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Alzheimers disease and related dementias (ADRD) are a spectrum of disorders characterized by cognitive decline, which pose significant challenges for both affected individuals and their caregivers. Previous literature has focused on patient family surveys which do not always capture the breadth of authentic experiences of the caregiver. Online social media platforms provide a space for individuals to share their experiences and obtain advice toward caring for those with ADRD. This study leverages Reddit, a platform frequented by caregivers seeking advice for caring for a family member with advice for ADRD. To identify the topics of discussion or advice that most caregivers seek and sought after, we employed structured topic modeling techniques such as BERTopic to analyze the content of these posts and use an intertopic distance map to discern the variation in themes across different Reddit categories. In addition, we analyze the sentiment of the Reddit postings using Valence Aware Dictionary and Sentiment Reasoner to deduce the degree of negative, positive, and neutral sentiment of the discussion posts. Our findings reveal that the topics that caregivers most frequently discuss and seek advice for were related to caregiver stories, community support, and concerns ADRD. Specifically, we aimed to reproduce an organic Reddit search of caregiving of abuse on family member, financial struggles, symptoms of hallucinations, and repetition in ADRD family members. These results underscore the importance of online communities for gaining a comprehensive understanding of the multifaceted experiences and challenges faced by ADRD caregivers.

The escalating global healthcare challenge posed by Alzheimer's Disease (AD) and compounded by the lack of effective treatments emphasizes the urgent need for innovative approaches to combat this devastating disease. Currently, passive and active immunotherapies remain the most promising strategy for AD. FDA-approved lecanemab significantly reduces Aβ aggregates from the brains of early AD patients administered biweekly with this humanized monoclonal antibody. Although the clinical benefits noted in these trials have been modest, researchers have emphasized the importance of preventive immunotherapy. Importantly, data from immunotherapy studies have shown that antibody concentrations in the periphery of vaccinated people should be sufficient for targeting Aβ in the CNS. To generate relatively high concentrations of antibodies in vaccinated people at risk of AD, we generated a universal vaccine platform, MultiTEP, and, based on it, developed a DNA vaccine, AV-1959D, targeting pathological Aβ, completed IND enabling studies, and initiated a Phase I clinical trial with early AD volunteers. Our current pilot study combined our advanced MultiTEP technology with a novel mRNA approach to develop an mRNA vaccine encapsulated in lipid-based nanoparticles (LNPs), AV-1959LR. Here, we report our initial findings on the immunogenicity of 1959LR in mice and non-human primates, comparing it with the immunogenicity of its DNA counterpart, AV-1959D.

Dementia and hepatic encephalopathy (HE) have symptom overlap and are challenging to differentiate. The presence of undiagnosed cirrhosis may lead to missed opportunities to treat HE, which was found in a veterans database. This needs validation in a non-veteran cohort. A retrospective cohort study was conducted between 2009 and 2019 using national non-Veteran patient data from the multi-center TriNetX database. Participants included 68,807 patients with a dementia diagnosis at ≥2 visits, no prior diagnosis of cirrhosis, and with sufficient laboratory test results to calculate the Fibrosis-4 (FIB-4) index, which indicates liver disease. Prevalences of high FIB-4 scores (>2.67 and >3.25) were measured within the cohort, and associations between high FIB-4 and comorbidities/demographics were examined. Within the cohort (44.7% male, 78.0% White, mean age 72.73 years (±11.09), 7.6% (n = 5815) had a FIB-4 index > 3.25 and 12.8% (n = 8683) had FIB-4 > 2.67. In multivariable logistic regression models, FIB-4 > 3.25 was associated with male gender (OR: 1.42 [1.33-1.51]), congestive heart failure (OR: 1.73 [1.59-1.87]), viral hepatitis (OR: 2.23 [1.84-2.68]), alcohol use disorder (OR: 1.39 [1.22-1.58]), and chronic kidney disease (OR: 1.38 [1.28-1.48]), and inversely associated with White race (OR: 0.76 [0.71-0.82]) and diabetes (OR: 0.82 [0.77-0.88]). Similar findings were associated with the FIB-4 > 2.67 threshold. The findings of this national cohort suggest that the FIB-4 index could be utilized to screen for potential undiagnosed cirrhosis in patients with dementia, and that hepatic encephalopathy might be misdiagnosed as dementia or cause worsening of cognitive function in patients with dementia. [ABSTRACT FROM AUTHOR]

Depression among older adults is a pressing public health concern, necessitating accurate assessment tools. The Geriatric Depression Scale (GDS) offers a brief and efficient means of screening depressive symptoms, yet its performance across ethno-racial groups remains understudied. This study aimed to compare the ability of various brief forms of the GDS to detect depressive symptoms and to assess potential ethno-racial differences in symptom endorsement among White, Black/African-American, and American Indian/Alaska Native older adults. Data were obtained from the Wisconsin Alzheimer's Disease Research Center (ADRC) clinical cohort, comprising 555 cognitively healthy individuals at risk for dementia. We used participants' baseline data for this cross-sectional analysis. Depressive symptoms were assessed using multiple brief forms of the GDS, derived from a systematic review and meta-analysis. We examined internal consistency and correlations with global Clinical Dementia Rating (CDR) scores. We conducted Kruskal-Wallis tests and post hoc pairwise comparisons to assess ethno-racial group differences in symptom endorsement. Descriptive statistics revealed a predominance of female and White participants, with notable representation from Black and American Indian/Alaska Native groups. All GDS versions demonstrated moderate to high internal consistency. Significant positive correlations were observed between GDS scores and global CDR scores. Ethno-racial group differences in depressive symptom endorsement were evident, with Black participants consistently reporting higher levels of symptoms across most GDS versions. However, American Indian/Alaska Native participants endorsed significantly fewer symptoms than Black participants in one GDS version. The study highlights the importance of considering ethno-racial differences in depressive symptomatology when assessing older adults. While the GDS demonstrates overall reliability, variations in symptom endorsement across different ethno-racial groups underscore the need for culturally sensitive assessment tools and interventions. Future research should further explore these group differences and develop tailored approaches to depression screening and treatment in diverse older adult populations. • Depression among older adults is a pressing public health concern, necessitating accurate assessment tools. • Ethno-racial group differences in depressive symptom endorsement were evident, with Black participants consistently reporting higher levels of symptoms. • American Indian/Alaska Native participants endorsed significantly fewer symptoms than Black participants in one GDS version. • The study highlights the importance of considering ethno-racial differences in depressive symptomatology when assessing older adults. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a progressive neurological disorder that is very common among older adults. In truth, taking care of Alzheimer's patients can be a very tedious job that requires a lot of time and effort. On the other hand, smartphone applications (apps) have become an essential part of all of our daily life fields. Almost every human activity can be related to an app from checking the weather forecasts to attending a business meeting online. As a natural result of this, many useful apps were developed to serve and help Alzheimer's patients and families around the world. Sadly, the apps launched in the Arabic area were very poor in their content and limited in their features. In this work, we present Alzheimer's care system (ACS) which is a smartphone Android app that aims to serve Alzheimer's early stages patients, their caregivers, and their doctors. ACS has an Arabic interface along with the English one to serve the patients in the Arabic talking countries who may struggle using similar apps in other languages. The app provides three account types and includes many useful features like contacting the caregivers and doctors through messages, keeping track of daily life tasks, reminding the patient of medication doses and times, and many more. Moreover, ACS has a Chatbot that provides general knowledge regarding the disease. Our app has been practically tested for one month by a group of users who were asked to fill out a 12 questions survey at the end of the test period. The survey results were very positive and encouraging in general. As future work, we plan to add other languages, develop an iOS version, and add new features to the app. [ABSTRACT FROM AUTHOR]

