Cognitively healthy centenarians are genetically protected against Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) prevalence increases with age, yet a small fraction of the population reaches ages > 100 years without cognitive decline. We studied the genetic factors associated with such resilience against AD. METHODS: Genome-wide association studies identified 86 single nucleotide polymorphisms (SNPs) associated with AD risk. We estimated SNP frequency in 2281 AD cases, 3165 age-matched controls, and 346 cognitively healthy centenarians. We calculated a polygenic risk score (PRS) for each individual and investigated the functional properties of SNPs enriched/depleted in centenarians. RESULTS: Cognitively healthy centenarians were enriched with the protective alleles of the SNPs associated with AD risk. The protective effect concentrated on the alleles in/near ANKH, GRN, TMEM106B, SORT1, PLCG2, RIN3, and APOE genes. This translated to >5-fold lower PRS in centenarians compared to AD cases (P = 7.69 × 10-71), and 2-fold lower compared to age-matched controls (P = 5.83 × 10-17). DISCUSSION: Maintaining cognitive health until extreme ages requires complex genetic protection against AD, which concentrates on the genes associated with the endolysosomal and immune systems. HIGHLIGHTS: Cognitively healthy cent enarians are enriched with the protective alleles of genetic variants associated with Alzheimer's disease (AD). The protective effect is concentrated on variants involved in the immune and endolysosomal systems. Combining variants into a polygenic risk score (PRS) translated to > 5-fold lower PRS in centenarians compared to AD cases, and ≈ 2-fold lower compared to middle-aged healthy controls.

The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis.

BACKGROUND: Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). METHODS: Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). RESULTS: Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). CONCLUSIONS: Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

Depressive Symptoms and Plasma Markers of Alzheimer's Disease and Neurodegeneration: A Coordinated Meta-Analysis of 8 Cohort Studies.

BACKGROUND: Depressive symptoms are associated with an increased risk of Alzheimer's disease (AD). There has been a recent emergence in plasma biomarkers for AD pathophysiology, such as amyloid-beta (Aß) and phosphorylated tau (p-tau), as well as for axonal damage (neurofilament light, NfL) and astrocytic activation (glial fibrillary acidic protein, GFAP). Hypothesizing that depressive symptoms may occur along the AD process, we investigated associations between plasma biomarkers of AD with depressive symptoms in individuals without dementia. METHODS: A two-stage meta-analysis was performed on 2 clinic-based and 6 population-based cohorts (N = 7210) as part of the Netherlands Consortium of Dementia Cohorts. Plasma markers (Aß42/40, p-tau181, NfL, and GFAP) were measured using Single Molecular Array (Simoa; Quanterix) assays. Depressive symptoms were measured with validated questionnaires. We estimated the cross-sectional association of each standardized plasma marker (determinants) with standardized depressive symptoms (outcome) using linear regressions, correcting for age, sex, education, and APOE ε4 allele presence, as well as subgrouping by sex and APOE ε4 allele. Effect estimates were entered into a random-effects meta-analysis. RESULTS: Mean age of participants was 71 years. The prevalence of clinically relevant depressive symptoms ranged from 1% to 22%. None of the plasma markers were associated with depressive symptoms in the meta-analyses. However, NfL was associated with depressive symptoms only in APOE ε4 carriers (ß 0.11; 95% CI: 0.05-0.17). CONCLUSIONS: Late-life depressive symptoms did not show an association to plasma biomarkers of AD pathology. However, in APOE ε4 allele carriers, a more profound role of neurodegeneration was suggested with depressive symptoms.

Genomics Research of Lifetime Depression in the Netherlands: The BIObanks Netherlands Internet Collaboration (BIONIC) Project.

