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Purpose: To evaluate different registration methods, setup margins and number of corrections for CBCT-based position verification for oesophageal cancer and to evaluate anatomical changes during the course of radiotherapy treatment. Methods: From 50 patients, 440 CBCT-scans were registered automatically using a soft tissue or bone registration algorithm and compared to the clinical match. Moreover, relevant anatomical changes were monitored. A sub-analysis was performed to evaluate if tumour location influenced setup variations. Margin calculation was performed and the number of setup corrections was estimated. Results were compared to a patient group previously treated with MV-EPID based position verification. Results: CBCT-based setup variations were smaller than EPID-based setup variations, resulting in smaller setup margins of 5.9 mm (RL), 7.5 mm (CC) and 4.7 mm (AP) versus 6.0 mm, 7.8 mm and 5.5 mm, respectively. A reduction in average number of setup corrections per patient was found from 0.75 to 0.36. From all automatically registered CBCT-scans, a clipbox around PTV and vertebras combined with soft tissue registration resulted in the smallest setup margins of 5.9 mm (RL), 7.7 mm (CC), 4.8 mm (AP) and smallest average number of corrections of 0.38. For distally located tumours, a setup margin of 7.7 mm (CC) was required compared to 5.6 mm for proximal tumours. Reduction of GTV volume, heart volume and change in diaphragm position were observed in 16, 10 and 15 patients, respectively. Conclusions: CBCT-based set-up variations are smaller than EPID-based variations and vary according to tumour location. When using kV-CBCT a large variety of anatomical changes is revealed, which cannot be observed with MV-EPID.

Dog-assisted therapy is hypothesized to lower stress in children with autism spectrum disorder (ASD) and children with Down syndrome (DS), which may be visible on a physiological level. In this study, we measured heart rate variability (HRV) and salivary cortisol of 20 children with DS or ASD at the beginning and end of six weekly sessions of dog-assisted therapy. We found a decrease of cortisol levels during single sessions, but no overall effect after six sessions (six weeks). The effect of dog-assisted therapy on the increase of HRV could not be confirmed. This study is one of the first to use physiological measurements to test the effects of DAT.

Human cytomegalovirus (HCMV) is the most frequent viral cause of congenital defects and can trigger devastating disease in immune-suppressed patients. Cytotoxic lymphocytes (CD8+ T cells and NK cells) control HCMV infection by releasing interferon-γ and five granzymes (GrA, GrB, GrH, GrK, GrM), which are believed to kill infected host cells through cleavage of intracellular death substrates. However, it has recently been demonstrated that the in vivo killing capacity of cytotoxic T cells is limited and multiple T cell hits are required to kill a single virus-infected cell. This raises the question whether cytotoxic lymphocytes can use granzymes to control HCMV infection in a noncytotoxic manner. Here, we demonstrate that (primary) cytotoxic lymphocytes can block HCMV dissemination independent of host cell death, and interferon-α/β/γ. Prior to killing, cytotoxic lymphocytes induce the degradation of viral immediate-early (IE) proteins IE1 and IE2 in HCMV-infected cells. Intriguingly, both IE1 and/or IE2 are directly proteolyzed by all human granzymes, with GrB and GrM being most efficient. GrB and GrM cleave IE1 after Asp398 and Leu414, respectively, likely resulting in IE1 aberrant cellular localization, IE1 instability, and functional impairment of IE1 to interfere with the JAK-STAT signaling pathway. Furthermore, GrB and GrM cleave IE2 after Asp184 and Leu173, respectively, resulting in IE2 aberrant cellular localization and functional abolishment of IE2 to transactivate the HCMV UL112 early promoter. Taken together, our data indicate that cytotoxic lymphocytes can also employ noncytotoxic ways to control HCMV infection, which may be explained by granzyme-mediated targeting of indispensable viral proteins during lytic infection.