The human brain contains multiple cell types that are spatially organized into functionally distinct regions. The proper development of the brain requires complex gene regulation mechanisms in both neurons and the non-neuronal cell types that support neuronal function. Studies across the last decade have discovered that the 3D nuclear organization of the genome is instrumental in the regulation of gene expression in the diverse cell types of the brain. In this review, we describe the fundamental biochemical mechanisms that regulate the 3D genome, and comprehensively describe in vitro and ex vivo studies on mouse and human brain development that have characterized the roles of the 3D genome in gene regulation. We highlight the significance of the 3D genome in linking distal enhancers to their target promoters, which provides insights on the etiology of psychiatric and neurological disorders, as the genetic variants associated with these disorders are primarily located in noncoding regulatory regions. We also describe the molecular mechanisms that regulate chromatin folding and gene expression in neurons. Furthermore, we describe studies with an evolutionary perspective, which have investigated features that are conserved from mice to human, as well as human gained 3D chromatin features. Although most of the insights on disease and molecular mechanisms have been obtained from bulk 3C based experiments, we also highlight other approaches that have been developed recently, such as single cell 3C approaches, as well as non-3C based approaches. In our future perspectives, we highlight the gaps in our current knowledge and emphasize the need for 3D genome engineering and live cell imaging approaches to elucidate mechanisms and temporal dynamics of chromatin interactions, respectively. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Most people with dementia (PWD) in the United States live in community settings supported by family and/or unpaid care partners. Firearms access is one of many decisions care partners navigate alongside PWD in efforts to prevent injuries and deaths. Conversations about firearms access are socially challenging, although specific challenges to be overcome have not been described.As part of the larger Safety in Dementia Trial, we interviewed care partners about their views and experiences regarding firearms access in the home where the PWD resides. Interviewees were English‐speaking adults (≥18 years) in the United States who are unpaid care partners of community‐dwelling PWD. Responses to interview discussions related to (1) a desire for safety, and (2) fear of firearm violence was analyzed using a focusing process to categorize views into essential themes.Fifty care partners, who were primarily female (58%), White (66%), adult children (56%), and living in the same household (64%), participated in interviews between February 2023–February 2024. Dominant themes emerging from the focusing technique included (1) firearms as a necessary component of home safety; (2) fear of accidental/impulsive firearm violence; (3) observed risk and “near misses”; and (4) differing views on home firearms as a source of conflict. Thematic descriptions did not differ according to care partner's relationship to the PWD (adult child, spouse, other).Considering whether and how to alter access to firearms where PWD reside can be difficult for care partners to navigate. Care partners expressed a desire to limit firearms access, but worried both about creating conflict with the PWD and the self‐defense implications of making firearms inaccessible. Findings were similar across subsets of care partners indicating that standardized tools and messaging to care partners may be effective in promoting safety in homes with PWD. [ABSTRACT FROM AUTHOR]

Biological, clinicobiological and clinical conceptions of Alzheimer's disease and related dementias are being promoted simultaneously to different practical ends. The co‐existence of contemporary conceptions and the ‘scary label’ associated with older diagnostic criteria create the possibility of misunderstanding and harm. In this comment, we argue in favour of socio‐ethical interventions targeted to health workers and the general public so as to lower the uncertainties introduced by contemporary diagnostic criteria and to articulate how they relate to established criteria. [ABSTRACT FROM AUTHOR]

The neurotoxicant trimethyltin (TMT) triggers cognitive impairment and hippocampal neurodegeneration. TMT is a useful research tool for the study of Alzheimer's disease (AD) pathogenesis and treatment. Although the antidiabetic agent metformin has shown promising neuroprotective effects, however, its precise modes of action in neurodegenerative disorders need to be further elucidated. In this study, we investigated whether metformin can mitigate TMT cognition impairment and hippocampal neurodegeneration. To induce an AD-like phenotype, TMT was injected i.p. (8 mg/kg) and metformin was administered daily p.o. for 3 weeks at 200 mg/kg. Our results showed that metformin administration to the TMT group mitigated learning and memory impairment in Barnes maze, novel object recognition (NOR) task, and Y maze, attenuated hippocampal oxidative, inflammatory, and cell death/pyroptotic factors, and also reversed neurodegeneration-related proteins such as presenilin 1 and p-Tau. Hippocampal level of AMP-activated protein kinase (AMPK) as a key regulator of energy homeostasis was also improved following metformin treatment. Additionally, metformin reduced hippocampal acetylcholinesterase (AChE) activity, glial fibrillary acidic protein (GFAP)-positive reactivity, and prevented the loss of CA1 pyramidal neurons. This study showed that metformin mitigated TMT-induced neurodegeneration and this may pave the way to develop new therapeutics to combat against cognitive deficits under neurotoxic conditions. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a chronic, advanced brain sickness disease that slowly destroys memory and thinking skills and, in the end, the ability to perform routine tasks. This disease is caused by the abnormal clumping of proteins such as amyloids around the brain cells. The identification of proteins involved in Alzheimer's is essential to understand the disease and to discover and design the drugs. Experimental processes involving in‐vitro or in‐vivo experiments for this purpose are very time‐consuming, laborious, and highly costly. However, costly and tedious experimental procedures can be performed efficiently by targeting the most probable proteins involved in Alzheimer's predicted and ranked through a computational method with better generalization accuracy. In this study, we have proposed a machine learning (ML)–based predictive model to identify proteins potentially involved in Alzheimer's. Through a series of simulation studies, we have shown that our proposed model by using protein sequence information only gives state‐of‐the‐art generalization performance with an area under the precision‐recall curve of 0.93 verified through various ML‐centric and biologically relevant techniques and metrics. Through data mining in this study, we have also performed feature analysis to identify the role of individual amino acids in such proteins. Python code for feature extraction, training, and evaluating our proposed models together with the dataset is available at the URL: https://sourceforge.net/projects/alzheimer-associated-proteins/files/. [ABSTRACT FROM AUTHOR]

This literature review explores the association between hypertension and major neurocognitive disorders, including delirium, Alzheimer's disease, vascular dementia, Lewy body dementia, and frontotemporal dementia, which contribute significantly to global mortality and morbidity. Hypertension is a potentially modifiable risk factor for cognitive decline, as it contributes to the progression of neurodegenerative pathologies via vascular damage, inflammation, and the disruption of the blood–brain barrier. Despite this, the effectiveness of antihypertensive treatments in preventing or alleviating cognitive decline remains contentious. While some research highlights the potential benefits of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, other studies show inconsistent results, complicated by variations in hypertension definitions, diagnostic criteria for cognitive disorders, and confounding factors like medication adherence. Furthermore, the complex bidirectional relationship between hypertension and major neurocognitive disorders warrants more investigation, as cognitive decline can exacerbate cardiovascular risks through heightened inflammatory responses and compromised autonomic regulation. This review underscores the need for prospective, long-term studies to elucidate the relationships between hypertension and cognitive disorders and to evaluate the potential therapeutic benefits of antihypertensive treatments. [ABSTRACT FROM AUTHOR]

Aluminum chloride (Al) is associated with Alzheimer's disease (AD) and reproductive disorders. But the relationship between gonadotropin-releasing hormone (GnRH) and c-Fos levels, the end product of MAP-kinase signaling, in AD is unknown, so we aimed to investigate this relationship. We exposed rats to Al dissolved in drinking water (10 and 50 mg/kg) for two and four weeks. The control group received only drinking water. At the end, the blood sample was collected under deep anesthesia and the brain was dissected on ice, and the testicular tissue was fixed in formalin. Amyloid beta (βA) plaques in brain regions and the number of CA1 neurons were evaluated by Congo red staining and cresyl violet staining. Activation of neuronal nitric oxide synthase (nNOS) was studied using NADPH-diaphorase. The levels of c-Fos and testosterone receptors in the target area were examined immunohistochemically. Brain GnRH levels were determined by blotting, and serum levels of gonadotropins and steroids were measured by enzyme-linked immunosorbent assay (ELISA). All data were analyzed using analysis of variance (ANOVA) at α = 0.05 level. The accumulation of βA plaque was observed along with a decrease in the number of CA1 pyramidal neurons and a significant decrease in the levels of c-Fos and GnRH in the brains of rats receiving Al, which was aligned with a significant decrease in serum levels of testosterone and LH. This study, for the first time, showed a link between dementia and a concomitant decrease in brain GnRH and c-Fos levels. [ABSTRACT FROM AUTHOR]