In this cohort profile article we describe the lifetime major depressive disorder (MDD) database that has been established as part of the BIObanks Netherlands Internet Collaboration (BIONIC). Across the Netherlands we collected data on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lifetime MDD diagnosis in 132,850 Dutch individuals. Currently, N = 66,684 of these also have genomewide single nucleotide polymorphism (SNP) data. We initiated this project because the complex genetic basis of MDD requires large population-wide studies with uniform in-depth phenotyping. For standardized phenotyping we developed the LIDAS (LIfetime Depression Assessment Survey), which then was used to measure MDD in 11 Dutch cohorts. Data from these cohorts were combined with diagnostic interview depression data from 5 clinical cohorts to create a dataset of N = 29,650 lifetime MDD cases (22%) meeting DSM-5 criteria and 94,300 screened controls. In addition, genomewide genotype data from the cohorts were assembled into a genomewide association study (GWAS) dataset of N = 66,684 Dutch individuals (25.3% cases). Phenotype data include DSM-5-based MDD diagnoses, sociodemographic variables, information on lifestyle and BMI, characteristics of depressive symptoms and episodes, and psychiatric diagnosis and treatment history. We describe the establishment and harmonization of the BIONIC phenotype and GWAS datasets and provide an overview of the available information and sample characteristics. Our next step is the GWAS of lifetime MDD in the Netherlands, with future plans including fine-grained genetic analyses of depression characteristics, international collaborations and multi-omics studies.

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.

Psychosocial factors, health behaviors and risk of cancer incidence: Testing interaction and effect modification in an individual participant data meta-analysis.

Depression, anxiety and other psychosocial factors are hypothesized to be involved in cancer development. We examined whether psychosocial factors interact with or modify the effects of health behaviors, such as smoking and alcohol use, in relation to cancer incidence. Two-stage individual participant data meta-analyses were performed based on 22 cohorts of the PSYchosocial factors and CAncer (PSY-CA) study. We examined nine psychosocial factors (depression diagnosis, depression symptoms, anxiety diagnosis, anxiety symptoms, perceived social support, loss events, general distress, neuroticism, relationship status), seven health behaviors/behavior-related factors (smoking, alcohol use, physical activity, body mass index, sedentary behavior, sleep quality, sleep duration) and seven cancer outcomes (overall cancer, smoking-related, alcohol-related, breast, lung, prostate, colorectal). Effects of the psychosocial factor, health behavior and their product term on cancer incidence were estimated using Cox regression. We pooled cohort-specific estimates using multivariate random-effects meta-analyses. Additive and multiplicative interaction/effect modification was examined. This study involved 437,827 participants, 36,961 incident cancer diagnoses, and 4,749,481 person years of follow-up. Out of 744 combinations of psychosocial factors, health behaviors, and cancer outcomes, we found no evidence of interaction. Effect modification was found for some combinations, but there were no clear patterns for any particular factors or outcomes involved. In this first large study to systematically examine potential interaction and effect modification, we found no evidence for psychosocial factors to interact with or modify health behaviors in relation to cancer incidence. The behavioral risk profile for cancer incidence is similar in people with and without psychosocial stress.

The Association between Education and Cognitive Performance Varies at Different Levels of Cognitive Performance: A Quantile Regression Approach.

INTRODUCTION: Educational differences in cognitive performance among older adults are well documented. Studies that explore this association typically estimate a single average effect of education on cognitive performance. We argue that the processes that contribute to the association between education and cognitive performance are unlikely to have equal effects at all levels of cognitive performance. In this study, we employ an analytical approach that enables us to go beyond averages to examine the association between education and five measures of global and domain-specific cognitive performance across the outcome distributions. METHODS: This cross-sectional study included 1,780 older adults aged 58-68 years from the Longitudinal Aging Study Amsterdam. Conditional quantile regression was used to examine variation across the outcome distribution. Cognitive outcomes included Mini-Mental State Examination (MMSE) score, crystallized intelligence, information processing speed, episodic memory, and a composite score of global cognitive performance. RESULTS: The results showed that the associations between education and different cognitive measures varied across the outcome distributions. Specifically, we found that education had a stronger association with crystallized intelligence, MMSE, and a composite cognitive performance measure in the lower tail of performance distributions. The associations between education and information processing speed and episodic memory were uniform across the outcome distributions. CONCLUSION: Larger associations between education and some domains of cognitive performance in the lower tail of the performance distributions imply that inequalities are primarily generated among individuals with lower performance rather than among average and high performers. Additionally, the varying associations across some of the outcome distributions indicate that estimating a single average effect through standard regression methods may overlook variations in cognitive performance between educational groups. Future studies should consider heterogeneity across the outcome distribution.