Pertussis is a highly contagious respiratory infection caused by the bacterium Bordetella pertussis. Humans are the only known natural reservoir of B. pertussis. In mice, macrophages and NK cells have a key role in confining B. pertussis to the respiratory tract. However, the mechanisms underlying this process, particularly during human infections, remain unclear. Here we characterized the activation of human macrophages and NK cells in response to B. pertussis and unraveled the role of inflammasomes in this process. NLRP3 inflammasome activation by B. pertussis in human macrophage-like THP-1 cells and primary monocyte-derived macrophages (mo-MΦ) was shown by the visualization of ASC-speck formation, pyroptosis, and the secretion of caspase-mediated IL-1β and IL-18. In contrast to macrophages, stimulation of human CD56+CD3− NK cells by B. pertussis alone did not result in activation of these cells. However, co-culture of B. pertussis-stimulated mo-MΦ and autologous NK cells resulted in high amounts of IFNγ secretion and an increased frequency of IL-2Rα+ and HLA-DR+ NK cells, indicating NK cell activation. This activation was significantly reduced upon inhibition of inflammasome activity or blocking of IL-18 in the mo-MΦ/NK cell co-culture. Furthermore, we observed increased secretion of proinflammatory cytokines in the B. pertussis-stimulated mo-MΦ/NK co-culture compared to the mo-MΦ single culture. Our results demonstrate that B. pertussis induces inflammasome activation in human macrophages and that the IL-18 produced by these cells is required for the activation of human NK cells, which in turn enhances the pro-inflammatory response to this pathogen. Our data provides a better understanding of the underlying mechanisms involved in the induction of innate immune responses against B. pertussis. These findings contribute to the knowledge required for the development of improved intervention strategies to control this highly contagious disease.

Background: We aimed to develop risk tools for dementia, stroke, myocardial infarction (MI), and diabetes, for adults aged ≥ 65 years using shared risk factors., Methods: Data were obtained from 10 population-based cohorts (N = 41,755) with median follow-up time (years) for dementia, stroke, MI, and diabetes of 6.2, 7.0, 6.8, and 7.4, respectively. Disease-free participants at baseline were included, and 22 risk factors (sociodemographic, medical, lifestyle, laboratory biomarkers) were evaluated. Two risk tools (DemNCD and DemNCD-LR based on Fine and Gray sub-distribution and logistic regression [LR], respectively) were developed and validated. Predictive accuracies of these risk tools were assessed using Harrel's C-statistics and area under the curve (AUC) and 95% confidence interval (CI). Model calibration was conducted using Hosmer-Lemeshow goodness of fit test along calibration plots., Results: Both the DemNCD and DemNCD-LR resulted in similar predictive accuracy for each outcome. The overall AUC (95% CI) for dementia, stroke, MI, and diabetes risk tool were 0·68 (0·65, 0·70), 0·58 (0·54, 0·61), 0·65 (0·61, 0·68), and 0·68 (0·64, 0·72), respectively, for males. For females, these figures were 0·65 (0·63, 0·67), 0·55 (0·52, 0·57), 0·65 (0·62, 0·68), and 0·61 (0·57, 0·65)., Conclusions: The DemNCD is the first tool to predict both dementia and multiple cardio-metabolic diseases using comprehensive risk factors and provided similar predictive accuracy to existing risk tools. It has similar predictive accuracy as tools designed for single outcomes in this age-group. DemNCD has the potential to be used in community and clinical settings as it includes self-reported and routinely available clinical measures., (© 2024. The Author(s).)

Objectives: This study investigated whether the association between modifiable dementia risk and rate of cognitive decline differs across socioeconomic status (SES) strata., Design, Setting and Participants: Data were used from Maastricht Aging Study, a prospective cohort study with a 12-year follow-up. The baseline sample consisted of 1023 adults over 40 years old., Measurements: The "LIfestyle for BRAin health" (LIBRA) index was used to assess modifiable dementia risk. Cognitive performance was assessed at baseline, 6 and 12 years, and measured in the domains of information processing speed, executive functioning and verbal memory function. An SES score was calculated from equivalent income and educational level (tertiles). Linear mixed models were used to study the association between LIBRA, SES and their interaction on the rate of cognitive decline., Results: Participants in the lowest SES tertile displayed more decline in information processing speed (vs. middle SES: X 2 = 7.08, P = 0.029; vs. high SES: X 2 = 9.49, P = 0.009) and verbal memory (vs. middle SES: X 2 = 9.28, P < 0.001; vs. high SES: X 2 = 16.68, P < 0.001) over 6 years compared to their middle- and high-SES counterparts. Higher (unhealthier) LIBRA scores were associated with more decline in information processing speed (X 2 = 12.66, P = 0.002) over 12 years and verbal memory (X 2 = 4.63, P = 0.032) over 6 years. No consistent effect modification by SES on the association between LIBRA and cognition was found., Conclusions: Results suggest that lifestyle is an important determinant of cognitive decline across SES groups. Yet, people with low SES had a more unfavorable modifiable risk score suggesting more potential for lifestyle-based interventions.