Background: People's wider culture plays a vital role in both dementia care and policy. This study aims to explore the cultural practice and policy influence around caring for People Living with Dementia (PLWD) in Nepal. Methods: An exploratory qualitative study was designed to investigate dementia care in Nepal. The study comprised four in-depth interviews and four focus group discussions with 29 participants, including family members, health care professionals, and other stakeholders. Data were analysed using thematic analysis. Result: Four major themes (each with several sub-themes) were identified: (1) Cultural practice in dementia care; (2) Impact of policy on the dementia care; (3) Service provision; and (4) Education and training. Conclusion: There is a need for community-based awareness raising on dementia and its care, to sensitise all relevant stakeholders to meet the needs of PLWD. In addition, capacity building of health workforce is needed to enhance their knowledge of and skills in providing culturally appropriate dementia care. [ABSTRACT FROM AUTHOR]

Microbes have been suspected to cause Alzheimer’s disease since at least 1908, but this has generally remained unpopular in comparison to the amyloid hypothesis and the dominance of Aβ and Tau. However, evidence has been accumulating to suggest that these earlier theories are but a manifestation of a common cause that can trigger and interact with all the major molecular players recognized in AD. Aβ, Tau and ApoE, in particular appear to be molecules with normal homeostatic functions but also with alternative antimicrobial functions. Their alternative functions confer the non-immune specialized neuron with some innate intracellular defenses that appear to be re-appropriated from their normal functions in times of need. Indeed, signs of infection of the neurons by biofilm-forming microbial colonies, in synergy with herpes viruses, are evident from the clinical and preclinical studies we discuss. Furthermore, we attempt to provide a mechanistic understanding of the AD landscape by discussing the antimicrobial effect of Aβ, Tau and ApoE and Lactoferrin in AD, and a possible mechanistic link with deficiency of vital copper-based systems. In particular, we focus on mitochondrial oxidative respiration via complex 4 and ceruloplasmin for iron homeostasis, and how this is similar and possibly central to neurodegenerative diseases in general. In the case of AD, we provide evidence for the microbial Alzheimer’s disease (MAD) theory, namely that AD could in fact be caused by a long-term microbial exposure or even long-term infection of the neurons themselves that results in a costly prolonged antimicrobial response that disrupts copper-based systems that govern neurotransmission, iron homeostasis and respiration. Finally, we discuss potential treatment modalities based on this holistic understanding of AD that incorporates the many separate and seemingly conflicting theories. If the MAD theory is correct, then the reduction of microbial exposure through use of broad antimicrobial and anti-inflammatory treatments could potentially alleviate AD although this requires further clinical investigation. [ABSTRACT FROM AUTHOR]

Circulating RNAs have been investigated systematically for over 20 years, both as constituents of circulating extracellular vesicles (EVs) or, more recently, non‐EV RNA carriers, such as exomeres and supermeres. The high level of variability and low reproducibility rate of EV/extracellular RNA (exRNA) results generated even on the same biofluids promoted several efforts to limit pre‐analytical variability by standardizing sample collection and sample preparation, along with instrument validation, setup and calibration. Anticoagulants (ACs) are often chosen based on the initial goal of the study and not necessarily for the later EV and/or exRNA analyses. We show the effects of blood collection on EV size, abundance, and antigenic composition, as well on the miRNAs. Our focus of this work was on the effect of ACs on the number and antigenic composition of circulating EVs and on a set of circulating miRNA species, which were shown to be relevant as disease markers in several cancers and Alzheimer's disease. Results show that while the number of plasma EVs, their relative size, and post‐fluorescence labeling profile varied with each AC, their overall antigenic composition, with few exceptions, did not change significantly. However, the number of EVs expressing platelet and platelet‐activation markers increased in serum samples. For overall miRNA expression levels, EDTA was a better AC, although this may have been associated with stimulation of cells in the blood collection tube. Citrate and serum rendered better results for a set of miRNAs that were described as circulating markers for Alzheimer's disease, colon, and papillary thyroid cancers. [ABSTRACT FROM AUTHOR]

Using fine organic synthesis methods and the latest capabilities of computational chemistry, for the first time, 2-(4-amino-6-phenyl-1,2,5,6-tetrahydro-1,3,5-triazine-2(1H)-ylidene)-malononitrile, which contains a triazine ring and various functional groups in the molecule, was synthesized without the presence of a catalyst through a one-step three-component reaction. Structural analyses were carried out using X-ray and Hirshfeld surface analysis, and it was determined that asymmetric molecules of 2-(4-amino-6-phenyl1,2,5,6-tetrahydro-1,3,5-triazine-2(1H)-ylidene)-malononitrile and a dimethylformamide solvent molecule in the asymmetric unit crystallize as a racemate in the monoclinic P21/c space group. These molecules exhibit stereochemical activity at the carbon atoms where the triazine rings are attached to the phenyl ring. For the first time, theoretical predictions using Density Functional Theory calculations for the synthesis reaction of tetrahydro-s-triazine via a one-step three-component condensation without a catalyst were experimentally tested. Comprehensive theoretical-experimental studies were conducted using quantum chemical calculations to simulate these chemical reactions, leading to significant results. The synthesis under milder conditions and atom-efficient methods obtained through computer simulations further enhances the importance of this work. This compound has shown high inhibitory effects on acetylcholinesterase in living organisms, and multiple analyses, including "molecular docking" studies, have revealed that in the future, representatives of these inhibitors with different functional groups could potentially be used as drugs against epilepsy, Alzheimer’s, and other neurological diseases. [ABSTRACT FROM AUTHOR]

Leisure‐time physical activity (LTPA) decreases the risk of dementia, whereas occupational physical activity (OPA) possibly increases the risk. Yet, previous findings are mixed. We therefore aimed to investigate the effect of LTPA and OPA, respectively, on dementia among men and women. In this observational, longitudinal study, we used data from the second wave of a population‐based cohort from the municipality of Copenhagen as baseline. Data were collected in 1981–1983, and 10 343 participants were followed until the end of 2016. LTPA and OPA were self‐reported, and information on dementia diagnoses and redemption of dementia medication was obtained at an individual level from national health registers. We used Poisson regression to analyze the association between LTPA/OPA and dementia and adjusted for self‐reported age, socioeconomic factors, stress, and cardiovascular risk factors (smoking, alcohol, body mass index, and blood pressure). A higher level of LTPA was associated with a lower dementia risk among men, but we found no clear association among women. OPA and dementia were not associated among men, but occupationally active women who reported OPA in terms of walking, lifting, and heavy work had a higher risk of dementia than women with sedentary jobs. This study supported earlier findings of a protective effect of LTPA on dementia among men. Women in physically demanding jobs possibly have a higher risk of dementia, yet this finding warrants further investigation in future studies. [ABSTRACT FROM AUTHOR]

Beta amyloid PET scans are a minimally invasive biomarker that may inform Alzheimer's disease (AD) diagnosis. The Caregiver's Reactions and Experience (CARE) study, an IDEAS supplement, aimed to understand experiences of PET scan recipients and their care partners regarding motivations for scans, reporting and interpreting results, and impact of results. Patients with mild cognitive impairment or dementia who agreed to join the CARE‐IDEAS study and their care partners participated in a baseline survey and follow‐up survey approximately 18 months later, supplemented by in‐depth qualitative interviews with subsets of participants. Patients who received scans and volunteered for follow‐up research were more likely to be male, better educated, and have higher income than the general population. Survey information was merged with Medicare data. This article integrates findings from several CARE‐IDEAS publications and provides implications for practice and research. Although most participants accurately reported scan results, they were often confused about their meaning for prognosis. Some participants reported distress with results, but there were no significant changes in measured depression, burden, or economic strain over time. Many respondents desired more information about prognosis and supportive resources. Scan results were not differentially associated with changes in service use over time. Findings suggest a need for carefully designed and tested tools for clinicians to discuss risks and benefits of scans and their results, and resources to support patients and care partners in subsequent planning. Learning of scan results provides a point‐of‐contact that should be leveraged to facilitate shared decision‐making and person‐centered longitudinal AD care. [ABSTRACT FROM AUTHOR]

