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Background: A core element of the Strengthening Responses to Dementia in Developing Countries (STRiDE) programme was to generate novel data on the prevalence, cost and impact of dementia in low- and middle-income countries, to build better health policy. Indonesia and South Africa are two middle-income countries in need of such data., Aims: To present the STRiDE methodology and generate estimates of dementia prevalence in Indonesia and South Africa., Method: We conducted community-based, single-phase, cross-sectional studies in Indonesia and South Africa, randomly sampling participants aged 65 years or older in each country. Dementia prevalence rates for each country were generated by using the 10/66 short schedule and applying its diagnostic algorithm. Weighted estimates were calculated with national sociodemographic data., Results: Data were collected between September and December 2021 in 2110 people in Indonesia and 408 people in South Africa. The adjusted weighted dementia prevalence was 27.9% (95% CI 25.2-28.9) in Indonesia and 12.5% (95% CI 9.5-16.0) in South Africa. Our results indicate that there could be >4.2 million people in Indonesia and >450 000 people in South Africa who have dementia. Only five participants (0.2%) in Indonesia and two (0.5%) in South Africa had been previously diagnosed with dementia., Conclusions: Despite prevalence estimates being high, formal diagnosis rates of dementia were very low across both countries (<1%). Further STRiDE investigations will provide indications of the impact and costs of dementia in these countries, but our results provide evidence that dementia needs to be prioritised within national health and social care policy agendas.

Objectives: We compared socio-demographic characteristics, health-related variables, vaccination-related beliefs and attitudes, vaccination acceptance, and personality traits of individuals who vaccinated against COVID-19 and who did not vaccinate by December 2021. Methods: This cross-sectional study used data of 10,642 adult participants from the Corona Immunitas eCohort, an age-stratified random sample of the population of several cantons in Switzerland. We used multivariable logistic regression models to explore associations of vaccination status with socio-demographic, health, and behavioral factors. Results: Non-vaccinated individuals represented 12.4% of the sample. Compared to vaccinated individuals, non-vaccinated individuals were more likely to be younger, healthier, employed, have lower income, not worried about their health, have previously tested positive for SARS-CoV-2 infection, express lower vaccination acceptance, and/or report higher conscientiousness. Among non-vaccinated individuals, 19.9% and 21.3% had low confidence in the safety and effectiveness of SARS-CoV-2 vaccine, respectively. However, 29.1% and 26.7% of individuals with concerns about vaccine effectiveness and side effects at baseline, respectively vaccinated during the study period. Conclusion: In addition to known socio-demographic and health-related factors, non-vaccination was associated with concerns regarding vaccine safety and effectiveness., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Sabatini, Kaufmann, Fadda, Tancredi, Noor, Van Der Linden, Cullati, Frank, Michel, Harju, Luedi, Frei, Ballouz, Menges, Fehr, Kohler, Kahlert, Scheu, Ortega, Chocano-Bedoya, Rodondi, Stringhini, Baysson, Lorthe, Zufferey, Suggs, Albanese, Vincentini, Bochud, D’Acremont, Nusslé, Imboden, Keidel, Witzig, Probst-Hensch and von Wyl.)

Introduction: COVID-19 infection can impact the central nervous system, and is often associated with cognitive decline. However, there are no studies linking serologically confirmed COVID-19 infection with objectively assessed cognitive functioning. We explored whether presence of SARS-CoV-2 antibodies account for variability in participants' scores on a neuropsychological assessment., Methods: In this cross-sectional study participants were 657 (mean age = 72.97; SD = 6.07 years; women = 47.7%) individuals randomly selected from the general population of the canton of Zurich and included in the Corona Immunitas study. We conducted serological tests between October 2020 and May 2021 to detect and quantify SARS-CoV-2 antibodies in peripheral venous blood samples. We assessed cognitive function, vaccination status (vaccinated; not vaccinated), number of health conditions, and demographic variables between January and August 2021. We studied the association between seropositivity and global cognitive function and five cognitive domains (language expression, language comprehension, temporal orientation, spatial orientation, and memory) with linear regression models. Based on SARS-CoV-2 antibodies and vaccination status, we stratified participants into three groups: No SARS-CoV-2 antibodies ( N  = 402); SARS-CoV-2 antibodies due to vaccination ( N  = 218); history of SARS-CoV-2 infection and no vaccination ( N  = 37)., Results: In the regression model adjusted for age, sex, educational level, and number of health conditions, compared to those without SARS-CoV-2 antibodies, those with SARS-CoV-2 antibodies due to vaccination had better global cognitive functioning (Standardized beta = 0.10; 95% CI = 0.02; 0.17), and those with SARS-CoV-2 antibodies due to infection had poorer cognitive functioning (Standardized beta = -0.10; 95% CI = -0.18; -0.03). Regarding cognitive domains, compared to those without SARS-CoV-2 antibodies, those with SARS-CoV-2 antibodies due to infection scored more poorly on language comprehension and temporal orientation, and those with SARS-CoV-2 antibodies due to vaccination scored better on memory., Discussion: By linking serologically confirmed presence of SARS-CoV-2 antibodies to poorer global cognitive functioning in community dwelling older adults we strengthen existing evidence in support of cognitive decline related to COVID-19. Given the large number of infected older adults, and the endurance of the pandemic, our results highlight the need to address COVID-19 related cognitive decline in the clinical and public health areas of prevention, diagnosis, and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sabatini, Pacifico, Frei, Graf, Puhan and Albanese.)