Background: Overweight and obesity impose a considerable individual and social burden, and the urban environments might encompass factors that contribute to obesity. Nevertheless, there is a scarcity of research that takes into account the simultaneous interaction of multiple environmental factors., Objectives: Our objective was to perform an exposome-wide association study of body mass index (BMI) in a multicohort setting of 15 studies., Methods: Studies were affiliated with the Dutch Geoscience and Health Cohort Consortium (GECCO), had different population sizes (688-141,825), and covered the entire Netherlands. Ten studies contained general population samples, others focused on specific populations including people with diabetes or impaired hearing. BMI was calculated from self-reported or measured height and weight. Associations with 69 residential neighborhood environmental factors (air pollution, noise, temperature, neighborhood socioeconomic and demographic factors, food environment, drivability, and walkability) were explored. Random forest (RF) regression addressed potential nonlinear and nonadditive associations. In the absence of formal methods for multimodel inference for RF, a rank aggregation-based meta-analytic strategy was used to summarize the results across the studies., Results: Six exposures were associated with BMI: five indicating neighborhood economic or social environments (average home values, percentage of high-income residents, average income, livability score, share of single residents) and one indicating the physical activity environment (walkability in 5 -km buffer area). Living in high-income neighborhoods and neighborhoods with higher livability scores was associated with lower BMI. Nonlinear associations were observed with neighborhood home values in all studies. Lower neighborhood home values were associated with higher BMI scores but only for values up to € 300,000 . The directions of associations were less consistent for walkability and share of single residents., Discussion: Rank aggregation made it possible to flexibly combine the results from various studies, although between-study heterogeneity could not be estimated quantitatively based on RF models. Neighborhood social, economic, and physical environments had the strongest associations with BMI. https://doi.org/10.1289/EHP13393.

Background: Several lifestyle, cardiovascular and psychosocial factors are associated with risk of cognitive decline and dementia. We studied the independent associations of a broad set of modifiable risk factors with decline in processing speed in three large population-based cohorts with up to 23 years of follow-up., Methods: We used data of 9,666 participants from the Doetinchem Cohort Study, the Longitudinal Aging Study Amsterdam, and the Maastricht Aging Study. Decline in processing speed was measured with the letter digit substitution task or the alphabet coding task and modeled using quadratic latent growth curves. Associations of modifiable risk factors with level and rate of decline in processing speed were investigated by estimating associations with level of processing speed at different centering ages., Results: Latent growth curves showed that decline in processing speed accelerated with age. Smoking, not drinking alcohol and depressive symptoms were associated with a lower level of processing speed in all cohorts. In two of the cohorts, more physical activity, drinking more than two glasses of alcohol per day, higher BMI and diabetes were associated with a lower level of processing speed. Depressive symptoms and diabetes were also associated with faster decline in processing speed., Conclusion: Several modifiable risk factors are associated with the level of processing speed in older age, while few are also related to the rate of decline., Competing Interests: The authors have no relevant financial or non-financial interests to disclose.

