Abstract NS1: Mobile Health Technology Is Feasible And Effective For Self-management Support Among Underserved Stroke Survivors

Background and Purpose: Self-management Support (SMS) helps stroke survivors control risk factors to prevent second stroke. Little is known about feasibility and effectiveness of using mobile health technology (MHT) for SMS among underserved stroke survivors. The investigators studied feasibility and effectiveness of using a video teleconference mobile application to deliver a SMS program to underserved, hard to reach stroke survivors. Methods: The Video teleconference Self-management TO Prevent stroke (V-STOP) program was evaluated using longitudinal design with measurements at baseline, immediately post intervention (6 weeks), intermediate (12 weeks), and at study end (18 weeks). Medically underserved stroke survivors with uncontrolled stroke risk factors were included. Feasibility was assessed as time in intervention, telehealth satisfaction, stroke knowledge and SMS effectiveness were measured as psychological (depression, PHQ-8; anxiety, GAD-7), social (community integration questionnaire), and stroke self-management (goal attainment) outcomes. Generalized estimating equations were used with site and time in intervention as covariates. Results: V-STOP was successfully delivered to 106 participants using MHT over 2 years. Mean age was 59.3 (±10.9), majority were white (82.1%), males (54.3%), not living alone (85.9%), married (52.8%), with low annual income (<$25,000) ( 58.5%), and health insurance (59.4%). Program feasibility indicated mean number of V-STOP sessions were 4.6 (±1.8), with 4.4 (±2.0) hours of total time for the intervention. Overall satisfaction at 6 weeks with V-STOP (4.8(±0.5)) and telehealth (4.7(±0.5)) was high. Stroke knowledge was high at 12 weeks (9.6(±0.7)). SMS effectiveness indicated improvement in psychological outcomes at 6, 12, and 18 weeks from baseline; depression (18 weeks - β = 0.64 (CI 0.49-0.84)) and anxiety (18 weeks - β = 0.66 (CI 0.51-0.85)). Community integration improved by 18 weeks - β = 1.08 (CI 1.01-1.16) and stroke self-management also improved long term at 12 and 18 weeks (β = 0.92 (CI 0.84-0.99). Conclusion: MHT is feasible to deliver SMS to underserved stroke survivors. It improves psycho-social and self-management goal setting and goal attainment outcomes.

Our Efforts for Ideal Stroke Prevention and Treatment in Japan

In the present short review for the Sherman Award, Dr Yamaguchi introduces studies at the National Cerebral and Cardiovascular Center, Osaka, which included development of intravenous thrombolysis using low-dose alteplase that was officially approved in Japan, long-term dual antiplatelet therapy using cilostazol together with aspirin or clopidogrel, and others. He also discusses efforts to ensure the passage of the “Stroke and Cardiovascular Disease Control Act,” the aims of which are better primary prevention, better acute treatment, rehabilitation, and secondary prevention of stroke for people living in Japan.

From the Heart to the Brain: Building Bridges to a Better Future

This Presidential Address was delivered at the International Stroke Conference in March 2021, during the coronavirus pandemic. Dr Elkind, the President of the American Heart Association (AHA) at the time, is a vascular neurologist with a research focus on stroke epidemiology. This address interweaves personal reflections on a career in clinical neurology, stroke research, and public health with a discussion of the role of the AHA in improving cardiovascular health at multiple levels. Throughout its history, the AHA has had leaders representing many different areas of cardiovascular science and medicine, including stroke. More recently, its focus has expanded from a traditional emphasis on cardiovascular events illness and events, like heart disease and stroke, to an appreciation of the role of the vascular system in brain health, healthy aging, cognitive decline, and dementia. During the pandemic, as the bidirectional effects of the coronavirus on cardiovascular disease has been elucidated, the benefits of a broad and multidisciplinary approach to cardiovascular disease and public health have become more apparent than ever. In addition, with growing awareness of the disproportionate effects of the pandemic on communities of color in the United States and globally, the AHA has redoubled its focus on addressing the social determinants of health, including structural racism. Central to these efforts is the construction of bridges between the generation of scientific knowledge and action for the public good. Our success will depend on the combination of basic, translational, clinical and population research with programs of public and professional education, advocacy, and social action.