Background: Despite consensus about the importance of implementing shared decision-making (SDM) in clinical practice, this ideal is inconsistently enacted today. Evidence shows that SDM practices differ in the degree of involvement of patients or family members, or in the amount of medical information disclosed to patients in order to "share" meaningfully in treatment decisions. Little is known on which representations and moral justifications physicians hold when realizing SDM. This study explored physicians' experiences of SDM in the management of paediatric patients with prolonged disorders of consciousness (PDOC). Specifically, we focused on physicians' SDM approaches, representations, and ethical justifications for engaging in SDM., Methods: We used a qualitative approach to explore the SDM experiences of 13 ICU physicians, paediatricians, and neurologists based in Switzerland who have been or were involved in the care of paediatric patients living with PDOC. A semi-structured interview format was used and interviews were audio-recorded and transcribed. Data were analysed through thematic analysis., Results: We found that participants followed three main decision-making approaches: the "brakes" approach, characterized by maximized family's decisional freedom, though conditional to physician's judgment regarding the medical appropriateness of a treatment; the "orchestra director" approach, characterized by a multi-step decision-making process led by the main physician aimed at eliciting the voices of the care team members and of the family; and the "sunbeams" approach, characterized by a process oriented to reach consensus with family members through dialogue, where the virtues of the physician are key to guide the process. We also found that participants differed in the moral justifications sustaining each approach, citing the duty to respect parental autonomy, to invest in an ethics of care, and to employ physicians' virtues to guide the decision-making process., Conclusion: Our results show that physicians come to perform SDM in different ways, with several representations, and distinct ethical justifications. SDM training among health care providers should clarify the ductility of SDM and the several ethical motivations underpinning it, rather than insisting on the principle of respect for patient's autonomy as its only moral foundation., (© 2023. The Author(s).)

Objectives: The COVID-19 pandemic continues, and evidence on infection- and vaccine-induced immunity is key. We assessed COVID-19 immunity and the neutralizing antibody response to virus variants across age groups in the Swiss population., Study Design: We conducted a cohort study in representative community-dwelling residents aged five years or older in southern Switzerland (total population 353,343), and we collected blood samples in July 2020 (in adults only, N = 646), November-December 2020 (N = 1457), and June-July 2021 (N = 885)., Methods: We used a previously validated Luminex assay to measure antibodies targeting the spike (S) and the nucleocapsid (N) proteins of the virus and a high-throughput cell-free neutralization assay optimized for multiple spike protein variants. We calculated seroprevalence with a Bayesian logistic regression model accounting for the population's sociodemographic structure and the test performance, and we compared the neutralizing activity between vaccinated and convalescent participants across virus variants., Results: The overall seroprevalence was 7.8% (95% CI: 5.4-10.4) by July 2020 and 20.2% (16.4-24.4) by December 2020. By July 2021, the overall seroprevalence increased substantially to 72.5% (69.1-76.4), with the highest estimates of 95.6% (92.8-97.8) among older adults, who developed up to 10.3 more antibodies via vaccination than after infection compared to 3.7 times more in adults. The neutralizing activity was significantly higher for vaccine-induced than infection-induced antibodies for all virus variants (all p values < 0.037)., Conclusions: Vaccination chiefly contributed to the reduction in immunonaive individuals, particularly those in older age groups. Our findings on the greater neutralizing activity of vaccine-induced antibodies than infection-induced antibodies are greatly informative for future vaccination campaigns.

Background: Frailty is an age-associated state of increased vulnerability to stressors that strongly predicts poor health outcomes. Epidemiological evidence on frailty is limited during the COVID-19 pandemic, and whether frailty is associated with the risk of infection is unknown., Objectives: We derived a robust Frailty Index (FI) to measure the prevalence of frailty and its risk factors in community-dwelling older adults in Southern Switzerland (Ticino), and we explored the association between frailty and serologically confirmed SARS-CoV-2 infection., Methods: In September 2020, we recruited a random sample of community-dwelling older adults (65 +) in the Corona Immunitas Ticino prospective cohort study (CIT) and assessed a variety of lifestyle and health characteristics. We selected 30 health-related variables, computed the Rockwood FI, and applied standard thresholds for robust (FI < 0.1), pre-frail (0.1 ≤ FI < 0.21), and frail (FI ≥ 0.21)., Results: Complete data for the FI was available for 660 older adults. The FI score ranged between zero (no frailty) and 0.59. The prevalence of frailty and pre-frailty were 10.3% and 48.2% respectively. The log-transformed FI score increased by age similarly in males and females, on average by 2.8% (p < 0.001) per one-year increase in age. Out of 481 participants with a valid serological test, 11.2% were seropositive to either anti-SARS-CoV-2 IgA or IgG. The frailty status and seropositivity were not statistically associated (p = 0.236)., Conclusion: Advanced age increases the risk of frailty. The risk of COVID-19 infection in older adults may not differ by frailty status., (© 2023. The Author(s).)

Background: Receiving a diagnosis that leads to severe disability in childhood can cause a traumatic experience with long-lasting emotional stress for patients and family members. In recent decades, emerging digital technologies have transformed how patients or caregivers of persons with disabilities manage their health conditions. As a result, information (eg, on treatment and resources) has become widely available to patients and their families. Parents and other caregivers can use digital platforms such as websites or social media to derive social support, usually from other patients and caregivers who share their lived experiences, challenges, and successes on these platforms. However, gaps remain in our understanding of platforms that are most frequently used or preferred among parents and caregivers of children with disabilities. In particular, it is not clear what factors primarily drive or discourage engagement with these digital tools and what the main ethical considerations are in relation to these tools., Objective: We aimed to (1) identify prominent digital platforms used by parents or caregivers of children with disabilities; (2) explore the theoretical contexts and reasons for digital platform use, as well as the experiences made with using these platforms reported in the included studies; and (3) identify any privacy and ethical concerns emerging in the available literature in relation to the use of these platforms., Methods: We conducted a scoping review of 5 academic databases of English-language articles published within the last 10 years for diseases with childhood onset disability and self-help or parent/caregiver-led digital platforms., Results: We identified 17 papers in which digital platforms used by parents of affected children predominantly included social media elements but also search engines, health-related apps, and medical websites. Information retrieval and social support were the main reasons for their utilization. Nearly all studies were exploratory and applied either quantitative, qualitative, or mixed methods. The main ethical concerns for digital platform users included hampered access due to language barriers, privacy issues, and perceived suboptimal advice (eg, due to missing empathy of medical professionals). Older and non-college-educated individuals and ethnic minorities appeared less likely to access information online., Conclusions: This review showed that limited scientifically sound knowledge exists on digital platform use and needs in the context of disabling conditions in children, as the evidence consists mostly of exploratory studies. We could highlight that affected families seek information and support from digital platforms, as health care systems seem to be insufficient for satisfying knowledge and support needs through traditional channels., (©Oliver Gruebner, Afua van Haasteren, Anna Hug, Suzanne Elayan, Martin Sykora, Emiliano Albanese, John Naslund, Markus Wolf, Marta Fadda, Michael von Rhein. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 06.12.2022.)

