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Background The Finnish Intervention Study to Prevent Cognitive Impairment and Disability is a randomized controlled trial that has tested the efficacy of a multidomain intervention targeting modifiable risk factors to prevent cognitive impairment/dementia. A combination of healthy diet, physical, social and cognitive activity, and management of cardiovascular risks was shown to be an effective model to promote brain health among older people. The aim of this qualitative study was to explore healthcare professionals’ perceptions of facilitators and barriers to implementing this lifestyle programme into health care. Methods Four semi-structured focus group interviews were conducted among healthcare professionals working in primary care and in non-governmental organizations (N=27). Participants were asked to discuss their perceptions of facilitators and barriers for implementing the multidomain intervention into clinical practice. Interviews were analyzed using content analysis. Results Barriers and facilitators described by the healthcare professionals were related to infrastructure and resources, client’s personal characteristics and the lifestyle intervention itself. These main categories included several sub-categories related to knowledge, motivation, resources, individualization and collaboration. The interviewees pointed out that more education on dementia prevention is needed, the work should be coordinated efficiently, resources to provide preventive health care should be adequate and multiprofessional collaboration is needed. Conclusions Transferring a lifestyle intervention from a trial-setting to real life requires knowledge about the factors that influence effective implementation. Identifying drivers and constraints of successful implementation helps to design and tailor future prevention programmes, increases motivation and adherence and supports system change.

Alzheimer’s disease is a multifactorial disorder with a heterogeneous patient population. Comorbidities such as hypertension, hypercholesterolemia and diabetes are known contributors to the disease progression. Indeed, therapies targeting these disorders have been shown efficient in dementia prevention. However, their mechanistic contribution to Alzheimer’s pathology and neurodegeneration has not been fully clarified.In the current study, we used CSF samples from a memory clinic cohort of 90 patients without diagnosed hypertension, hypercholesterolemia, or diabetes nor other neurodegenerative disorder, to investigate 13 molecular markers representing key mechanisms underlying Alzheimer’s pathogenesis. Levels were compared between clinical groups of subjective cognitive decline, mild cognitive impairment, and Alzheimer’s disease. Associations between markers and groups of markers were analyzed by linear regression. Two-step cluster analysis was used to determine patient clusters. Two key markers were further analyzed by immunofluorescence staining in hippocampus from control and AD individuals without hypertension, hypercholesterolemia nor diabetes.CSF angiotensinogen, thioredoxin-1, and interleukin-15 were the biomarkers with the most prominent associations with Alzheimer’s pathology, synaptic and axonal damage. Synaptosomal-associated protein 25 kDa and neurofilament light chain were increased in mild cognitive impairment and Alzheimer cases. When we grouped biomarkers by biological function, we found that inflammatory and survival components were associated with Alzheimer’s pathology, synaptic dysfunction and axonal damage. Moreover, a vascular/metabolic component was associated with synaptic dysfunction. In data-driven analysis, two patient clusters were identified; Older participants with increased CSF markers of oxidative stress, vascular pathology and neuroinflammation were assigned to cluster 1, that was also smaller and characterized by increased synaptic and axonal damage, compared to individuals in cluster 2. Clinical groups were evenly distributed between the clusters.Analysis of post-mortem hippocampal tissue, showed that, compared to controls, angiotensinogen staining was higher in Alzheimer’s disease and was also found to co-localize with phosphorylated-tau.In a population free of common comorbidities, we could still find associations between Alzheimer’s disease biomarkers and markers of pathways associated with increased risk for Alzheimer’s disease (i.e., neuroinflammation, vascular function, oxidative stress and cholesterol homeostasis), suggesting that these pathways are contributing to Alzheimer’s disease mechanisms even in absence of clinically diagnosed comorbidities. The identification of distinct biomarker-driven endophenotypes of cognitive disorder patients, further highlights the biological heterogeneity of Alzheimer’s disease and the importance of developing tailored prevention and treatment strategies.

