Treatment and Outcomes of Cervical Artery Dissection in Adults: A Scientific Statement From the American Heart Association.

Cervical artery dissection is an important cause of stroke, particularly in young adults. Data conflict on the diagnostic evaluation and treatment of patients with suspected cervical artery dissection, leading to variability in practice. We aim to provide an overview of cervical artery dissection in the setting of minor or no reported mechanical trigger with a focus on summarizing the available evidence and providing suggestions on the diagnostic evaluation, treatment approaches, and outcomes. Writing group members drafted their sections using a literature search focused on publications between January 1, 1990, and December 31, 2022, and included randomized controlled trials, prospective and retrospective observational studies, meta-analyses, opinion papers, case series, and case reports. The writing group chair and vice chair compiled the manuscript and obtained writing group members' approval. Cervical artery dissection occurs as a result of the interplay among risk factors, minor trauma, anatomic and congenital abnormalities, and genetic predisposition. The diagnosis can be challenging both clinically and radiologically. In patients with acute ischemic stroke attributable to cervical artery dissection, acute treatment strategies such as thrombolysis and mechanical thrombectomy are reasonable in otherwise eligible patients. We suggest that the antithrombotic therapy choice be individualized and continued for at least 3 to 6 months. The risk of recurrent dissection is low, and preventive measures may be considered early after the diagnosis and continued in high-risk patients. Ongoing longitudinal and population-based observational studies are needed to close the present gaps on preferred antithrombotic regimens considering clinical and radiographic prognosticators of cervical artery dissection.

Association of Brain Arterial Elongation With Risk of Stroke and Death in Stroke-Free Individuals: Results From NOMAS.

BACKGROUND: Brain arterial dilation and elongation characterize dolichoectasia, an arteriopathy associated with risk of stroke and death. We aim to determine whether brain arterial elongation increases the risk of stroke and death independent of brain arterial diameters. METHODS: We analyzed 1210 stroke-free participants (mean age 71±9 years, 41% men, 65% Hispanic) with available time-of-flight magnetic resonance angiogram from the Northern Manhattan Study, a population-based cohort study across a multiethnic urban community. We obtained baseline middle cerebral artery M1-segment (MCA-M1) and basilar artery (BA) mean lengths and diameters using a semi-automated software. Cox proportional hazards models adjusted for brain arterial diameters and potential confounders yielded adjusted hazards ratios with 95% CIs for the primary outcomes of incident stroke and all-cause mortality, as well as secondary outcomes including noncardioembolic stroke, vascular death, and any vascular event. RESULTS: Neither MCA-M1 nor BA lengths correlated with incident stroke or all-cause mortality. Both MCA-M1 and BA larger diameters correlated with all-cause mortality (MCA-M1 aHR, 1.52 [95% CI, 1.03-2.23], BA aHR, 1.28 [95% CI, 1.02-1.61]), as well as larger MCA-M1 diameters with vascular death (aHR, 1.84 [95% CI, 1.02-3.31]). Larger MCA-M1 and BA diameters did not correlate with incident stroke. However, larger BA diameters were associated with posterior circulation noncardioembolic stroke (aHR, 2.93 [95% CI, 1.07-8.04]). There were no statistical interactions between brain arterial lengths and diameters in relation to study outcomes. CONCLUSIONS: In a multiethnic cohort of stroke-free adults, brain arterial elongation did not correlate with risk of stroke or death, nor influenced the significant association between brain arterial dilation and vascular risk.

Immune Markers Are Associated With Asymptomatic Intracranial Large Artery Stenosis and Future Vascular Events in NOMAS.

BACKGROUND: Inflammation contributes to atherosclerosis but is incompletely characterized in intracranial large artery stenosis (ICAS). We hypothesized that immune markers would be associated with ICAS and modify the risk ICAS confers on future vascular events. METHODS: This study included a subsample of stroke-free participants in the prospective NOMAS (Northern Manhattan Study), who had blood samples analyzed with a 60-plex immunoassay (collected from 1993 to 2001) and ICAS assessment with time-of-flight magnetic resonance angiography (obtained from 2003 to 2008). We dichotomized ICAS as either ≥50% stenosis or not (including no ICAS). We ascertained post-magnetic resonance imaging vascular events. We used least absolute shrinkage and selection operator procedures to select immune markers independently associated with ICAS. Then, we grouped selected immune markers into a derived composite Z score. Using proportional odds regression, we quantified the association of the composite immune marker Z score, ICAS, and risk of vascular events. RESULTS: Among 1211 participants (mean age, 71±9 years; 59% women; 65% Hispanic participants), 8% had ≥50% ICAS. Using least absolute shrinkage and selection operator regression, we identified CXCL9 (C-X-C motif chemokine ligand 9), HGF (hepatocyte growth factor), resistin, SCF (stem cell factor), and VEGF-A(vascular endothelial growth factor A) to have the strongest positive relationships with ≥50% ICAS in fully adjusted models. Selected markers were used to derive a composite immune marker Z score. Over an average follow-up of 12 years, we found that each unit increase in immune marker Z scores was associated with an 8% (95% CI, 1.05-1.11), 11% (95% CI, 1.06-1.16), and 5% (95% CI, 1.01-1.09) increased hazard of death, vascular death, and any vascular event, respectively, in adjusted models. We did not find a significant interaction between immune marker Z scores and ICAS in their relationship with any longitudinal outcome. CONCLUSIONS: Among a diverse stroke-free population, selected serum immune markers were associated with ICAS and future vascular events. Further study is needed to better understand their role in the pathogenesis of ICAS and as a potential therapeutic target in stroke prevention.