Despite the incredible challenges of caring for a family member with Alzheimer's disease or a related dementia, many dementia family caregivers exhibit resilience. Framed by the communication theory of resilience, this study examines how resilience processes unfold within dementia caregivers' relationships with their family member, and dementia caregivers' experiences of resilience. Analysis of 27 interviews with adult children and spousal caregivers revealed acknowledging dementia as an actor in the relationship as a central facilitating mechanism that enabled caregivers to enact other communicative resilience processes within their relationship. Resilience processes were enacted through shifting blame to dementia, accommodating dementia, and relying on memories. Caregivers experienced resilience through personal growth, enhanced relational closeness, and ambivalent resilience. We discuss implications for dementia caregiver resilience and forward facilitating mechanisms as an extension of communication resilience theorizing. [ABSTRACT FROM AUTHOR]

Background: Persons living with dementia and informal caregivers are at a higher risk for malnutrition. Most caregivers are not experts at identifying nutritional complications of dementia. Therefore, we aimed to identify nutrition knowledge and challenges related to feeding and caring for persons with dementia to develop a meaningful intervention. Methods: A mixed‐methods approach was used. Eight focus groups were conducted with caregivers of persons living with dementia (n = 28) and healthcare professionals (n = 23). Data was analysed using NVivo software. A questionnaire was administered to identify nutritional challenges. A modified food frequency questionnaire assessed food patterns of caregivers and persons with dementia. Results were compared to Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) dietary guidelines. Data were analysed using SPSS software. Results: Four major themes emerged: forgetting to eat, developing food aversions, strong preferences for sweets and weight changes. Findings revealed common strategies used to improve nutrition intake included cueing, supplements and quiet eating environment. Caregivers were impacted by stress leading to poorer food choices and exhaustion. Recommendations for a caregiver program made by participants included education, resources and support. Findings from the food frequencies questionnaire survey showed most participants had a lower dietary diversity compared to the MIND diet guidelines. Conclusions: With both groups being more prone to malnutrition, this research shows that participants were less likely to obtain adequate nutrition for brain health. Additionally, caregivers are dealing with nutrition issues themselves and their person living with dementia. The findings support the need for registered dietitians to provide tailored nutrition interventions for these families. Highlights: Caregivers for individuals living with dementia are stressed and exhausted leading to poorer food choices and low diet quality.Most persons living with dementia and their caregivers fell short on food choices in the Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet recommendations.Caregivers want a program that includes support, resources, and nutrition education. [ABSTRACT FROM AUTHOR]

Poetic inquiry as a form of arts-based research can penetrate the complexity, ambiguity, and multidimensional nature of representing participant emotions. This methodological approach allows researchers to explore the sensitive intersection of competing emotions without flattening the layered and often conflicting experience of participants' embodied experiences. In this article, we share participant-voiced poems generated from interviews with family caregivers of Alzheimer's patients and invite readers to sit with how these poems transcend mere descriptions and instead offer an emotive experience that defies words alone. [ABSTRACT FROM AUTHOR]

Neurodegenerative disorder refers to malfunctioning of neurons their degradation leading to death of neurons. Among various neurodegenerative disorders APHD (Alzheimer's, Parkinson's, and Huntington's Disease) are particularly concerning due to their progressive and debilitating nature. The therapeutic agent used for treatment and management of APHD often show unsatisfactory clinical outcome owing to poor solubility and limited permeability across blood brain barrier (BBB). The nose-to brain delivery can overcome this BBB challenge as it can transport drug directly to brain though olfactory pathways bypassing BBB. Additionally, the nanotechnology has emerged as a cutting-edge methodology to address this issue and specifically mucoadhesive micro/nanoemulsion can improve the overall performance of the drug when administered intranasally. Beyond the therapy neurotechnology has emerged as are revolutionary AI-driven BCI (Brain computer interface) aimed to restore independence in patients with function loss due to neuron degeneration/death. A promising BCI Neuralink has been recently explored for clinical trials and results revealed that a quadriplegia bearing person with implanted Neuralink chip was able to perform few normal functions of daily routine such as playing online games, text messaging, reading, and learning foreign languages online through accessing the particular websites. This review will discuss the fundamental concepts of neurodegeneration, application of micro/nanoemulsion through intranasal route and integration of neurotechnology for the management and treatment of APHD. [ABSTRACT FROM AUTHOR]

ANRIL is known as a lncRNA that has many linear and circular isoforms and its polymorphisms are observed to be associated with the pathogenesis of many diseases including age-related diseases. Age-related diseases including atherosclerosis, ischemic heart disease, and Alzheimer's and Parkinson's disease are the most common cause of mortality in both developed and undeveloped countries and that is why a better understanding of their pathogenesis and underlying mechanisms is necessary for controlling their healthcare burden. In this review, we aim to gather the data of researches which have investigated the role of ANRIL in aging and its related diseases. The conclusions of this paper might give a new insight for decreasing the mortality rate of these diseases. [ABSTRACT FROM AUTHOR]

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]

Background: During the COVID-19 pandemic, patients with Alzheimer's disease and related dementias (ADRD) were especially vulnerable, and modes of medical care delivery shifted rapidly. This study assessed the impact of the pandemic on care for people with ADRD, examining the use of primary, emergency, and long-term care, as well as deaths due to COVID and to other causes. Methods: Among 4.2 million beneficiaries aged 66 and older with ADRD in traditional Medicare, monthly deaths and claims for routine care (doctors' office and telehealth visits), inpatient/emergency department (ED) visits, and long-term care facility use from March or June 2020 through December 2022 are compared to monthly rates predicted from January–December 2019 using OLS and logistic/negative binomial regression. Correlation analyses examine the association between excess deaths — due to COVID and non-COVID causes — and changes in care use in the beneficiary's state of residence. Results: Increased telehealth visits more than offset reduced office visits, with primary care visits increasing overall (by 9 percent from June 2020 onward relative to the predicted rate from 2019, p <.001). Emergency/inpatient visits declined (by 9 percent, p <.001) and long-term care facility use declined, remaining 14% below the 2019 trend from June 2020 onward (p <.001). Both COVID and non-COVID deaths rose, with 231,000 excess deaths (16% above the prediction from 2019), over 80 percent of which were attributable to COVID. Excess deaths were higher among women, non-White patients, those in rural and isolated zip codes, and those with higher social deprivation index scores. States with the largest increases in primary care visits had the lowest excess deaths (correlation -0.49). Conclusions: Older adults with ADRD had substantial deaths above pre-pandemic projections during the COVID-19 pandemic, 80 percent of which were attributed to COVID-19. Routine care increased overall due to a dramatic increase in telehealth visits, but this was uneven across states, and mortality rates were significantly lower in states with higher than pre-pandemic visits. [ABSTRACT FROM AUTHOR]

