Genetic and environmental influences on longitudinal frailty trajectories from adulthood into old age

BACKGROUND: Frailty is a complex, dynamic geriatric condition, but limited evidence has shown how genes and environment may contribute to its longitudinal changes. We sought to investigate sources of individual differences in the longitudinal trajectories of frailty, considering potential selection bias when including a sample of oldest-old twins. METHODS: Data were from two Swedish twin cohort studies: a younger cohort comprising 1,842 adults aged 29-96 years followed up to 15 waves, and an older cohort comprising 654 adults aged ≥79 years followed up to five waves. Frailty was measured using the frailty index (FI). Age-based latent growth curve models were used to examine longitudinal trajectories, and extended to a biometric analysis to decompose variability into genetic and environmental etiologies. RESULTS: A bilinear model with an inflection point at age 75 best described the data, indicating a four- to five-fold faster FI increase after 75 years. Twins from the older cohort had significantly higher mean FI at baseline but slower rate of increase afterwards. FI level at age 75 was moderately heritable in both men (42%) and women (55%). Genetic influences were relatively stable across age for men and increasing for women, although the most salient amplification in FI variability after age 75 was due to individual-specific environmental influences for both men and women; conclusions were largely consistent when excluding the older cohort. CONCLUSION: Increased heterogeneity of frailty in late life is mainly attributable to environmental influences, highlighting the importance of targeting environmental risk factors to mitigate frailty in older adults.publishedVersionPeer reviewe

Capability in research on cognition and well-being in ageing and retirement

In this chapter, we outline our thoughts on capability in relation to previous and ongoing research projects conducted by the Adult Development and Ageing (ADA-Gero) Research Group located at the Department of Psychology, University of Gothenburg, Sweden. More specifically, we relate our research on cognitive ageing and subjective well-being to the overarching capability framework implemented as a theoretical platform in the AgeCap research consortium

Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men:A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia

OBJECTIVE: Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. RESEARCH DESIGN AND METHODS: A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. RESULTS: Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45-1.80]; men: pooled RR 1.58 [95% CI 1.38-1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86-2.94) in women and 1.73 (95% CI 1.61-1.85) in men, and for nonvascular dementia the RRs were 1.53 (95% CI 1.35-1.73) in women and 1.49 (95% CI 1.31-1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08-1.30]; P < 0.001). CONCLUSIONS: Individuals with type 2 diabetes are at ~60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

What Matters, and What Matters Most, for Change in Life Satisfaction in the Oldest-Old? A Study over 6 Years among Individuals 80+

Objectives: The study investigates whether markers of life satisfaction identified in a cross-sectional study – quality of social network, self-rated health, depressive symptoms, locus of control and widowhood, in addition to financial satisfaction and the personality traits of extraversion and neuroticism - predict change in life satisfaction (LSI-Z) across four measurement occasions during a 6-year period in individuals aged 80+. Method: Data were drawn from the Swedish OCTO-Twin-study of individuals aged 80 and older. Results: Growth curve analysis showed a relatively consistent significant linear decline in life satisfaction, but certain markers predicted change in life satisfaction. The loss of spouse, in particular in men, and higher levels of depressive symptoms were related to lower levels of life satisfaction over time. Conclusion: The results from the study question the notion of a life-long stability of life satisfaction

Alcohol Consumption Over the Retirement Transition in Sweden : Different Trajectories Based on Education

Retirement is a major life transition that involves changes to everyday routines, roles, and habits. Previous studies suggest that retirement may influence drinking habits. Many natural inhibitors of alcohol consumption disappear with the removal of work constraints. The potential impact depends on both individual and contextual factors. Women in the cohorts undergoing retirement now have been more active on the labor market, including the occupation of higher status jobs, which indicates more financial resources as well as a larger role loss after retirement. Also, the current cohorts who retire have had more liberal drinking habits throughout their lives compared to previous cohorts. We therefore examined changes in alcohol consumption surrounding retirement in different education groups among women and men undergoing retirement using annual data from the Health, Aging and Retirement Transitions in Sweden (HEARTS) study, a longitudinal national study of 60- to 66-year-olds (n = 5,913), from 2015 to 2018. Latent growth curve models were used to estimate trajectories of alcohol consumption. Results showed that those who retired during the follow-up increased their usual weekly alcohol consumption while those who worked or were retired throughout the period had stable drinking habits. Those who were retired reported the highest alcohol consumption. The increase surrounding retirement was driven by people with higher education. Women with tertiary education and men with intermediate or tertiary education increased their weekly alcohol intake after retirement, while those with low education had unchanged drinking habits. Mechanisms and motivations that may fuel increased alcohol intake among people with higher education should be further investigated