Determinants and Temporal Trends of Dual Antiplatelet Therapy After Mild Noncardioembolic Stroke.

BACKGROUND: Short-term dual antiplatelet therapy (DAPT) reduces early stroke recurrence after mild noncardioembolic ischemic stroke (NCIS). We aim to evaluate temporal trends and determinants of DAPT prescription after mild NCIS in the Florida Stroke Registry, a statewide registry across Get With The Guidelines-Stroke participating hospitals. METHODS: In this cross-sectional analysis of a cohort study, we included patients with mild NCIS (National Institutes of Health Stroke Scale score ≤3) who were potentially eligible for DAPT across 168 Florida Stroke Registry participating hospitals between January 2010 and September 2022. Using antiplatelet prescription as the dependent variable (DAPT versus single antiplatelet therapy), we fit logistic regression models adjusted for patient-related factors, hospital-related factors, clinical presentation, vascular risk factors, and ischemic stroke subtype, to obtain adjusted odds ratios (aORs) with 95% CIs. RESULTS: From 283 264 Florida Stroke Registry ischemic stroke patients during the study period, 109 655 NCIS were considered eligible. Among these, 37 058 patients with National Institutes of Health Stroke Scale score >3 were excluded, resulting in a sample of 72 597 mild NCIS (mean age 68±14 years; female 47.3%). Overall, 24 693 (34.0%) patients with mild NCIS were discharged on DAPT and 47 904 (66.0%) on single antiplatelet therapy. DAPT prescription increased from 25.7% in 2010 to 52.8% in 2022 (ß/year 2.5% [95% CI, 1.5%-3.4%]). Factors associated with DAPT prescription were premorbid antiplatelet therapy (aOR, 4.66 [95% CI, 2.20-9.88]), large-artery atherosclerosis (aOR, 1.68 [95% CI, 1.43-1.97]), diabetes (aOR, 1.29 [95% CI, 1.13-1.47]), and hyperlipidemia (aOR, 1.24 [95% CI, 1.10-1.39]), whereas female sex (aOR, 0.83 [95% CI, 0.75-0.93]), being non-Hispanic Black patients (compared with non-Hispanic White patients; aOR, 0.78 [95% CI, 0.68-0.90]), admission to a Thrombectomy-capable Stroke Center (compared with Comprehensive Stroke Center; aOR, 0.78 [95% CI, 0.66-0.92]), time-to-presentation 1 to 7 days from last seen well (compared with <24 h; aOR, 0.86 [95% CI, 0.76-0.96]), and small-vessel disease stroke (aOR, 0.81 [95% CI, 0.72-0.94]) were associated with not receiving DAPT at discharge. CONCLUSIONS: Despite a temporal trend increase in DAPT prescription after mild NCIS, we found substantial underutilization of evidence-based DAPT associated with significant disparities in stroke care.

High Social Risk Influence Progression of White Matter Hyperintensities of Presumed Vascular Origin: A Prospective Study in Community-Dwelling Older Adults.

BACKGROUND: Information on cerebrovascular consequences of high social risk, as determined by the social determinants of health, is limited. We sought to evaluate the impact of high social risk on the progression of white matter hyperintensities (WMHs) of presumed vascular origin. METHODS: Following a longitudinal prospective study design, participants of the Atahualpa Project Cohort received baseline social risk determinations by means of social determinants of health components included in the Gijon's Social-Familial Evaluation Scale together with clinical interviews and brain magnetic resonance imagings. Those who also received follow-up brain magnetic resonance imaging at the end of the study were included. We used Poisson regression models adjusted for demographics, education levels and traditional cardiovascular risk factors to assess the incidence rate ratio of WMH progression according to the Gijon's Social-Familial Evaluation Scale score. RESULTS: The study included 263 individuals aged ≥60 years (mean age, 65.7±6.2 years; 57% women). The Gijon's Social-Familial Evaluation Scale mean score was 8.9±2.2 points. Follow-up magnetic resonance imagings revealed WMH progression in 103 (39%) individuals after a mean follow-up of 6.5 years (SD±1.4 years). Poisson regression models showed increased WMH progression rate among individuals in the third tertile of the Gijon's Social-Familial Evaluation Scale score compared with those in the first tertile (incidence rate ratio, 1.65 [95% CI, 1.05-2.61]; P=0.032). Separate Poisson regression models using individual social determinants of health components showed that poor social relationships (incidence rate ratio, 1.39 [95% CI, 1.10-1.77]; P=0.006) and deficient support networks (incidence rate ratio, 1.79 [95% CI, 1.19-2.69]; P=0.005) were independently associated with WMH progression, whereas family situation, economic status, and housing did not. CONCLUSIONS: Poor social relationships and deficient support networks were significantly associated with WMH progression in community-dwelling older adults living in a rural setting. Our findings may help planning cost-effective preventive policies to reduce progression of cerebral small vessel disease among vulnerable populations.