The accumulation of β‐amyloid in Alzheimer's disease greatly impacts neuronal health and synaptic function. To maintain network stability in the face of altered synaptic activity, neurons engage a feedback mechanism termed homeostatic scaling; however, this process is thought to be disrupted during disease progression. Previous proteomics studies have shown that one of the most highly regulated proteins in cell culture models of homeostatic scaling is the small secretory chaperone proSAAS. Our prior work has shown that proSAAS exhibits anti‐aggregant behavior against alpha‐synuclein and β‐amyloid fibrillation in vitro and is up‐regulated in cell models of proteostatic stress. However, the specific role that this protein might play in homeostatic scaling, and its anti‐aggregant role in Alzheimer's progression, is not clear. To learn more about the role of proSAAS in maintaining hippocampal proteostasis, we compared its expression in a primary neuron model of homeostatic scaling to other synaptic components using western blotting and qPCR, revealing that proSAAS protein responses to homeostatic up‐ and down‐regulation were significantly higher than those of two other synaptic vesicle components, 7B2 and carboxypeptidase E. However, proSAAS mRNA expression was static, suggesting translational control and/or altered protein degradation. ProSAAS was readily released upon depolarization of differentiated hippocampal cultures, supporting its synaptic localization. Immunohistochemical analysis demonstrated abundant proSAAS within the mossy fiber layer of the hippocampus in both wild‐type and 5xFAD mice; in the latter, proSAAS was also concentrated around amyloid plaques. Importantly, overexpression of proSAAS in the CA1 region via stereotaxic injection of proSAAS‐encoding AAV2/1 significantly decreased amyloid plaque burden in 5xFAD mice. We hypothesize that dynamic changes in proSAAS expression play a critical role in hippocampal proteostatic processes, both in the context of normal homeostatic plasticity and in the control of protein aggregation during Alzheimer's disease progression. [ABSTRACT FROM AUTHOR]

Women have a higher incidence of Alzheimer's disease (AD), even after adjusting for increased longevity. Thus, there is an urgent need to identify genes that underpin sex-associated risk of AD. PIN1 is a key regulator of the tau phosphorylation signaling pathway; however, potential differences in PIN1 expression, in males and females, are still unknown. We analyzed brain transcriptomic datasets focusing on sex differences in PIN1 mRNA levels in an aging and AD cohort, which revealed reduced PIN1 levels primarily within females. We validated this observation in an independent dataset (ROS/MAP), which also revealed that PIN1 is negatively correlated with multiregional neurofibrillary tangle density and global cognitive function in females only. Additional analysis revealed a decrease in PIN1 in subjects with mild cognitive impairment (MCI) compared with aged individuals, again driven predominantly by female subjects. Histochemical analysis of PIN1 in AD and control male and female neocortex revealed an overall decrease in axonal PIN1 protein levels in females. These findings emphasize the importance of considering sex differences in AD research. • Reduced PIN1 levels are driven by females in aging and Alzheimer's disease. • PIN1 is negatively correlated with neurofibrillary tangle density in females. • PIN1 levels are negatively correlated with global cognitive function in females. • PIN1 levels are decreased in subjects with mild cognitive impairment. [ABSTRACT FROM AUTHOR]

• Agitation in Alzheimer's disease is a common condition experienced by many of the 6.9 million older adults in America living with Alzheimer's for which an evidence-based care pathway exists. • Care teams in any setting can use Agitation in Alzheimer's screener for caregivers (AASCTM) to screen for agitation in one minute. • Detecting and appropriately treating agitation in Alzheimer's disease can improve quality of life for the individual with the condition and their caregiver. Agitation in Alzheimer's disease (AAD) is a troubling condition experienced by many of the 6.9 million people living with Alzheimer's disease in the United States. The Gerontological Society of America (GSA) initially published an evidence-based care pathway to treat this condition, Agitation in Alzheimer's Disease: A Decision Tree for Healthcare Providers, in 2022 and updated this resource in 2023 with the International Psychogeriatric Association (IPA) consensus definition of agitation. A new, research-informed screening tool launched in November 2023, the Agitation in Alzheimer's Screener for Caregivers (AASCTM), supports care teams in identifying individuals with AAD who can benefit from the evidence-based care outlined in the decision tree. This column features an interview with interprofessional dementia care experts from Emory Integrated Memory Care who share their insights into AAD, the significance of the condition, and how care teams can use the AASCTM and other strategies to detect AAD. By detecting AAD and implementing person-centered care to address the condition, care teams can improve quality of life for the individual with the condition and their caregiver. [ABSTRACT FROM AUTHOR]

Alzheimer's Disease, a progressive brain disorder that impairs memory, thinking, and behavior, has started to benefit from advancements in deep learning. However, the application of deep learning in medicine faces the challenge of limited data resources for training models. Transfer learning offers a solution by leveraging pre-trained models from similar tasks, reducing the data and computational requirements to achieve high performance. Additionally, data augmentation techniques, such as rotation and scaling, help increase the dataset size. In this study, we worked with magnetic resonance imaging (MRI) datasets and applied various pre-processing and augmentation techniques including include intensity normalization, affine registration, skull stripping, entropy-based slicing, flipping, zooming, shifting, and rotating to clean and expand the dataset. We applied transfer learning to high-performing pre-trained models—ResNet-50, DenseNet-201, Xception, EfficientNetB0, and Inception V3, originally trained on ImageNet. We fine-tuned these models using the feature extraction technique on augmented data. Furthermore, we implemented ensemble learning techniques, such as stacking and boosting, to enhance the final prediction performance. The novel methodology we applied achieved high precision (95%), recall (94%), F1 score (95%), and accuracy (95%) for Alzheimer's disease detection. Overall, this study establishes a robust framework for applying machine learning to diagnose Alzheimer's using MRI scans. The combination of transfer learning, via pre-trained neural networks fine-tuned on a processed and augmented dataset, with ensemble learning, has proven highly effective, marking a significant advancement in medical diagnostics. [ABSTRACT FROM AUTHOR]

Abstract Background People’s wider culture plays a vital role in both dementia care and policy. This study aims to explore the cultural practice and policy influence around caring for People Living with Dementia (PLWD) in Nepal. Methods An exploratory qualitative study was designed to investigate dementia care in Nepal. The study comprised four in-depth interviews and four focus group discussions with 29 participants, including family members, health care professionals, and other stakeholders. Data were analysed using thematic analysis. Result Four major themes (each with several sub-themes) were identified: (1) Cultural practice in dementia care; (2) Impact of policy on the dementia care; (3) Service provision; and (4) Education and training. Conclusion There is a need for community-based awareness raising on dementia and its care, to sensitise all relevant stakeholders to meet the needs of PLWD. In addition, capacity building of health workforce is needed to enhance their knowledge of and skills in providing culturally appropriate dementia care.

Abstract Background Middle age is increasingly acknowledged as a critical window for prevention of Alzheimer’s disease and related dementia (ADRD) since research has shown that AD develops in the course of 20–30 years (1) but we know very little about middle-aged individuals’ perspectives on ADRD. Knowledge gaps are particularly large for Latinas living in regions typically underrepresented in ADRD research, such as rural and/or agricultural regions. This is important given that over the next 40 years Latinos are projected to have the largest increase in ADRD cases in the U.S. Therefore, this study aims to assess knowledge, perceptions, and feelings associated with ADRD among a sample of middle-age, Spanish-speaking Latina women. Method Using qualitative methods involving semi-structured interviews, we examined knowledge, perceptions, and feelings associated with ADRD among a subsample of the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) study. Participants are Latina women residing in an underserved agricultural community entering mid-life (mean = 46.5 years old). Interviews were conducted with 20 women and data was analyzed with inductive thematic content analysis. Results We identified themes regarding perceptions, knowledge, and feelings. First, participants perceive ADRD as involving (1) Loss of memory, (2) Getting lost; (3) Losing the person they once were. With regard to knowledge about ADRD, participants reported: (1) Some knowledge about protective and risk factors for ADRD, (2) No awareness of the links between cardiovascular risk factors and ADRD; (3) A desire to learn prevention methods alongside signs and symptoms of ADRD. Themes related to feelings about ADRD were: (1) Fear of developing ADRD and not being aware of reality or who they are; (2) Worry about losing relationships with loved ones and caretaking if diagnosed with ADRD; (3) Sadness about forgetting one’s family and depending on others if diagnosed with ADRD. Conclusion The knowledge gaps and negative feelings associated with ADRD highlighted in this study underscore the need for ADRD interventions to include CVD prevention, particularly for mid-life Latino populations residing in rural regions.

