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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.

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]

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]

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]

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]

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]

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]

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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]

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]

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 FROM AUTHOR]

There is a paucity of literature demonstrating the efficacy of psychoanalytic psychotherapy for patients with Alzheimer's or other dementias. This paper examines the challenges and richness of this kind of treatment for both patients and analyst through the use of a narrative case study. [ABSTRACT FROM AUTHOR]

Dementia is one of the 10 causes of mortality in the world, which tends to increase with the aging of the population. Alzheimer's disease is characterized by the degeneration of neurons in the hippocampus and cerebral cortex, areas responsible for processing episodic memory and cognitive functions such as learning and attention. Recent epidemiological studies have shown that India, where curcumin is frequently used in the production of meals, has shown a significantly lower incidence of Alzheimer's disease cases when compared to the United States. Research studies and analyzes carried out in an animal model with induction of Alzheimer's disease were used, and the administration of curcumin as a form of prevention and control of signs and symptoms of the disease within the last 10 years. In the electronic search, 94 studies were obtained, of which only 16 were included for analysis because they met the inclusion criteria, 15 clinical trials carried out in an animal model and 1 clinical trial carried out in humans. All clinical trial studies analyzed in this review showed positive effects on cognitive, behavioral and inflammatory parameters of curcumin administration in animal models induced Alzheimer’s disease. Curcumin has also been shown to reduce levels of inflammatory markers in brain tissue and even stimulate antiinflammatory and antioxidant proteins by regulating the process of neuroinflammation. Conclusion: Taken together, the studies showed that curcumin upregulates insulinsignaling proteins in the brain, reduces hyperinsulinemia, and improves glucose levels in rats with Alzheimer’s disease. Results also showed that curcumin administration increased anti-inflammatory proteins with positive effects on cognition and inflammation. [ABSTRACT FROM AUTHOR]

The Scottish Intercollegiate Guidelines Network (SIGN) have recently published their guideline SIGN168 on 'Assessment, Diagnosis, Care, and Support for People with Dementia and their Carers'. The guideline makes evidence-based recommendations for best practice in the assessment, care and support of adults living with dementia. Topics featured in this guideline are limited to those prioritised by stakeholders, especially people with lived and living experience, and those not well covered under pre-existing guidance. We summarise the guideline recommendations related to identification and diagnosis of dementia, investigative procedures, postdiagnostic support living with dementia, including non-pharmacological approaches for distressed behaviours, using technology to support people with dementia, grief and dementia and changing needs of people with dementia. The guideline content is summarised as officially published, with additional commentary in the final section. [ABSTRACT FROM AUTHOR]

Objectives Using the concept of relational solidarity, we examine how autonomy, equality, dignity, and personhood are practiced in the care of people living with dementia at home in urban India. Methods Video interviews with 19 family carers and 25 health providers conducted in English, Hindi, and Kannada in Bengaluru between March and July 2022. Data were translated into English and thematically analyzed. Results Family carers and providers unanimously agreed that people with dementia should be respected and cared for. Concurrently, they perceived people with dementia as being "like a kid" and used the analogy of a parent–child relationship to understand their care responsibilities. This analogy informed how ethical principles such as personhood and equality were reframed in the relationships between family carers and people with dementia, as well as how carers and providers maintained the safety but undermined the autonomy of people with dementia through restricting their movements inside and outside the home. Discussion There can be relational solidarity in dementia care at home in urban India but also contradictions in the interpretations and applications of the ethical principles of autonomy, equality, dignity, and personhood. As such, a more organic, grassroots model of ethical practice is needed to frame care and provide material support to families in India. [ABSTRACT FROM AUTHOR]

