of neuron-derived cfDNA in blood plasma accurately identifies 100% of patients diagnosed with AD, showing promising potential for early disease detection. Additionally, this method effectively differentiated between patients with mild cognitive impairment (MCI) who later progressed to AD and those who did not, highlighting its prognostic capabilities. Importantly, the differentiation between patients with neurodegenerative diseases and healthy controls demonstrated the specificity of our approach. Furthermore, this cfDNAbased diagnostic strategy outperforms recently developed protein-based assays, which often lack accuracy and convenience. While our current approach focused on a limited set of loci, future research should explore the development of a more comprehensive model incorporating multiple loci to increase diagnostic accuracy further. Although certain limitations, such as technical variance associated with PCR amplification and bisulfite conversion, need to be addressed, this study emphasizes the potential of cfDNA analysis as a valuable tool for pre-symptomatic detection and monitoring of neurodegenerative diseases. With further development and validation, this innovative diagnostic strategy has the potential to significantly impact the field of neurodegenerative disease research and patient care, offering a promising avenue for early intervention and personalized therapeutic approaches. [ABSTRACT FROM AUTHOR]

Multimodal neuroimaging data of various brain disorders provides valuable information to understand brain function in health and disease. Various neuroimaging-based databases have been developed that mainly consist of volumetric magnetic resonance imaging (MRI) data. We present the comprehensive web-based neuroimaging platform "SWADESH" for hosting multidisease, multimodal neuroimaging, and neuropsychological data along with analytical pipelines. This novel initiative includes neurochemical and magnetic susceptibility data for healthy and diseased conditions, acquired using MR spectroscopy (MRS) and quantitative susceptibility mapping (QSM) respectively. The SWADESH architecture also provides a neuroimaging database which includes MRI, MRS, functional MRI (fMRI), diffusion weighted imaging (DWI), QSM, neuropsychological data and associated data analysis pipelines. Our final objective is to provide a master database of major brain disease states (neurodegenerative, neuropsychiatric, neurodevelopmental, and others) and to identify characteristic features and biomarkers associated with such disorders. [ABSTRACT FROM AUTHOR]

This editorial discusses the importance of proteins and protein-complexes in maintaining mitochondrial structure and function, and their implications in diseases. It emphasizes the need for a comprehensive analysis of protein complexes to understand their role in mitochondrial functions and diseases. The document mentions specific research articles that focus on the role of mitochondrial complexomes in human diseases, particularly Alzheimer's disease. It also highlights the significance of ubiquitylation and SUMOylation in the functioning of endoplasmic reticulum and mitochondrial proteins, and their potential therapeutic implications in cardiovascular health. The text further discusses the formation of a protein complex that leads to the release of calcium ions and apoptosis in leukemia cells, and its relevance to neurodegenerative diseases and mitochondrial function dysregulation. [Extracted from the article]

This document is an editorial titled "The role and mechanism of metabolic dysfunction in the development of neurodegenerative disease." It discusses the intersection of metabolic dysfunction and neurodegenerative diseases, such as Alzheimer's disease. The editorial highlights several research studies that provide insights into how metabolic processes influence the development and progression of these diseases. The studies examine the effects of diet-induced obesity, genetic risk factors, metabolic alterations in astrocytes, and the role of microRNAs in obstructive sleep apnea and its associated metabolic complications. The editorial emphasizes the importance of a comprehensive approach to understanding and managing neurodegenerative disorders, integrating insights from various disciplines. It suggests that interventions targeting metabolic health could have significant impacts on the prevention and management of these diseases. [Extracted from the article]

IntroductionAlzheimer’s Disease (AD) constitutes a major societal problem with devastating neuropsychiatric involvement in over 90% of those diagnosed. The large spectrum of AD neuropsychiatric symptoms leads to polypharmacological prescribing that, in turn, poses a major risk for increased side effects. Non-pharmacological interventions such as music therapy (MT) are therefore recommended as first-line treatments. The amalgamation of an aging population, long lifespan, and shortage of qualified music therapists limits access to MT services for AD.ObjectiveThe purpose of this paper is to provide a rationale for a protocolized music teletherapy (MTT) intervention to increase accessibility for MT as a psychosocial intervention for neuropsychiatric symptoms in people with AD by conducting a narrative review of the existing MT and AD literature.MethodsWe conducted a narrative review of MT and MTT publications indexed in PubMed and Google Scholar wherein authors used the Neuropsychiatric Inventory. We examined the impact of MT on neuropsychiatric symptoms of AD and identified MTT as a way to increase access to clinical services.ResultsMT can have positive impacts on neuropsychiatric symptoms in AD. However, we identified an ensuing need for protocolized MT interventions, access to services, and increased awareness. MTT is an option that can address these needs.DiscussionAlthough MT can have positive effects on neuropsychiatric symptoms and can be beneficial and safe for individuals with AD, the current approach to MT practice is enormously heterogeneous with studies demonstrating variable therapist qualifications, uses of music, therapy approaches, and clinical populations. Congruently, the existing literature indicates that MT has not been standardized with protocolized interventions, making it difficult for clinicians and researchers to objectively assess the evidence, and thus, prescribe MT interventions. The lack of MT standardization, coupled with a low number of music therapists relative to people with AD, result in a lack of awareness that hinders access to MT as a psychosocial treatment for neuropsychiatric symptoms in people with AD. We therefore propose that protocolized MTT interventions are needed to increase access to better address neuropsychiatric symptoms associated with AD.