Background Prader-Willi syndrome (PWS) is a complex rare genetic disorder associated with hypothalamic dysfunction, pituitary hormone deficiencies, hyperphagia and (morbid) obesity. PWS is caused by loss of expression of paternally expressed genes on chromosome 15q11.2-q13. The most common genetic mechanisms leading to PWS are paternal deletion (DEL) and maternal uniparental disomy (mUPD). DELs can be subdivided in type 1 and (smaller) type 2 deletions (DEL-1, DEL-2). Most research has focused on behavioral, cognitive and psychological differences between patients with a DEL-1, DEL-2 or mUPD. However, little is known about the genetic subtype differences in relation to physical health problems. Methods We reviewed the medical files of all adults with genetically confirmed PWS who visited the outpatient clinic of the Center for Adults with Complex Rare Genetic Syndromes at the Erasmus University Medical Center, Rotterdam, the Netherlands, between January 2015 and June 2021. All patients underwent a systematic health screening, including a structured interview, a medical questionnaire, a complete physical examination, biochemical measurements, and a review of the medical records. Health problems, physical complaints, symptoms of disease and behavioral challenges were compared between adults with an mUPD and DEL and between adults with a DEL-1 and DEL-2. Results Twenty-eight adults had an mUPD and 65 a DEL (13 DEL-1, 27 DEL-2, 25 unspecified). Gender, age and BMI did not differ between the genetic subgroups. Although psychiatric problems (psychotic episodes) were significantly more often present in adults with an mUPD (P < 0.001) and scoliosis was more prevalent among patients with DEL (P = 0.04), there was only a slight difference in prevalence of other medical problems like hypertension, cold intolerance, edema, hyperphagia, skin picking, abdominal pain and fatigue. There were no significant differences between DEL-1 and DEL-2. However, fatigue, cold intolerance, edema and hyperphagia were slightly more prevalent among adults with a DEL-1, whereas osteopenia, constipation and skin picking were more prevalent among adults with a DEL-2. Conclusion The differences in health problems between PWS adults with DEL-1, DEL-2 and mUPD are mostly present in the psychological domain. Especially psychotic episodes were more frequent in adults with an mUPD. Apart from scoliosis, there were no significant differences in physical health outcomes between the genetic subtypes. Presentation: Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ATN (β-amyloid [Aβ], tau, neurodegeneration) system categorizes individuals based on their core Alzheimer disease (AD) biomarkers. An important potential future use for ATN is therapeutic decision-making in clinical practice once disease-modifying treatments (e.g., anti-amyloid), become widely available. In this cross-sectional study, we applied ATN and estimated potential eligibility for anti-amyloid treatment in a real-life memory clinic with biomarker assessments integrated into the routine diagnostic procedure and all specialized resources available for the implementation of novel treatments.We included all consecutive patients at the Karolinska University Hospital Memory clinic in Solna, Stockholm, Sweden, who had their first diagnostic visit in April 2018-February 2021, informed consent for the clinic research database, and available clinical and biomarker (CSF and imaging) data. ATN classification was based on CSF Aβ42 (or Aβ42/40; A), CSF phosphorylated tau (T), and medial temporal lobe atrophy (N). For CSF markers, we applied laboratory cutoffs and data-driven cutoffs for comparison (determined with Gaussian mixture modeling). Eligibility for anti-amyloid treatment was assessed following the published recommendations for aducanumab (AD dementia or mild cognitive impairment [MCI] with no evidence of non-AD etiology, appropriate level of cognition, and AD-consistent CSF profile).The study population consisted of 410 patients (52% subjective cognitive impairment, 23% MCI, and 25% any dementia; age 59 ± 7 years, 56% women). Regardless of biomarker cutoffs, most patients were A-T-N- (54%-57%). A+ prevalence was 17%-30% (higher with data-driven cutoffs). Up to 13% of all patients (27% of those with MCI and 28% of those with dementia) were potentially eligible for anti-amyloid treatment when AD-consistent CSF was defined as any A+ profile. When A+T+ profile was required, treatment was targeted more to the dementia than MCI stage (eligibility up to 14% in MCI and 22% in dementia). The opposite applied to earlier-stage intervention (A+T-N-; eligibility up to 12% in MCI and 2% in dementia).In a memory clinic setting with all necessary infrastructure and national guidelines in place for dementia diagnostic examination (best-case scenario), most of the patients did not meet the eligibility criteria for anti-amyloid treatment. Continuing the development of disease-modifying treatments with different mechanisms of action is a priority.

