A Systematic Review and Meta-Analysis

We evaluated the relevance of plasma homocysteine (HC) and the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in sickle cell disease (SCD) and associated vaso-occlusive crisis (VOC) and ischemic stroke (IS). We identified in Embase and Medline 22 studies on plasma HC and 22 on MTHFR genotypes. Due to age-related HC differences, adult and paediatric SCD were separated: 879 adult SCD and 834 controls (CTR) yielded a neutral effect size; 427 paediatric SCD and 625 CTR favoured SCD (p = 0.001) with wide heterogeneity (I2 = 95.5%) and were sub-grouped by country: six studies (Dutch Antilles n = 1, USA n = 5) yielded a neutral effect size, four (India n = 1, Arab countries n = 3) favoured SCD (p < 0.0001). Moreover, 249 SCD in VOC and 419 out of VOC yielded a neutral effect size. The pooled prevalence of the MTHFR TT genotype in 267 SCD equalled that of 1199 CTR (4.26% vs. 2.86%, p = 0.45), and in 84 SCD with IS equalled that of 86 without IS (5.9% vs. 3.7%, p = 0.47); removal of one paediatric study yielded a significant effect size (p = 0.006). Plasma HC in paediatric SCD from Middle East and India was higher, possibly due to vitamin deficiencies. Despite its low prevalence in SCD, the MTHFR TT genotype relates to adult IS.publishersversionpublishe

A Randomized Trial of a Physical Conditioning Program to Enhance the Driving Performance of Older Persons

BACKGROUND: As the number of older drivers increases, concern has been raised about the potential safety implications. Flexibility, coordination, and speed of movement have been associated with older drivers’ on road performance. OBJECTIVE: To determine whether a multicomponent physical conditioning program targeted to axial and extremity flexibility, coordination, and speed of movement could improve driving performance among older drivers. DESIGN: Randomized controlled trial with blinded assignment and end point assessment. Participants randomized to intervention underwent graduated exercises; controls received home, environment safety modules. PARTICIPANTS: Drivers, 178, age ≥ 70 years with physical, but without substantial visual (acuity 20/40 or better) or cognitive (Mini Mental State Examination score ≥24) impairments were recruited from clinics and community sources. MEASUREMENTS: On-road driving performance assessed by experienced evaluators in dual-brake equipped vehicle in urban, residential, and highway traffic. Performance rated three ways: (1) 36-item scale evaluating driving maneuvers and traffic situations; (2) evaluator’s overall rating; and (3) critical errors committed. Driving performance reassessed at 3 months by evaluator blinded to treatment group. RESULTS: Least squares mean change in road test scores at 3 months compared to baseline was 2.43 points higher in intervention than control participants (P = .03). Intervention drivers committed 37% fewer critical errors (P = .08); there were no significant differences in evaluator’s overall ratings (P = .29). No injuries were reported, and complaints of pain were rare. CONCLUSIONS: This safe, well-tolerated intervention maintained driving performance, while controls declined during the study period. Having interventions that can maintain or enhance driving performance may allow clinician–patient discussions about driving to adopt a more positive tone, rather than focusing on driving limitation or cessation

Liver Cirrhosis Patients Homozygous for MTHFR C677T Develop Portal Vein Thrombosis 8 Years Earlier Than Wild Type

Background and Aim Age at portal vein thrombosis (PVT) in liver cirrhosis (LC) carriers of the methylene tetrahydrofolate reductase (MTHFR) rs1801133 (C -&gt; T667 transition) polymorphism has never been addressed; we compared age at PVT in LC patients genotyped for the MTHFR and explored the interrelated clinical and laboratory factors predicting age at PVT. Approach and Results Retrospective cross-sectional cohort study. PVT participants: MTHFR CC n = 36, MTHFR CT n = 53, MTHFR TT n = 19; age, sex, age at PVT, Child-Pugh score, rs1799963 PT polymorphisms (G -&gt; A 20,210 transition), plasma HC and natural anticoagulants available for all participants. Age at PVT was lower in MTHFR TT than CT and CC (56 +/- 13 vs. 57 +/- 13 vs. 64 +/- 9 years, p = 0.001); median (IQR) plasma HC was higher in MTHFR TT than in the other groups [(17 (9.4, 23.3) vs 13 (8,14.7) vs 11 (8.9, 12.7) mu mol/l, p = 0.03)]. MTHFR TT, male gender and protein C predicted age at PVT (p = 0.02, p = 0.04 and p = 0.08); MTHFR TT and Child-Pugh score predicted plasma HC (p = 0.005 and p = 0.01) as well as low plasma protein C (p &lt; 0.0001 and p = 0.0002). Plasma HC inversely related to protein C in the MTHFR TT group (p &lt; 0.0001). Compound MTHFR TT with PT GA had lower age at PVT compared to MTHFR TT alone (49 +/- 18 vs 58 +/- 12 years). Conclusions MTHFR TT anticipates PVT associated with LC by an average of 8 years; MTHFR TT associates with severity of liver disease and to high plasma HC; the latter may contribute to the prematurity of PVT by interfering with the anticoagulant activity of protein C