In January 2021, the Swiss government introduced the first COVID-19 vaccines and prioritized allocation to at-risk individuals and professionals working with them. Despite this opportunity, vaccine uptake among staff employed in retirement homes and institutes for people with disabilities was suboptimal. This study aimed to capture real-time decision-making about COVID-19 vaccine among staff employed in nursing homes and institutes for people with disabilities in Southern Switzerland. We conducted semi-structured phone-interviews with 25 staff employed in retirement homes and institutes for people with disabilities between February and May 2021, i.e., when participants had to decide whether they wanted to adhere to the priority vaccination programme. Among participants, 21 either signed up for the COVID-19 vaccination or were fully or partly vaccinated at the time of the interview. For most participants, the vaccination choice was a challenging process: information appeared to be lacking and conflicting; numerous moral principles were at stake and contradictory; the way vaccination was organized clashed with the health values to which respondents had been previously exposed; finally, the fear of discrimination for those who decided not to get vaccinated loomed over the vaccination choice. Participants decided for or against vaccination based on principles, traditions, emotions, and a reflexive assessment of the personal vs. collective benefit of the vaccination, the latter being the most common within the investigated sample. This study shows that deciding to get vaccinated against COVID-19 is a nuanced process and that individuals cannot simply be categorized as "novax" or "provax" based on their vaccination decision., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: L. Suzanne Suggs reports a relationship with MSD European Vaccines that includes: board membership., (© 2022 The Authors.)

Background: Subjective cognitive decline (SCD) and subjective memory decline (SMD) are common among older people. Evidence linking SCD and SMD with cognitive and memory impairment is inconsistent. Moreover, little is known about the associations of SCD and SMD with disability. We aimed to explore the associations of SCD and SMD with objective cognitive and memory performance, disability, and depressive symptoms., Materials and Methods: In a cross-sectional study we conducted face to face interviews in a randomized sample of people aged ≥65 years living in the Canton of Ticino, southern Switzerland, between May 2021 and April 2022. We measured subjective cognitive decline with the MyCog, a subsection of the Subjective Cognitive Decline Questionnaire (SCD-Q); cognitive functioning with the Community Screening Instrument for Dementia; memory with the consortium to establish a registry for alzheimer's disease (CERAD) 10-word list learning task; and disability and depressive symptoms with the world health organization disability assessment schedule 2.0 (WHO-DAS 2.0) and the Euro-Depression (EURO-D) scales, respectively., Results: Of the 250 participants 93.6% reported at least one cognitive difficulty, and 40.0% SMD. Both SCD and SMD were associated with poorer objective cognitive/memory performance, and independently with greater disability, and more depressive symptoms. But in participants with high disability and depressive symptoms subjective and objective cognition were no longer associated. Disability fully mediated the associations of poorer objective cognitive and memory performance with subjective cognitive and memory decline., Conclusion: Routine clinical assessments of cognitive function should include formal enquires about SCD and SMD, and also account for disability and depressive symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pacifico, Sabatini, Fiordelli and Albanese.)

Functional immunity (defined here as serum neutralising capacity) critically contributes to conferring protection against SARS-CoV-2 infection and severe COVID-19. This cross-sectional analysis of a prospective, population-based cohort study included 1,894 randomly-selected 16 to 99-year-old participants from two Swiss cantons in March 2022. Of these, 97.6% (95% CI: 96.8-98.2%) had anti-spike IgG antibodies, and neutralising capacity was respectively observed for 94%, 92% and 88% against wild-type SARS-CoV-2, Delta and Omicron variants. Studying functional immunity to inform and monitor vaccination campaigns is crucial.

Background: We aimed to determine whether living in a household with children is associated with SARS-CoV-2 seropositivity in adults and investigated interacting factors that may influence this association., Methods: SARS-CoV-2 serology testing was performed in randomly selected individuals from the general population between end of October 2020 and February 2021 in 11 cantons in Switzerland. Data on sociodemographic and household characteristics, employment status, and health-related history was collected using questionnaires. Multivariable logistic regression was used to examine the association of living with children <18 years of age (number, age group) and SARS-CoV-2 seropositivity. Further, we assessed the influence of reported non-household contacts, employment status, and gender., Results: Of 2393 working age participants (18-64 years), 413 (17.2%) were seropositive. Our results suggest that living with children and SARS-CoV-2 seropositivity are likely to be associated (unadjusted odds ratio (OR) 1.22, 95% confidence interval [0.98-1.52], adjusted OR 1.25 [0.99-1.58]). A pattern of a positive association was also found for subgroups of children aged 0-11 years (OR 1.21 [0.90-1.60]) and 12-17 years (OR 1.14 [0.78-1.64]). Odds of seropositivity were higher with more children (OR 1.14 per additional child [1.02-1.27]). Men had higher risk of SARS-CoV-2 infection when living with children than women (interaction: OR 1.74 [1.10-2.76])., Conclusions: In adults from the general population living with children seems associated with SARS-CoV-2 seropositivity. However, child-related infection risk is not the same for every subgroup and depends on factors like gender. Further factors determining child-related infection risk need to be identified and causal links investigated., Trial Registration: https://www.isrctn.com/ISRCTN18181860 ., (© 2022. The Author(s).)