Approximately two-thirds of individuals diagnosed with Alzheimer’s disease are women. Although women tend to have longer life expectancy than men, this does not entirely explain the differences in the prevalence of dementia and Alzheimer’s disease. Some evidence suggests that men and women have different patterns of risk and protective factors across the lifespan. The goal of this chapter is to summarize the current evidence on sex differences in genetic and modifiable lifestyle factors that are associated with dementia risk. These include demographic factors such education, vascular, metabolic, lifestyle, and psychosocial factors, and sex-specific factors such as menopause and andropause. Potential mechanisms such as neural reserve and resilience are also summarized. The chapter also summarizes the evidence from recent multidomain lifestyle intervention trials, and the intervention response observed in men and women. While there have been insightful advancements in the field, many important questions still remain. Considerations for future research and risk reduction initiatives are also highlighted.

The Nordic countries of Denmark, Finland, Iceland, Norway and Sweden, together with Greenland, the Faroe Islands and Aland, have a long history of cooperating and sharing knowledge on gender equali ...

Background The oldest old is the fastest growing age group worldwide and the most prone to severe disability, especially in relation to loss of cognitive function. Improving our understanding of the predictors of cognitive, physical and psychosocial wellbeing among the oldest old can result in substantial benefits for the individuals and for the society as a whole. The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study investigated risk factors and determinants of cognitive impairment in a population-based longitudinal cohort, which was first examined between 1972 and 1992, when individuals were in their midlife, and re-assessed in 1998 and 2005–2009. Most of the study participants are currently aged 85 years or older. We aim to re-examine the cohort’s survivors and gain further insights on the mechanisms underlying both cognitive and overall healthy ageing at old age. Methods CAIDE85+ is the third follow-up of the CAIDE study participants. All individuals still alive and living in the Kuopio and Joensuu areas of Eastern Finland, from the original CAIDE cohort (two random samples, N = 2000 + ~ 900), will be invited to a re-examination. The assessment includes self-reported data related to basic demographics and lifestyle, as well as psychosocial and physical health status. Cognitive and physical evaluations are also conducted. Blood biomarkers relevant for dementia and ageing are assessed. Primary outcomes are the measurements related to cognition and daily life functioning (CERAD, Trail Making Test-A, Letter-Digit Substitution Test, Clinical Dementia Rating and Activities of Daily Living). Secondary endpoints of the study are outcomes related to physical health status, psychosocial wellbeing, as well as age-related health indicators. Discussion Through a follow-up of more than 40 years, CAIDE85+ will provide invaluable information on the risk and protective factors that contribute to cognitive and physical health, as well as ageing and longevity. Study registration The present study protocol has been registered at https://clinicaltrials.gov/ (registration nr NCT03938727 , date 03.05.2019).

Objectives To explore older adults' reasons for participating in a multinational eHealth prevention trial, and compare motivations between countries. Design Cross-sectional mixed methods research using quantitative and qualitative approaches (the ACCEPT-HATICE study). Setting and Participants Substudy conducted during the recruitment phase of an 18-month RCT testing the efficacy of an eHealth intervention for self-management of risk factors for cardiovascular disease (CVD) and cognitive decline in older adults in Finland, France, and the Netherlands. Participants were 343 dementia-free community dwellers aged 65+ with basic computer literacy and either ≥2 cardiovascular risk factors or a history of CVD/diabetes. Measures Online questionnaire (quantitative data) and semistructured interviews (qualitative data). Results Contributing to scientific progress, wanting to improve one's lifestyle, and benefiting from additional medical monitoring were the predominant reasons for participating. Altruistic reasons were particularly relevant among the French, whereas Finnish and Dutch participants mainly emphasized the benefits of lifestyle changes and regular medical checkups. During interviews, preventing functional dependency emerged as a key underlying motivation. Although some trial design features influenced the decision to participate, the use of an eHealth intervention was not an important motivator in this population. Conclusions/Implications Altruism and personal benefits motivated older adults to participate in the trial; emphasizing such aspects could facilitate recruitment in future RCTs. Additional medical monitoring may be particularly appealing when access to public health care is considered limited. Furthermore, maintaining autonomy and preventing functional dependency emerged as a key concern in this population of young older adults.