Predictors of mortality in primary antiphospholipid syndrome. A single-centre cohort study.

The vascular mortality of antiphospholipid syndrome (APS) ranges from 1.4 % to 5.5 %, but its predictors are poorly known. It was the study objective to evaluate the impact of baseline lupus anticoagulant assays, IgG anticardiolipin (aCL), plasma fibrinogen (FNG) and von Willebrand factor (VWF), platelets (PLT) and of genetic polymorphisms of methylenetetrahydrofolate reductase C677T, of prothrombin G20210A and of paraoxonase-1 Q192R on mortality in primary APS (PAPS). Cohort study on 77 thrombotic PAPS and 33 asymptomatic carriers of aPL (PCaPL) seen from 1989 to 2015 and persistently positive for aPL as per annual review. At baseline all participants were tested twice for the ratios of kaolin clotting time (KCTr), activated partial thromboplastin time (aPTTr), dilute Russell viper venom time (DRVVTr), IgG aCL, FNG, VWF and once for PLT. All thrombotic PAPS were on warfarin with regular INR monitoring. During follow-up 11 PAPS deceased (D-PAPS) of recurrent thrombosis despite adequate anticoagulation yielding an overall vascular mortality of 10 %. D-PAPS had the strongest baseline aPTTr and DRVVTr and the highest mean baseline IgG aCL, FNG, VWF and PLT. Cox proportional hazards model identified baseline DRVVTr and FNG as main predictors of mortality with adjusted hazard ratios of 5.75 (95 % confidence interval [CI]: 1.5, 22.4) and of 1.03 (95 %CI: 1.01, 1.04), respectively. In conclusion, plasma DRVVTr and FNG are strong predictors of vascular mortality in PAPS; while FNG lowering agents exist further research should be directed at therapeutic strategies able to dampen aPL production

Peripheral Inflammation, \u3cem\u3eApolipoprotein E4\u3c/em\u3e, and Amyloid-β Interact to Induce Cognitive and Cerebrovascular Dysfunction

Cerebrovascular dysfunction is rapidly reemerging as a major process of Alzheimer’s disease (AD). It is, therefore, crucial to delineate the roles of AD risk factors in cerebrovascular dysfunction. While apolipoprotein E4 (APOE4), Amyloid-β (Aβ), and peripheral inflammation independently induce cerebrovascular damage, their collective effects remain to be elucidated. The goal of this study was to determine the interactive effect of APOE4, Aβ, and chronic repeated peripheral inflammation on cerebrovascular and cognitive dysfunction in vivo. EFAD mice are a well-characterized mouse model that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce human Aβ42 via expression of 5 Familial Alzheimer’s disease (5xFAD) mutations. Here, we utilized EFAD carriers [5xFAD+/−/APOE+/+ (EFAD+)] and noncarriers [5xFAD−/−/APOE+/+ (EFAD−)] to compare the effects of peripheral inflammation in the presence or absence of human Aβ overproduction. Low-level, chronic repeated peripheral inflammation was induced in EFAD mice via systemic administration of lipopolysaccharide (LPS; 0.5 mg/kg/wk i.p.) from 4 to 6 months of age. In E4FAD+ mice, peripheral inflammation caused cognitive deficits and lowered post-synaptic protein levels. Importantly, cerebrovascular deficits were observed in LPS-challenged E4FAD+ mice, including cerebrovascular leakiness, lower vessel coverage, and cerebral amyloid angiopathy-like Aβ deposition. Thus, APOE4, Aβ, and peripheral inflammation interact to induce cerebrovascular damage and cognitive deficits