Abstract Background During the COVID-19 pandemic, patients with Alzheimer’s disease and related dementias (ADRD) were especially vulnerable, and modes of medical care delivery shifted rapidly. This study assessed the impact of the pandemic on care for people with ADRD, examining the use of primary, emergency, and long-term care, as well as deaths due to COVID and to other causes. Methods Among 4.2 million beneficiaries aged 66 and older with ADRD in traditional Medicare, monthly deaths and claims for routine care (doctors’ office and telehealth visits), inpatient/emergency department (ED) visits, and long-term care facility use from March or June 2020 through December 2022 are compared to monthly rates predicted from January–December 2019 using OLS and logistic/negative binomial regression. Correlation analyses examine the association between excess deaths — due to COVID and non-COVID causes — and changes in care use in the beneficiary’s state of residence. Results Increased telehealth visits more than offset reduced office visits, with primary care visits increasing overall (by 9 percent from June 2020 onward relative to the predicted rate from 2019, p

BACKGROUND: Mounting evidence is revealing disparities in cognitive function and heightened dementia risk among refugees, yet research in this area remains scant. Despite bearing most of the worlds refugee burden, limited-resource countries like Jordan are facing challenges when dealing with refugee health. There is a lack of research on the attitudes toward dementia and the cognitive healthcare gaps among refugees in Jordan. METHODS: 32 older (≥ 55 years) Syrian refugees resettled in Jordan were recruited through a local community-based organization and interviewed in four focus groups (2 female and 2 male groups). Interviews were transcribed and translated, then coded using inductive thematic analysis. RESULTS: Mean age of the sample was 60.1 years and 53.1% were female. Only 34.4% rated their memory as good or excellent. Themes were organized using the socioecological model: 1) At the individual level, participants believed high levels of stress, including low socioeconomic status, poor health, and traumatic history from their refugee experience increased their dementia risk. 2) Interpersonally, there is a fear of dementia due to the possible impact and burden on loved ones, particularly with the stigma surrounding dementia. 3) At the community level, participants noted that resettlement in Jordan - with a shared language, religion, and culture - offered protective effects due to facilitated access to social connection, information, and mental health self-care. 4) At the institution and policy level, participants believed older refugees faced restrictive policies for economic aid, healthcare, and employment, presenting a significant barrier to healthy aging. CONCLUSIONS: Findings from this study are the first to examine the attitudes of Syrian refugees in Jordan toward dementia and cognitive aging. These results could provide essential data inclusive of refugees as Jordan develops its National Dementia Plan. Investing in dementia awareness interventions and age-friendly neighborhoods may benefit aging refugees in limited-resources settings.

BACKGROUND: Myostatin, a cytokine produced by skeletal muscle, may influence Alzheimers disease (AD) pathogenesis, but sparse evidence exists in humans. We assessed the association between circulating levels of myostatin at Year 1 and plasma levels of β-amyloid 42/40 at Year 2, a marker of AD pathology, in a biracial cohort of older adults. METHODS: We studied 403 community-dwelling older adults enrolled in the Health, Aging and Body Composition Study from Memphis, Tennessee, and Pittsburgh, PA. Mean age was 73.8 ± 3 years; 54% were female; and 52% were Black. Serum myostatin levels were measured at Year 1, plasma β-amyloid 42/40 levels in Year 2 (higher ratio indicating lower amyloid load). Multivariable linear regression analyses tested the association of serum myostatin with plasma levels of β-amyloid 42/40 adjusted for computed-tomography-derived thigh muscle cross-sectional area, demographics, APOe4 allele, and risk factors for dementia. We tested for 2-way.interactions between myostatin and race or sex; results were stratified by race and sex. RESULTS: In multivariable models, myostatin was positively associated with plasma levels of β-amyloid 42/40 (standardized regression coefficient: 0.145, p = .004). Results were significant for white men and women (0.279, p = .009, and 0.221, p = .035, respectively) but not for Black men or women; interactions by race and gender were not statistically significant. CONCLUSIONS: Higher serum myostatin was associated with lower amyloid burden, independently of APOe4 alleles, muscle area and other established risk factors for dementia. The role of myostatin in AD pathogenesis and the influence of race should be further investigated.

Objectives: Many single nucleotide polymorphisms affect the incidence of Alzheimer’s disease (AD). This investigation aimed to consider the frequency of the C677T single nucleotide polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in Alzheimer’s patients. Materials and Methods: This study was conducted in two groups of control (n = 80) and patient (n = 80) with a ratio of 1: 1 male to female. Amplification-refractory mutation system-Polymerase Chain Reaction (ARMS-PCR) method was used to study mutations and ELISA was used to measure homocysteine and the chemiluminescence method was used to measure cholesterol, vitamin B12 and folate. Results: Based on the results of the PCR test of the MTHFR gene, the incidence rate of mutation in the healthy allele was 44.6% and in the mutant allele was 27.9% of the total study population. Conclusion: In this study, it was discovered that an increase in cholesterol levels is related with an increased risk of developing the disease, but more studies are needed to confirm this. It should also be noted that this increase is not related to the MTHFR gene polymorphism at the C677T position.

Abstract Background Dementia is an important public health and geriatric concern for sub-Saharan African countries, including Ghana. Evidence shows that persons living with dementia are often supported and cared for by family caregivers in the community. In the execution of these services to the persons living with dementia, family caregivers are overwhelmed and experience heightened stress that results in serious repercussions. Therefore, the aim of this study was to explore family caregivers’ experiences on coping in dementia care in Ghana. Methods Adopting a descriptive phenomenological design, individual face-to-face interviews were conducted among thirty unpaid family caregivers of persons living with dementia in Ghana. Semi-structured interview guides were used. The data analysis process followed Clarke and Braun’s framework analysis. Results Six themes were generated from the textual data. These themes were captioned as: (1) empathy and perspective-taking; (2) family support and cohesion; (3) coaxing and pampering of persons living with dementia; (4) humour and positive communication; (5) spiritual support; and (6) ethical/moral consideration in dementia caregiving. Conclusion We conclude that unpaid family caregivers of persons living with dementia in Ghana adopt varied strategies to cope with the strains of caregiving. Healthcare facilities that provide services to persons living with dementia could incorporate caregiver preparatory training or education for family caregivers. This training should focus on briefing family caregivers about the potential strains that they are likely to encounter. Also, the training could focus on equipping family caregivers with the knowledge and skills to effectively communicate and care for the persons living with dementia using person-centered approaches. Key stakeholders such as the Ghana Health Service and Alzheimer’s Ghana must raise awareness about the dangers of caregivers’ violation of the autonomy and freedom of persons living with dementia as they navigate through the challenges of caregiving. Lastly, faith-based institutions need to be considered as key stakeholders in dementia interventions since they could play a critical role.