Supportive measures and training interventions can improve the care of people with dementia and reduce the burden on informal caregivers, whose needs remain largely unmet. iSupport is an evidence-based online intervention developed by the World Health Organization to provide support and self-guided education to informal family caregivers of people with dementia. This qualitative study explored barriers and facilitators in the access and use of supportive measures for family caregivers of people with dementia living in Southern Switzerland (Ticino). We conducted five focus groups and explored experiences, beliefs, and attitudes toward seeking help (SH), and used thematic analysis to identify key themes. Participants (N = 13) reported a general reluctance to SH. We identified four main barriers to SH: high level of burden; sense of duty; fear of being misunderstood by others; and difficulty in reaching information. We also identified facilitators of help seeking behaviors and unveiled the need of caregivers to be assisted by a dementia case manager to facilitate access to support resources. Local services and interventions should be adapted to caregivers' needs and expectations, with the aim of facilitating the acceptance of, access to, and service integration of existing and future support measures, including iSupport.

Background: Alzheimer's disease (AD) pathology is present many years before the onset of clinical symptoms. AD dementia cannot be treated. Timely and early detection of people at risk of developing AD is key for primary and secondary prevention. Moreover, understanding the underlying pathology that is present in the earliest stages of AD, and the genetic predisposition to that might contribute to the development of targeted disease-modifying treatments., Objectives: In this study, we aimed to explore whether genetic disposition to AD in asymptomatic individuals is associated with altered intrinsic functional connectivity as well as cognitive performance on neuropsychological tests., Methods: We examined 136 cognitively healthy adults (old group: mean age = 69.32, SD = 4.23; young group: mean age = 31.34, SD = 13.12). All participants had undergone resting-state functional magnetic resonance imagining (fMRI), DNA genotyping to ascertain polygenic risk scores (PRS), and neuropsychological testing for global cognition, working memory, verbal fluency, and executive functions., Results: Two-step hierarchical regression analysis revealed that higher PRS was significantly associated with lower scores in working memory tasks [Letter Number Span: Δ R 2 = 0.077 ( p < 0.05); Spatial Span: Δ R 2 = 0.072 ( p < 0.05)] in older adults (>60 years). PRS did not show significant modulations of the intrinsic functional connectivity of the posterior cingulate cortex (PCC) with other regions of interest in the brain that are affected in AD., Conclusion: Allele polymorphisms may modify the effect of other AD risk factors. This potential modulation warrants further investigations, particularly in cognitively healthy adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ibnidris, Fußer, Kranz, Prvulovic, Reif, Pantel, Albanese, Karakaya and Matura.)

Social media platforms are increasingly used across many population groups not only to communicate and consume information, but also to express symptoms of psychological distress and suicidal thoughts. The detection of suicidal ideation (SI) can contribute to suicide prevention. Twitter data suggesting SI have been associated with negative emotions (e.g., shame, sadness) and a number of geographical and ecological variables (e.g., geographic location, environmental stress). Other important research contributions on SI come from studies in neuroscience. To date, very few research studies have been conducted that combine different disciplines (epidemiology, health geography, neurosciences, psychology, and social media big data science), to build innovative research directions on this topic. This article aims to offer a new interdisciplinary perspective, that is, a Population Neuroscience perspective on SI in order to highlight new ways in which multiple scientific fields interact to successfully investigate emotions and stress in social media to detect SI in the population. We argue that a Population Neuroscience perspective may help to better understand the mechanisms underpinning SI and to promote more effective strategies to prevent suicide timely and at scale., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Morese, Gruebner, Sykora, Elayan, Fadda and Albanese.)

Objectives: This study examined factors associated with COVID-19 vaccination intention at the very beginning of the vaccination campaign in a representative sample of the population in southern Switzerland. Methods: In March 2021, we measured vaccination intention, beliefs, attitudes, and trust in a sample of the Corona Immunitas Ticino study. Results: Of the 2681 participants, 1933 completed the questionnaire (response rate = 72%; 55% female; mean age = 41, SD = 24, range age = 5-91). Overall, 68% reported an intention to get vaccinated. Vaccination intention was higher in social/healthcare workers, and increased with age, trust in public health institutions, and confidence in the vaccine efficacy. Prior infection of a family member, predilection for waiting for more evidence on the safety and efficacy of the vaccine, and for alternative protective means were negatively associated with intention. Conclusion: In view of needs of COVID-19 vaccine boosters and of suboptimal vaccination coverage, our results have relevant public health implications and suggest that communication about vaccine safety and efficacy, and aims of vaccination programs, should be bi-directional, proportionate, and tailored to the concerns, expectations, and beliefs of different population subgroups., Competing Interests: Author LS served on the MSD European Vaccines Advisory Board in 2019. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fadda, Camerini, Fiordelli, Corna, Levati, Amati, Piumatti, Crivelli, Suggs and Albanese.)