Objectives: This systematic review and meta-analysis was conducted to provide an analysis of the published data about the effects of cognitive behavioral therapies on the depression of older adults with a diagnosis of Alzheimer's disease. Methods: This study was performed following the PRISMA 2020 guidelines. The search was performed between March and April 2023, using four electronic databases: PubMed, Web of Science, Cinhal and Scopus. Different keywords combined with Boolean operators were utilized. Only 11 articles were included out of the initial 212. Results: Cognitive behavioral therapy was found to reduce depression in individuals with Alzheimer's, including treatments with low frequency but a longer intervention time. Conclusion: This systematic review and meta-analysis found that the psychosocial therapy cognitive behavioral therapy is effective in improving depression in individuals with a diagnosis of Alzheimer's. However, results are inconclusive due to the disparity of the findings and the heterogeneity of the applied protocols, so more studies are needed on this topic. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases, such as Alzheimer’s disease (AD), pose significant challenges in early diagnosis, leading to irreversible brain damage and cognitive decline. In this study, we present a novel diagnostic approach that utilizes whole molecule analysis of neuron-derived cell-free DNA (cfDNA) as a biomarker for early detection of neurodegenerative diseases. By analyzing Differential Methylation Regions (DMRs) between purified cortical neurons and blood plasma samples, we identified robust biomarkers that accurately distinguish between neuronal and non-neuronal cfDNA. The use of cfDNA offers the advantage of convenient and minimally invasive sample collection compared to traditional cerebrospinal fluid or tissue biopsies, making this approach more accessible and patient friendly. Targeted sequencing at the identified DMR locus demonstrated that a conservative cutoff of 5% of neuron-derived cfDNA in blood plasma accurately identifies 100% of patients diagnosed with AD, showing promising potential for early disease detection. Additionally, this method effectively differentiated between patients with mild cognitive impairment (MCI) who later progressed to AD and those who did not, highlighting its prognostic capabilities. Importantly, the differentiation between patients with neurodegenerative diseases and healthy controls demonstrated the specificity of our approach. Furthermore, this cfDNA-based diagnostic strategy outperforms recently developed protein-based assays, which often lack accuracy and convenience. While our current approach focused on a limited set of loci, future research should explore the development of a more comprehensive model incorporating multiple loci to increase diagnostic accuracy further. Although certain limitations, such as technical variance associated with PCR amplification and bisulfite conversion, need to be addressed, this study emphasizes the potential of cfDNA analysis as a valuable tool for pre-symptomatic detection and monitoring of neurodegenerative diseases. With further development and validation, this innovative diagnostic strategy has the potential to significantly impact the field of neurodegenerative disease research and patient care, offering a promising avenue for early intervention and personalized therapeutic approaches.

Multimodal neuroimaging data of various brain disorders provides valuable information to understand brain function in health and disease. Various neuroimaging-based databases have been developed that mainly consist of volumetric magnetic resonance imaging (MRI) data. We present the comprehensive web-based neuroimaging platform “SWADESH” for hosting multi-disease, multimodal neuroimaging, and neuropsychological data along with analytical pipelines. This novel initiative includes neurochemical and magnetic susceptibility data for healthy and diseased conditions, acquired using MR spectroscopy (MRS) and quantitative susceptibility mapping (QSM) respectively. The SWADESH architecture also provides a neuroimaging database which includes MRI, MRS, functional MRI (fMRI), diffusion weighted imaging (DWI), QSM, neuropsychological data and associated data analysis pipelines. Our final objective is to provide a master database of major brain disease states (neurodegenerative, neuropsychiatric, neurodevelopmental, and others) and to identify characteristic features and biomarkers associated with such disorders.

Objective: To provide a rigorous comparison between patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) and healthy elderly, as well as to assess the value of electroencephalography (EEG) in terms of early diagnosis, we conducted a neutral image recognition memory task involving individuals with positive biomarkers including b amyloid deposition, pathologic tau or neurodegeneration. Methods: The task involving study and test blocks was designed to evaluate participants' recognition memory. Electroencephalogram was recorded synchronously to elicit event-related potentials in patients with MCI-AD and healthy control subjects. We further analyzed differences between groups or conditions in terms of behavioral performance, time domain, and timefrequency domain. Results: The MCI-AD cohort showed a slower response time to old/new images and had low accuracy regarding behavioral performance. The amplitude of the late positive complex for the old/new effects was significantly suppressed in the MCI-AD cohort when compared with that in the HC cohort. The amplitude of the late old/new effects was correlated with the Auditory Verbal Learning Test recognition score in all participants. The time-frequency domain analysis revealed that correct recognition of old items elicited a decrease in beta power, mainly limited to the HC cohort. Moreover, the combination of behavioral (processing speed and accuracy) and electrophysiological (average amplitude and relative power of delta band) measures contributes to classifying patients with MCI-AD from healthy elderly people. Conclusion: Changes of old/new effects, accuracy and response time are sensitive to the impairment of recognition memory in patients with MCI-AD and have moderate value in predicting the incipient stage of AD. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has significantly impacted public health, putting people with Alzheimer's disease at significant risk. This study used bibliometric analysis method to conduct in-depth research on the relationship between COVID-19 and Alzheimer's disease, as well as to predict its development trends. Methods: The Web of Science Core Collection was searched for relevant literature on Alzheimer's and Coronavirus-19 during 2019-2023. We used a search query string in our advanced search. Using Microsoft Excel 2021 and VOSviewer software, a statistical analysis of primary high-yield authors, research institutions, countries, and journals was performed. Knowledge networks, collaboration maps, hotspots, and regional trends were analyzed using VOSviewer and CiteSpace. Results: During 2020-2023, 866 academic studies were published in international journals. United States, Italy, and the United Kingdom rank top three in the survey; in terms of productivity, the top three schools were Harvard Medical School, the University of Padua, and the University of Oxford; Bonanni, Laura, from Gabriele d'Annunzio University (Italy), Tedeschi, Gioacchino from the University of Campania Luigi Vanvitelli (Italy), Vanacore, Nicola from Natl Ctr Dis Prevent and Health Promot (Italy), Reddy, P. Hemachandra from Texas Tech University (USA), and El Haj, Mohamad from University of Nantes (France) were the authors who published the most articles; The Journal of Alzheimer's Disease is the journals with the most published articles; "COVID-19," "Alzheimer's disease," "neurodegenerative diseases," "cognitive impairment," "neuroinflammation," "quality of life," and "neurological complications" have been the focus of attention in the last 3 years. Conclusion: The disease caused by the COVID-19 virus infection related to Alzheimer's disease has attracted significant attention worldwide. The major hot topics in 2020 were: "Alzheimer' disease," COVID-19," risk factors," care," and "Parkinson's disease." During the 2 years 2021 and 2022, researchers were also interested in "neurodegenerative diseases," "cognitive impairment," and "quality of life," which require further investigation. [ABSTRACT FROM AUTHOR]