Abstract Background Alzheimer’s disease is a neurodegenerative age-related disease that primarily affects the elderly population leading to progressive memory impairments and neural deficits. It is counted as a major cause of geriatric dependency and disability. The pathogenesis of Alzheimer’s disease incidence is complex and involves various hypotheses, including the cholinergic hypothesis, deposition of β-amyloid plaques, neuroinflammation, oxidative stress, and apoptosis. Conventional treatments such as donepezil aim to delay the symptoms but do not affect the progression of the disease and may cause serious side effects like hepatoxicity. The use of natural candidates for Alzheimer’s disease treatment has drawn the attention of many researchers as it offers a multitargeted approach. Methods This current study investigates the metabolic profiles of total defatted methanolic extract of Vitex pubescens bark and its polar fractions, viz. ethyl acetate and n-butanol, using ultra-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight tandem mass spectrometry(UPLC-ESI-QTOF/MS/MS) technique as well as evaluate the antioxidant using free radical scavenging assays, viz. DPPH and ABTS assays and in-vitro acetylcholinesterase inhibitory activities using Ellman’s microplate assay. Results Metabolic profiling revealed a total of 71, 43, and 55 metabolites tentatively identified in the defatted methanolic extract, ethyl acetate, and n-butanol fractions, respectively. Phenolic acids were the most abundant class, viz. benzoic acids, and acyl quinic acid derivatives followed by flavonoids exemplified mainly by luteolin-C-glycosides and apigenin-C-glycosides. Quantification of the total phenolic and flavonoid contents in the total defatted methanolic extract confirmed its enrichment with phenolics and flavonoids equivalent to 138.61 ± 9.39 µg gallic acid/mg extract and 119.63 ± 4.62 µg rutin/mg extract, respectively. Moreover, the total defatted methanolic extract exhibited promising antioxidant activity confirmed through DPPH and ABTS assays with a 50% inhibitory concentration (IC50) value equivalent to 52.79 ± 2.16 µg/mL and 10.02 ± µg/mL, respectively. The inhibitory activity of acetylcholine esterase (AchE) was assessed using in-vitro Ellman’s colorimetric assay, the total defatted methanolic extract, ethyl acetate, and n-butanol fractions exhibited IC50 values of 52.9, 15.1 and 108.8 µg/mL that they proved the significant inhibition of AchE activity. Conclusion The results obtained herein unraveled the potential use of the total methanolic extract of Vitex pubescens bark and its polar fractions as natural candidates for controlling Alzheimer’s disease progression.

Abstract Background Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions. Methods In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-Seq datasets using both within-region and pan-regional frameworks. Results We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals. These analyses also highlight regional differences in the extent of sex-differential gene expression. We observe an increase in specific neuronal transcripts in male brains and an increase in immune and glial function-related transcripts in female brains. Integration with single-nucleus data suggests this corresponds to sex differences in cellular states rather than cell abundance. Integration with case–control gene expression studies suggests a female molecular predisposition towards Alzheimer’s disease, a female-biased disease. Autism, a male-biased diagnosis, does not exhibit a male predisposition pattern in our analysis. Conclusion Overall, these analyses highlight mechanisms by which sex differences may interact with sex-biased conditions in the brain. Furthermore, we provide region-specific analyses of sex differences in brain gene expression to enable additional studies at the interface of gene expression and diagnostic differences. Graphical Abstract

Abstract Background Evidence links lifestyle factors with Alzheimer’s disease (AD). We report the first randomized, controlled clinical trial to determine if intensive lifestyle changes may beneficially affect the progression of mild cognitive impairment (MCI) or early dementia due to AD. Methods A 1:1 multicenter randomized controlled phase 2 trial, ages 45-90 with MCI or early dementia due to AD and a Montreal Cognitive Assessment (MoCA) score of 18 or higher. The primary outcome measures were changes in cognition and function tests: Clinical Global Impression of Change (CGIC), Alzheimer’s Disease Assessment Scale (ADAS-Cog), Clinical Dementia Rating–Sum of Boxes (CDR-SB), and Clinical Dementia Rating Global (CDR-G) after 20 weeks of an intensive multidomain lifestyle intervention compared to a wait-list usual care control group. ADAS-Cog, CDR-SB, and CDR-Global scales were compared using a Mann-Whitney-Wilcoxon rank-sum test, and CGIC was compared using Fisher’s exact test. Secondary outcomes included plasma Aβ42/40 ratio, other biomarkers, and correlating lifestyle with the degree of change in these measures. Results Fifty-one AD patients enrolled, mean age 73.5. No significant differences in any measures at baseline. Only two patients withdrew. All patients had plasma Aβ42/40 ratios

Abstract Background Nearly two-thirds of family caregivers of persons living with Alzheimer’s disease or related dementias (AD/ADRD) provide complex care, including medical care. Family caregivers typically receive little to no training on how to provide this care. Furthermore, family caregivers simultaneously grapple with the presence of behavioral and psychological symptoms of dementia (BPSD), diminished communication abilities, and comorbidities such as diabetes. We developed Learning Skills Together (LST), a 6-week digitally delivered psychoeducational program, to facilitate family caregiver abilities to administer complex care tasks. The goal of the present study is to test the efficacy of LST and to reduce adverse outcomes associated with caregiving, such as depressive symptomology and negative appraisal of BPSD. Methods To test the efficacy of LST, we will conduct a two-arm single-site randomized controlled trial (RCT) with N = 200 family caregivers of persons living with AD/ADRD. Eligible family caregivers will be randomly assigned to participate in either the LST intervention or a structurally equivalent control condition focused on healthy living. All family caregivers will complete four surveys, including a baseline survey administered prior to randomization, a post-intervention survey, and a 3- and 6-month follow-up survey to assess change in study outcomes. Between-group comparisons of each outcome will be evaluated using generalized estimating equation models. Mediation analyses will assess family caregiver self-efficacy as the intervention’s mechanism of change in depressive symptomology and BPSD. We will also examine caregiver race, ethnicity, and gender as effect modifiers of the intervention. Discussion LST findings will inform the field of AD/ADRD and caregiving regarding optimally supporting family caregivers in managing complex care tasks. If efficacious, the LST intervention will support family caregivers in preserving their own mental health while providing complex care. Trial registration Clinical Trials.gov NCT05846984 . This study was registered on May 6, 2023.

Background: The VALCODIS (Valencian Cognitive Diseases Study) cohort was designed and studied at the Hospital Universitari i Politècnic La Fe (Valencia, Spain) for the research of cognitive diseases, especially in the search for new biomarkers of Alzheimer's disease (AD). Methods: Participants in the VALCODIS cohort had cerebrospinal fluid (CSF) and blood samples, neuroimaging, and neuropsychological tests. The ApoE genotype was evaluated to identify its relationship with CSF biomarkers and neuropsychological tests in AD and non-AD participants. Results: A total of 1249 participants were included. They were mainly AD patients (n = 547) but also patients with other dementias (frontotemporal lobar dementia (n = 61), Lewy body dementia without AD CSF signature (n = 10), vascular dementia (n = 24) and other specific causes of cognitive impairment (n = 442), and patients with subjective memory complaints (n = 165)). In the ApoE genotype evaluation, significant differences were found for Aβ42 levels between genotypes in both AD and non-AD patients, as well as a negative correlation between tau values and a cognitive test in non-carriers and ε4 heterozygous. Conclusions: The VALCODIS cohort provides biologically diagnosed patients with demographical, clinical and biochemical data, and biological samples for further studies on early AD diagnosis. Also, the ApoE genotype evaluation showed correlations between CSF biomarkers and neuropsychological tests. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMethodResultsConclusionThis study aimed to evaluate the effects of a multicomponent psychotherapy programme for people with mild Alzheimer’s dementia (AD) and their caregivers on depression and related neuropsychiatric symptoms.The cognitive behavioural therapy (CBT)-based treatment consisted of 25 weekly sessions, including behavioural activation, behaviour management, interventions for the caregiver, reminiscence, couples counselling, and cognitive restructuring. 41 participants and their caregivers were randomised to either the CBT or the control group, which received treatment-as-usual (TAU). Follow-ups took place at 6 and 12 months posttreatment. The primary outcome was depression in the patient with AD. The secondary outcomes were apathy, other neuropsychiatric symptoms, functional abilities, quality of life, and quality of the relationship with the caregiver.Linear mixed models revealed a statistically significant superiority of CBT regarding clinician-rated depression at the 12-month follow-up with large effect sizes (within-subject d = 1.22, between-subject d = 1.00). Effect sizes were only moderate for self-rated depression and small for informant-rated depression. There was also a significant advantage for CBT regarding clinician-rated apathy, relationship quality, and informant-rated quality of life (QoL) but not for the other neuropsychiatric symptoms or self-rated QoL.The results are very encouraging and support an adequately powered multicentre study.Trial registration: ClinicalTrials.gov NCT01273272. Date of registration: 3 Jan 2011. [ABSTRACT FROM AUTHOR]

