Alzheimer Disease: A Life-Limiting Disease With a Burden of a Terminal Illness.

Purpose of Review: An estimated 6.5 million Americans live with Alzheimer dementia. Better understanding of advanced stages of Alzheimer disease (AD) and timely monitoring of its preventable complications would translate to improved survival and quality of life in this population. Recent Findings: In this perspective review, we proposed shifting the narrative to recognizing AD as a chronic life-limiting illness instead of a terminal disease. In support of this view, we discussed the following: (1) the biochemical, cellular (preclinical), and clinical phases of AD; (2) survival after AD; (3) AD therapeutics and potential implications for the population with AD in the advanced stages. Summary: On the bases of the prolonged preclinical phase in AD, promising advances in AD therapeutics and the varying survival after AD, we proposed a new classification for AD and more broadly neurodegenerative disorders to be recognized as chronic life-limiting illnesses rather than terminal diseases with important implications for patients with AD in the advanced stages given the challenges that are specific to this population.

Measures of Aging Biology in Saliva and Blood as Novel Biomarkers for Stroke and Heart Disease in Older Adults.

BACKGROUND AND OBJECTIVES: The role of aging biology as a novel risk factor and biomarker for vascular outcomes in different accessible body tissues such as saliva and blood remain unclear. We aimed to (1) assess the role of aging biology as a risk factor of stroke and heart disease among individuals of same chronologic age and sex and (2) compare aging biology biomarkers measured in different accessible body tissues as novel biomarkers for stroke and heart disease in older adults. METHODS: This study included individuals who consented for blood and saliva draw in the Venous Blood Substudy and Telomere Length Study of the Health and Retirement Study (HRS). The HRS is a population-based, nationally representative longitudinal survey of individuals aged 50 years and older in the United States. Saliva-based measures included telomere length. Blood-based measures included DNA methylation and physiology biomarkers. Propensity scores-matched analyses and Cox regression models were conducted. RESULTS: This study included individuals aged 50 years and older, who consented for blood (N = 9,934) and saliva (N = 5,808) draw in the HRS. Blood-based biomarkers of aging biology showed strong associations with incident stroke as follows: compared with the lowest tertile of blood-based biomarkers of aging, biologically older individuals had significantly higher risk of stroke based on DNA methylation Grim Age clock (adjusted hazard ratio [aHR] = 2.64, 95% CI 1.90-3.66, p < 0.001) and Physiology-based Phenotypic Age clock (aHR = 1.75, 95% CI 1.27-2.42, p < 0.001). In secondary analysis, biologically older individuals had increased risk of heart disease as follows: DNA methylation Grim Age clock (aHR = 1.77, 95% CI 1.49-2.11, p < 0.001) and Physiology-based Phenotypic Age clock (aHR = 1.61, 95% CI 1.36-1.90, p < 0.001). DISCUSSION: Compared with saliva-based telomere length, blood-based aging physiology and some DNA methylation biomarkers are strongly associated with vascular disorders including stroke and are more precise and sensitive biomarkers of aging. Saliva-based telomere length and blood-based DNA methylation and physiology biomarkers likely represent different aspects of biological aging and accordingly vary in their precision as novel biomarkers for optimal vascular health.

Telehealth After Stroke Care Pilot Randomized Trial of Home Blood Pressure Telemonitoring in an Underserved Setting.

BACKGROUND: Hypertension is the most important modifiable stroke risk factor, but blood pressure (BP) remains poorly controlled after stroke, especially among Black and Hispanic patients. We tested the feasibility of TASC (Telehealth After Stroke Care), a post-acute stroke care model integrating nurse-supported home BP telemonitoring, tailored infographics, and multidisciplinary team video visits. METHODS: Acute stroke patients with hypertension were randomized at discharge to usual care or usual care with TASC. Usual care patients received video visits with primary care and stroke. TASC included a tablet and monitor to wirelessly transmit BP data to the electronic health record, with telenursing support, tailored infographics to explain BP readings, and pharmacist visits. Outcomes assessment was blinded. Feasibility outcomes included recruitment, randomization, adherence, and retention. Systolic BP from baseline to 3 months after discharge was evaluated using generalized linear modeling. RESULTS: Fifty patients (64±14 years; 36% women' 44% Hispanic, 32% Black, 54% ≤high school education, 30% private insurance), and 75% of all eligible were enrolled over 6.3 months. Baseline systolic BP was similar in both (TASC n=25, 140±19 mm Hg; usual care n=25, 142±19 mm Hg). At 3 months, adherence to video visits (91% versus 75%, P=0.14) and retention (84% versus 64%, P=0.11) were higher with TASC. Home systolic BP declined by 16±19 mm Hg from baseline in TASC and increased by 3±24 mm Hg in usual care (P=0.01). Among Black patients, systolic BP control (<130 mm Hg) improved from 40% to 100% with TASC versus 14% to 29%, and among Hispanic patients, from 23% to 62% with TASC, versus 33% to 17% in usual care. CONCLUSIONS: Enhancing post-acute stroke care with home BP telemonitoring is feasible to improve hypertension in an underserved setting and should be tested in a definitive randomized clinical trial. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04640519.