The glutamate-gated ion channels known as N-methyl-d-aspartate receptors (NMDARs) are important for both normal and pathological brain function. Subunit-selective antagonists have high therapeutic promise since many pathological conditions involve NMDAR over activation, although few clinical successes have been reported. Allosteric inhibitors of GluN2B-containing receptors are among the most potential NMDAR targeting drugs. Since the discovery of ifenprodil, a variety of GluN2B-selective compounds have been discovered, each with remarkably unique structural motifs. These results expand the allosteric and pharmacolog-ical spectrum of NMDARs and provide a new structural basis for the development of next-generation GluN2B antagonists that have therapeutic potential in brain diseases. Small molecule therapeutic inhibitors targeting NMDA have recently been developed to target CNS disorders such as Alzheimer's disease. In the current study, a cheminformatics method was used to discover potential antagonists and to identify the structural requirements for Gly/NMDA antagonism. In this case we have created a useful pharmacophore model with solid statistical values. Through pharmacophore mapping, the verified model was used to filter out virtual matches from the ZINC database. Assessing receptorligand binding mechanisms and affinities used molecular docking. To find the best hits, the GlideScore and the interaction of molecules with important amino acids were considered essential features. We found some molecular inhibitors, namely, ZINC13729211, ZINC07430424, ZINC08614951, ZINC60927204, ZINC12447511, and ZINC18889258 with high binding affinity using computational methods. The molecules in our studies showed characteristics such as good stability, hydrogen bonding and higher binding affinities in the solvation-based assessment method than ifenprodil with acceptable ADMET profile. Moreover, these six leads have been proposed as potential new perspectives for exploring potent Gly/NMDA receptor antagonists. In addition, it can be tested in the laboratory for potential therapeutic strategies for both in vitro and in vivo research. [ABSTRACT FROM AUTHOR]

A feasible system for measuring patient outcomes of rehabilitation is required for assessing the real-world cost-effectiveness of rehabilitation. This study aims to assess the feasibility of measuring outcomes of rehabilitation among elderly individuals with early-stage Alzheimer's. We used the principles of Design Science to construct a set of metrics consisting of standardized PROM (Patient-Reported Outcome Measure) questionnaires, clinician-reported measures, and observational measures of functioning. We used standardized questionnaires whenever possible to ensure the validity and reliability of the questionnaires. The set of metrics was piloted on 16 individuals living at home with regular home care services. After the pilot, we further refined the set of metrics based on relevance, sensitivity to change, and applicability. We found that measurement was feasible and we propose the final set of metrics as a minimum set, which could be further improved upon by addition of metrics relevant to each subgroup of elderly individuals. We also found that using self-reported questionnaires in this population is not without difficulties. We therefore suggest that the role of informal caregivers be considered, and that accessibility of outcome questionnaires be improved.

ObjectivesThis systematic review and meta-analysis was conducted to provide an analysis of the published data about the effects of cognitive behavioral therapies on the depression of older adults with a diagnosis of Alzheimer’s disease.MethodsThis study was performed following the PRISMA 2020 guidelines. The search was performed between March and April 2023, using four electronic databases: PubMed, Web of Science, Cinhal and Scopus. Different keywords combined with Boolean operators were utilized. Only 11 articles were included out of the initial 212.ResultsCognitive behavioral therapy was found to reduce depression in individuals with Alzheimer’s, including treatments with low frequency but a longer intervention time.ConclusionThis systematic review and meta-analysis found that the psychosocial therapy cognitive behavioral therapy is effective in improving depression in individuals with a diagnosis of Alzheimer’s. However, results are inconclusive due to the disparity of the findings and the heterogeneity of the applied protocols, so more studies are needed on this topic.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=416396, CRD42023416396.

The blood-brain barrier (BBB) is a crucial part of brain anatomy as it is a specialized, protective barrier that ensures proper nutrient transport to the brain, ultimately leading to regulating proper brain function. However, it presents a major challenge in delivering pharmaceuticals to treat central nervous system (CNS) diseases due to this selectivity. A variety of different vehicles have been designed to deliver drugs across this barrier to treat neurodegenerative diseases, greatly impacting the patient’s quality of life. The two main types of vehicles used to cross the BBB are polymers and liposomes, which both encapsulate pharmaceuticals to allow them to transcytose the cells of the BBB. For Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and glioblastoma brain cancer, there are a variety of different nanoparticle treatments in development that increase the bioavailability and targeting ability of existing drugs or new drug targets to decrease symptoms of these diseases. Through these systems, nanomedicine offers a new way to target specific tissues, especially for the CNS, and treat diseases without the systemic toxicity that often comes with medications used currently.

Pro-and prebiotics have been indicated to modulate the gut-brain axis, which have supportive impacts on central nervous systems, and decrease or control the incidence of some mental disorders such as depression, anxiety, autism, Schizophrenia, and Alzheimer’s. In this review, complex communications among microbiota, gut, and the brain, and also recent scientific findings of the impacts and possible action mechanisms of pro-and prebiotics on mental disorders have been discussed. The results have shown that pro-and prebiotics can improve the function of central nervous system and play an important role in the prevention and treatment of some brain disorders; however, in order to prove these effects conclusively and firmly and to use these compounds in a therapeutic and supportive way, more studies are needed, especially human studies/clinical trials.