Cross-cultural adaptation is an important part of using validated questionnaires across countries and settings. Here we describe the cross-cultural process adopted in the STRiDE (STrengthening Responses to dementia in DEveloping countries) program. We adopted a cross-cultural adaptation process including forward translation, back translations, and cognitive interviews of the STRiDE toolkit. In total, 50 older adults and 41 carers across sites in Indonesia and South Africa participated in cognitive interviews; field notes and verbatim quotes are reported. We describe the cross-cultural adaptation process of the STRiDE toolkit. During the process, issues were identified with the translated toolkit, including aspects related to cultural appropriateness, terminology equivalence, and timings. The data demonstrate that a rigorous, yet pragmatic, cross-cultural adaptation process can be achieved even with limited resources. Our process should help the design and conduct of future dementia research in various contexts., Competing Interests: There are no conflicts of interest to declare., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Background: There is sparse evidence on the impact on vulnerable populations of the COVID-19 pandemic. The aim of our study was to explore burden and mental wellbeing (including depressive, anxiety, and stress symptoms) in caregivers of people with dementia during the first wave of the pandemic in Italy and southern Switzerland, two bordering regions severely hit by the COVID-19 pandemic., Methods: We conducted an online cross-sectional survey with family carers of people with dementia between May and June 2020. We registered socio-demographic characteristics, and information about the relationship with the care recipient, dementia subtype, care inputs from others, and the need of care of the person with dementia. We measured caregiver burden with the Zarit Burden Interview (ZBI), psychological distress with the Depression, Anxiety and Stress Scale (DASS-21), and perceived isolation with the 3-item UCLA Loneliness Scale (UCLALS3)., Results: Caregivers (N =571) reported moderate to severe care-related burden (mean=54.30; SD=18.33), moderate anxiety symptoms (mean=10.04; SD=6.93), mild depressive symptoms (mean=11.79; SD=6.12) and mild stress (mean=12.95; SD=5.53), and 72.3% of participants reported to feel lonely. All scores were significantly more severe in Swiss compared to Italian caregivers (all p values<0.001)., Conclusions: We found that caregivers' burden, anxiety symptoms, depression and perceived loneliness were marked during the first wave of the COVID-19 pandemic, in two severely hit bordering countries. Regional differences in the impact of the epidemic on caregivers could be due to contextual, societal, and cultural circumstances. As the pandemic endures, support to caregivers of people with dementia should be proportionate and tailored to needs and adapted to contextual factors., (© 2022. The Author(s).)

Introduction: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts., Methods: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives., Results: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes., Discussion: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond., (© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Crisis Resolution and Home Treatment (CRHT) teams represent a community-based mental health service offering a valid alternative to hospitalization. CRHT teams have been widely implemented in various mental health systems worldwide, and their goal is to provide care for people with severe acute mental disorders who would be considered for admission to acute psychiatric wards. The evaluation of several home-treatment experiences shows promising results; however, it remains unclear which specific elements and characteristics of CRHT are more effective and acceptable., Objective: This study aims to assess the acceptability, effectiveness, and cost-effectiveness of a new CRHT intervention in Ticino, Southern Switzerland., Methods: This study includes an interventional, nonrandomized, quasi-experimental study combined with a qualitative study and an economic evaluation to be conducted over a 48-month period. The quasi-experimental evaluation involves two groups: patients in the northern area of the region who were offered the CRHT service (ie, intervention group) and patients in the southern area of the region who received care as usual (ie, control group). Individual interviews will be conducted with patients receiving the home treatment intervention and their family members. CRHT members will also be asked to participate in a focus group. The economic evaluation will include a cost-effectiveness analysis., Results: The project is funded by the Swiss National Science Foundation as part of the National Research Program NRP74 for a period of 48 months starting from January 2017. As of October 2021, data for the nonrandomized, quasi-experimental study and the qualitative study have been collected, and the results are expected to be published by the end of the year. Data are currently being collected for the economic evaluation., Conclusions: Compared to other Swiss CRHT experiences, the CRHT intervention in Ticino represents a unique case, as the introduction of the service is backed by the closing of one of its acute wards. The proposed study will address several areas where there are evidence gaps or contradictory findings relating to the home treatment of acute mental crisis. Findings from this study will allow local services to improve their effectiveness in a challenging domain of public health and contribute to improving access to more effective care for people with severe mental disorders., Trial Registration: ISRCTN registry ISRCTN38472626; https://www.isrctn.com/ISRCTN38472626., International Registered Report Identifier (irrid): DERR1-10.2196/28191., (©Sara Levati, Zefiro Mellacqua, Maria Caiata-Zufferey, Emiliano Soldini, Emiliano Albanese, Maddalena Alippi, Emilio Bolla, Raffaella Ada Colombo, Severino Cordasco, Wolfram Kawohl, Giuseppina Larghi, Angela Lisi, Mario Lucchini, Simona Rossa, Rafael Traber, Luca Crivelli. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 09.11.2021.)

Background: The Covid-19 pandemic is causing unprecedented disruption and suffering to people across the globe, with a disproportionate toll on the elderly. The development and equitable distribution of a vaccine seems to be the most promising and sustainable route ahead. The goal of this study was to explore older adults' attitudes towards and beliefs regarding the Covid-19 vaccination in Southern Switzerland., Methods: We conducted a qualitative study employing telephone interviews to understand older adults' attitudes towards and beliefs about the Covid-19 vaccine. No Covid-19 vaccine had yet been approved at the moment of data collection. A convenience and snowball sample of 19 participants was recruited. Participants had to be at least 65 years old, without any hearing impairments, and be resident in the Canton of Ticino., Results: Most participants were women (n = 12), Swiss nationals (n = 14), retired (n = 18), resident in urban areas (n = 14), and had obtained a secondary school degree (n = 14). The average age was 75 (SD = 6.04; range = 64-85). We found that the majority of participants were in favor of the vaccination and highlighted its positive consequences, such as the abandonment of current freedom-limiting protective measures. Those participants who were against or unsure about the vaccination had concerns regarding the novelty of the vaccine and its impact on its safety and efficacy, stated they would prefer other protective measures rather than the vaccination, and identified contextual and individual drivers of their concerns., Conclusions: Independently from the outbreak's trajectory, efforts to foster vaccination acceptance should focus on the benefit of relapsing freedom-limiting protective measures. Vaccination strategies should be grounded in an evidence-based, participatory approach, ongoing community engagement, trust-building activities, and communication about vaccine developments and how the vaccine will be combined with other outbreak response measures., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [The authors declare that they have no conflict of interest. LSS served on the MSD European Vaccines Advisory Board in 2019]., (© 2021 The Author(s).)

