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In a randomized trial, solanezumab, a humanized monoclonal antibody against soluble amyloid, did not slow cognitive decline over a period of 80 weeks in patients with mild Alzheimer’s disease and with PET or CSF biomarkers of amyloid-related disease.

Background Suicide among young people in Alaska Native (AN) communities was nearly unheard of through the establishment of statehood in 1959, but from 1960–1995, the suicide rate increased by approximately 500% during this period of rapid, imposed social transition. These disruptions increased conditions associated with suicide risk (e.g., substance use disorders, cultural disconnection), and challenged the community-level social safety net of youth protective factors. The purpose of this paper is to outline development and evaluation methodology for a comparative effectiveness trial of two virtual, culturally grounded, brief interventions to address suicide prevention among AN young people. The proposed study addresses significant gaps in culturally appropriate evidence-based programming to address suicide prevention among AN young people by comparing effectiveness of these two interventions. Findings from this study have potential to expand the range of accessible, critically important services to this population. Methods Our interventions will be targeted toward AN young people ages 14–24 who present with suicide attempt, ideation, or associated risk behaviors, including alcohol-related injury in the Yukon-Kuskokwim region or the Interior of Alaska. In this randomized controlled comparative effectiveness trial, 14–24-year-old AN individuals will receive either BeWeL (Because We Love You) which will comprise a 45-min virtual wisdom talk addressing family strengths and increasing protective factors ( n  = 185), or BeWeL + MISN (plus motivational interviewing about social networks), which will include an additional 15 min focused on discussion of the individual’s social networks ( n  = 185). Both interventions will have two follow-up visits at 2 and 6 weeks. We will evaluate changes in both intervention groups from the baseline survey at 3, 6, and 12 months on primary outcomes of suicide-intent risk, depression, anxiety, frequency of alcohol use, and alcohol consequences and compare effectiveness between the two interventions. In our secondary aim, we will evaluate changes in both groups from the baseline survey at 3, 6, and 12 months on individual and community protective factors, social networks, and awareness of connectedness and compare effectiveness between the two interventions. Discussion This project has the potential to expand the range and effectiveness of suicide prevention services for AN young people and will help meet the need in Alaska to link clinical behavioral health services to AN community-based networks, and to engage local cultural resources in aftercare for individuals at risk for suicide. Findings have potential to provide practical information to advance the field of suicide prevention and enhance protective factors and resiliency among this population. Trial registration ClinicalTrials.gov Identifier: NCT05360888; Registered December 22, 2022. https://clinicaltrials.gov/study/NCT05360888 .

With now over 50 million people worldwide with dementia (Prince et al., 2013), there are almost certainly well over 100 million people with cognitive concerns and many of these will attend their health professional keen to know what is going on. We need those without intensive training in this field to be more confident and correct in their diagnosis when such a concerned person turns up. Many simple diagnostic tests have been proposed and some assessed – these include the walk and talk (divided attention) test (those who stop when asked a question while walking may be cognitively impaired) (Lamoth et al., 2011), the clock drawing test (Brodaty and Moore, 1997), the “handbag” sign (those clutching their personal possessions are more likely to be cognitively impaired) and the “hippopotamus sign” (calling the rhinoceros, in those tests that include this, a hippopotamus). Simple screening tests have been extensively validated and are important to the clinician in formulating a diagnosis (Lorentz et al., 2002). The “head-turning” and the “attended with/alone” signs are frequently observed, and many clinicians assessing such individuals would be well aware of them and probably even unknowingly factor them into their diagnosis. In this issue, Pinar Soysal and colleagues (Soysal et al., 2017) have evaluated these signs and, in those older people attending with cognitive concerns, found they had quite good diagnostic value. They were not very specific but showed good sensitivity and negative predictive value. Indeed, at the recent Alzheimer's Association International Conference in London there were several posters evaluating “soft but simple” signs although not all performed as expected – one group found gait actually sped up in those with cognitive impairment that were asked a question.