Introduction: Refugees experience higher rates of mental illness such as depression and post-traumatic stress disorder (PTSD) which are documented risk factors for dementia. Faith and spiritual practices have been shown to play a significant role in patients' understanding and coping with illness, however, this field of study among refugee populations remains lacking. This study aims to address this literature gap by examining the role of faith on mental health and cognitive health among Arab refugees resettled in Arab and Western countries. Materials andmethods: A total of 61 Arab refugees were recruited through ethnic community-based organizations in San Diego, California, United States (N = 29) and Amman, Jordan (N = 32). Participants were interviewed through in-depth, semi-structured interviews or focus groups. Interviews and focus groups were transcribed, translated, and coded using inductive thematic analysis and organized based on Leventhal's Self-Regulation Model. Results: Faith and spiritual practices significantly impact participants' illness perceptions and coping procedures regardless of resettlement country or gender. Several themes emerged: (1) participants believe in the interdependent relationship between mental and cognitive health. (2) There is a self-awareness of the impact of the refugee experience and trauma on participants' mental health problems, leading to a belief of increased personal risk for developing dementia. (3) Spiritual fatalism (belief that events are predetermined by God, fate, or destiny) greatly informs these perceptions of mental and cognitive health. (4) Participants acknowledge that practicing faith improves their mental and cognitive health, and many read scripture to prevent dementia. (5) Finally, spiritual gratitude and trust are important coping procedures that build resilience among participants. Conclusions: Faith and spirituality play an important role in shaping Arab refugees' illness representations and coping procedures of mental and cognitive health. Holistic public health and clinical interventions tailored to the spiritual needs of Frontiers in aging refugees and incorporating religion in prevention strategies are increasingly needed to improve the brain health and wellbeing of refugees. [ABSTRACT FROM AUTHOR]

Of all our organs, the brain is perhaps the best protected from trauma. The skull has evolved to enclose it and, within the skull, the brain floats in a protective bath of cerebrospinal fluid. It is becoming evident, however, that head trauma experienced in young adult life can cause a dementia that appears decades later. The level of trauma that induces such destruction is still being assessed but includes levels well below that which cracks the skull or causes unconsciousness or concussion. Clinically this damage appears as dementia, in people who played body-contact sports in their youth or have survived accidents or the blasts of combat; and appears also, we argue, in old age, without a history of head trauma. The dementias have been given different names, including dementia pugilistica (affecting boxers), chronic traumatic encephalopathy (following certain sports, particularly football), traumatic brain injury (following accidents, combat) and Alzheimer’s (following decades of life). They share common features of clinical presentation and neuropathology, and this conceptual analysis seeks to identify features common to these forms of brain injury and to identify where in the brain the damage common to them occurs; and how it occurs, despite the protection provided by the skull and cerebrospinal fluid. The analysis suggests that the brain’s weak point in the face of trauma is its capillary bed, which is torn by the shock of trauma. This identification in turn allows discussion of ways of delaying, avoiding and even treating these traumainduced degenerations. [ABSTRACT FROM AUTHOR]

Sustained exposures to ubiquitous outdoor/indoor fine particulate matter (PM2.5), including combustion and friction ultrafine PM(UFPM) and industrial nanoparticles (NPs) starting in utero, are linked to early pediatric and young adulthood aberrant neural protein accumulation, including hyperphosphorylated tau (p-tau), beta-amyloid (Ab1-42), a-synuclein (a syn) and TAR DNA-binding protein 43 (TDP-43), hallmarks of Alzheimer's (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). UFPM from anthropogenic and natural sources and NPs enter the brain through the nasal/olfactory pathway, lung, gastrointestinal (GI) tract, skin, and placental barriers. On a global scale, the most important sources of outdoor UFPM are motor traffic emissions. This study focuses on the neuropathology heterogeneity and overlap of AD, PD, FTLD, and ALS in older adults, their similarities with the neuropathology of young, highly exposed urbanites, and their strong link with sleep disorders. Critical information includes how this UFPM and NPs cross all biological barriers, interact with brain soluble proteins and key organelles, and result in the oxidative, endoplasmic reticulum, and mitochondrial stress, neuroinflammation, DNA damage, protein aggregation and misfolding, and faulty complex protein quality control. The brain toxicity of UFPM and NPs makes them powerful candidates for early development and progression of fatal common neurodegenerative diseases, all having sleep disturbances. A detailed residential history, proximity to high-traffic roads, occupational histories, exposures to high-emission sources (i.e., factories, burning pits, forest fires, and airports), indoor PM sources (tobacco, wood burning in winter, cooking fumes, and microplastics in house dust), and consumption of industrial NPs, along with neurocognitive and neuropsychiatric histories, are critical. Environmental pollution is a ubiquitous, early, and cumulative risk factor for neurodegeneration and sleep disorders. Prevention of deadly neurological diseases associated with air pollution should be a public health priority. [ABSTRACT FROM AUTHOR]

There is increasing evidence of a positive association of type 2 diabetes with Alzheimer's disease (AD), the most prevalent form of dementia. Suggested pathways include cerebral vascular dysfunction; central insulin resistance, or exaggerated brain abundance of potentially cytotoxic amyloid-b (Ab), a hallmark feature of AD. However, contemporary studies find that Ab is secreted in the periphery by lipogenic organs and secreted as nascent triglyceride-rich lipoproteins (TRL's). Pre-clinical models show that exaggerated abundance in blood of TRL-Ab compromises blood-brain barrier (BBB) integrity, resulting in extravasation of the TRL-Ab moiety to brain parenchyme, neurovascular inflammation and neuronal degeneration concomitant with cognitive decline. Inhibiting secretion of TRL-Ab by peripheral lipogenic organs attenuates the early-AD phenotype indicated in animal models, consistent with causality. Poorly controlled type 2 diabetes commonly features hypertriglyceridemia because of exaggerated TRL secretion and reduced rates of catabolism. Alzheimer's in diabetes may therefore be a consequence of heightened abundance in blood of lipoprotein-Ab and accelerated breakdown of the BBB. This review reconciles the prevailing dogma of amyloid associated cytotoxicity as a primary risk factor in lateonset AD, with substantial evidence of a microvascular axis for dementia-indiabetes. Consideration of potentially relevant pharmacotherapies to treat insulin resistance, dyslipidaemia and by extension plasma amyloidemia in type 2 diabetes are discussed. [ABSTRACT FROM AUTHOR]

