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

Association of anthropometry and weight change with risk of dementia and its major subtypes : A meta-analysis consisting 2.8 million adults with 57 294 cases of dementia

Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m(2)), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m(2)) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.Peer reviewe

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

Light Alcohol Consumption Does Not Protect Cognitive Function: A Longitudinal Prospective Study

Studies show that light to moderate alcohol consumption is related to better health and higher cognitive performance. However, it has been suggested that this association is caused by a systematic bias in the control group as many people abstain from drinking or quit because of health issues. Therefore, the group of non-drinkers is biased towards poor health and may not be suitable as a control group. The present study examined the effect of alcohol on cognitive performance while addressing this bias by excluding the non-drinkers. Thus, instead of comparing different levels of alcohol consumption to a non-drinking control group, a dose-response association was calculated between all levels of alcohol intake and cognitive performance. The study used information from a sample of people in the Swedish Twin Registry, who in their midlife (1967) participated in a survey on alcohol intake and 25 years later participated in a longitudinal study on cognitive aging (N = 486). The cognitive aging study took place on five occasions, at 2-year intervals, and included the Mini Mental State Examination (MMSE), tests of episodic memory, semantic memory and spatial ability. The association between midlife alcohol consumption and later cognitive performance was analyzed using growth curve models, adjusting for background variables. The findings showed that there was a significant negative dose-response association between alcohol intake in midlife and the MMSE, and the tests of episodic memory, such that higher intake in midlife was related to lower performance in old age. The associations between alcohol and semantic memory, and spatial ability respectively, were not significant. In contrast to findings from other studies, which show that low to moderate alcohol intake promotes cognitive function, the current study showed that alcohol intake was related to lower cognitive performance in a dose-response manner, even at low levels. The results from this study indicate that the observed benefits of moderate alcohol intake for cognitive function reported by others might be solely due to comparisons to an inappropriate control group, a group that is biased towards poor health. Hence, it is concluded that light alcohol intake may not protect cognitive function

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