Neurobiological changes in the hippocampus are a common consequence of aging. However, there are differences in the rate of decline and overall volume loss in people with no cognitive impairment compared to those with mild cognitive impairment (MCI) and Alzheimer's disease (AD). This systematic literature review was conducted to determine the relationship between hippocampal atrophy and changes in hippocampal volume in the non-cognitively impaired brain and those with MCI or AD. This systematic review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. The PubMed database was searched up to September 15, 2022, for longitudinal magnetic resonance imaging studies reporting hippocampal atrophy or volume change in cognitively normal aging individuals and patients with MCI and/or AD. Study selection was divided into two steps: (1) identification and retrieval of relevant studies; (2) screening the studies by (a) title/abstract and (b) full text. Two teams, each consisting of two independent reviewers, determined whether the publications met the inclusion criteria for the systematic review. An evidence table was populated with data extracted from eligible publications and inclusion in the final systematic review was confirmed. The systematic search identified 357 publications that were initially screened by title/abstract, of which, 115 publications were retrieved and reviewed by full text for eligibility. Seventeen publications met the eligibility criteria; however, during data extraction, two studies were determined to not meet the inclusion criteria and were excluded. The remaining 15 studies were included in the systematic review. Overall, the results of these studies demonstrated that the hippocampus and hippocampal subfields change over time, with both decreased hippocampal volume and increased rate of hippocampal atrophy observed. Hippocampal changes in AD were observed to be greater than hippocampal changes in MCI, and changes in MCI were observed to be greater than those in normal aging populations. Published literature suggests that the rate of hippocampal decline and extent of loss is on a continuum that begins in people without cognitive impairment and continues to MCI and AD, and that differences between no cognitive impairment, MCI, and AD are quantitative rather than qualitative.

The viral-inflammatory hypothesis of Alzheimer’s disease offers a new paradigm, yet interventions like antivirals and vaccination present a paradox that challenge therapeutic development. This perspective examines the critical research gap concerning cerebrospinal fluid (CSF) synaptic biomarkers in immunomodulatory therapy trials. Following decades of partially successful amyloid-centric trials, focus has shifted to upstream triggers including viral infections like Herpes Simplex Virus Type 1, Varicella Zoster Virus, and Severe Acute Respiratory Syndrome Coronavirus 2. While large observational and quasi-experimental studies suggest antivirals and vaccines reduce long-term dementia risk, the first major antiviral randomized controlled trial (Valacyclovir for Alzheimer’s Disease) was negative. This perspective posits that this paradox arises from a fundamental flaw in trial design: the absence of synaptic integrity biomarkers. Synaptic loss, not amyloid or tau burden, is the strongest correlate of cognitive decline. Therefore, CSF synaptic protein biomarkers such as the prognostic YWHAG: NPTX2 ratio, postsynaptic Neurogranin (Ng), and presynaptic Growth-Associated Protein 43 (GAP-43) are the most clinically relevant endpoints. The paradoxical trial results may arise from omitting these synaptic measures, creating a mechanistic “black box” obscuring their true biological effects. A strategic framework is proposed, centered on the mandatory inclusion of CSF synaptic biomarkers and relevant co-pathology markers like TAR DNA-Binding Protein 43 (TDP-43; a proteinopathy linked to viral triggers) in all antiviral and vaccine trials. This approach is critical to resolve existing paradoxes, elucidate mechanisms of neuroprotection, and accelerate developing effective therapies that preserve synaptic integrity to prevent and treat dementia.

Background There has been limited research into potentially inappropriate medication (PIM) use and anticholinergic burden in patients attending memory clinics. Objectives The aim of this study was to explore the use of PIMs related to cognitive impairment (PIMcog), anticholinergic cognitive burden (ACB) and concomitant use of anticholinergic medications with cholinesterase inhibitors (ChEIs) in patients attending memory clinics. Methods Cross-sectional analysis of baseline data from the Prospective Research In MEmory clinics (PRIME) study was performed. Participants were community-dwelling patients who attended nine memory clinics and had a diagnosis of mild cognitive impairment or dementia. PIMcog were defined as any medication considered potentially inappropriate for patients with cognitive impairment according to the Beers or STOPP criteria. Clinically significant ACB was defined as total score of ≥3 on the ACB scale. Results A total of 964 patients, mean age 77.6 years, were included. PIMcog were used by 206 (21.4 %) patients. Anticholinergics and sedatives were the most common PIMcog. PIMcog use was associated with higher number of medications (adjusted OR 1.26; 95 % CI 1.19–1.33) and with not having completed secondary level education (adjusted OR 1.71; 95 % CI 1.01–2.89). One hundred and thirteen (11.7 %) patients had a clinically significant ACB score (≥3). ChEIs were used by 575 patients and 65 (11.3 %) of these had an ACB score ≥3. There was no statistically significant difference in ChEI use between patients with and without an ACB score ≥3. Conclusion PIMcog use, clinically significant anticholinergic burden, and concurrent use of anticholinergics with ChEIs were prevalent in patients attending memory clinics. Efforts are needed to improve prescribing for people with cognitive impairment.