National Institutes of Health Stroke Scale as an Outcome in Stroke Research: Value of ANCOVA Over Analyzing Change From Baseline

National Institutes of Health Stroke Scale (NIHSS), measured a few hours to days after stroke onset, is an attractive outcome measure for stroke research. NIHSS at the time of presentation (baseline NIHSS) strongly predicts the follow-up NIHSS. Because of the need to account for the baseline NIHSS in the analysis of follow-up NIHSS as an outcome measure, a common and intuitive approach is to define study outcome as the change in NIHSS from baseline to follow-up (ΔNIHSS). However, this approach has important limitations. Analyzing ΔNIHSS implies a very strong assumption about the relationship between baseline and follow-up NIHSS that is unlikely to be satisfied, drawing into question the validity of the resulting statistical analysis. This reduces the precision of the estimates of treatment effects and the power of clinical trials that use this approach to analysis. ANCOVA allows for the analysis of follow-up NIHSS as the dependent variable while adjusting for baseline NIHSS as a covariate in the model and addresses several challenges of using ΔNIHSS outcome using simple bivariate comparisons (eg, a t test, Wilcoxon rank-sum, linear regression without adjustment for baseline) for stroke research. In this article, we use clinical trial simulations to illustrate that variability in NIHSS outcome is less when follow-up NIHSS is adjusted for baseline compared to ΔNIHSS and how a reduction in this variability improves the power. We outline additional, important clinical and statistical arguments to support the superiority of ANCOVA using the final measurement of the NIHSS adjusted for baseline over, and caution against using, the simple bivariate comparison of absolute NIHSS change (ie, delta).

Epidemiologic Trends, Social Determinants, and Brain Health: The Role of Life Course Inequalities

Brain health as expressed in our mental health and occurrence of specific disorders such as dementia and stroke is vitally important to quality of life, functional independence, and risk of institutionalization. Maintaining brain health is, therefore, a societal imperative, and public health challenge, from prevention of acquisition of brain disorders, through protection and risk reduction to supporting those with such disorders through effective societal and system approaches. To identify possible mechanisms that explain the differential effect of potentially modifiable risk factors, and factors that may mitigate risk, a life course approach is needed. This is key to understanding how poor health can accumulate from the earliest life stages. It also allows us to integrate and investigate key material, behavioral, and psychological factors that generate health inequalities within and across communities and societies. This review provides a narrative on how brain health is intimately linked to wider health determinants, thus importance for clinicians and societies alike. There is compelling evidence accumulated from research over decades that socioeconomic status, higher education, and healthy lifestyle extend life and compress major morbidities into later life. Brain health is part of this, but collective action has been limited, partly because of the separation of disciplines and focus on highly reductionist approaches in that clinicians and associated research have focused more on mitigation and early detection of specific diseases. However, clinicians could be part of the drive for better brain health for all society to support life courses that have more protection and less risk. There is evidence of change in such risks for conditions such as stroke and dementia across generations. The evidence points to the importance of starting with parental health and life course inequalities as a central focus.

Trials and Treatments for Vascular Brain Health: Risk Factor Modification and Cognitive Outcomes

There is robust evidence linking vascular health to brain health, cognition, and dementia. In this article, we present evidence from trials of vascular risk factor treatment on cognitive outcomes. We summarize findings from randomized controlled trials of antihypertensives, lipid-lowering medications, diabetes treatments (including antidiabetic drugs versus placebo, and intensive versus standard glycemic control), and multidomain interventions (that target several domains simultaneously such as control of vascular and metabolic factors, nutrition, physical activity, and cognitive stimulation etc). We report that evidence on the efficacy of vascular risk reduction interventions is promising, but not yet conclusive, and several methodological limitations hamper interpretation. Evidence mainly comes from high-income countries and, as cognition and dementia have not been the primary outcomes of many trials, evaluation of cognitive changes have often been limited. As the cognitive aging process occurs over decades, it is unclear whether treatment during the late-life window is optimal for dementia prevention, yet older individuals have been the target of most trials thus far. Further, many trials have not been powered to explore interactions with modifiers such as age, race, and apolipoprotein E, even though sub-analyses from some trials indicate that the success of interventions differs depending on patient characteristics. Due to the complex multifactorial etiology of dementia, and variations in risk factors between individuals, multidomain interventions targeting several risk factors and mechanisms are likely to be needed and the long-term sustainability of preventive interventions will require personalized approaches that could be facilitated by digital health tools. This is especially relevant during the coronavirus disease 2019 (COVID-19) pandemic, where intervention strategies will need to be adapted to the new normal, when face-to-face engagement with participants is limited and public health measures may create changes in lifestyle that affect individuals’ vascular risk profiles and subsequent risk of cognitive decline.