The glutamate-gated ion channels known as N-methyl-d-aspartate receptors (NMDARs) are important for both normal and pathological brain function. Subunit-selective antagonists have high therapeutic promise since many pathological conditions involve NMDAR over activation, although few clinical successes have been reported. Allosteric inhibitors of GluN2B-containing receptors are among the most potential NMDAR targeting drugs. Since the discovery of ifenprodil, a variety of GluN2B-selective compounds have been discovered, each with remarkably unique structural motifs. These results expand the allosteric and pharmacolog-ical spectrum of NMDARs and provide a new structural basis for the development of next-generation GluN2B antagonists that have therapeutic potential in brain diseases. Small molecule therapeutic inhibitors targeting NMDA have recently been developed to target CNS disorders such as Alzheimer’s disease. In the current study, a cheminformatics method was used to discover potential antagonists and to identify the structural requirements for Gly/NMDA antagonism. In this case we have created a useful pharmacophore model with solid statistical values. Through pharmacophore mapping, the verified model was used to filter out virtual matches from the ZINC database. Assessing receptor-ligand binding mechanisms and affinities used molecular docking. To find the best hits, the GlideScore and the interaction of molecules with important amino acids were considered essential features. We found some molecular inhibitors, namely, ZINC13729211, ZINC07430424, ZINC08614951, ZINC60927204, ZINC12447511, and ZINC18889258 with high binding affinity using computational methods. The molecules in our studies showed characteristics such as good stability, hydrogen bonding and higher binding affinities in the solvation-based assessment method than ifenprodil with acceptable ADMET profile. Moreover, these six leads have been proposed as potential new perspectives for exploring potent Gly/NMDA receptor antagonists. In addition, it can be tested in the laboratory for potential therapeutic strategies for both in vitro and in vivo research.

IntroductionRefugees experience higher rates of mental illness such as depression and post-traumatic stress disorder (PTSD) which are documented risk factors for dementia. Faith and spiritual practices have been shown to play a significant role in patients' understanding and coping with illness, however, this field of study among refugee populations remains lacking. This study aims to address this literature gap by examining the role of faith on mental health and cognitive health among Arab refugees resettled in Arab and Western countries.Materials and methodsA total of 61 Arab refugees were recruited through ethnic community-based organizations in San Diego, California, United States (N = 29) and Amman, Jordan (N = 32). Participants were interviewed through in-depth, semi-structured interviews or focus groups. Interviews and focus groups were transcribed, translated, and coded using inductive thematic analysis and organized based on Leventhal's Self-Regulation Model.ResultsFaith and spiritual practices significantly impact participants' illness perceptions and coping procedures regardless of resettlement country or gender. Several themes emerged: (1) participants believe in the interdependent relationship between mental and cognitive health. (2) There is a self-awareness of the impact of the refugee experience and trauma on participants' mental health problems, leading to a belief of increased personal risk for developing dementia. (3) Spiritual fatalism (belief that events are predetermined by God, fate, or destiny) greatly informs these perceptions of mental and cognitive health. (4) Participants acknowledge that practicing faith improves their mental and cognitive health, and many read scripture to prevent dementia. (5) Finally, spiritual gratitude and trust are important coping procedures that build resilience among participants.ConclusionsFaith and spirituality play an important role in shaping Arab refugees' illness representations and coping procedures of mental and cognitive health. Holistic public health and clinical interventions tailored to the spiritual needs of aging refugees and incorporating religion in prevention strategies are increasingly needed to improve the brain health and wellbeing of refugees.

Of all our organs, the brain is perhaps the best protected from trauma. The skull has evolved to enclose it and, within the skull, the brain floats in a protective bath of cerebrospinal fluid. It is becoming evident, however, that head trauma experienced in young adult life can cause a dementia that appears decades later. The level of trauma that induces such destruction is still being assessed but includes levels well below that which cracks the skull or causes unconsciousness or concussion. Clinically this damage appears as dementia, in people who played body-contact sports in their youth or have survived accidents or the blasts of combat; and appears also, we argue, in old age, without a history of head trauma. The dementias have been given different names, including dementia pugilistica (affecting boxers), chronic traumatic encephalopathy (following certain sports, particularly football), traumatic brain injury (following accidents, combat) and Alzheimer’s (following decades of life). They share common features of clinical presentation and neuropathology, and this conceptual analysis seeks to identify features common to these forms of brain injury and to identify where in the brain the damage common to them occurs; and how it occurs, despite the protection provided by the skull and cerebrospinal fluid. The analysis suggests that the brain’s weak point in the face of trauma is its capillary bed, which is torn by the shock of trauma. This identification in turn allows discussion of ways of delaying, avoiding and even treating these trauma-induced degenerations.

Sustained exposures to ubiquitous outdoor/indoor fine particulate matter (PM2.5), including combustion and friction ultrafine PM (UFPM) and industrial nanoparticles (NPs) starting in utero, are linked to early pediatric and young adulthood aberrant neural protein accumulation, including hyperphosphorylated tau (p-tau), beta-amyloid (Aβ1 − 42), α-synuclein (α syn) and TAR DNA-binding protein 43 (TDP-43), hallmarks of Alzheimer's (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). UFPM from anthropogenic and natural sources and NPs enter the brain through the nasal/olfactory pathway, lung, gastrointestinal (GI) tract, skin, and placental barriers. On a global scale, the most important sources of outdoor UFPM are motor traffic emissions. This study focuses on the neuropathology heterogeneity and overlap of AD, PD, FTLD, and ALS in older adults, their similarities with the neuropathology of young, highly exposed urbanites, and their strong link with sleep disorders. Critical information includes how this UFPM and NPs cross all biological barriers, interact with brain soluble proteins and key organelles, and result in the oxidative, endoplasmic reticulum, and mitochondrial stress, neuroinflammation, DNA damage, protein aggregation and misfolding, and faulty complex protein quality control. The brain toxicity of UFPM and NPs makes them powerful candidates for early development and progression of fatal common neurodegenerative diseases, all having sleep disturbances. A detailed residential history, proximity to high-traffic roads, occupational histories, exposures to high-emission sources (i.e., factories, burning pits, forest fires, and airports), indoor PM sources (tobacco, wood burning in winter, cooking fumes, and microplastics in house dust), and consumption of industrial NPs, along with neurocognitive and neuropsychiatric histories, are critical. Environmental pollution is a ubiquitous, early, and cumulative risk factor for neurodegeneration and sleep disorders. Prevention of deadly neurological diseases associated with air pollution should be a public health priority.