Background: Evidence on modifiable risk factors for dementia is accumulating rapidly, including e.g. smoking, hypertension, and diabetes. Comparing knowledge of risk factors for dementia and factors associated with knowledge and motivation to learn about dementia risk reduction in different countries may support the design of tailored public health campaigns. We investigated (1) differences in knowledge of risk and protective factors for dementia between the Netherlands and Germany, and interest in (2) information on brain health and (3) eHealth for brain health., Materials and Methods: Population-based telephone (Germany) or web-based surveys (Netherlands) were conducted among adults aged 60-75 (n total =614; Germany: n = 270; Netherlands: n = 344), assessing sociodemographic factors, knowledge of risk and protective factors for dementia, interest in information on brain health and respective eHealth-tools. Correlates of knowledge, interest in information on brain health and eHealth for brain health were analyzed using multivariable regression, by country and in pooled analyses., Results: In the total sample (M age : 67.3 (SD: 4.3) years; % female : 48.6), knowledge of risk and protective factors (sum score assessing number of correctly identified factors) was higher among German participants (M (SD) = 7.6 (2.5) vs. 6.0 (4.3), p < .001). This was confirmed using linear regression analyses, controlling for sociodemographic covariates (b = 1.51; 95% CI: 1.00; 2.01). High education was linked to better knowledge of risk and protective factors (b = 1.61; 95% CI: 0.89; 2.34). Controlling for covariates, interest in information on brain health (OR: 0.05, 95% CI: 0.02; 0.09) and eHealth for brain health (OR: 0.40, 95% CI: 0.25; 0.65) was lower in German participants. Widowed participants were less interested in information on brain health, while widowed and single participants expressed less interest in eHealth for brain health in pooled analyses. Further associations between sociodemographic factors, interest in information on brain health and eHealth for brain health by country were detected., Discussion: Engaging older adults in the design of eHealth interventions and cooperation with trusted sources, e.g., general practitioners, might enhance appreciation of eHealth for brain health. Education on risk and protective factors for dementia is warranted in both countries. However, differences in recruitment and assessment need to be acknowledged., (© 2023. The Author(s).)

Background: Informal care for people with dementia not only affects the well-being of the primary caregiver but also changes their roles and interactions with the social environment. New online interventions might facilitate access to social support. Recently, an online social support platform, Inlife, was developed in the Netherlands and aims to enhance social support and positive interactions in informal support networks., Objective: This study aimed to evaluate the effectiveness of Inlife for caregivers of people with dementia., Methods: A randomized controlled trial with 96 caregivers of people with dementia was performed. Participants were randomly assigned to the Inlife intervention or the waiting list control group. After 16 weeks of Inlife use, the waiting list control group could start using Inlife. Effects were evaluated at baseline (T 0 ), 8 weeks (T 1 ), and 16 weeks (T 2 ). The 16-week follow-up assessment (T 2 ) served as the primary endpoint to evaluate the results for the primary and secondary outcome variables evaluated with online self-report questionnaires. The primary outcomes included feelings of caregiver competence and perceived social support. The secondary outcomes included received support, feelings of loneliness, psychological complaints (eg, anxiety, stress), and quality of life., Results: No significant improvements were demonstrated for the intervention group (n=48) relative to the control group (n=48) for the primary outcomes (feeling of carer competence: b=-0.057, 95% CI -0.715 to 0.602, P=.87; perceived social support: b=-15.877, 95% CI -78.284 to 46.530, P=.62) or any secondary outcome. This contrasts with our qualitative findings showing the potential of Inlife to facilitate the care process in daily life. Adherence was not optimal for all Inlife users. Additional per-protocol and sensitivity analyses also revealed no beneficial results for high active Inlife users or specific subgroups. Inlife users were more active when part of a larger network., Conclusions: Researchers should be modest regarding the effectiveness of online caregiver interventions in terms of quantitative measures of well-being and quality of life. Nevertheless, online tools have the potential to facilitate the caregiver process in daily life. Lessons learned include the importance of harnessing the power of human interaction in eHealth, making use of the user's social capital, and the need to develop research methods that can identify benefits in daily life that are ecologically valid for caregivers., Trial Registration: Netherlands Trial Register NTR6131; https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6131., International Registered Report Identifier (irrid): RR2-10.1186/s13063-017-2097-y., (©Hannah Liane Christie, Alieske Elisabeth Henrike Dam, Martin van Boxtel, Sebastian Köhler, Frans Verhey, Marjolein Elisabeth de Vugt. Originally published in JMIR Aging (https://aging.jmir.org), 07.12.2022.)

Background: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts., Methods: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence., Results: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades., Conclusions: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.