African Americans experience higher incidence and prevalence of Alzheimer's disease (AD). Yet, they continue to be underrepresented in AD research, limiting the ability to generalize findings to the increasingly diverse US population. To reduce AD disparities, targeted efforts are needed to increase the representation of African Americans in AD research. This mini review identified evidence-based strategies that increased research participation among older African Americans. Four recruitment strategies emerged from eight published peer-reviewed studies that directly evaluated the effectiveness of strategies aimed at increasing the number of African American participants in Alzheimer's research. The strategies include community outreach and education, face-to-face discussions, remote access, and referral and partnership with local organizations. Across different locations, these strategies increased the number of African Americans enrolled into AD research, the number of people that signed up to donate their brains for AD research upon death, and the knowledge and perception of AD in the communities. Targeted efforts are effective in increasing AD research participation among older African Americans, especially when combined with approaches that emphasize transparency and mutual trust and involve the community as stakeholders in the research process. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Intraneuronal inclusions composed of tau protein are found in Alzheimer's disease (AD) and other tauopathies. Tau normally binds microtubules (MTs), and its disengagement from MTs and misfolding in AD is thought to result in MT abnormalities. We previously identified triazolopyrimidine‐containing MT‐stabilizing compounds that provided benefit in AD mouse models and herein describe the characterization and efficacy testing of an optimized candidate, CNDR‐51997. METHODS: CNDR‐51997 underwent pharmacokinetic, pharmacodynamic, safety pharmacology, and mouse tolerability testing. In addition, the compound was examined for efficacy in 5XFAD amyloid beta (Aβ) plaque mice and PS19 tauopathy mice. RESULTS: CNDR‐51997 significantly reduced Aβ plaques in 5XFAD mice and tau pathology in PS19 mice, with the latter also showing attenuated axonal dystrophy and gliosis. CNDR‐51997 was well tolerated at doses that exceeded efficacy doses, with a good safety pharmacology profile. DISCUSSION: CNDR‐51997 may be a candidate for advancement as a potential therapeutic agent for AD and/or other tauopathies. Highlights: There is evidence of microtubule alterations (MT) in Alzheimer's disease (AD) brain and in mouse models of AD pathology.Intermittent dosing with an optimized, brain‐penetrant MT‐stabilizing small‐molecule, CNDR‐51997, reduced both Aβ plaque and tau inclusion pathology in established mouse models of AD.CNDR‐51997 attenuated axonal dystrophy and gliosis in a tauopathy mouse model, with a strong trend toward reduced hippocampal neuron loss.CNDR‐51997 is well tolerated in mice at doses that are meaningfully greater than required for efficacy in AD mouse models, and the compound has a good safety pharmacology profile. [ABSTRACT FROM AUTHOR]

Neurological disorders refer to a variety of problems affecting the neurological system, which includes the brain, spinal cord, and nerves. Alzheimer's disease, Parkinson's disease, and epilepsy are all illnesses that can have an impact on cognition, movement, and feeling. Understanding their processes and therapies is critical to improve patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

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.

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

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.

BackgroundThe existing literature suggests that impaired olfaction may be an early marker for cognitive decline. Tracking the earliest stages of the progression to dementia is paramount, and yet the importance of olfactory ability throughout cognitive states and death remains unclear.MethodsDrawing data from the Rush Memory and Aging Project (N = 1 501; 74% female), olfactory ability was assessed using the Brief Smell Identification Test (range = 0-16), while cognitive states (unimpaired, mild cognitive impairment [MCI], and dementia) were determined using a 3-step neuropsychological diagnostic protocol at up to 15 annual occasions. Multistate survival models simultaneously estimated the association of olfactory ability on transitions through cognitive states and death, while multinomial regression models estimated cognitively unimpaired and total life expectancies.ResultsHigher olfactory scores were associated with a reduced risk of transitioning from unimpaired cognition to MCI (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.82-0.88) and from MCI to dementia (HR = 0.89, 95% CI = 0.86-0.93), indicating that 1-unit increase in olfactory scores was associated with an approximate 14% and 11% reduction in risk, respectively. Additionally, higher olfactory scores were associated with a greater likelihood of transitioning backward from MCI to unimpaired cognition (HR = 1.07, 95% CI = 1.02-1.12). Furthermore, higher baseline olfactory scores were associated with more years of longevity without cognitive impairment. However, olfaction was not associated with the transition to death when accounting for transitions through cognitive states.ConclusionsFindings suggest that higher olfactory identification scores are associated with a decreased risk of transitioning to impaired cognitive states and that associations between olfaction and mortality may occur primarily through the pathway of neurodegeneration.

Traumatic brain injury (TBI) can lead to neurodegenerative diseases such as Alzheimer's disease (AD) through mechanisms that remain incompletely characterized. Similar to AD, TBI models present with cellular metabolic alterations and modulated cleavage of amyloid precursor protein (APP). Specifically, AD and TBI tissues display increases in amyloid-β as well as its precursor, the APP C-terminal fragment of 99 a.a. (C99). Our recent data in cell models of AD indicate that C99, due to its affinity for cholesterol, induces the formation of transient lipid raft domains in the ER known as mitochondria-associated endoplasmic reticulum (ER) membranes ("MAM" domains). The formation of these domains recruits and activates specific lipid metabolic enzymes that regulate cellular cholesterol trafficking and sphingolipid turnover. Increased C99 levels in AD cell models promote MAM formation and significantly modulate cellular lipid homeostasis. Here, these phenotypes were recapitulated in the controlled cortical impact (CCI) model of TBI in adult mice. Specifically, the injured cortex and hippocampus displayed significant increases in C99 and MAM activity, as measured by phospholipid synthesis, sphingomyelinase activity and cholesterol turnover. In addition, our cell type-specific lipidomics analyses revealed significant changes in microglial lipid composition that are consistent with the observed alterations in MAM-resident enzymes. Altogether, we propose that alterations in the regulation of MAM and relevant lipid metabolic pathways could contribute to the epidemiological connection between TBI and AD.