Estrogen exposure during menstrual years has been associated with late-life neuroprotection. We explored the presence of an age-sensitive menarche window for cognition in old age and the impact of socioeconomic status and education. We compared neuropsychological performance of 1082 older women [MeanAGE = 72.69 (5.48)] with menarche in childhood, early-, mid-, and late-adolescence and dementia prevalence, severity, and type, including the effects of education and socioeconomic status. Adjusting for covariates, menarche at 11–14 years of age was associated with better memory, executive and global cognitive functioning in old age, and stronger positive effects of education and socioeconomic status on cognition than those with menarche at 15–17 years. We found a critical age window for the neuroprotective effects of estrogens during early adolescence, putting women with later menarche at higher risk for cognitive decline. Effects of socioeconomic status and education in adulthood should be a focus of future research. [ABSTRACT FROM AUTHOR]

Objectives: How dementia affects lesbian, gay, bisexual, trans, queer people or those with other minoritised sexual/gender identities (LGBTQ+) is not well understood. Furthermore, existing research often excludes the voices of LGBTQ+ people living with dementia and focuses instead on their care partners. This study addresses this evidence gap by drawing on the ESRC/NIHR funded DETERMIND cohort, consisting of 940 newly diagnosed people with dementia, to explore the peri‐diagnostic experiences of people living with dementia who identify as LGBTQ+. Methods: We recruited five people (who identified as lesbian, gay or bisexual [LGB]) and completed semi‐structured interviews with them and their partner caregivers (n = 3) discussing their experiences of (1) engaging with dementia health care services, (2) receiving a dementia diagnosis, and (3) the support they were offered after diagnosis. Interviews were shaped by the Candidacy Framework, a theoretical model for understanding accessibility of health services, and an inductive thematic analysis was employed to develop common themes. Findings: Participants did not routinely disclose their LGBTQ+ identities to health service professionals, despite feeling this was an essential aspect of who they are. They relied on their resilience of overcoming previous experiences of lifetime discrimination to navigate complicated dementia care systems. The importance of 'chosen families' as informal support networks for LGBTQ+ people living with dementia was highlighted, particularly given the lack of formal care services they felt comfortable accessing. All participants were concerned about their future care needs and whether they would receive home‐based or community‐based support that respected their LGBTQ+ identities. Conclusions: This study adds to the limited evidence base that can be used to inform future research, policy and practice seeking to address inequalities across the dementia care pathway. We only interviewed people who identified as LGB so generalizability to the whole LGBTQ+ population is limited, however our data suggest dementia health care professionals should encourage and support disclosures of LGBTQ+ identities so that inclusive care and support planning can be provided to LGBTQ+ people at every stage of dementia. [ABSTRACT FROM AUTHOR]

Inconsistencies between Alzheimer's disease (AD) clinical trials and prevention studies using omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation can be largely attributed to differences in age, environmental factors, genetic factors, baseline n-3/n-6 intake, and disease stage. Changes in docosahexaenoic acid (DHA) brain uptake throughout AD progression are influenced by the apolipoprotein E ε4 (APOE4) allele and lifestyle factors, such as DHA intake or exercise, and can be monitored by DHA positron emission tomography (PET) brain imaging. APOE4 carriers are more susceptible to blood–brain barrier dysfunction, oxidative stress, neuroinflammation, and fatty acid oxidation with aging compared to noncarriers. We hypothesize that increasing n-3 PUFA intake provides APOE4 carriers with the highest potential for protection against AD dementia when implemented early in life, many years before the onset of cognitive decline. During the AD dementia phase, alternative strategies targeting neuroinflammation and PUFA metabolism may offer potential benefits. Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA), have important roles in human nutrition and brain health by promoting neuronal functions, maintaining inflammatory homeostasis, and providing structural integrity. As Alzheimer's disease (AD) pathology progresses, DHA metabolism in the brain becomes dysregulated, the timing and extent of which may be influenced by the apolipoprotein E ε4 (APOE4) allele. Here, we discuss how maintaining adequate DHA intake early in life may slow the progression to AD dementia in cognitively normal individuals with APOE4 , how recent advances in DHA brain imaging could offer insights leading to more personalized preventive strategies, and how alternative strategies targeting PUFA metabolism pathways may be more effective in mitigating disease progression in patients with existing AD dementia. [ABSTRACT FROM AUTHOR]

Dementia is a disease most prevalent in the older adult population. The cognitive symptoms of dementia include impairments in problem-solving, memory, and language. Some patients experience noncognitive symptoms in addition to the cognitive symptoms of dementia. These noncognitive symptoms are called behavioral and psychological symptoms of dementia or BPSD. The primary objective of our study was to examine the therapeutic options, guidelines, and clinical considerations for the management of BPSD. The existing literature about BPSD was reviewed with searches in PubMed, MEDLINE, and online search platforms. Dysregulation of neurotransmission involving acetylcholine, dopamine, and serotonin has been shown to cause behavioral and psychological symptoms of Alzheimer's disease. BPSD can include hallucinations, agitation, delusions, anxiety, apathy, abnormal body movements, irritability, depression, disinhibition, and sleep or appetite changes. Pharmacologic therapies used in the treatment of BPSD include antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Treatment can be tailored to the specific noncognitive symptoms that are experienced. The use of these agents may be limited based on recommendations from the Beers Criteria®, STOPP criteria, treatment guidelines, and FDA warnings. [ABSTRACT FROM AUTHOR]

Criticality, observed during second-order phase transitions, is an emergent phenomenon. The brain operates near criticality where complex systems exhibit high correlations. As a system approaches criticality, it develops "domain"-like regions with competing phases and increased spatio-temporal correlations that diverge. The dynamics of these domains depend on the system's proximity to criticality. This study explores the differences in the proximity to criticality of Alzheimer's-afflicted and cognitively normal brains through the use of a spin–lattice model derived from resting-state fMRI data and investigates the type of criticality found in the human brain - whether it is of the Ising class or something more complex. The temporal correlations in both groups display a stretched exponential nature, indicating closer alignment with the criticality of the spin-glass class rather than the Ising class. Longer relaxation times observed in cognitively normal subjects suggest increased proximity to the phase boundary. The weak distinction observed in the spatial characteristics related to proximity to criticality might once more point to a spin-glass scenario, necessitating nuanced order parameters to distinguish between phase-ordering in Alzheimer's and cognitively normal brains. [ABSTRACT FROM AUTHOR]

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AbstractObjective: Subjective cognitive decline (SCD) is an important part of the aging process and may be a sign of neurodegenerative disease. Current measures of SCD are subject to the limits of retrospective recall of symptoms over a long span of time, which might be addressed by using ecological momentary assessment (EMA) methods. However, there are no currently available measures of SCD validated for use in EMA. Thus, our goal was to develop and pilot test the mobile Everyday Cognition Scale (mECog). Method: 31 community-dwelling older adults completed in lab measures of cognition and mental health symptoms, followed by daily mECog ratings on a smart phone for 28 days. Results: Most participants completed at least 75% of mECog assessments (n = 27, 87%), and the average number of assessments completed was 22. Further, respondents rated the mobile assessment platform and measures as easy to use and non-interfering with daily life. Test-retest reliability of mECog scores was very strong (RKRN = .99), and within-person reliability was moderate (RCN = .41). mECog scores demonstrated strong positive associations with scores from the original ECog (ρ = .62–69, p < .001) and short form ECog (ρ = .63-.69, p < .001) and non-significant associations with demographics (ρ = –0.25–.04, p = .21-.94) and mental health symptoms (ρ = –0.06-.34, p = .08–.99). mECog scores also exhibited small-to-moderate negative correlations with objective cognitive test scores, though these relationships did not reach statistical significance (ρ = –0.32 to −0.22, p = .10–.27). Conclusions: Results suggest that mobile assessment of SCD via the mECog is feasible and acceptable. Further, mECog scores demonstrated good psychometric properties, including evidence of strong reliability, convergent validity, and divergent validity. [ABSTRACT FROM AUTHOR]