Objectives: Evaluate the effect of a health promotion campaign aimed at increasing awareness about dementia risk reduction in middle-aged community-dwelling individuals in the Netherlands., Design: A 10-month public health campaign using mass media and community participation, supported by eHealth. Population-level difference in awareness before and after the campaign, including variation between demographic groups, was assessed in two independent cross-sectional samples from the same target population., Setting: The public health campaign was launched in the Province of Limburg, the Netherlands, targeting all inhabitants aged 40-75 years old. Three specific districts within the Province were chosen for an additional community participation approach, in which local stakeholders were invited to support the campaign., Results: No pre- (n=590) post- (n=602) difference was observed in people agreeing to the statement that dementia risk reduction is possible (X 2 (1)=1.27, p=0.260). For the individual lifestyle factors, physical activity (7.6% increase (X 2 (1)=7.48, p=0.006)) and healthy diet (10.5% increase (X 2 (1)=12.37, p≤0.001)) were identified more often as being protective against dementia after the campaign. Of all risk/protective factors assessed, cognitive activity was identified most often at both preassessment (79.4%) and postassessment (80.4%), but there was no increase in awareness (X 2 (1)=0.17, p=0.677). Self-reported exposure to the campaign was associated with greater awareness and motivation for behavioural change (X 2 (1)=6.52, p=0.011). Compared with mass media only, the addition of community participation resulted in better recognition of campaign material and the eHealth platform., Conclusions: This study was not able to reach a population-level increase of awareness of dementia risk reduction. Two out of the three lifestyle factors that formed the foundation of the campaign were identified more often after the campaign. Those reported having been exposed to the campaign were more aware and more inclined towards behavioural change., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied., Methods: We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype., Results: Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10-1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38-6.47) and Latin America (OR = 1.49, 95% CI = 1.04-2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33-3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81-26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07-3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44-8.35) in Asia., Conclusion: Parity is associated with women's risk of dementia, though this is not uniform across regions and dementia subtypes.

Background: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups., Methods and Findings: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife., Conclusions: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: AEA is a consultant for Kinsa Inc. and has received an unrestricted gift from Gojo Inc. CB is a member of the Editorial Board of PLOS Medicine. HB is on the Advisory Board of Nutricia Australia. MG was on Biogen Inc’s “Patient Journey Advisory Group” in 2016 and 2017. NS reports personal fees from Merck Consumer Health and the NIH outside the submitted work. RBL is the Edwin S. Lowe Professor of Neurology at the Albert Einstein College of Medicine in New York. He receives research support from the NIH: 2PO1 AG003949 (mPI), 5U10 NS077308 (PI), RO1 NS082432 (Investigator), 1RF1 AG057531 (Site PI), RF1 AG054548 (Investigator), 1RO1 AG048642 (Investigator), R56 AG057548 (Investigator), K23 NS09610 (Mentor), K23AG049466 (Mentor), 1K01AG054700 (Mentor). He also receives support from the Migraine Research Foundation and the National Headache Foundation. He serves on the editorial board of Neurology, senior advisor to Headache, and associate editor to Cephalalgia. He has reviewed for the NIA and NINDS, holds stock options in eNeura Therapeutics and Biohaven Holdings; serves as consultant, advisory board member, or has received honoraria from: American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, Vedanta. He receives royalties from Wolff’s Headache 7th and 8th Edition, Oxford Press University, 2009, Wiley and Informa. PSS received grant funding from the NIH/NIA (USA) and the NHMRC (Australia), as well as philanthropic funding through The Dementia Momentum. He is on the Australian Advisory Board of Biogen Pharmaceuticals. All other authors have declared that no competing interests exist.

Background: The total number of people with dementia is increasing worldwide, due to our aging society. Without a disease-modifying drug available, risk reduction strategies are to date the only promising way to reduce dementia incidence in the future. Substantial evidence exists that lifestyle factors contribute to the risk of dementia, such as physical exercise, mental activity and (non-)smoking. Still, most people seem unaware of a relationship between lifestyle and brain health. This paper investigates dementia literacy and knowledge of modifiable risk and protective factors of dementia in a Dutch population-based sample., Methods: An online-survey was carried out among 590 community-dwelling people between 40 and 75 years old in the Province of Limburg, the Netherlands. The total group comprises both of a provincial sample (n = 381) and a sample of three specific districts within the province (n = 209). Dementia awareness and knowledge about 12 risk and protective factors was assessed with items derived from the British Social Attitudes (BSA) survey, supplemented with custom items developed by the research team., Results: The majority of participants (56%) were unaware of a relationship between lifestyle and dementia risk. Most individuals identified low cognitive activity, physical inactivity and unhealthy diet as dementia risk factors. Particular gaps in knowledge existed with regard to major cardiovascular risk factors such as hypertension, hypercholesterolemia and coronary heart disease. Although the level of awareness varied by age and level of education, most people (70%) were eager to learn more about the topic of brain health, and indicated to be interested in using eHealth (54%) to measure or improve brain health., Conclusions: Most people still are unaware of the relation between lifestyle and brain health, indicating the need for public health campaigns. Increasing awareness in the general population about the presence of modifiable dementia risk and protective factors is a crucial first step prior to implementation of preventative measures. Targeting specific subgroups, such as individuals with low socioeconomic status and low health literacy, is essential for the reach and effect of a prevention campaign. Outcome of this study was the rationale for an awareness campaign in The Netherlands, called "MijnBreincoach" ("MyBraincoach").