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]

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]

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: Canine cognitive dysfunction (CCD) is considered the canine version of human Alzheimer's disease (AD). As with AD, CCD is a multifactorial and progressive neurodegenerative disorder for which effective treatment options are continuously being sought. Transcranial photobiomodulation (tPBMT), or transcranial laser therapy, has shown promise as a treatment for cognitive impairment in rodent AD investigations and several human AD clinical trials. Aim: The purpose of this prospective case series was to evaluate the effect of transcranial photobiomodulation (tPBMT) on cognitive scores when applied to senior dogs with CCD over a 60-day period. Methods: Five senior (>9-year-old) dogs with moderate (16-33) to severe (>33) cognitive scores were enrolled. Owners were instructed on the use of a Class IM laser device and administered a specific dose of laser energy transcranially to both sides of the patient's head, 3 times per week for one month and 2 times per week for a second month. No additional therapeutic measures aimed at enhancing cognitive ability were permitted during the 60-day evaluation time. Baseline cognitive scores were compared with scores obtained at 30-and 60-days post-treatment. Results: Cognitive scores showed improvement in 4/5 dogs at 30 days (27.6% reduction) and all dogs at 60 days (43.4% reduction). There were no adverse effects attributable to tPBMT. Conclusion: Results of our small case series suggest that tPBMT may improve cognitive scores in dogs with moderate to severe CCD by 30 days of application and the improvement is sustained at 60 days. Further studies are needed to ascertain optimal tPBMT protocols for CCD. [Open Vet J 2024; 14(5.000): 1167-1171]

Abstract Background Persons living with dementia (PLWD) may experience communication difficulties that impact their ability to process written and pictorial information. Patient-facing education may help promote discontinuation of potentially inappropriate medications for older adults without dementia, but it is unclear how to adapt this approach for PLWD. Our objective was to solicit feedback from PLWD and their care partners to gain insights into the design of PLWD-facing deprescribing intervention materials and PLWD-facing education material more broadly. Methods We conducted 3 successive focus groups with PLWD aged ≥ 50 (n = 12) and their care partners (n = 10) between December 2022 and February 2023. Focus groups were recorded and transcripts were analyzed for overarching themes. Results We identified 5 key themes: [1] Use images and language consistent with how PLWD perceive themselves; [2] Avoid content that might heighten fear or anxiety; [3] Use straightforward delivery with simple language and images; [4] Direct recipients to additional information; make the next step easy; and [5] Deliver material directly to the PLWD. Conclusion PLWD-facing educational material should be addressed directly to PLWD, using plain, non-threatening and accessible language with clean, straightforward formatting.

Abstract Background Dementia is often associated with functional impairments that limit the independence of persons living with dementia (PwD). As such, many PwD often require a higher level of support provided by persons referred to as caregivers. Such caregiving activities tend to strain and stress the caregiver. Nonetheless, Ghana lacks empirical evidence and understanding of the effects of caring for PwD on the lives of primary caregivers. To help narrow this knowledge gap, we explored the perspectives of primary caregivers about the impacts of caring for PwD in Ghana. Methods Using a descriptive phenomenological design, we conducted in-depth interviews with primary caregivers in the Ashanti region, Ghana. A semi-structured interview guide was used as the data collection instrument. The data analysis followed Collazi’s thematic analysis framework. All coding and categorization were done in NVivo-12. Results Five themes emerged from the analysis. These themes included (a) sacrifice of personal interests, and time commitments; (b) financial strain and negative impact on job; (c) feelings of stress and burnout; (d) experience of abuse and stigma; and (e) perceived blessing of caregiving. Conclusion The study’s findings resonate with existing literature, highlighting the consistent struggles faced by caregivers. Sacrificing personal interests, navigating financial strains, and grappling with stress and burnout emerged as pervasive themes. We conclude that despite the negative impacts of caring for PwD, caregivers perceived their role as associated with blessings, deriving positive meaning and fulfilment from their caregiving journey. This study underscores a need to build more compassionate communities in rural settings of Ghana.