ObjectivesGlobal ageing is linked to an increased burden of cardiovascular disease and dementia, which calls for better prevention strategies. Self-management and eHealth applications are regarded as promising strategies to support prevention. The aim of this study was to explore nurses’ best practices concerning behaviour change guidance for cardiovascular (CV) prevention in order to learn how to optimally integrate them into a coach-supported internet platform for CV self-management.DesignQualitative focus group study in Finland and the Netherlands. Discussions were audiotaped and transcribed. Data were thematically analysed following principles of grounded theory.SettingDutch and Finnish primary care settings.ParticipantsSix Finnish and seven Dutch primary care nurses with experience in CV prevention.ResultsSimilar best practices were found in both countries and comprised of (1) establishing a relationship of trust, (2) managing awareness and expectations and (3) appropriate timing and monitoring of the process of behaviour change. However, the Finnish and Dutch nurses used different approaches for accomplishment of these practices, which was reflected in their recommendations for online support. Both groups emphasised that online support should be combined with human support and integrated into regular care. Finnish nurses had more confidence in patient self-management and remote communication than Dutch nurses, who emphasised the importance of face-to-face contact and preferred to keep control of medical aspects of prevention.ConclusionsDifferences in Dutch and Finnish’s nurses’ practices for supporting CV prevention appear to reflect their local healthcare practices, which should be taken into account when designing internet platforms for health self-management. Including cognitive health as a goal of CV prevention might stimulate motivation for health behaviour change.Trial registration numberISRCTN48151589; Pre-results.

Alzheimer’s disease (AD) and dementia are a global public health priority, and prevention has been highlighted as a pivotal component in managing the dementia epidemic. Modifiable risk factors of dementia and AD include lifestyle-related factors, vascular and metabolic disorders, and psychosocial factors. Randomized controlled clinical trials (RCTs) are needed to clarify whether modifying such factors can prevent or postpone cognitive impairment and dementia in older adults. Given the complex, multifactorial, and heterogeneous nature of late-onset AD and dementia, interventions targeting several risk factors and mechanisms simultaneously may be required for optimal preventive effects. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is the first large, long-term RCT to demonstrate that a multidomain lifestyle-based intervention ameliorating vascular and lifestyle-related risk factors can preserve cognitive functioning and reduce the risk of cognitive decline among older adults at increased risk of dementia. To investigate the multidomain intervention in other populations and diverse cultural and geographical settings, the World-Wide FINGERS (WW-FINGERS) network was recently launched (https://alz.org/wwfingers). Within this network, new FINGER-type trials with shared core methodology, but local culture and context-specific adaptations, will be conducted in several countries. The WW-FINGERS initiative facilitates international collaborations, provides a platform for testing multidomain strategies to prevent cognitive impairment and dementia, and aims at generating high-quality scientific evidence to support public health and clinical decision-making. Furthermore, the WW-FINGERS network can support the implementation of preventive strategies and translation of research findings into practice.

Background Determination of β-amyloid (Aβ) positivity and likelihood of underlying Alzheimer’s disease (AD) relies on dichotomous biomarker cut-off values. Individuals with mild cognitive impairment (MCI) and Aβ within the normal range may still have a substantial risk of developing dementia, primarily of Alzheimer type. Their prognosis, as well as predictors of clinical progression, are not fully understood. The aim of this study was to explore the associations of cerebrospinal fluid (CSF) biomarkers (Aβ42, total tau, phosphorylated tau) and other characteristics, including modifiable vascular factors, with the risk of progression to dementia among patients with MCI and normal CSF Aβ42. Methods Three hundred eighteen memory clinic patients with CSF and clinical data, and at least 1-year follow-up, were included. Patients had normal CSF Aβ42 levels based on clinical cut-offs. Cox proportional hazard models with age as time scale and adjusted for sex, education, and cognition (Mini-Mental State Examination) were used to investigate predictors of progression to dementia and Alzheimer-type dementia. Potential predictors included CSF biomarkers, cognitive performance (verbal learning and memory), apolipoprotein E (APOE) ε4 genotype, medial temporal lobe atrophy, family history of dementia, depressive symptoms, and vascular factors, including the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score. Predictive performance of patient characteristics was further explored with Harrell C statistic. Results Lower normal Aβ42 and higher total tau and phosphorylated tau were associated with higher dementia risk, and the association was not driven by Aβ42 values close to cut-off. Additional predictors included poorer cognition, APOE ε4 genotype, higher systolic blood pressure, and lower body mass index, but not the CAIDE dementia risk score. Aβ42 individually and in combination with other CSF biomarkers improved the risk prediction compared to age and cognition alone. Medial temporal lobe atrophy or vascular factors did not increase the predictive performance. Conclusions Possibility of underlying AD pathology and increased dementia risk should not be ruled out among MCI patients with CSF Aβ42 within the normal range. While cut-offs may be useful in clinical practice to identify high-risk individuals, personalized risk prediction tools incorporating continuous biomarkers may be preferable among individuals with intermediate risk. The role of modifiable vascular factors could be explored in this context.