Risk Factors, Lifestyle Behaviors, and Vascular Brain Health

Although a relationship between traditional cardiovascular risk factors and stroke has long been recognized, these risk factors likely play a role in other aspects of brain health. Clinical stroke is only the tip of the iceberg of vascular brain injury that includes covert infarcts, white matter hyperintensities, and microbleeds. Furthermore, an individual’s risk for not only stroke but poor brain health includes not only these traditional vascular risk factors but also lifestyle and genetic factors. The purpose of this narrative review is to summarize the state of the evidence on traditional and nontraditional vascular risk factors and their contributions to brain health. Additionally, we will review important modifiers that interact with these risk factors to increase, or, in some cases, reduce risk of adverse brain health outcomes, with an emphasis on genes and biomarkers associated with Alzheimer disease. Finally, we will consider the importance of social determinants of health in brain health outcomes.

Vascular Contributions to Brain Health: Cross-Cutting Themes

As life expectancy grows, brain health is increasingly seen as central to what we mean by successful aging—and vascular brain health as central to overall brain health. Cerebrovascular pathologies are highly prevalent independent contributors to age-related cognitive impairment and at least partly modifiable with available treatments. The current Focused Update addresses vascular brain health from multiple angles, ranging from pathophysiologic mechanisms and neuroimaging features to epidemiologic risk factors, social determinants, and candidate treatments. Here we highlight some of the shared themes that cut across these distinct perspectives: 1) the lifetime course of vascular brain injury pathogenesis and progression; 2) the scientific and ethical imperative to extend vascular brain health research in non-White and non-affluent populations; 3) the need for improved tools to study the cerebral small vessels themselves; 4) the potential role for brain recovery mechanisms in determining vascular brain health and resilience; and 5) the cross-pathway mechanisms by which vascular and neurodegenerative processes may interact. The diverse perspectives featured in this Focused Update offer a sense of the multidisciplinary approaches and collaborations that will be required to launch our populations towards improved brain health and successful aging.

Imaging Markers of Vascular Brain Health: Quantification, Clinical Implications, and Future Directions

Cerebrovascular disease (CVD) manifests through a broad spectrum of mechanisms that negatively impact brain and cognitive health. Oftentimes, CVD changes (excluding acute stroke) are insufficiently considered in aging and dementia studies which can lead to an incomplete picture of the etiologies contributing to the burden of cognitive impairment. Our goal with this focused review is 3-fold. First, we provide a research update on the current magnetic resonance imaging methods that can measure CVD lesions as well as early CVD-related brain injury specifically related to small vessel disease. Second, we discuss the clinical implications and relevance of these CVD imaging markers for cognitive decline, incident dementia, and disease progression in Alzheimer disease, and Alzheimer-related dementias. Finally, we present our perspective on the outlook and challenges that remain in the field. With the increased research interest in this area, we believe that reliable CVD imaging biomarkers for aging and dementia studies are on the horizon.

Inflammation and the Link to Vascular Brain Health: Timing Is Brain

Inflammation and its myriad pathways are now recognized to play both causal and consequential roles in vascular brain health. From acting as a trigger for vascular brain injury, as evidenced by the coronavirus disease 2019 (COVID-19) pandemic, to steadily increasing the risk for chronic cerebrovascular disease, distinct inflammatory cascades play differential roles in varying states of cerebrovascular injury. New evidence is regularly emerging that characterizes the role of specific inflammatory pathways in these varying states including those at risk for stroke and chronic cerebrovascular injury as well as during the acute, subacute, and repair phases of stroke. Here, we aim to highlight recent basic science and clinical evidence for many distinct inflammatory cascades active in these varying states of cerebrovascular injury. The role of cerebrovascular infections, spotlighted by the severe acute respiratory syndrome coronavirus 2 pandemic, and its association with increased stroke risk is also reviewed. Rather than converging on a shared mechanism, these emerging studies implicate varied and distinct inflammatory processes in vascular brain injury and repair. Recognition of the phasic nature of inflammatory cascades on varying states of cerebrovascular disease is likely essential to the development and implementation of an anti-inflammatory strategy in the prevention, treatment, and repair of vascular brain injury. Although advances in revascularization have taught us that time is brain, targeting inflammation for the treatment of cerebrovascular disease will undoubtedly show us that timing is brain.