Abstract Background Trans-differentiation of human-induced pluripotent stem cells into neurons via Ngn2-induction (hiPSC-N) has become an efficient system to quickly generate neurons a likely significant advance for disease modeling and in vitro assay development. Recent single-cell interrogation of Ngn2-induced neurons, however, has revealed some similarities to unexpected neuronal lineages. Similarly, a straightforward method to generate hiPSC-derived astrocytes (hiPSC-A) for the study of neuropsychiatric disorders has also been described. Results Here, we examine the homogeneity and similarity of hiPSC-N and hiPSC-A to their in vivo counterparts, the impact of different lengths of time post Ngn2 induction on hiPSC-N (15 or 21 days), and the impact of hiPSC-N/hiPSC-A co-culture. Leveraging the wealth of existing public single-cell RNA-seq (scRNA-seq) data in Ngn2-induced neurons and in vivo data from the developing brain, we provide perspectives on the lineage origins and maturation of hiPSC-N and hiPSC-A. While induction protocols in different labs produce consistent cell type profiles, both hiPSC-N and hiPSC-A show significant heterogeneity and similarity to multiple in vivo cell fates, and both more precisely approximate their in vivo counterparts when co-cultured. Gene expression data from the hiPSC-N show enrichment of genes linked to schizophrenia (SZ) and autism spectrum disorders (ASD) as has been previously shown for neural stem cells and neurons. These overrepresentations of disease genes are strongest in our system at early times (day 15) in Ngn2-induction/maturation of neurons, when we also observe the greatest similarity to early in vivo excitatory neurons. We have assembled this new scRNA-seq data along with the public data explored here as an integrated biologist-friendly web-resource for researchers seeking to understand this system more deeply: https://nemoanalytics.org/p?l=DasEtAlNGN2&g=NES . Conclusions While overall we support the use of the investigated cellular models for the study of neuropsychiatric disease, we also identify important limitations. We hope that this work will contribute to understanding and optimizing cellular modeling for complex brain disorders.

The scientific understanding of gratitude has grown in recent years. However, research on the role gratitude plays in the lives of family caregivers of persons with Alzheimer’s disease in the early or begnning stages is limited. Therefore, the aim of the current study was to gain a rich understanding of gratitude through the narratives of 27 family caregivers of persons with early-stage Alzheimer’s. Interpretative phenomenological analysis, a qualitative methodology, was used to identify the following themes: (1) A caregiver’s individual affinity towards having a grateful life orientation influences their unique caregiving experience; (2) Gratitude for a range of resources, including what the person with Alzheimer’s continues to contribute, makes a difference; (3) Gratitude for the efforts of other people, including how caregiving strengthened relationships, was present; and (4) Spirituality is a gratitude-related resource which may be expressed behaviorally to enhance well-being among caregivers. This study provides an in depth understanding of gratitude in this unique and growing population which can inform the development of clinical interventions for improving well-being. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder and a leading cause of dementia. Aging is a significant risk factor for AD, emphasizing the importance of early detection since symptoms cannot be reversed once the advanced stage is reached. Currently, there is no established method for early AD diagnosis. However, emerging evidence suggests that the microbiome has an impact on cognitive function. The gut microbiome and the brain communicate bidirectionally through the gut–brain axis, with systemic inflammation identified as a key connection that may contribute to AD. Gut dysbiosis is more prevalent in individuals with AD compared to their cognitively healthy counterparts, leading to increased gut permeability and subsequent systemic inflammation, potentially causing neuroinflammation. Detecting brain activity traditionally involves invasive and expensive methods, but electroencephalography (EEG) poses as a non-invasive alternative. EEG measures brain activity and multiple studies indicate distinct patterns in individuals with AD. Furthermore, EEG patterns in individuals with mild cognitive impairment differ from those in the advanced stage of AD, suggesting its potential as a method for early indication of AD. This review aims to consolidate existing knowledge on the microbiome and EEG as potential biomarkers for early-stage AD, highlighting the current state of research and suggesting avenues for further investigation. [ABSTRACT FROM AUTHOR]

Platelets have a fundamental role in mediating hemostasis and thrombosis. However, more recently, a new idea is making headway, highlighting the importance of platelets as significant actors in modulating immune and inflammatory responses. In particular, platelets have an important role in the development of vascular amyloid-b-peptide(ab) deposits, known to play a relevant role in Alzheimer's disease (AD) through accumulation and deposition within the frontal cortex and hippocampus in the brain. The involvement of platelets in the pathogenesis of AD opens up the highly attractive possibility of applying antiplatelet therapy for the treatment and/or prevention of AD, but conclusive results are scarce. Even less is known about the potential role of platelets in mild cognitive impairment (MCI). The aim to this brief review is to summarize current knowledge on this topic and to introduce the new perspectives on the possible role of platelet activation as therapeutic target both in AD and MCI. [ABSTRACT FROM AUTHOR]