For centuries, the marine quarantine system was the major protection of the public health against serious infectious diseases around the world. The present study reconstructs the history of the Quarantine Station of Piraeus, one of the largest Mediterranean ports, known as the "Lazaretto of Saint George", as a vital element in the maritime sanitary protection of Greece. Our research will investigate the impact left by this institution on public health, as well as on the economic life of the port of Piraeus and the adjacent capital city of Athens. With regard to the first issue, we will seek to evaluate its role in relation to major outbreaks in the capital, as well as the arrival of 1.3 million Greek refugees after the Greco-Turkish War of 1922. The opening of Suez Canal (1865) was a great challenge and the institution was problematic at administrative and sanitary levels. During 20th century, the station complied with the national public health legislation and the international sanitary conventions. Until the Second World War, the Lazaretto of Saint George played a key role in both the protection of public health in general, but also in the economic and industrial progress of Piraeus and Athens.

For centuries, the marine quarantine system was the major protection of the public health against serious infectious diseases around the world. The present study reconstructs the history of the Quarantine Station of Piraeus, one of the largest Mediterranean ports, known as the “Lazaretto of Saint George”, as a vital element in the maritime sanitary protection of Greece. Our research will investigate the impact left by this institution on public health, as well as on the economic life of the port of Piraeus and the adjacent capital city of Athens. With regard to the first issue, we will seek to evaluate its role in relation to major outbreaks in the capital, as well as the arrival of 1.3 million Greek refugees after the Greco-Turkish War of 1922. The opening of Suez Canal (1865) was a great challenge and the institution was problematic at administrative and sanitary levels. During 20th century, the station complied with the national public health legislation and the international sanitary conventions. Until the Second World War, the Lazaretto of Saint George played a key role in both the protection of public health in general, but also in the economic and industrial progress of Piraeus and Athens.

Purpose: The aim of this study was to improve concordance by investigating important sources of information on self-management for families of children with paediatric cataracts from the perspective of parents and ophthalmologists. Methods: This mixed methods study involved a deductive approach using a questionnaire administered to 69 families of children operated on and registered with the Swedish Pediatric Cataract Register (PECARE Sweden) in southern Sweden, as well as 30 paediatric ophthalmologists who monitored the patients on their return to the local health care facility. An inductive approach was applied through an analysis of open-ended questions on self-management. Both groups were asked about their perception of the value of strategies for providing information and the timing of this. Results: The response rate was 68% for families and 93% for ophthalmologists. Both groups agreed that ophthalmology visits were the most important source of information, followed by written and online information. Parents of children diagnosed before the age of three months were more likely to prefer written information. Content analysis revealed that a person-centred approach is important. Conclusions: Parents, particularly those whose children were diagnosed at a young age, need more and better-directed information. Promoting self-management may play a decisive role in treatment outcomes.

The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multidomain lifestyle intervention trial (NCT01041989) demonstrated beneficial effects on cognition. We investigated whether sociodemographics, socioeconomic status, baseline cognition, or cardiovascular factors influenced intervention effects on cognition.The FINGER recruited 1260 people from the general Finnish population (60-77 years, at risk for dementia). Participants were randomized 1:1 to multidomain intervention (diet, exercise, cognition, and vascular risk management) and regular health advice. Primary outcome was change in cognition (Neuropsychological Test Battery z-score). Prespecified analyses to investigate whether participants' characteristics modified response to intervention were carried out using mixed-model repeated-measures analyses.Sociodemographics (sex, age, and education), socioeconomic status (income), cognition (Mini-Mental State Examination), cardiovascular factors (body mass index, blood pressure, cholesterol, fasting glucose, and overall cardiovascular risk), and cardiovascular comorbidity did not modify response to intervention (P-values for interaction.05).The FINGER intervention was beneficial regardless of participants' characteristics and can thus be implemented in a large elderly population at increased risk for dementia.