Association of Neighborhood Deprivation and Depressive Symptoms With Epigenetic Age Acceleration: Evidence From the Canadian Longitudinal Study on Aging.

BACKGROUND: Neighborhood deprivation and depression have been linked to epigenetic age acceleration. The next-generation epigenetic clocks including the DNA methylation (DNAm) GrimAge, and PhenoAge have incorporated clinical biomarkers of physiological dysregulation by selecting cytosine-phosphate-guanine sites that are associated with risk factors for disease, and have shown improved accuracy in predicting morbidity and time-to-mortality compared to the first-generation clocks. The aim of this study is to examine the association between neighborhood deprivation and DNAm GrimAge and PhenoAge acceleration in adults, and assess interaction with depressive symptoms. METHODS: The Canadian Longitudinal Study on Aging recruited 51 338 participants aged 45-85 years across provinces in Canada. This cross-sectional analysis is based on a subsample of 1 445 participants at baseline (2011-2015) for whom epigenetic data were available. Epigenetic age acceleration (years) was assessed using the DNAm GrimAge and PhenoAge, and measured as residuals from regression of the biological age on chronological age. RESULTS: A greater neighborhood material and/or social deprivation compared to lower deprivation (b = 0.66; 95% confidence interval [CI] = 0.21, 1.12) and depressive symptoms scores (b = 0.07; 95% CI = 0.01, 0.13) were associated with higher DNAm GrimAge acceleration. The regression estimates for these associations were higher but not statistically significant when epigenetic age acceleration was estimated using DNAm PhenoAge. There was no evidence of a statistical interaction between neighborhood deprivation and depressive symptoms. CONCLUSIONS: Depressive symptoms and neighborhood deprivation are independently associated with premature biological aging. Policies that improve neighborhood environments and address depression in older age may contribute to healthy aging among older adults living in predominantly urban areas.

The phenotypic and genotypic association of grip strength with frailty, physical performance and functional limitations over time in older adults.

OBJECTIVES: To replicate the phenotypic associations of grip strength with frailty, physical performance and functional limitations in older adults for longer follow-up periods and to examine whether these associations are due to shared genetic factors. METHODS: In total 2,262 participants 55 years and older with follow-up data up to 23 years (Nobservations = 8,262) from the Longitudinal Aging Study Amsterdam were included. Weighted polygenic risk scores for grip strength (PRS-GS) were built using the genome-wide meta-analysis results from UK Biobank as reference. Grip strength was measured two times on each hand using a dynamometer. Frailty index (FI) and frailty phenotype were operationalised following standard procedures. Performance tests included a timed walk test, a repeated chair stands test and put on-take off cardigan test. Functional limitations were assessed using a questionnaire with six items. RESULTS: Higher grip strength was phenotypically associated with lower FI (b = -0.013, 95% CI (-0.016, -0.009)), better physical performance (b = 0.040, 95% CI (0.026, 0.054)) and less functional limitations (OR = 0.965, 95% CI (0.954, 0.977)) over time for follow-up periods up to 23 years. However, PRS-GS was not associated with any of the traits. CONCLUSION: The phenotypic associations between grip strength, frailty, physical performance and functional limitations were replicated for follow-up periods up to 23 years. However, the associations between the traits could not be explained by shared genetics potentially indicating a more relevant involvement of non-genetic factors.

Depression, anxiety, and the risk of cancer: An individual participant data meta-analysis.

BACKGROUND: Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, prostate, colorectal, alcohol-related, and smoking-related cancers), individual participant data (IPD) meta-analyses were performed within the Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. METHODS: The PSY-CA consortium includes data from 18 cohorts with measures of depression or anxiety (up to N = 319,613; cancer incidences, 25,803; person-years of follow-up, 3,254,714). Both symptoms and a diagnosis of depression and anxiety were examined as predictors of future cancer risk. Two-stage IPD meta-analyses were run, first by using Cox regression models in each cohort (stage 1), and then by aggregating the results in random-effects meta-analyses (stage 2). RESULTS: No associations were found between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers. Depression and anxiety (symptoms and diagnoses) were associated with the incidence of lung cancer and smoking-related cancers (hazard ratios [HRs], 1.06-1.60). However, these associations were substantially attenuated when additionally adjusting for known risk factors including smoking, alcohol use, and body mass index (HRs, 1.04-1.23). CONCLUSIONS: Depression and anxiety are not related to increased risk for most cancer outcomes, except for lung and smoking-related cancers. This study shows that key covariates are likely to explain the relationship between depression, anxiety, and lung and smoking-related cancers. PREREGISTRATION NUMBER: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=157677.