Objective: Studies have shown preliminary support for mindfulness-based interventions benefitting people with dementia and their caregivers. However, most studies focus on these two groups separately. This study examined whether it would be possible and beneficial for people with dementia and their caregiver to jointly undergo an adjusted Mindfulness-Based Stress Reduction (MBSR) training, named TANDEM., Methods: The 8-week MBSR training was adjusted based on a literature review and interviews with experts (clinicians and mindfulness trainers). Seven couples (a person with early-stage dementia and their caregiver) participated together in the 8-week TANDEM program. Semi-structured qualitative interviews were conducted after completion. Questionnaires (administered before and after the intervention) assessed the primary outcomes of quality of life and psychological distress (stress, anxiety and depressive symptoms). Secondary outcomes were mindfulness, self-compassion, positive mental health, worrying, and perceived burden (for caregivers)., Results: All participants completed the program and reported beneficial effects (relaxation, awareness, acceptance, and resilience). Most managed to integrate exercises into their daily lives and planned to continue their practice. Participating in a group was considered valuable and supportive. Furthermore, it was appreciated that participants could follow the training together (as a couple). The quantitative results showed a small effect on increased quality of life for caregivers. No substantial decrease in psychological distress was apparent. Caregivers displayed a large increase in mindfulness., Conclusion: The results of this mixed-methods study suggest that an adjusted mindfulness program is feasible and well-received among couples of persons with early-stage dementia and their caregiver, warranting further research in this area.

In an effort to better quantify the impact of adulthood socioeconomic circumstances on prediabetes and type 2 diabetes (T2DM), we set out to examine the relative importance of four adulthood socioeconomic indicators. Using cross-sectional data from The Maastricht Study on 2011 middle-aged older men and women, our findings indicate that low educational level (OR = 1.81, 95% CI = 1.24-2.64), low occupational level (OR = 1.42, 95% CI = 0.98-2.05), and material deprivation (OR = 1.78, 95% CI = 1.33-2.38) were independently associated with T2DM. Low income (OR = 1.28, 95% CI = 0.88-1.87) was the strongest, albeit not significant, SEP (socioeconomic position) correlate of prediabetes. This association confirms SEP as a multifaceted concept and indicates the need to measure SEP accordingly. In order to tackle the social gradient in prediabetes and T2DM, one should, therefore, address multiple SEP indicators and their possible pathways.

The world population is aging and the prevalence of dementia is increasing. By 2050, those aged 60 years and older are expected to make up a quarter of the population. With that, the number of people with dementia is increasing. Unfortunately, there is no cure for dementia. The progression of symptoms with no hope of improvement is difficult to cope with, both for patients and their caregivers. New and evidence-based strategies are needed to support the well-being of both caregiver and patient. Mindfulness training is a body-mind intervention that has shown to improve psychological well-being in a variety of mental health conditions. Mindfulness, a non-judgmental attention to one's experience in the present moment, is a skill that can be developed with a standard 8-week training. Research has shown preliminary but promising results for mindfulness-based interventions to benefit people with dementia and caregivers. The aim of this review is (a) to provide a rationale for the application of mindfulness in the context of dementia care by giving an overview of studies on mindfulness for people with dementia and/or their caregivers and (b) to provide suggestions for future projects on mindfulness in the context of dementia and to give recommendations for future research.

A common activity carried out by healthcare professionals is to test various hypotheses on longitudinal study data in an effort to develop new and more reliable algorithms that might determine the possibility of developing certain illnesses. The INnovative, Midlife INtervention for Dementia Deterrence project provides input from a number of European dementia experts to identify the most accurate model of inter-related risk factors which can yield a personalized dementia-risk quotient and profile. This model is then validated against the large population-based prospective Maastricht Aging Study dataset. As part of this overall goal, the research presented in this article demonstrates how we can automate the process of mapping modifiable risk factors against large sections of the aging study and thus use information technology to provide more powerful query interfaces., (© The Author(s) 2015.)