Metastasis formation is strongly dependent on the migration capabilities of tumor cells. Recently it has become apparent that nuclear structure and morphology affect the cellular ability to migrate. Previously we found that migration of melanoma cells is both associated with and dependent on global chromatin condensation. Therefore, we anticipated that tumor progression would be associated with increased chromatin condensation. Interestingly, the opposite has been reported for melanoma. In trying to resolve this contradiction, we show that during growth conditions, tumor progression is associated with global chromatin de-condensation that is beneficial for faster proliferation. However, upon induction of migration, in both low- and high-metastatic mouse melanoma cells chromatin undergoes condensation to support cell migration. Our results reveal that throughout tumor progression induction of chromatin condensation by migration signals is maintained, whereas the organization of chromatin during growth conditions is altered. Thus, tumor progression is associated with an increase in chromatin dynamics.

With an aging population on the rise, there is a projected exponential expansion in the prevalence of dementia, particularly Alzheimer's disease (AD). AD is the most common form of dementia, characterized by senile plaques and tangles in the brain. Although the pathophysiology and clinical symptoms are well described, the etiology and pathogenesis of the disease are still unknown. Over the past few decades, research has shown that a number of hormones and their respective systems are dysregulated in the course of cognitive aging and AD. This chapter summarizes some of the implicated hormones, including gonadal hormones, adrenal hormones, insulin, and melatonin. Finally, the chapter ends with a brief summary of some of the genetic variants that have been found to modulate the aforementioned hormones in relation to pathological cognitive decline.

Greece is a case particularly worthy of attention within the panorama of Federico Garcia Lorca's worldwide reception. In comparison to other countries, Lorca's presence in Greece has remained uninterrupted since his first appearance and remains current, with new translations, rewritings, adaptations, and stagings of his plays continually being produced. Lorca has also spurred a wide range of creative responses inspired by his life and death such as essays, music, poetry, and dramas. He has also stimulated debates over aesthetic, literary, cultural, ideological and political issues, and has thus become indissolubly bound to the Greek cultural environment both as a Greek and a Spanish icon. This paper examines the ways Lorca has been received and treated in Greece in relation to the cultural and historical context.

Ethical issues abound in any relationship that is defined by differences between the parties in rank, status, and power. Such is the case in the relationship between a doctoral student in clinical psychology and his or her mentor. In this article, we examine several potential areas of ethical concern within the mentor-student relationship. We present a series of vignettes and our analyses of the issues that arise within them as we examine romantic dual relationships, nonromantic dual relationships, and other ways in which the mentor's power may be intentionally or unintentionally misused for personal gain. We also look at several examples of unhelpful mentoring. Problematic situations often arise when there is the potential for loss of objectivity by either party or exploitation of the student by the mentor. Although the relationship with one's mentor may be one of the most important and gratifying aspects of the graduate school experience, both mentors and students should keep in mind that behavioral choices within this relationship are often complex ones that require forethought, self-monitoring, and discussion between the parties.

Previous research indicates that people with social anxiety disorder tend to experience escalating distress when thinking about past social situations. We investigated whether such distress could be limited by either an intervention or the participant's pre-existing abilities. Participants were 38 undergraduate students who reported problematic levels of social anxiety. Participants who endorsed a poor ability to purposefully engage with thoughts about stressful social situations reported a deterioration of mood after 25 min of unstructured writing about a recent problematic social situation, whereas those who demonstrated low levels of purposeful engagement but received writing prompts (based on cognitive restructuring techniques) did not show a strong deterioration of mood. In contrast, participants who endorsed greater purposeful engagement ability did not show such deterioration. Results suggest that the negative effects of thinking about social situations might be ameliorated, for at least some participants, if they are provided with structure.