End-of-life treatment preference discussions between older people and their physician before and during the COVID-19 pandemic: cross sectional and longitudinal analyses from the Longitudinal Aging Study Amsterdam.

BACKGROUND: COVID-19 could lead to hospitalisation and ICU admission, especially in older adults. Therefore, during the pandemic, it became more important to discuss wishes and preferences, such as older peoples' desire for intensive treatment in a hospital in acute situations, or not. This study explores what percentage of Dutch older people aged 75 and over discussed Advance Care Planning (ACP) topics with a physician during the first months of the COVID-19 pandemic and whether this was different in these people before the COVID-19 pandemic. METHODS: Data of two ancillary data collections of the Longitudinal Aging Study Amsterdam were used: the LASA 75 PLUS study and the LASA COVID-19 study. The latter provided cross sectional data (during COVID-19; n = 428) and longitudinal data came from participants in both studies (before and during COVID-19; n = 219). RESULTS: Most older adults had thought about ACP topics during COVID-19 (76,4%), and a minority had also discussed ACP topics with a physician (20.3%). Thinking about ACP topics increased during COVID-19 compared to before COVID-19 in a sample with measurements on both timeframes (82,5% vs 68,0%). Not thinking about ACP topics decreased in the first months of the COVID-pandemic compared to before COVID-19 for all ACP topics together (68.0% vs 82.2%) and each topic separately (hospital 42.0% vs 63.9%; nursing home 36.5% vs 53.3%; treatment options 47.0% vs 62.1%; resuscitation 53.0% vs 70.7%). CONCLUSIONS: Older people do think about ACP topics, which is an important first step in ACP, and this has increased during COVID-19. However, discussing ACP topics with a physician is still not that common. General practitioners could therefore take the initiative in broaching the subject of ACP. This can for instance be done by organizing information meetings.

Personality traits and health care use: A coordinated analysis of 15 international samples.

Some people use health care services more than others. Identifying factors associated with health care use has the potential to improve the effectiveness, efficiency, and equity of health care. In line with the Andersen behavioral model of health care utilization and initial empirical findings, personality traits may be key predisposing factors associated with health care use. Across 15 samples, the present study examined cross-sectional and prospective associations between Big Five personality traits and the likelihood of dental visits, general medical practitioner visits, and hospitalizations. Using coordinated data analysis, we estimated models within each of 15 samples individually (sample Ns ranged from 516 to 305,762), and then calculated weighted mean effect sizes using random-effects meta-analysis across samples (total N = 358,803). According to the synthesized results, people higher in conscientiousness, agreeableness, extraversion, and openness, and lower in neuroticism were more likely to visit the dentist; people higher in neuroticism were more likely to visit general medical practitioners; and people lower in conscientiousness and agreeableness and higher in neuroticism were more likely to be hospitalized. Associations tended to be small with odds ratios around 1.20 (rs ≈ .05). These findings provide evidence across 15 international samples for small but consistent associations between personality traits and health care use and demonstrate that personality-health care associations differ by type of care. We discuss directions for future research, including examining more specific personality facets (e.g., productiveness vs. responsibility) as well as important dimensions of health care (e.g., preventative vs. reactive care; acute vs. chronic care). (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Social and physical neighbourhood characteristics and 10-year incidence of depression and anxiety in older adults: Results from the Longitudinal Aging Study Amsterdam.