This paper uses longitudinal data to analyze the relation between retirement and cognitive development in the Netherlands. Controlling for individual fixed effects and lagged cognition, we find that retirees face lower declines in their cognitive flexibility than those who remain employed, which appears to be persistent 6 years after retirement. However, the information processing speed of low-educated retirees declines faster. The magnitude of both changes in cognition is such that retirees appear 5-6 years younger in terms of cognitive flexibility, and older in terms of information processing speed. We show that these relationships between retirement and cognitive development cannot be explained by (1) feeling relieved from routine work, (2) changes in mood, (3) changes in lifestyle, and (4) changes in blood pressure. The decline in information processing speed after retirement particularly holds for the low educated. This could increase the social costs of an aging society., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Cognitive interventions for older persons that may diminish the burden of cognitive problems and could delay conversion to dementia are of great importance. The underlying mechanisms of such interventions might be psychological compensation and neuronal plasticity. This review provides an overview of the literature concerning the evidence that cognitive interventions cause brain activation changes, even in damaged neural systems., Method: A systematic search of the literature was conducted in several international databases, Medline, Embase, Cinahl, Cochrane, and Psychinfo. The methodological quality was assessed according to the guidelines of the Dutch Institute for Health Care Improvement (CBO)., Results: Nineteen relevant articles were included with varied methodological quality. All studies were conducted in diverse populations from healthy elderly to patients with dementia and show changes in brain activation after intervention., Conclusions: The results thus far show that cognitive interventions cause changes in brain activation patterns. The exact interpretation of these neurobiological changes remains unclear. More study is needed to understand the extent to which cognitive interventions are effective to delay conversion to dementia. Future studies should more explicitly try to relate clinically significant improvement to changes in brain activation. Long-term follow-up data are necessary to evaluate the stability of the effects.

Background and Aims: Functional independence (FI) is commonly measured by checklist questionnaires that grade whether specific daily living tasks can be performed with or without ancillary assistance. Among older adults who are functioning independently precursory measures of daily living may be useful in gauging how long an individual can remain independent in advanced age. This study examined the SF-36, a standardized self-report measure of health-related quality of life, as a precursory marker of FI in a representative sample of healthy older adults., Methods: The study consisted of 696 Dutch enrollees from the Maastricht Aging Study (MAAS) who were 50 years and older and had been screened for health and cognitive deficits. They were assessed at two time points separated by a nine-year interval on standardized activities of daily living (ADL) and instrumental activities of daily living (IADL) items that measure the presence or absence of assistance need across five functional domains. MAAS enrollees also received the SF-36 at both time points., Results: The SF- 36 Physical Component Summary (PCS) predicted change in ADL/IADL assistance need after nine years (OR 0.94, CI 0.92-0.97)., Conclusion: In older adults from MAAS who were otherwise functioning independently at baseline, the SF-36 PCS was a suitable precursory measure of the emergence of assistance need after nine years.

Background and Aims: According to the concepts of 'use it or lose it' and cognitive reserve, cognitively challenging activities may boost cognitive abilities in older adults. Using computers and the internet provides divergent cognitive challenges to older persons, and the positive effects of computers and internet use on the quality of life have been found in earlier studies., Methods: We investigated whether prolonged guided computer use by healthy older adults (64-75) may be beneficial to cognitive ability in a randomized controlled study. The intervention consisted of brief training and subsequent use of a personal computer with an internet connection at home for a 12-month period. 191 participants were randomly assigned to three groups: Intervention, Training/No intervention, or No training/No intervention. A fourth group consisted of 45 participants with no interest in computer use. The effect of the intervention was assessed by a range of well-established cognitive instruments that probed verbal memory, information processing speed, and cognitive flexibility. Data were collected at baseline and after four and twelve months., Results: Intensive interaction with a personal computer with standard software applications had no effect on cognitive measures; no differences in changes in cognitive parameters over time were found between groups., Conclusion: Learning to use a computer and the internet does not benefit healthy, communitydwelling older adults with respect to many domains of cognitive functions. The implications of these findings for future studies that use cognitive challenge to counteract usual cognitive aging are discussed.