Introduction: Alzheimer’s (AD) and Parkinson’s disease (PD) are neurodegenerative conditions characterized by incremental deposition of β-amyloid (Aβ) and α-synuclein in AD and PD brain, respectively, in relatively conserved patterns. Both are associated with neuroinflammation, with a proposed microbial component for disease initiation and/or progression. Notably, Aβ and α-synuclein have been shown to possess antimicrobial properties. There is evidence for bacterial presence within the brain, including the oral pathobiont Porphyromonas gingivalis, with cognitive impairment and brain pathology being linked to periodontal (gum) disease and gut dysbiosis. Methods: Here, we use high resolution 16S rRNA PCR-based Next Generation Sequencing (16SNGS) to characterize bacterial composition in brain areas associated with the early, intermediate and late-stage of the diseases. Results and discussion: This study reveals the widespread presence of bacteria in areas of the brain associated with AD and PD pathology, with distinctly different bacterial profiles in blood and brain. Brain area profiles were overall somewhat similar, predominantly oral, with some bacteria subgingival and oronasal in origin, and relatively comparable profiles in AD and PD brain. However, brain areas associated with early disease development, such as the locus coeruleus, were substantially different in bacterial DNA content compared to areas affected later in disease etiology. [ABSTRACT FROM AUTHOR]

Deposition of misfolded proteins and synaptic failure affects the brain in Alzheimer's disease (AD). Its progression results in amnesia and cognitive impairment. Absence of treatment is due to excessive loss of neurons in the patients and the delayed effects of drugs. The enhanced pluripotency, proliferation, differentiation, and recombination characteristics of stromal cells into nerve cells and glial cells present them as a potential treatment for AD. Successful evidence of action in animal models along with positive results in preclinical studies further encourage its utilization for AD treatment. With regard to humans, cell replacement therapy involving mesenchymal stromal cells, induced-pluripotent stromal cells, human embryonic stromal cells, and neural stems show promising results in clinical trials. However, further research is required prior to its use as stromal cell therapy in AD related disorders. The current review deals with the mechanism of development of anomalies such as Alzheimer's and the prospective applications of stromal cells for treatment. [ABSTRACT FROM AUTHOR]

IntroductionAlzheimer’s (AD) and Parkinson’s disease (PD) are neurodegenerative conditions characterized by incremental deposition of β-amyloid (Aβ) and α-synuclein in AD and PD brain, respectively, in relatively conserved patterns. Both are associated with neuroinflammation, with a proposed microbial component for disease initiation and/or progression. Notably, Aβ and α-synuclein have been shown to possess antimicrobial properties. There is evidence for bacterial presence within the brain, including the oral pathobiont Porphyromonas gingivalis, with cognitive impairment and brain pathology being linked to periodontal (gum) disease and gut dysbiosis.MethodsHere, we use high resolution 16S rRNA PCR-based Next Generation Sequencing (16SNGS) to characterize bacterial composition in brain areas associated with the early, intermediate and late-stage of the diseases.Results and discussionThis study reveals the widespread presence of bacteria in areas of the brain associated with AD and PD pathology, with distinctly different bacterial profiles in blood and brain. Brain area profiles were overall somewhat similar, predominantly oral, with some bacteria subgingival and oronasal in origin, and relatively comparable profiles in AD and PD brain. However, brain areas associated with early disease development, such as the locus coeruleus, were substantially different in bacterial DNA content compared to areas affected later in disease etiology.

Deposition of misfolded proteins and synaptic failure affects the brain in Alzheimer’s disease (AD). Its progression results in amnesia and cognitive impairment. Absence of treatment is due to excessive loss of neurons in the patients and the delayed effects of drugs. The enhanced pluripotency, proliferation, differentiation, and recombination characteristics of stromal cells into nerve cells and glial cells present them as a potential treatment for AD. Successful evidence of action in animal models along with positive results in preclinical studies further encourage its utilization for AD treatment. With regard to humans, cell replacement therapy involving mesenchymal stromal cells, induced-pluripotent stromal cells, human embryonic stromal cells, and neural stems show promising results in clinical trials. However, further research is required prior to its use as stromal cell therapy in AD related disorders. The current review deals with the mechanism of development of anomalies such as Alzheimer’s and the prospective applications of stromal cells for treatment.