Background: Hospital healthcare workers (HCW), in particular those involved in the clinical care of COVID-19 cases, are presumably exposed to a higher risk of acquiring the disease than the general population., Methods: Between April 16 and 30, 2020 we conducted a prospective, SARS-CoV-2 seroprevalence study in HCWs in Southern Switzerland. Participants were hospital personnel with varying COVID-19 exposure risk depending on job function and working site. They provided personal information (including age, sex, occupation, and medical history) and self-reported COVID-19 symptoms. Odds ratio (OR) of seropositivity to IgG antibodies was estimated by univariate and multivariate logistic regressions., Findings: Among 4726 participants, IgG antibodies to SARS-CoV-2 were detected in 9.6% of the HCWs. Seropositivity was higher among HCWs working on COVID-19 wards (14.1% (11.9-16.5)) compared to other hospital areas at medium (10.7% (7.6-14.6)) or low risk exposure (7.3% (6.4-8.3)). OR for high vs. medium wards risk exposure was 1.42 (0.91-2.22), P  = 0.119, and 1.98 (1.55-2.53), P <0.001 for high vs. low wards risk exposure. The same was for true for doctors and nurses (10.1% (9.0-11.3)) compared to other employees at medium (7.1% (4.8-10.0)) or low risk exposure (6.6% (5.0-8.4)). OR for high vs. medium profession risk exposure was 1.37 (0.89-2.11), P  = 0.149, and 1.75 (1.28-2.40), P  = 0.001 for high vs. low profession risk exposure. Moreover, seropositivity was higher among HCWs who had household exposure to COVID-19 cases compared to those without (18.7% (15.3-22.5) vs. 7.7% (6.9-8.6), OR 2.80 (2.14-3.67), P <0.001)., Interpretation: SARS-CoV-2 antibodies are detectable in up to 10% of HCWs from acute care hospitals in a region with high incidence of COVID-19 in the weeks preceding the study. HCWs with exposure to COVID-19 patients have only a slightly higher absolute risk of seropositivity compared to those without, suggesting that the use of PPE and other measures aiming at reducing nosocomial viral transmission are effective. Household contact with known COVID-19 cases represents the highest risk of seropositivity., Funding: Henry Krenter Foundation, Ente Ospedaliero Cantonale and Vir Biotechnology., Competing Interests: LP, C.S-F and NS report that the work was supported in part by Vir Biotechnology. DC, AL, IB, EC and SJ report that they owns shares of Vir Biotechnology and that the work was supported in part by Vir Biotechnology. FS owns shares of Vir Biotechnology. EB reports other from Gilead Sciences, other from Merck Sharp & Dohme, other from ViiV Healthcare, other from Pfizer, other from Abbvie, other from Sandoz, outside the submitted work. CG reports to be an external scientific consultant of Humabs BioMed SA, outside the submitted work. AC, PF, LE, OG, MU, EA, BFR, IG-S, SJ, FM, GP and TT have nothing to disclose., (© 2020 The Authors.)

Objectives: Seroprevalence studies to assess the spread of SARS-CoV-2 infection in the general population and subgroups are key for evaluating mitigation and vaccination policies and for understanding the spread of the disease both on the national level and for comparison with the international community., Methods: Corona Immunitas is a research program of coordinated, population-based, seroprevalence studies implemented by Swiss School of Public Health (SSPH+). Over 28,340 participants, randomly selected and age-stratified, with some regional specificities will be included. Additional studies in vulnerable and highly exposed subpopulations are also planned. The studies will assess population immunological status during the pandemic., Results: Phase one (first wave of pandemic) estimates from Geneva showed a steady increase in seroprevalence up to 10.8% (95% CI 8.2-13.9, n = 775) by May 9, 2020. Since June, Zurich, Lausanne, Basel City/Land, Ticino, and Fribourg recruited a total of 5973 participants for phase two thus far., Conclusions: Corona Immunitas will generate reliable, comparable, and high-quality serological and epidemiological data with extensive coverage of Switzerland and of several subpopulations, informing health policies and decision making in both economic and societal sectors. ISRCTN Registry: https://www.isrctn.com/ISRCTN18181860 .

Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics., Competing Interests: Declaration of Interests L.P., N.C., M. Beltramello, C.S.-F., D.P., L.E.R., F.Z., N.S., J.B., A.P., S. Jaconi, B.G., A.M., A.D.M., M.S.P., E.C., S.V.G., F.J., C.H.-D., M.S., D.H., G.S., K.F., H.W.V., A.L., and D.C. are employees of Vir Biotechnology Inc. and may hold shares in Vir Biotechnology Inc. D.C. is currently listed as an inventor on multiple patent applications, which disclose the subject matter described in this manuscript. The Veesler laboratory has received a sponsored research agreement from Vir Biotechnology Inc. The other authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: There is an agreement that the methodological quality of randomized trials should be assessed in systematic reviews, but there is a debate on how this should be done. We conducted a construct validation study of the Physiotherapy Evidence Database (PEDro) scale, which is widely used to assess the quality of trials in physical therapy and rehabilitation., Methods: We analyzed 345 trials that were included in Cochrane reviews and for which a PEDro summary score was available. We used one- and two-parameter logistic item response theory (IRT) models to study the psychometric properties of the PEDro scale and assessed the items' difficulty and discrimination parameters. We ran goodness of fit post estimations and examined the IRT unidimensionality assumption with a multidimensional IRT (MIRT) model., Results: Out of a maximum of 10, the mean PEDro summary score was 5.46 (SD = 1.51). The allocation concealment and intention-to-treat scale items contributed most of the information on the underlying construct (with discriminations of 1.79 and 2.05, respectively) at similar difficulties (0.63 and 0.65, respectively). The other items provided little additional information and did not distinguish trials of different quality. There was substantial evidence of departure from the unidimensionality assumption, suggesting that the PEDro items relate to more than one latent trait., Conclusions: Our findings question the construct validity of the PEDro scale to assess the methodological quality of clinical trials. PEDro summary scores should not be used; rather, the physiotherapy community should consider working with the individual items of the scale., (© 2019 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.)