Plenary Session II – Policy Track: Policies That Work

This session will describe policies related to medical fitness to drive and medical reporting. Jake Nelson will provide an overview of the research related to medical fitness to drive. Best practices will be highlighted by Dr. Meuser, and clinical geriatric issues will be discussed by Dr. Marottoli

Older peoples' experiences of informal support after giving up driving

Using a phenomenological approach, this study explored people who have given up driving's experiences of informal support following driving cessation based upon individual, semi-structured in-depth interviews with seven individuals who had retired from driving (n = 7). Findings highlight the complex nature of informal support as an alternative to driving in later life for older adults, showing there is no clear cut, linear process which occurs relating to this type of support. Retired older driver's experiences of informal support are multi-faceted, which include a broad range of practical and psychosocial factors. Informal support was usually provided in very practical terms but the receiver would often also need psychosocial and social support. Motivation for informal support stemmed from ill health, health concerns and was often coupled with living in an area with poor bus service. It was common for the participants to feel a burden on others and use strategies to reduce that feeling including rationing, trip chaining and providing reciprocation through gifts. The findings suggest the need for novel interventions which recognise the changing face of informal support, ensuring this is not the only viable alternative to driving in later life

An intervention encouraging planned self-regulation and goal setting in drivers across the lifespan:testing an extended theory of planned behaviour

Previous work has demonstrated that planning behaviours may be more adaptive than avoidance strategies in driving self-regulation, but ways of encouraging planning have not been investigated. The efficacy of an extended theory of planned behaviour (TPB) plus implementation intention based intervention to promote planning self-regulation in drivers across the lifespan was tested. An age stratified group of participants (N=81, aged 18-83 years) was randomly assigned to an experimental or control condition. The intervention prompted specific goal setting with action planning and barrier identification. Goal setting was carried out using an agreed behavioural contract. Baseline and follow-up measures of TPB variables, self-reported, driving self-regulation behaviours (avoidance and planning) and mobility goal achievements were collected using postal questionnaires. Like many previous efforts to change planned behaviour by changing its predictors using models of planned behaviour such as the TPB, results showed that the intervention did not significantly change any of the model components. However, more than 90% of participants achieved their primary driving goal, and self-regulation planning as measured on a self-regulation inventory was marginally improved. The study demonstrates the role of pre-decisional, or motivational components as contrasted with post-decisional goal enactment, and offers promise for the role of self-regulation planning and implementation intentions in assisting drivers in achieving their mobility goals and promoting safer driving across the lifespan, even in the context of unchanging beliefs such as perceived risk or driver anxiety

Geographical Perspectives on Transport and Ageing

In terms of ageing, we are living in unprecedented times. People across the globe are living longer than ever before and societies are ageing at increasing rates. In low to middle income countries reductions in mortality at young ages have fuelled this growth. A person born today in Brazil, for example, can expect to live 20 years longer than someone born 50 years ago (WHO, 2015). For the first time life expectancy across the globe is over 60 years of age. In high Income countries, someone born now can expect to live up to around 80 years of age on average (ONS, 2015). There are not simply a growing number of older people, but also a growing number of older people as a total percentage of the population due to people living longer and declining birth rates in many countries. Across Europe, for example, people aged over 65 years will account for 29.5% of the population in 2060 compared to around 19% now (EUROSTAT, 2017). The share of those aged 80 years or above across Europe will almost triple by 2060 (EUROSTAT, 2017)The macro level demographics and associated trends mask big differences within the ageing populations. There can be as much as 10 years difference in life expectancy within high income countries, for example in the UK someone born a baby boy born in Kensington and Chelsea has a life expectancy of 83.3 years, compared with a boy born in Glasgow who has a life expectancy of 10 years lower (73.0 years) (ONS, 2015). For newborn baby girls, life expectancy is highest in Chiltern at 86.7 years and 8 years lower Glasgow at 78.5 years (ONS, 2015; NRS, 2016). There is also considerable variation within cities, spatially and socially.This volume brings together contributions from a broad range of human geographers, with different disciplinary perspectives of transport and ageing. This chapter outlines some of the key contemporary issues for an ageing society in terms of transport and mobility, highlights the importance of considering transport and mobility for ageing populations and outlines the contribution that a geographical approach can offer to studies of transport and ageing