Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

On Facebook I met old friends again:The use of ICTs in the process of reminiscence among older adults

Background: Reminiscence can be beneficial for social and emotional wellbeing at older ages, yet little is known about what this process looks like as well as about Information and Communication Technologies’ (ICTs) potentials. Broader understanding would allow us to better tailor interventions and make them more effective using ICTs. Objective: This qualitative study aims to gain insight into the process of recalling memories in daily life among independent older adults, with special attention to the role of ICTs. Method: We used a two-step approach, starting with explorative interviews with older adults (N=20), aged 75 to 95, about their experiences with recalling memories. After this, participants used a diary to track examples of memories over three weeks. We returned to elaborate on the cases described by the participants. Results: Four stages were derived from the data, including the start of a memory; motivations for pursuing or ignoring a memory; engagement with the memory; and next steps. We found that ICTs are used mainly at the beginning of the process as well as in the stage of engaging with the memory. Conclusion: ICTs can facilitate sensory triggers, unlock information to complete a memory, and facilitate the company of others – either triggering or sharing memories. Whereas existing interventions mainly focus on initiating memories, often with old triggers, our findings suggest that recalling memories can play a valuable role in connecting older adults with others across age groups. ICTs can facilitate this interaction in several ways

Capturing the Diversity of Successful Aging: An Operational Definition Based on 16-Year Trajectories of Functioning

Purpose of the Study : To determine the prevalence and extent of successful aging (SA) when various suggestions proposed in the previous literature for improving models of SA are incorporated into one holistic operational definition. These suggestions include defining and measuring SA as a developmental process, including subjective indicators alongside more objective ones, and expressing SA on a continuum. Design and Methods : Data were used from 2,241 respondents in the Longitudinal Aging Study Amsterdam, a multidisciplinary study in a nationally representative sample of older adults in the Netherlands. Latent class growth analysis was used to identify successful 16-year trajectories within nine indicators of physical, cognitive, emotional, and social functioning. SA was quantified as the number of indicators in which individual respondents showed successful trajectories (range 0-9). Results : Successful trajectories were characterized by stability, limited decline, or even improvement of functioning over time. Of the respondents, 39.6% of men and 29.3% of women were successful in at least seven indicators; 7% of men and 11% of women were successful in less than three indicators. Proportions of successful respondents were largest in life satisfaction (>85%) and smallest in social activity (<25%). Correlations of success between separate indicators were low to moderate (range r = .02-.37). Implications : Many older adults age relatively successfully, but the character of successful functioning over time varies between indicators, and the combinations of successful indicators vary between individuals

The effects of life events and socioeconomic position in childhood and adulthood on successful aging

Objectives: Building on social stress theory, this study has 2 aims. First, we aim to estimate the effects of stressful life events in childhood and adulthood on Successful Aging (SA). Second, we examine how unequal exposure to such life events between individuals with different socioeconomic position (SEP) contributes to socioeconomic inequalities in SA. Method: We used 16-year longitudinal data from 2,185 respondents aged 55-85 years in 1992 in the Dutch nationally representative Longitudinal Aging Study Amsterdam. Measurement of SA was based on earlier work, in which we integrated trajectories in 9 indicators of functioning into an index of SA. Using path analysis, we investigated direct and indirect effects of parental and adulthood SEP as well as of self-reported childhood and adulthood life events on SA. Results: Almost all included life events had negative direct effects on SA. Parental SEP had no direct effect on SA, whereas adulthood SEP had. Higher Parental SEP increased the likelihood of parental problems and parental death in childhood, resulting in negative indirect effects on SA. Higher adulthood SEP had both positive and negative indirect effects on SA, through increasing the likelihood of divorce and unemployment, but decreasing the likelihood of occupational disability. Discussion: SEP and particular stressful life events are largely, but not entirely independent predictors of SA. We found that high and low SEP may increase exposure to particular events that negatively affect SA. Findings suggest that low (childhood) SEP and stressful life events are interrelated factors that may limit individual opportunities to age successfully

The joint effects of clinically relevant depressive symptoms and cardiovascular risk factors on incident cardiovascular disease among older adults in the community