OBJECTIVE: A growing literature suggests that neighbourhood characteristics are associated with mental health outcomes, but the evidence in older adults is inconsistent. We investigated the association of neighbourhood characteristics, pertaining to demographic, socio-economic, social and physical environment domains, with the subsequent 10-year incidence of depression and anxiety, in Dutch older adults. METHODS: In the Longitudinal Aging Study Amsterdam depressive and anxiety symptoms were assessed four times between 2005/2006 and 2015/2016, using the Center for Epidemiological Studies Depression Scale (n = 1365) and the Anxiety subscale of the Hospital Anxiety and Depression Scale (n = 1420). Neighbourhood-level data on urban density, percent population over 65 years of age, percent immigrants, average house price, average income, percent low-income earners, social security beneficiaries, social cohesion, safety, proximity to retail facilities, housing quality, percent green space, percent water coverage, air pollution (particulate matter (PM2.5)), and traffic noise, were obtained for study baseline years 2005/2006. Cox proportional hazard regression models, clustered within neighbourhood, were used to estimate the association between each neighbourhood-level characteristic and the incidence of depression and anxiety. RESULTS: The incidence of depression and anxiety was 19.9 and 13.2 per 1000 person-years, respectively. Neighbourhood characteristics were not associated with the incidence of depression. However, various neighbourhood characteristics were associated with an increased incidence of anxiety, including: higher urban density level, higher percent immigrants, greater proximity to retail facilities, lower housing quality score, lower safety score, higher PM2.5 levels and less green space. CONCLUSION: Our results indicate that several neighbourhood characteristics are associated with anxiety but not with depression incidence in older age. Several of these characteristics have the potential to be modifiable and thus could serve as a target for interventions at the neighbourhood-level in improving anxiety, provided that future studies replicate our findings and provide further evidence for a causal effect.

Differences in the Mediating Role of HL in Socioeconomic Inequalities in Health Across Age Groups: Results from the Dutch Doetinchem Cohort Study.

BACKGROUND: Although it is known that health literacy (HL) plays an explanatory role in educational inequalities in health, it is unknown whether this role varies across age groups. OBJECTIVE: The purpose of this study was to investigate whether the mediating role of HL in educational inequalities in four health outcomes varies across age groups: age 46 to 58 years, age 59 to 71 years, and age 72 to 84 years. METHODS: We used data from the Dutch Doetinchem Cohort Study, which included 3,448 participants. We included years of education as predictor, chronic illness prevalence and incidence, mental and self-perceived health as outcomes, and HL, based on self-report, as mediator. We used multiple-group mediation models to compare indirect effects across age groups. KEY RESULTS: In the complete sample without age stratification, HL partly mediated the effect of education on all health outcomes except for incidence of chronic diseases. These indirect effect estimates were larger for subjective (self-perceived health, proportion mediated [PM] = 37%, and mental health, PM = 37%) than for objective health outcomes (prevalence of chronic disease, PM = 17%). For the prevalence of chronic disease, the indirect effect estimate was significantly larger among individuals age 46 to 58 years compared to individuals age 59 to 71 years and for incidence of chronic disease also compared to individuals age 72 to 84 years. All other indirect effect estimates did not differ significantly between age groups. Using an alternative cut-off point for HL or adjusting for cognitive functioning did not meaningfully change the results. CONCLUSIONS: Overall, we found that the explanatory role of HL in educational inequalities in mental and subjective health was stable but that it varied across age groups for chronic diseases, where it was largest among individuals age 46 to 58 years. Future studies may investigate the benefits of starting to intervene on HL from a younger age but means to improve HL may also benefit the subjective health of older adults with lower education. [HLRP: HL Research and Practice. 2023;7(1):e26-e38.] Plain Language Summary: This study examined age-group differences in the mediating role of HL in the relationship between education and health. Overall, we found that the explanatory role of HL in educational inequalities in mental and subjective health was stable but that it varied across age groups for chronic diseases, where it was largest among individuals age 46 to 58 years compared to individuals age 59 to 71 years and individuals age 72 to 84 years.

Supporting Resilience of Older Adults with Cognitive Decline Requires a Multi-Level System Approach.