Introduction: In China, the increasing number of people with Alzheimer's disease (AD) poses a great challenge to families and the country. Economic and cultural differences cause a urban-rural gap in medical resources. This multicenter survey aimed to investigate the real-world practice of disease treatment among people with AD. Methods: People with AD and their caregivers from 30 provincial regions in mainland China were enrolled from October 2020 to December 2020 to be surveyed for their treatment experience. Logistic regression was used to explore the factors that influence medication adherence in all areas, urban areas, and rural areas. Results: In this survey, 1,427 participants came from urban areas, and 539 participants came from rural areas. Patients in urban areas were older (mean age 74 vs. 70, p=0.001), less frequently hadmild AD (36.0 vs. 52.1%, p < 0.001), and more often were cared for at professional institutions (8.8 vs. 3.2%, p < 0.001). In terms of pharmacotherapy, 77.8% of people accepted taking lifelong medication, whereas 61.3% of patients insisted on taking medications. Although 72.0% of rural people believed in taking lifelong medication, only 30.0% adhered to drug use. The major factors that influenced medication adherence for all patients with AD were regional distribution (p < 0.001, OR = 6.18, 95% CI: 4.93-7.74) and family earnings (p = 0.003, OR = 1.22, 95% CI: 1.07-1.38). In rural areas, family earnings (p = 0.008, OR = 1.44, 95% CI: 1.10-1.89) and severity of AD (p = 0.033, OR = 1.31, 95% CI: 1.02-1.68) were the main factors. Family earnings (p = 0.038, OR = 1.16, 95% CI: 1.01-1.34) was the only factor among urban areas. Among all non-pharmaceutical activities except for cognitive intervention, the participation rates of rural patients were significantly higher than those of urban patients (p < 0.05). Conclusion: Although national progress has been made in the public awareness of disease treatment, adequate diagnosis and medication adherence need to be prompted, especially in rural areas. Furthermore, lifelong treatment should be improved based on regional characteristics through the joint efforts of the government, health workers, and social volunteers. [ABSTRACT FROM AUTHOR]

Background: Due to their low cost, less invasive nature, and ready availability, plasma biomarkers of Alzheimer's disease have been proposed as one-time screening tools for clinical trials and research. The impact of ethnoracial factors on these biomarkers has received little attention. The current cross-sectional study investigated the levels of Ab40, Ab42, total tau (t tau), and neurofilament light (NfL) across diagnoses for each of the three major ethnoracial groups in the United States in a community-based cohort of older adults. Methods: A total of 1,862 participants (852 Mexican Americans (MAs); 775 non-Hispanic Whites (NHWs), and 235 African Americans (AAs)) drawn fromThe Health & Aging Brain Study--Health Disparities (HABS-HD) study were included. Diagnoses were assigned using an algorithm(decision tree) verified by consensus review. Plasma samples were assayed using Simoa technology. Levels of each biomarker were compared for the three ethnoracial groups across cognitive diagnoses using ANOVA covarying sex and age. Results: Significant differences were found across the groups at each level of cognitive impairment. Cognitively unimpaired (CU) AA had significantly lower levels of each of the biomarkers than cognitively unimpaired MA or NHW and NHW had higher levels of Ab40, and NfL than the other two groups. MA had higher t tau than AA or NHW. Mild cognitive impairment (MCI) group NHWhad the highest levels on all the biomarkers and AA had the lowest. NHW and MA have higher levels of Ab40, Ab42, and t tau there was no difference between the groups for Ab42. NHW had significantly higher levels of Ab40, t tau, and NfL than AA. AA had a higher Ab42/Ab40 ratio than either NHW or MA for CU MCI. Conclusions: The use of plasma biomarkers of cognitive decline is promising given their advantages over other biomarkers such as CSF and imaging but as the current research shows, ethnoracial differences must be considered to enhance accuracy and utility. Developing ethnoracial-specific cut points and establishing normative ranges by assay platform for each of the biomarkers are needed. Longitudinal research to assess changes in biomarkers during a cognitive decline is ongoing. [ABSTRACT FROM AUTHOR]

Ether glycerophospholipids (GPL) are involved in membrane fluidity and fusion. Vinyl-ether GPL are also conjectured to provide antioxidant capacity in the brain. The roles of these lipids in the processes involved in the development of dementia are not understood but choline and ethanolamine vinyl-ether GPL (i.e., plasmalogens) are decreased in the brains of subjects with dementia. In contrast, serine ether and vinyl-ether GPL have not been investigated in human brain. We therefore undertook an evaluation of these lipids, utilizing high-resolution mass spectrometry (HR-MS), in tissues from control and dementia subjects that we had previously characterized in-depth. We can report for the first time that a number of serine ether GPL and a more limited number of serine plasmalogens are present in human frontal cortex. In addition, we found that some of these frontal cortex lipids are decreased in Mild Cognitive Impairment (MCI), early-onset Alzheimer's disease (EOAD), and late-onset AD (LOAD). In contrast no alterations in serine ether GPL were monitored in the frontal cortex of donors with schizophrenia, demonstrating disease specificity. These data suggest that further studies of the roles of ether GPL, including serine ether GPL, in brain function are worthy of undertaking. [ABSTRACT FROM AUTHOR]

Introduction/Objectives: In addition to cognitive decline, one of the most important problems for caregivers of patients with Alzheimer's is neuropsychiatric symptoms (NPS). This study aimed to evaluate the NPS in patients with Alzheimer's disease (AD) and investigate its relationship with caregiver burden (CB). Methods: In a cross-sectional study of 85 patients with AD referred to Shafa Hospital in Rasht and their caregivers in 2020, information was collected using a demographic questionnaire, Neuropsychiatric Inventory Questionnaire (NPI-Q), and the Caregiver Burden Inventory (CBI). Data were analyzed by Spearman correlation, t-test, and linear regression, with SPSS version 22. Results: The mean age of the patients and their caregivers were 74.95 ± 8.87 years and 43.98 ± 11.38 years, respectively. The mean total score of NPS in patients with AD was 44.25 (0-144) and the mean CB score was 36.27 (0-96), which was a moderate level. According to the results, 91% of patients had apathy, while happiness/euphoria was reported as the most uncommon symptom. In addition, there was a significant relationship between the score of NPS and CB (r = 0.542, P < 0.0001), as well as all its sub-components, time-dependence burden with more correlation (r = 0.509, P < 0.0001), and social burden with less correlation (r = 0.352, P < 0.001). NPS, hallucination, aberrant motor behavior (AMB), delusion, and depression were most correlated with CB. Also, the mean score of CB was significantly higher in women than in men (P = 0.045). Living in a rural area had a significant relationship with NPS score (P = 0.026). Also, linear regression showed that with increasing 1 year of patients' age, the mean score of patient's NPS decreased by 0.374 (P = 0.048). Conclusion: Neuropsychiatric symptoms, especially hallucination, aberrant motor behavior (AMB), delusion, and depression were associated with caregiver burden. Apathy was the most common symptom in patients with AD. [ABSTRACT FROM AUTHOR]