Background The limited allocation of resources to rural and regional communities is a major contributor to healthcare inequities in Australia. Distribution of health service resources between metropolitan and rural communities commonly sees highly populated areas prioritised over more sparsely populated and geographically vast areas. As such, challenges impacting dementia diagnosis, management, and care in metropolitan areas are experienced more acutely in rural areas. This study aimed to examine equity of access to dementia diagnosis, management, and care services amongst people who experienced the process of dementia diagnosis as a patient or significant other (partner/spouse, adult children, siblings, and friends) throughout rural and metropolitan Australia. Methods This exploratory qualitative study consisted of thirty-three online semi-structured interviews with thirty-seven people with experience of the dementia diagnosis process as a patient and/or significant other. Interviews explored symptoms of dementia, health professionals consulted, tests conducted, and challenges faced throughout the diagnosis and post-diagnosis process. Rurality was defined by the Australian Statistical Geography Standard Remoteness Areas (ASGS-RA) and the Modified Monash Model (MMM). Thematic analysis was conducted, with Russell’s (2013) Dimensions of Access framework (geography, affordability, availability, acceptability, accommodation, awareness, and timeliness) guiding data analysis. Results Participants were distributed across various regions of Australia: seven interviews from inner regional Australia, five interviews from outer regional Australia, and twenty-one interviews from metropolitan areas. Disparities in access between metropolitan and rural areas emerged in five key dimensions: 1) geography impeding ability to access services; 2) affordability of travel expenses; 3) availability of healthcare and support services; 4) acceptability of available health professionals and services; and 5) awareness of local services and resources. The dimensions of accommodation and timeliness of care were experienced as challenges irrespective of location, with lengthy appointment wait times and difficulty navigating complex systems. However, rurality often compounded the challenges in dementia diagnosis, management, and care. Conclusions Significant health inequities persist between rural and metropolitan communities that must be prioritised in endeavours to promote equitable dementia diagnosis, management, and care. Targeted action to address disparities is vital to mitigate the impact of rurality, particularly as clinical practice evolves with research advancements.

Background Nonmedical use of prescription opioids (defined as taking opioid medications for hedonic effects or in a manner other than prescribed) and the use of heroin have emerged in recent years as major public health concerns in the United States. Of particular concern is the prevalence of opioid use among emerging adults (ages 18–25), as this is a developmental period of heightened vulnerability and critical social, neurological, and psychological development. Data from 2015 show that American Indian/Alaska Native (AI/AN) people have the highest rates of diagnosis for opioid use disorders (OUDs). One recent study found that the overdose death rate among urban-dwelling AI/AN individuals was 1.4 times higher compared to those living in rural areas. To date, there are no evidence-based prevention programs addressing opioid use among urban AI/AN emerging adults that integrate culturally-appropriate strategies with evidence-based treatment. Traditions and Connections for Urban Native Americans (TACUNA) builds on our prior work with AI/AN communities across California to develop and evaluate culturally appropriate programming to address opioid, alcohol, and cannabis use among urban AI/AN emerging adults. Methods/design In a randomized controlled trial, 18–25 year old urban AI/AN emerging adults will receive either TACUNA (n = 185), which comprises three virtual workshops utilizing motivational interviewing, social network visualization, and integrating traditional practices and a wellness circle, or one virtual culturally sensitive opioid education workshop (n = 185). We will evaluate intervention effects on primary outcomes of frequency of opioid, alcohol, and cannabis use, as well as secondary outcomes of social network characteristics and cultural connectedness, over a 12-month period. Discussion This project has the potential to expand the range and effectiveness of opioid, alcohol, and cannabis services for urban AI/AN emerging adults by addressing the opioid epidemic and use of other substances at both the community and individual level. In addition, it provides important culturally grounded conceptual and practical information to advance the field of substance use interventions and enhance resiliency among this population. Trial registration : ClinicalTrials.gov Identifier: NCT04617938. Registered October 26, 2020 https://clinicaltrials.gov/ct2/show/record/NCT04617938 .

This paper considers the feasibility of using augmented reality (AR) as a tool for enhancing visualization in maritime operations to avoid collision in different environmental conditions. According to the International Maritime Organization (IMO 2010), 90% of maritime accidents due to collisions at sea are caused in part by human error. This study investigates the new technology (AR) used to superimpose holographic images onto the real world; now reaching a state of readiness for commercial application. This paper demonstrates the competence of AR technology to serve as a maritime navigational aid. The research explores the viability of improving navigational safety in low visibility by projecting holograms of real-world objects in the same geo-location as the real object to make them “visible”. The paper presents the logical deconstruction of the technical problems and identified solutions, together with results of experiments used to validate the concept and technology readiness for real word maritime application. The paper presents a verified demonstrator; a proposed holographic bridge interface with an innovative way of presenting information using AR technology. Furthermore, it identifies that new technologies offer the opportunity for enhanced operator performances, with the expectation being that this should lead to reduce risk to persons, property, and the environment.