The concept of resilience, i.e., the capacity of a system to bounce back after a stressor, is gaining interest across many fields of science, policy, and practice. To date, resilience research in people with cognitive decline has predominantly addressed the early stages of decline. We propose that: (1) resilience is a relevant concept in all stages of cognitive decline; and (2) a socio-ecological, multisystem perspective on resilience is required to advance understanding of, and care and support for people with cognitive decline and their support networks. We substantiate our position with literature and examples. Resilience helps understand differences in response to risk factors of (further) cognitive decline and informs personalised prevention. In a curative context, interventions to strengthen resilience aim to boost recovery from cognitive decline. In care for people with dementia, resilience-focused interventions can strengthen coping mechanisms to maintain functioning and well-being of the individual and their support network. A good example of improving resilience in the social and policy context is the introduction of age-friendly cities and dementia-friendly communities. Good care for people with cognitive decline requires a health and social care system that can adapt to changes in demand. Given the interdependency of resilience at micro-, meso- and macro-levels, an integrative socio-ecological perspective is required. Applying the concept of resilience in the field of cognitive decline opens new horizons for research to improve understanding, predicting, intervening on health and social care needs for the increasing population with cognitive decline.

Cardiovascular risk indicators among depressed persons: A special case?

BACKGROUND: Traditional cardiovascular risk indicators only partially explain cardiovascular risks in depressed persons. Depressed persons may exhibit a profile of cardiovascular risk indicators that goes beyond traditional cardiovascular risk indicators, such as symptom severity, insomnia, loneliness and neuroticism, yet research on the added value of these depression-related characteristics in predicting cardiovascular risks of depressed persons is scarce. METHODS: Data from N = 1028 depressed Dutch adults without prevalent CVD were derived from two longitudinal depression cohort studies. The outcome was medication-confirmed self-reported CVD. Fifteen depression-related clinical and psychological characteristics were included and tested against traditional cardiovascular risk indicators. Data were analysed using Cox regression models. Incremental values of these characteristics were calculated using c-statistics. RESULTS: After a median follow-up of 65.3 months, 12.7% of the participants developed CVD. Only anxiety and depressive symptom severity were associated with incident CVD beyond traditional cardiovascular risk indicators. The c-statistic of the model with traditional cardiovascular risk indicators was 85.47%. This increased with 0.56 or 0.33 percentage points after inclusion of anxiety or depression severity, respectively. LIMITATIONS: Other relevant depression-related characteristics were not available in the datasets used. CONCLUSION: Anxiety and depressive symptom severity were indicative of an increased cardiovascular risk. Including these as additional risk indicators barely improved the ability to assess cardiovascular risks in depressed persons. Although traditional cardiovascular risk indicators performed well in depressed persons, existing risk prediction algorithms need to be validated in depressed persons.

Development and validation of an intrinsic capacity composite score in the Longitudinal Aging Study Amsterdam: a formative approach.

BACKGROUND: Intrinsic capacity (IC) defined by the WHO refers to the composite of five domains of capacities. So far, developing and validating a standardized overall score of the concept have been challenging partly because its conceptual framework has been unclear. We consider that a person's IC is determined by its domain-specific indicators suggesting a formative measurement model. AIMS: To develop an IC score applying a formative approach and assess its validity. METHODS: The study sample (n = 1908) consisted of 57-88-year-old participants from the Longitudinal Aging Study Amsterdam (LASA). We used logistic regression models to select the indicators to the IC score with 6-year functional decline as an outcome. An IC score (range 0-100) was constructed for each participant. We examined the known-groups' validity of the IC score by comparing groups based on age and number of chronic diseases. The criterion validity of the IC score was assessed with 6-year functional decline and 10-year mortality as outcomes. RESULTS: The constructed IC score included seven indicators covering all five domains of the construct. The mean IC score was 66.7 (SD 10.3). The scores were higher among younger participants and those who had lower number of chronic diseases. After adjustment for sociodemographic indicators, chronic diseases, and BMI, a one-point higher IC score was associated with a 7% decreased risk for 6-year functional decline and a 2% decreased risk for 10-year mortality. CONCLUSIONS: The developed IC score demonstrated discriminative ability according to age and health status and is associated with subsequent functional decline and mortality.

Toward a paradigm shift in healthcare: using the International Classification of Functioning, Disability and Health (ICF) and the capability approach (CA) jointly in theory and practice.