TASC (Telehealth After Stroke Care): a study protocol for a randomized controlled feasibility trial of telehealth-enabled multidisciplinary stroke care in an underserved urban setting.

BACKGROUND: Hypertension is the most important modifiable risk factor for recurrent stroke, and blood pressure (BP) reduction is associated with decreased risk of stroke recurrence. However, hypertension remains poorly controlled in many stroke survivors. Black and Hispanic patients have a higher prevalence of uncontrolled BP and higher rates of stroke. Limited access to care contributes to challenges in post-stroke care. Telehealth After Stroke Care (TASC) is a telehealth intervention that integrates remote BP monitoring (RBPM) including nursing telephone support, tailored BP infographics and telehealth video visits with a multidisciplinary team approach including pharmacy to improve post-stroke care and reduce stroke disparities. METHODS: In this pilot trial, 50 acute stroke patients with hypertension will be screened for inclusion prior to hospital discharge and randomized to usual care or TASC. Usual care patients will be seen by a primary care nurse practitioner at 1-2 weeks and a stroke neurologist at 1 and 3 months. In addition to these usual care visits, TASC intervention patients will see a pharmacist at 4 and 8 weeks and will be enrolled in RBPM consisting of home BP monitoring with interval calls by a centralized team of telehealth nurses. As part of RBPM, TASC patients will be provided with a home BP monitoring device and electronic tablet that wirelessly transmits home BP data to the electronic health record. They will also receive tailored BP infographics that help explain their BP readings. The primary outcome will be feasibility including recruitment, adherence to at least one video visit and retention rates. The clinical outcome for consideration in a subsequent trial will be within-patient change in BP from baseline to 3 months after discharge. Secondary outcomes will be medication adherence self-efficacy and satisfaction with post-stroke telehealth, both measured at 3 months. Additional patient reported outcomes will include depression, cognitive function, and socioeconomic determinants. Multidisciplinary team competency and fidelity measures will also be assessed. CONCLUSIONS: Integrated team-based interventions may improve BP control and reduce racial/ethnic disparities in post-stroke care. TASC is a post-acute stroke care model that is novel in providing RBPM with tailored infographics, and a multidisciplinary team approach including pharmacy. Our pilot will determine if such an approach is feasible and effective in enhancing post-stroke BP control and promoting self-efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04640519.

Self-Reported Race as a Social Determinant of Stroke Risk in Observational Versus Clinical Trial Datasets.

OBJECTIVES: Self-reported Black (SRB) Americans are approximately twice as likely to have a stroke as self-reported White (SRW) Americans. While social determinants of health and vascular risk factors account for some of the disparity, half the increased risk remains unexplained and may be related to unmeasured real-world factors of the racialized experience. MATERIALS: and Methods In this cohort study, we compared SRB and SRW participants in the Systolic Blood Pressure Intervention Trial (SPRINT) to the same groups in the observational Atherosclerosis Risk in Communities (ARIC) study to evaluate if clinical trial participation mitigates disparities in stroke risk. We set the ARIC baseline at visit 4 and excluded participants with prior stroke to create an ARIC cohort similar in age to SPRINT participants. The study outcome was incident primary stroke. We report hazard ratios from Cox models and inverse-probability weighted Cox models with propensity score matching on participant age, sex, diabetes, atrial fibrillation, and smoking. RESULTS: We included 10,094 patients from ARIC and 8,869 from SPRINT, of which 26.1% were SRB. The risk of stroke between SRW participants in SPRINT versus ARIC was not significantly different (IPW-Weighted HR 0.78 [0.52-1.19]). SRB ARIC participants were twice as likely to have a stroke as SRW ARIC participants (IPW-Weighted HR = 1.96 [1.41-2.71]). However, SRB SPRINT participants did not have higher stroke risk compared to SRW SPRINT or ARIC participants (IPW-Weighted HR 0.99 [0.68--1.77] and 0.95 [.57-1.59], respectively). SRB SPRINT participants in the intensive BP control group had a lower risk of stroke compared to SRB ARIC participants (IPW-Weighted HR = 0.39 [0.20-0.75]). CONCLUSIONS: SRB race, compared to SRW race, is associated with an increase in primary stroke risk in the ARIC study but not in the SPRINT trial. The absence of the racial disparity in stroke incidence in SPRINT indicates that aspects of the disparity are modifiable. Population-based interventions that test this hypothesis deserve further attention.