Objective: To determine if there is a synergistic effect between clinically relevant depressive symptoms and cardiovascular risk factors that disproportionately increases the risk of cardiovascular disease (CVD) among older adults with depressive symptoms. Methods: Data were obtained from the Longitudinal Aging Study Amsterdam, a longitudinal cohort study. N = 3091 respondents with up to seven years of follow-up were included. Incident CVD was based on self-report, medication use, general practitioners’ diagnoses and causes of death. A score of ≥16 points on the Center for Epidemiological Studies Depression Scale indicated clinically relevant depressive symptoms. Risk factors included were sex, education, obesity, smoking, alcohol use, physical inactivity and diabetes mellitus. Data were analysed with Cox regression models. Measures of multiplicative and additive interaction were calculated to determine if the presence of both depressive symptoms and a risk factor amplified the risk of CVD. Results: Of all participants, 12.6% had clinically relevant depressive symptoms and, after a median follow-up of six years, 15.7% developed CVD. Only the additive interaction between physical inactivity and depressive symptoms was statistically significant and explained 40.6% of the CVD risk among inactive persons with depressive symptoms. Conclusion: In the general population, we did not detect synergistic effects for most risk factors. However, older adults with clinically relevant depressive symptoms and a physically inactive lifestyle appeared to be at a particularly high risk to develop CVD and may represent an important target for cardiovascular prevention

Psychosocial and Health-Related Factors Associated With Discordance Between 13-Year Trajectories of Self-Reported Functional Limitations and Performance-Based Physical Functioning in Old Age

Objective: The objective of this study was to examine correlates of discordance between 13-year trajectories of self-reported functional limitations and performance-based physical functioning in older adults. Method: We included 2,135 participants from the population-based Longitudinal Aging Study Amsterdam, the Netherlands, followed across 1995-2008. Self-reported functional limitations included six (instrumental) activities of daily living. Performance-based functioning was a composite of four tests. We used latent class growth analysis and multinomial logistic regression to examine discordance and its correlates. Results: Patterns of discordance and concordance (41% concordance, 46% “overestimation” of daily functioning, 13% “underestimation”) appeared to be persistent over 13 years. Older age, male sex, cognitive impairment, absence of pain, and light alcohol use were associated with overestimation. Younger age, female sex, and lower self-rated health were associated with underestimation. Discussion: Factors associated with overestimation partly differ from those associated with underestimation. Factors that are highly stable over time are particularly good indicators of persistent discordance

Factors across life associated with remaining free from functional limitations despite lifelong exposure to socioeconomic adversity

Background: There are substantial socioeconomic inequalities in functional limitations in old age. Resilience may offer new insights into these inequalities by identifying constellations of factors that protect some individuals from developing functional limitations despite socioeconomic adversity. Methods: Data from 1973 participants in the Medical Research Council National Survey of Health and Development (Great Britain), followed from birth until age 60-64, were used. Functional limitations were defined as reporting difficulty with at least 1 of 16 activities at age 60-64. Lifetime socioeconomic adversity was based on socioeconomic trajectories, categorised into three adversity levels. Analysis of covariance and regression models were used to compare psychosocial factors and health-related behaviours between a Resilient' group (high adversity but no functional limitations) and five groups with other combinations of adversity and limitations. Results: Prevalence of functional limitations in high, intermediate and low adversity groups was 44%, 30% and 23% in men, and 61%, 55% and 49% in women, respectively. Compared with the other high adversity group, the resilient group had a lower prevalence of childhood illness (12% vs 19%) and obesity throughout ages 43-64 (70% vs 55%). Partially adjusted models also showed higher adolescent self-management, lower neuroticism, higher prevalence of volunteer work and physical activity (age 60-64) and lower prevalence of smoking (age 43) in the resilient. Marital status and contact frequency were not associated with resilience. Conclusion: Results suggest protection against childhood illness, health-behavioural factors and self-regulation as targets for interventions across life that may particularly benefit those with long-term exposure to socioeconomic adversity

Heterogeneity in depressive and anxiety symptoms and loneliness during the COVID-19 pandemic: Results from three Dutch psychiatric case-control cohorts from April 2020 to February 2022