PURPOSE: Over the past two decades, healthcare systems have shifted to adopt a more holistic, patient-centered care system. However, operationalization in practice remains challenging. Two frameworks have contributed substantially to the transformation toward more holistic and patient-centered care: the International Classification of Functioning, Disability and Health (ICF) and the capability approach (CA). Using these frameworks jointly can contribute to improved patient-centered care in clinical practice. METHODS: This article explores the strengths and weaknesses of the use of the two frameworks in care and investigates whether using them jointly might contribute to more appropriate and patient-centered care. We will present a practical example of this integration in the form of a novel e-health application. RESULTS: The exploration indicated that if the frameworks are used jointly, the individual weaknesses can be overcome. The application, used to exemplify the joint use of the frameworks, contains all categories of the ICF. It offers a unique tool that allows a person to self-assess, record, and evaluate their functioning and capabilities and formulate related goals. CONCLUSIONS: Using the ICF jointly with the CA can foster holistic, patient-centered care. The e-health application provides a concrete example of how the frameworks can be used jointly. Implications for rehabilitationUsing the International Classification of Functioning, Disability and Health jointly with the capability approach can foster holistic, patient-centered care.The joint use of the frameworks is demonstrated by an e-health application which enables users to evaluate their functioning in relation to their own goals, provides them with the opportunity to increase control over their health and have a more active role in their care.Tools to record both functioning and goals from a patient's perspective can support professionals in offering patient-centered care in daily practice.Individual recording, monitoring and evaluation of functioning, capabilities and goals regarding functioning can provide a basis for research and quality improvement.

The Disability Paradox? Trajectories of Well-Being in Older Adults With Functional Decline.

Objectives: The 'disability paradox' (DP) suggests that most older adults maintain subjective well-being (SWB) despite functional decline. However, this may depend the SWB component: positive affect (PA), negative/depressed affect (NA/DA) or life satisfaction (LS). We assessed trajectories of these components in older adults with substantial functional decline. Methods: Data originated from the Longitudinal Aging Study Amsterdam (N = 2545) observed during 1992-2008. Using latent class growth analysis, we distinguished a group with substantial functional decline and examined their SWB trajectories and individual characteristics. Results: The DP occurred more frequently for DA (Men:73%, Women:77%) and LS (Men:14%, Women:83%) than for PA (Men:26%, Women:17%). Higher perceived control (mastery) emerged as the most consistent factor associated with higher odds of the DP. Discussion: We provide a nuanced view of the DP, shifting the question from whether it exists to for which dimension of SWB and for whom it is more or less apparent.

Longitudinal Aging Study Amsterdam COVID-19 exposure index: a cross-sectional analysis of the impact of the pandemic on daily functioning of older adults.

OBJECTIVES: The aim of this study was to develop an index to measure older adults' exposure to the COVID-19 pandemic and to study its association with various domains of functioning. DESIGN: Cross-sectional study. SETTING: The Longitudinal Aging Study Amsterdam (LASA), a cohort study in the Netherlands. PARTICIPANTS: Community-dwelling older adults aged 62-102 years (n=1089) who participated in the LASA COVID-19 study (June-September 2020), just after the first wave of the pandemic. PRIMARY OUTCOME MEASURES: A 35-item COVID-19 exposure index with a score ranging between 0 and 1 was developed, including items that assess the extent to which the COVID-19 situation affected daily lives of older adults. Descriptive characteristics of the index were studied, stratified by several sociodemographic factors. Logistic regression analyses were performed to study associations between the exposure index and several indicators of functioning (functional limitations, anxiety, depression and loneliness). RESULTS: The mean COVID-19 exposure index score was 0.20 (SD 0.10). Scores were relatively high among women and in the southern region of the Netherlands. In models adjusted for sociodemographic factors and prepandemic functioning (2018-2019), those with scores in the highest tertile of the exposure index were more likely to report functional limitations (OR: 2.24; 95% CI: 1.48 to 3.38), anxiety symptoms (OR: 3.14; 95% CI: 1.82 to 5.44), depressive symptoms (OR: 2.49; 95% CI: 1.55 to 4.00) and loneliness (OR: 2.97; 95% CI: 2.08 to 4.26) than those in the lowest tertile. CONCLUSIONS: Among older adults in the Netherlands, higher exposure to the COVID-19 pandemic was associated with worse functioning in the physical, mental and social domain. The newly developed exposure index may be used to identify persons for whom targeted interventions are needed to maintain or improve functioning during the pandemic or postpandemic.