Cilostazol for Secondary Stroke Prevention: History, Evidence, Limitations, and Possibilities.

Cilostazol is a PDE3 (phosphodiesterase III) inhibitor with a long track record of safety that is Food and Drug Administration and European Medicines Agency approved for the treatment of claudication in patients with peripheral arterial disease. In addition, cilostazol has been approved for secondary stroke prevention in several Asian countries based on trials that have demonstrated a reduction in stroke recurrence among patients with noncardioembolic stroke. The onset of benefit appears after 60 to 90 days of treatment, which is consistent with cilostazol's pleiotropic effects on platelet aggregation, vascular remodeling, blood flow, and plasma lipids. Cilostazol appears safe and does not increase the risk of major bleeding when given alone or in combination with aspirin or clopidogrel. Adverse effects such as headache, gastrointestinal symptoms, and palpitations, however, contributed to a 6% increase in drug discontinuation among patients randomized to cilostazol in a large secondary stroke prevention trial (CSPS.com [Cilostazol Stroke Prevention Study for Antiplatelet Combination]). Due to limitations of prior trials, such as open-label design, premature trial termination, large loss to follow-up, lack of functional or cognitive outcome data, and exclusive enrollment in Asia, the existing trials have not led to a change in clinical practice or guidelines in Western countries. These limitations could be addressed by a double-blind placebo-controlled randomized trial conducted in a broader population. If positive, it would increase the evidence in support of long-term treatment with cilostazol for secondary prevention in the millions of patients worldwide who have experienced a noncardioembolic ischemic stroke.

Manhattan Vision Screening and Follow-Up Study in Vulnerable Populations: 1-Month Feasibility Results.

Purpose/Aim: In the United States, high rates of vision impairment and eye disease disproportionately impact those who lack access to eye care, specifically vulnerable populations. The objective of our study was to test instruments, implement protocols, and collect preliminary data for a larger 5-year study, which aims to improve detection of eye diseases and follow-up eye care in vulnerable populations using community health workers (CHW) and patient navigators. In the study, trained CHWs conducted vision screening and patient navigators scheduled on-site eye exams and arranged appointments for those referred to ophthalmology to improve adherence to follow-up eye care.Materials and Methods: Eligible individuals age 40-and-older were recruited from the Riverstone Senior Center in Upper Manhattan, New York City. Participants underwent on-site vision screening (visual acuity with correction, intraocular pressure measurements, and fundus photography). Individuals who failed the vision screening were scheduled with an on-site optometrist for an eye exam; those with ocular pathologies were referred to an ophthalmologist. Participants were also administered the National Eye Institute Visual Function Questionnaire-8 (NEI-VFQ-8) and Stopping Elderly Accidents, Deaths, and Injuries (STEADI) test by community health workers.Results:Participants (n = 42) were predominantly older adults, with a mean age of 70.0 ± 9.8, female (61.9%), and Hispanic (78.6%). Most individuals (78.6%, n = 33) failed vision screening. Of those who failed, 84.8% (n = 28) attended the on-site eye exam with the optometrist. Ocular diagnoses: refractive error 13/28 (46.4%), glaucoma/glaucoma suspect 9/28 (32.1%), cataract 7/28 (25.0%), retina abnormalities 6/28 (21.4%); 13 people required eyeglasses.Conclusion: This study demonstrates the feasibility of using CHWs and patient navigators for reducing barriers to vision screening and optometrist-based eye exams in vulnerable populations, ultimately improving early detection of eye disease and linking individuals to additional eye care appointments. The full five-year study aims to further examine these outcomes.