Background: The region of central and eastern Europe is estimated to have high rates of premature mortality due to mental disorders. However, epidemiological evidence is scarce and insufficient to inform policy actions and health system development. We aimed to assess mortality associated with mental disorders in the Czech Republic., Methods: We did a nationwide, register-based, retrospective cohort study using routinely collected health data from two nationwide registries in the Czech Republic: the register of inpatient discharges (from Jan 1, 1994, to Dec 31, 2013) and the causes of death registry (from Jan 1, 1994, to Dec 31, 2014). We first identified all individuals discharged from mental health institutions with WHO International Classification of Diseases tenth edition (ICD-10) diagnoses of mental and behavioural disorders (from 1994 to 2013). We then did a deterministic individual-level linkage of these data with all-cause mortality data for the whole period (1994-2014). Standardised mortality ratios (SMRs) and 95% CIs were calculated for the year 2014, comparing deaths in people with mental and behavioural disorders discharged from psychiatric hospitals with deaths in the general population., Findings: The final study population comprised 283 618 individuals. 3819 of these individuals died in 2014, corresponding to a mortality risk more than two times higher than that of the general population (SMR estimate 2·2; 95% CI 2·2-2·3). Differences in SMR estimates across diagnostic groups were substantial, with the highest SMR for substance use disorders (3·5; 95% CI 3·4-3·7) followed by schizophrenia, schizotypal, and delusional disorders (2·3; 2·1-2·5), personality disorders (2·3; 2·0-2·6), neurotic, stress-related, and somatoform disorders (1·8; 1·6-1·9), and mood (affective) disorders (1·6; 1·5-1·7)., Interpretation: Mortality among people with mental disorders in the Czech Republic is markedly higher than in the general population. Our findings should stimulate and inform policy in the central and eastern Europe region, as well as ongoing national mental health-care reforms in the Czech Republic., Funding: Czech Ministry of Education, Youth and Sports., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Over recent decades, epidemiology has made significant contributions to our understanding of dementia, translating scientific discoveries into population health. Here, we propose reframing dementia epidemiology as "population neuroscience," blending techniques and models from contemporary neuroscience with those of epidemiology and biostatistics. On the basis of emerging evidence and newer paradigms and methods, population neuroscience will minimize the bias typical of traditional clinical research, identify the relatively homogenous subgroups that comprise the general population, and investigate broader and denser phenotypes of dementia and cognitive impairment. Long-term follow-up of sufficiently large study cohorts will allow the identification of cohort effects and critical windows of exposure. Molecular epidemiology and omics will allow us to unravel the key distinctions within and among subgroups and better understand individuals' risk profiles. Interventional epidemiology will allow us to identify the different subgroups that respond to different treatment/prevention strategies. These strategies will inform precision medicine. In addition, insights into interactions between disease biology, personal and environmental factors, and social determinants of health will allow us to measure and track disease in communities and improve population health. By placing neuroscience within a real-world context, population neuroscience can fulfill its potential to serve both precision medicine and population health.

Introduction: We conducted a meta-analysis of the conflicting epidemiologic evidence on the association between midlife body mass index (BMI) and dementia., Methods: We searched standard databases to identify prospective, population-based studies of dementia risk by midlife underweight, overweight, and obesity. We performed random-effects meta-analyses and meta-regressions of adjusted relative risk (RR) estimates and formally explored between-study heterogeneity., Results: We included 19 studies on 589,649 participants (2040 incident dementia cases) followed up for up to 42 years. Midlife (age 35 to 65 years) obesity (BMI ≥ 30) (RR, 1.33; 95% confidence interval [CI], 1.08-1.63), but not overweight (25 < BMI < 30) (RR, 1.07; 95% CI, 0.96-1.20), was associated with dementia in late life. The association with midlife underweight (RR, 1.39; 95% CI, 1.13-1.70) was potentially driven by residual confounding ( P from meta-regression = .004), selection ( P  = .046), and information bias ( P  = .007)., Discussion: Obesity in midlife increases the risk of dementia. The association between underweight and dementia remains controversial.

