Activities of NEW Brain Aging

The Network for Emotional Well-being and Brain Aging (NEW Brain Aging) was funded by NIA with the goal of forming a national, transdisciplinary collaborative that includes investigators with research expertise in emotional well-being (EWB), Alzheimer’s disease and related dementias (ADRD), human and animal neuroimaging, stress regulation, and computational/quantitative methods. Our objective is to stimulate mechanistic research identifying and testing mechanisms by which brain aging influences EWB and how EWB may impact risk for and progression of ADRD. This presentation will explain the structure and functions of the network that serve as a resource for investigators interested in EWB and aging research, and how to access them: a transdisciplinary community of scholars interested in brain, aging, and EWB research from both human and animal fields; webinars; workgroups to establish priorities for NEW Brain Aging activities; a resource repository; and pilot project funding opportunities to which network members can apply.

The Impact of ApoE and FOXO3 Genotype on the Risk of Intracerebral Hemorrhage Among American Men of Japanese Ancestry

This study assessed the impact of APOE e2, e4 minor alleles and the FOXO3 longevity-associated genotype (carrier of SNP rs2802292 “G” allele) on 34-year incidence of intracerebral hemorrhage (ICH). Cox regression models were performed to assess the impact of the APOE e2, e4 and FOXO3 G alleles on the incidence of ICH. A total of 6483 participants were eligible for the analyses. 213 participants developed ICH. Cox-regression model showed neither APOE minor allele vs. common genotype (APOE e3/e3: RR 0.89, 95% CI: 0.64-1.22, p=0.46) nor FOXO3 G carrier status (RR 0.97, 95% CI: 0.72-1.29, p=0.82) was associated with incident ICH. Conversely, both hypertension (RR: 1.46, 95% CI: 1.07-2.00, p=0.02) and low cholesterol level (RR: 0.99, 95% CI: 0.99-1.00, p=0.001) were associated with incident ICH. Carriage of APOE e2 or E4 alleles and the FOXO3 G allele do not appear to impact risk of ICH over 34 years in this cohort.

New Brain Aging Center

Evidence indicates an association between emotional well-being (EWB) and underlying brain processes, and that those processes change with both normal and pathological brain aging. However, the nature of these associations, the mechanisms by which EWB and its component domains change with brain aging, and how those changes may be associated with common neuropathologies like Alzheimer’s disease and related dementias (ADRD), are largely unexplored. The NIA-funded Network for Emotional Well-being and Brain Aging (NEW Brain Aging) has the goal of developing a nationwide community of investigators dedicated to research that identifies and tests mechanisms by which brain aging influences EWB and how EWB may impact risk for and progression of ADRD. Synthesizing human and animal literature, our premise is that relationships between EWB and ADRD are bidirectional – normal and pathological changes in aging brain influence EWB and EWB contributes to brain health and illness, such as ADRD. NEW Brain Aging will identify and coalesce resources for interested investigators and provide pilot funding opportunities to stimulate research and development of the field. Component presentations of this symposium will include (1) an overview by Dr. Robert Kaplan of the current state of research on EWB; (2) the role of animal studies (Kuan Hong Wang) and (3) human subjects research (Feng Vankee Lin) in EWB and aging; and (4) design of NEW Brain Aging and resources it will provide (Yeates Conwell). Janine Simmons will explain NIA’s vision for EWB research and lead open discussion.

The Cascading Climate Crisis

• Risk cascades are where an adverse climatic impact or trend triggers or amplifies a set of risks, including through maladaptive responses. • Climate risk cascades have already occurred and are set to increase going into the future. Some of these could be non-linear and high impact. • Risk cascades can occur through a unilinear chain – a ‘domino’ effect—or when the cascades reinforce the initial risk or driver – a ‘spiral’ or ‘cycle effect. At worst, these can snowball into crises that cross sectors and countries. • Predicting risk cascades will be inherently difficult, if not impossible. Yet we can likely understand the different pathways they may take, and the thresholds past which they are likely to occur. • Protecting again risk cascades means faster decarbonisation, supporting the most vulnerable, and building more resilient socio-economic systems. This will require indirect measures, such as remedying inequalities.

A Case–Control Study of Tackle-Based Head Injury Assessment (HIA) Risk Factors in the National Rugby League

Background The tackle is the in-game activity carrying the greatest risk for concussion in rugby. A recent evaluation of tackle characteristics in rugby union precipitated a rule modification to reduce head impact risk during tackles. This study aims to replicate the work conducted in rugby union by examining the association between tackle characteristics and head injury events in professional rugby league. Methods There were 446 tackles resulting in a head injury assessment (HIA) and 5,694 tackles that did not result in a head injury from two National Rugby League (NRL) seasons that were reviewed and coded. Tackle height, body position of players, and contact area on an opponent’s body were evaluated, with the propensity of each situation to cause an HIA calculated as HIAs per 1000 events. Results The propensity for tacklers to sustain a head injury was 0.99 HIAs per 1000 tackles, 1.74-fold greater than for the ball carrier (0.57 HIAs per 1000 tackles). There was a 3.2-fold higher risk for an HIA when the tackler was upright compared to bent-at-the-waist. The greatest risk of a tackler HIA occurred when head contact was very low (knee, boot) or high (head and elbow). HIAs were most common following head-to-head impacts. The lowest propensity for tackler HIA was found when the tackler’s head was in proximity with the ball carrier’s torso. Conclusions The result of this study replicated the findings in professional rugby union. This has implications for the injury prevention initiatives implemented to reduce HIA risk because the majority of injuries are sustained by the tackler.

Smoking is significantly associated with increased risk of COVID-19 and other respiratory infections

Observational studies suggest smoking, cannabis use, alcohol consumption, and substance use disorders (SUDs) may impact risk for respiratory infections, including coronavirus 2019 (COVID-2019). However, causal inference is challenging due to comorbid substance use. Using summary-level European ancestry data (>1.7 million participants), we performed single-variable and multivariable Mendelian randomization (MR) to evaluate relationships between substance use behaviors, COVID-19 and other respiratory infections. Genetic liability for smoking demonstrated the strongest associations with COVID-19 infection risk, including the risk for very severe respiratory confirmed COVID-19 (odds ratio (OR) = 2.69, 95% CI, 1.42, 5.10, P-value = 0.002), and COVID-19 infections requiring hospitalization (OR = 3.49, 95% CI, 2.23, 5.44, P-value = 3.74 × 10−8); these associations generally remained robust in models accounting for other substance use and cardiometabolic risk factors. Smoking was also strongly associated with increased risk of other respiratory infections, including asthma-related pneumonia/sepsis (OR = 3.64, 95% CI, 2.16, 6.11, P-value = 1.07 × 10−6), chronic lower respiratory diseases (OR = 2.29, 95% CI, 1.80, 2.91, P-value = 1.69 × 10−11), and bacterial pneumonia (OR = 2.14, 95% CI, 1.42, 3.24, P-value = 2.84 × 10−4). We provide strong genetic evidence showing smoking increases the risk for COVID-19 and other respiratory infections even after accounting for other substance use behaviors and cardiometabolic diseases, which suggests that prevention programs aimed at reducing smoking may be important for the COVID-19 pandemic and have substantial public health benefits.