Manhattan Vision Screening and Follow-up Study in Vulnerable Populations (NYC-SIGHT): Design and Methodology.

PRCIS: The Manhattan Vision Screening and Follow-up Study in Vulnerable Populations is a 5-year prospective, cluster-randomized study to improve detection and management of glaucoma and other eye diseases in vulnerable populations living in affordable housing developments. PURPOSE: To describe the study design and methodology of the Manhattan Vision Screening and Follow-up Study in Vulnerable Populations, which aims to investigate whether community-based vision screenings can improve detection and management of glaucoma, vision impairment, cataract, and other eye diseases among vulnerable populations living in affordable housing developments in upper Manhattan. MATERIALS AND METHODS: This 5-year prospective, cluster-randomized, controlled trial consists of vision screening and referral for follow-up eye care among eligible residents aged 40 and older. Visual acuity, intraocular pressure (IOP), and fundus photography are measured. Participants with visual worse than 20/40, or IOP 23 to 29 mm Hg, or unreadable fundus images fail the screening and are scheduled with the on-site optometrist. Those with an abnormal image and/or IOP ≥30 mm Hg, are assigned as "fast-track" and referred to ophthalmology. Participants living in 7 developments randomized to the Enhanced Intervention Group who fail the screening and need vision correction receive complimentary eyeglasses. Those referred to ophthalmology receive enhanced support with patient navigators to assist with follow-up eye care. Participants living in 3 developments randomized to the Usual Care Group who fail the screening and need vision correction are given an eyeglasses prescription only and a list of optical shops. No enhanced support is given to the Usual Care Group. All participants referred to ophthalmology are assisted in making their initial eye exam appointment. CONCLUSION: This study targets vulnerable populations where they live to ensure improved access to and utilization of eye care services in those who are least likely to seek eye care.

A decade of racial and ethnic stroke disparities in the United States.

Stroke is the fourth leading cause of death and the leading cause of long-term disability in the United States. Stroke incidence and prevalence is not uniform. It occurs more frequently in some geographical areas of the United States and the rates are higher in minority groups.(1,2) Some proposed causes for these disparities include increased rate of vascular risk factors that disproportionally affect some minority groups, differential effect of hypertension on stroke risk across racial groups, lack of access to health care and other social determinants of health, suboptimal control of risk factors, and although lacking substantive data to date, an inherited predisposition to stroke associated with genetic differences. The Reasons for Geographic and Racial Differences in Stroke (REGARDS) investigators found that the rate of suboptimal control of vascular risk factors and unhealthy lifestyles were significantly greater in African Americans compared to non-Hispanic whites (NHW).(2) Moreover, regarding high blood pressure (BP), a triple threat has been described: blacks are not only more likely to have high BP, they are less likely, once diagnosed, to have their high BP controlled, and this suboptimal control has been shown to confer a stroke risk that is 3 times higher among blacks compared to whites for every 10-mm Hg increase in systolic BP (SBP).(3.)

The use of an audience response system in an elementary school-based health education program.

BACKGROUND: The audience response system (ARS) allows students to respond and interact anonymously with teachers via small handheld wireless keypads. Despite increasing popularity in classroom settings, the application of these devices to health education programming has not been studied. We assessed feasibility, engagement, and learning among children using an ARS compared with traditional pencil-paper formats, (ARS) for a stroke health education program. METHOD: We compared outcome data generated via an ARS-based intervention to pencil-paper controls, including test scores and missing data rates among 265 schoolchildren 9 to 11 years old participating in stroke education. Among 119 children, we evaluated the feasibility of ARS use and explored student motivation with a 10-item questionnaire. We assessed facilitator experience with both methods. RESULTS: ARS use is feasible. Students reported having more fun (p < .001), increased attention (p < .001), participation (p < .001), and perceived learning outcomes (p < .001) compared with pencil-paper controls. Test scores showed highly positive improvement for both ARS and paper without additional benefits of ARS on learning. There was no difference in missing data rates (p < .001). Educators preferred the ARS. CONCLUSION: The use of an ARS among children is feasible and improves student and facilitator engagement without additional benefits on stroke learning.