There is great interest in the use of biomarkers to assist in the timely identification of Alzheimer's disease (AD) in individuals with mild symptoms. However, the inclusion of AD biomarkers in clinical criteria poses socioethical challenges. The Geneva Task Force for the Roadmap of Alzheimer's Biomarkers was established to deliver a systematic strategic research agenda (aka roadmap) to promote efficient and effective validation of AD biomarkers and to foster their uptake in clinical practice. In this article, we summarize the workshop discussion of the Geneva Task Force "ethical and societal issues" working group, which comprised bioethicists, clinicians, health economists, and representatives of those affected by AD. The working group identified the following key issues that need to be included in the roadmap: improving access to services through timely diagnosis, the need for a diagnostic research protocol before moving to clinical routine, recruitment in diagnostic research protocols in the absence of effective therapy, respect for the autonomy of the individual with mild cognitive impairment in information and consent process and the right not to know biomarkers results, need for counseling programs, disclosure of the diagnosis in a structured environment and the involvement of family members, health policies including the individuals' views and the protection of their interests, and the economic costs for society., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The classic view of blood pressure (BP) reactivity to psychological stress in relation to cardiovascular risks assumes that excess reactivity is worse and lower reactivity is better. Evidence addressing how stress-induced BP reactivity in young adults is associated with midlife cognitive function is sparse., Methods and Results: We assessed BP reactivity during a star tracing task and a video game in adults aged 20 to 32 years. Twenty-three years later, cognitive function was assessed with use of the Digit Symbol Substitution Test (a psychomotor speed test), the Rey Auditory Verbal Learning Test (a verbal memory test), and the modified Stroop test (an executive function test). At the time of follow-up, participants (n=3021) had a mean age of 50.2 years; 56% were women, and 44% were black. In linear regression models adjusted for demographic and clinical characteristics including baseline and follow-up resting BP, lower systolic BP (SBP) reactivity during the star tracing and video game was associated with worse Digit Symbol Substitution Test scores (β [SE]: 0.11 [0.02] and 0.05 [0.02], respectively) and worse performance on the Stroop test (β [SE]: -0.06 [0.02] and -0.05 [0.02]; all P<0.01). SBP reactivity was more consistently associated than diastolic BP reactivity with cognitive function scores. The associations between SBP reactivity and cognitive function were mostly similar between blacks and whites., Conclusions: Lower psychological stress-induced SBP reactivity in younger adults was associated with lower cognitive function in midlife. BP reactivity to psychological stressors may have different associations with target organs in hypertension., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: We aimed to investigate the association between dementia severity and weight loss in countries with low and middle incomes, where most prevalent cases reside., Methods: Cross-sectional catchment area surveys were performed in Cuba, Mexico, Venezuela, Peru, Dominican Republic, Puerto Rico, China, and India. In 16,538 older adults (≥65 years of age), significant weight loss was self-reported and confirmed by an informant. We conducted neuropsychological testing and clinical and neurological assessments. Dementia severity was determined by applying a validated algorithm and was quantified by the Clinical Dementia Rating Scale., Results: The characteristics of those who reported weight loss varied across countries. In Poisson models, after controlling for relevant covariates and for waist and arm circumferences, dementia severity was associated with reported weight loss (pooled prevalence ratios [95% confidence intervals {CI}] 2.19 [1.98, 2.41]; 3.81 [3.35, 4.33]; and 5.18 [4.41, 6.10] for CDR 0.5, 1, and 2/3, respectively, compared with CDR 0). The association increased linearly through stages of dementia severity in all countries (P for trend < .001), and between-country heterogeneity was minimal., Conclusions: We found a strong gradient effect in the direct association between dementia severity and reported weight loss, homogeneous across sites from eight countries, consistent with mechanistic data on the role of neurodegenerative processes on energy balance and with dietary changes due to disease severity. Considering the well-recognized effect of weight loss on morbidity and mortality and the large number affected by dementia in less resourced countries, amelioration of weight loss in dementia patients should be considered with priority in these settings., (Published by Elsevier Inc.)

Background: The evidence base on the prevalence of dementia is expanding rapidly, particularly in countries with low and middle incomes. A reappraisal of global prevalence and numbers is due, given the significant implications for social and public policy and planning., Methods: In this study we provide a systematic review of the global literature on the prevalence of dementia (1980-2009) and metaanalysis to estimate the prevalence and numbers of those affected, aged ≥60 years in 21 Global Burden of Disease regions., Results: Age-standardized prevalence for those aged ≥60 years varied in a narrow band, 5%-7% in most world regions, with a higher prevalence in Latin America (8.5%), and a distinctively lower prevalence in the four sub-Saharan African regions (2%-4%). It was estimated that 35.6 million people lived with dementia worldwide in 2010, with numbers expected to almost double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050. In 2010, 58% of all people with dementia lived in countries with low or middle incomes, with this proportion anticipated to rise to 63% in 2030 and 71% in 2050., Conclusion: The detailed estimates in this study constitute the best current basis for policymaking, planning, and allocation of health and welfare resources in dementia care. The age-specific prevalence of dementia varies little between world regions, and may converge further. Future projections of numbers of people with dementia may be modified substantially by preventive interventions (lowering incidence), improvements in treatment and care (prolonging survival), and disease-modifying interventions (preventing or slowing progression). All countries need to commission nationally representative surveys that are repeated regularly to monitor trends., (Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Background: The association between lifelong body mass index (BMI) and cognitive function has not been comprehensively studied., Methods: In more than 2000 men and women born in 1946, we tested associations between BMI gain at 15, 20, 26, 36, 43, and 53 years with respect to the previous measure (gain at age 15 years with respect to BMI at age 11 years), and semantic fluency (animal naming) and cognitive reserve (the National Adult Reading Test) at age 53 years, and verbal memory (word list recall) and speed/concentration (letter cancellation) at ages 43 and 53 years. Measures of BMI gain were adjusted in stages for childhood intelligence, education, socioeconomic position (SEP), lifestyle, and vascular risk factors., Results: Independent of childhood intelligence, BMI gain between ages 26 and 36 years was associated with lower memory scores (β per SD increase in BMI in men = -0.11; 95% confidence interval [CI]: -0.19, -0.02), verbal fluency (β in women = -0.11; 95% CI: -0.20, -0.02), and lower National Adult Reading Test score (β in women = -0.08; 95% CI: -0.15, -0.01), but not with speed/concentration (β in men = 0.02; 95% CI: -0.11, 0.07). Associations were largely explained by educational attainment and SEP (P ≥ .10). However, BMI gain at 53 years in men was independently associated with better memory (β = 0.12; 95% CI: 0.03, 0.22), and both underweight (β = -1.54; 95% CI: -2.52, -0.57) and obese (β = -0.30; 95% CI: -2.52, -0.57) women at 53 years had significantly lower memory scores., Conclusion: The adverse effect of higher BMI gain on midlife cognitive function and cognitive reserve is independent of childhood intelligence but not of education and SEP. The independent association between greater BMI gain in midlife and better cognitive function deserves further investigation., (Published by Elsevier Inc.)