Elucidating the impact of the gut microbiome on Alzheimer's Disease (AD) is an area of intense interest. Short chain fatty acids (SCFAs) are major microbiota metabolites that have been implicated as a mediator of gut microbiome effects in the brain. Here, we tested the effects of SCFA-treated water vs. saline-treated water on APPswe/PSEN1dE9 mice maintained under standard laboratory conditions. Mice were treated with SCFAs from five months of age until ten months of age, when they were evaluated for microbiome profile, impaired spatial memory as evaluated with the radial arm water maze, astrocyte activation as measured by Gfap expression and amyloid burden as assessed by histochemistry and MSD ELISA. We report that SCFA treatment increased alpha-diversity and impacted the gut microbiome profile by increasing, in part, the relative abundance of several bacteria that typically produce SCFAs. However, SCFA treatment did not significantly affect behavior. Similarly, SCFAs did not affect cortical or hippocampal astrocyte activation observed in the APP/PS1 mice. Lastly, although robust levels of soluble and insoluble amyloid were present in the APP/PS1 mice, SCFA treatment had no effect on these indices. Overall, our findings are that SCFA treatment modifies the microbiome in a fashion that may increase further SCFA production. However, SCFA treatment did not alter behavior, astrocyte activation, nor amyloid neuropathology in APP/PS1 mice maintained with a conventional microbiome. [ABSTRACT FROM AUTHOR]

BackgroundDue to their low cost, less invasive nature, and ready availability, plasma biomarkers of Alzheimer's disease have been proposed as one-time screening tools for clinical trials and research. The impact of ethnoracial factors on these biomarkers has received little attention. The current cross-sectional study investigated the levels of Aβ40, Aβ42, total tau (t tau), and neurofilament light (NfL) across diagnoses for each of the three major ethnoracial groups in the United States in a community-based cohort of older adults.MethodsA total of 1,862 participants (852 Mexican Americans (MAs); 775 non-Hispanic Whites (NHWs), and 235 African Americans (AAs)) drawn from The Health & Aging Brain Study—Health Disparities (HABS-HD) study were included. Diagnoses were assigned using an algorithm (decision tree) verified by consensus review. Plasma samples were assayed using Simoa technology. Levels of each biomarker were compared for the three ethnoracial groups across cognitive diagnoses using ANOVA covarying sex and age.ResultsSignificant differences were found across the groups at each level of cognitive impairment. Cognitively unimpaired (CU) AA had significantly lower levels of each of the biomarkers than cognitively unimpaired MA or NHW and NHW had higher levels of Aβ40, and NfL than the other two groups. MA had higher t tau than AA or NHW. Mild cognitive impairment (MCI) group NHW had the highest levels on all the biomarkers and AA had the lowest. NHW and MA have higher levels of Aβ40, Aβ42, and t tau there was no difference between the groups for Aβ42. NHW had significantly higher levels of Aβ40, t tau, and NfL than AA. AA had a higher Aβ42/Aβ40 ratio than either NHW or MA for CU MCI.ConclusionsThe use of plasma biomarkers of cognitive decline is promising given their advantages over other biomarkers such as CSF and imaging but as the current research shows, ethnoracial differences must be considered to enhance accuracy and utility. Developing ethnoracial-specific cut points and establishing normative ranges by assay platform for each of the biomarkers are needed. Longitudinal research to assess changes in biomarkers during a cognitive decline is ongoing.

Ether glycerophospholipids (GPL) are involved in membrane fluidity and fusion. Vinyl-ether GPL are also conjectured to provide antioxidant capacity in the brain. The roles of these lipids in the processes involved in the development of dementia are not understood but choline and ethanolamine vinyl-ether GPL (i.e., plasmalogens) are decreased in the brains of subjects with dementia. In contrast, serine ether and vinyl-ether GPL have not been investigated in human brain. We therefore undertook an evaluation of these lipids, utilizing high-resolution mass spectrometry (HR-MS), in tissues from control and dementia subjects that we had previously characterized in-depth. We can report for the first time that a number of serine ether GPL and a more limited number of serine plasmalogens are present in human frontal cortex. In addition, we found that some of these frontal cortex lipids are decreased in Mild Cognitive Impairment (MCI), early-onset Alzheimer’s disease (EOAD), and late-onset AD (LOAD). In contrast no alterations in serine ether GPL were monitored in the frontal cortex of donors with schizophrenia, demonstrating disease specificity. These data suggest that further studies of the roles of ether GPL, including serine ether GPL, in brain function are worthy of undertaking.

Elucidating the impact of the gut microbiome on Alzheimer’s Disease (AD) is an area of intense interest. Short chain fatty acids (SCFAs) are major microbiota metabolites that have been implicated as a mediator of gut microbiome effects in the brain. Here, we tested the effects of SCFA-treated water vs. saline-treated water on APPswe/PSEN1dE9 mice maintained under standard laboratory conditions. Mice were treated with SCFAs from five months of age until ten months of age, when they were evaluated for microbiome profile, impaired spatial memory as evaluated with the radial arm water maze, astrocyte activation as measured by Gfap expression and amyloid burden as assessed by histochemistry and MSD ELISA. We report that SCFA treatment increased alpha-diversity and impacted the gut microbiome profile by increasing, in part, the relative abundance of several bacteria that typically produce SCFAs. However, SCFA treatment did not significantly affect behavior. Similarly, SCFAs did not affect cortical or hippocampal astrocyte activation observed in the APP/PS1 mice. Lastly, although robust levels of soluble and insoluble amyloid were present in the APP/PS1 mice, SCFA treatment had no effect on these indices. Overall, our findings are that SCFA treatment modifies the microbiome in a fashion that may increase further SCFA production. However, SCFA treatment did not alter behavior, astrocyte activation, nor amyloid neuropathology in APP/PS1 mice maintained with a conventional microbiome.