Objective: While research found heterogeneous changes in mental health during the COVID-19 pandemic, less is known about the long-term changes in mental health in psychiatric groups. Therefore, we applied a data-driven method to detect sub-groups with distinct trajectories across two years into the pandemic in psychiatric groups, and described their differences in socio-demographic and clinical characteristics. Method: We conducted sixteen rounds of questionnaires between April 2020 and February 2022 among participants (n = 1722) of three psychiatric case–control cohorts that started in the 2000's. We used Growth Mixture Modelling and (multinomial) logistic regression to identify characteristics associated with trajectory membership. Results: We found low decreasing (1228 [72%] participants), intermediate (n = 348 [22%] participants) and high stable (106 [6%] participants) trajectories of depressive symptoms; decreasing low/intermediate (1507 [90%] participants) and high stable (161 [10%] participants) trajectories of anxiety symptoms; and stable low (1109 [61%] participants), stable high (315 [17%] participants), temporary lowered (123 [9%]) and temporary heightened (175 [13%] participants) trajectories of loneliness. Chronicity and severity of pre-pandemic mental disorders predicted unfavourable sub-group membership for all outcomes. Being female, having a low education and income level were associated with unfavourable trajectories of depression, being younger with unfavourable trajectories of anxiety and being female and living alone with unfavourable trajectories of loneliness. Conclusion: We found relatively stable trajectories of depression and anxiety symptoms over two years, suggesting low heterogeneity in outcomes during the pandemic. For loneliness, we found two specific sub-groups with temporary increase and decrease in loneliness during the pandemic

Network structure of time-varying depressive symptoms through dynamic time warp analysis in late-life depression

OBJECTIVES: Late‐life major depressive disorder (MDD) can be conceptualized as a complex dynamic system. However, it is not straightforward how to analyze the covarying depressive symptoms over time in case of sparse panel data. Dynamic time warping (DTW) analysis may yield symptom networks and dimensions both at the patient and group level. METHODS: In the Netherlands Study of Depression in Older People (NESDO) depressive symptoms were assessed every 6 months using the 30‐item Inventory of Depressive Symptomatology (IDS) with up to 13 assessments per participant. Our sample consisted of 182 persons, aged ≥ 60 years, with an IDS total score of 26 or higher at baseline. Symptom networks dimensions, and centrality metrics were analyzed using DTW and Distatis analyses. RESULTS: The mean age was 69.8 years (SD 7.1), with 69.0% females, and a mean IDS score of 38.0 (SD = 8.7). DTW enabled visualization of an idiographic symptom network in a single NESDO participant. In the group‐level nomothetic approach, four depressive symptom dimensions were identified: “core symptoms”, “lethargy/somatic”, “sleep”, and “appetite/atypical”. Items of the “internalizing symptoms” dimension had the highest centrality, whose symptom changes over time were most similar to those changes of other symptoms. CONCLUSIONS: DTW revealed symptom networks and dimensions based on the within‐person symptom changes in older MDD patients. Its centrality metrics signal the most influential symptoms, which may aid personalized care

Physical comorbidity in Older-Age Bipolar Disorder (OABD) compared to the general population - a 3-year longitudinal prospective cohort study

Background: The aim of this study was to examine the accumulation of chronic physical diseases in Older-Age Bipolar Disorder (OABD) as well as in individuals from the general aging population over a 3-year period. Methods: This prospective longitudinal study compared 101 patients with OABD receiving outpatient care (DOBi cohort) with 2545 individuals from the general aging population (LASA cohort). The presence of eight major chronic diseases was asked at baseline and 3-year follow-up. Total number of diseases was the main outcome measure. Self-rated health (SRH, scale 1-5) was examined as a secondary outcome. Multilevel linear modelling of change was performed to estimate and test the observed change in both samples. Results: At baseline, the number of chronic diseases was lower (b= -0.47, p<0.01) and self-rated health comparable (b=0.27, p=0.13) in DOBi than in LASA. Over 3 years the number of chronic diseases increased faster in DOBi than in LASA (b=0.51 versus b=0.35, p(interaction)=0.03). When corrected for employment, depressive symptoms, waist circumference, smoking, and alcohol use, this difference was no longer significant. SRH decreased faster in DOBi than in LASA (b=-0.24 versus b=-0.02, p(interaction)=0.04). Limitations: Information on chronic diseases was collected using self-report. Conclusions: A faster accumulation of chronic physical diseases and a faster decline in health perception was observed in OABD than in participants from the general population. The observed differences could partly be attributed to baseline differences in psychosocial, lifestyle, and health behaviour factors. Our findings urgently call for the use of integrated care in BD