Patterns of progression of cerebral small vessel disease markers in older adults of Amerindian ancestry: a population-based, longitudinal prospective cohort study.

BACKGROUND: Progression of cerebral small vessel disease (cSVD) markers has been studied in different races/ethnic groups. However, information from individuals of Amerindian ancestry is lacking. We sought to evaluate progression patterns of cSVD markers in community-dwelling older adults of Amerindian ancestry. METHODS: Following a longitudinal prospective study design, participants of the Atahualpa Project Cohort aged ≥ 60 years received a baseline brain MRI and clinical interviews. Those who also received a brain MRI at the end of the study were included. Poisson regression models were fitted to assess cSVD markers progression according to their baseline load after a median follow-up of 6.5 ± 1.4 years. Logistic regression models were fitted to assess interrelations in the progression of the different cSVD markers at the end of the study. RESULTS: The study included 263 individuals (mean age: 65.7 ± 6.2 years). Progression of white matter hyperintensities (WMH) was noticed in 103 (39%) subjects, cerebral microbleeds in 25 (12%), lacunes in 12 (5%), and enlarged basal ganglia-perivascular spaces (BG-PVS) in 56 (21%). Bivariate Poisson regression models showed significant associations between WMH severity at baseline and progression of WMH and enlarged BG-PVS. These associations became non-significant in multivariate models adjusted for clinical covariates. Logistic regression models showed interrelated progressions of WMH, cerebral microbleeds and enlarged BG-PVS. The progression of lacunes was independent. CONCLUSIONS: Patterns of cSVD marker progression in this population of Amerindians are different than those reported in other races/ethnic groups. The independent progression of lacunes suggests different pathogenic mechanisms with other cSVD markers.

Decreased Nighttime Heart Rate Variability and Progression of White Matter Hyperintensities of Presumed Vascular Origin. A Prospective Study in Community-Dwelling Older Adults.

OBJECTIVES: Evidence on the role of autonomic dysfunction on white matter hyperintensities (WMH) progression is limited. This study aims to assess the impact of a low nighttime heart rate variability (HRV) on WMH progression in community-dwelling older adults. MATERIALS AND METHODS: Following a prospective longitudinal study design, all individuals aged ≥60 years enrolled in the Atahualpa Project Cohort from 2012 to 2019 were invited to receive baseline HRV determinations through 24-h Holter monitoring, together with clinical interviews and brain MRIs. These individuals were periodically followed by means of annual door-to-door surveys, and those who also received brain MRIs at the end of the study (May 2021) were included in the analysis. Poisson regression models, adjusted for relevant confounders, were fitted to assess the incidence rate ratio (IRR) of WMH progression according to nighttime standard deviation of normal-to-normal R-R intervals (SDNN). RESULTS: This study included 254 individuals aged ≥60 years (mean age: 65.4 ± 5.9 years; 55% women). The mean nighttime SDNN was 116.8 ± 36.3 ms. Follow-up MRIs showed WMH progression in 103 (41%) individuals after a median follow-up of 6.5 years. In unadjusted analyses, nighttime SDNN was lower among participants who developed WMH progression than in those who did not (p < 0.001). A Poisson regression model, adjusted for relevant covariates, disclosed a significantly inverse association between nighttime SDNN and WMH progression (IRR: 0.99; 95% C.I.: 0.98-0.99; p = 0.014). CONCLUSIONS: Study results show an inverse association between nighttime SDNN and WMH progression, and provide support for the role of sympathetic overactivity in this relationship.

Internal Carotid Artery Angle Variations are Poorly Explained by Vascular Risk Factors: The Northern Manhattan Study.

OBJECTIVES: The internal carotid artery (ICA) angle of origin may contribute to atherogenesis by altered hemodynamics. We aim to determine the contribution of vascular risk factors and arterial wall changes to ICA angle variations. METHODS: We analyzed 1,065 stroke-free participants from the population-based Northern Manhattan Study who underwent B-mode ultrasound (mean age 68.7±8.9 years; 59% women). ICA angle was estimated at the intersection between the common carotid artery and the ICA center line projections. Narrower external angles translating into greater carotid bifurcation bending were considered unfavorable. Linear regression models were fitted to assess the relationship between ICA angle and demographics, vascular risk factors, and arterial wall changes including carotid intima-media thickness (cIMT) and plaque presence. RESULTS: ICA angles were narrower on the left compared to the right side (153±15.4 degrees versus 161.4±12.7 degrees, p<0.01). Mean cIMT was 0.9±0.1 mm and 54.3% had at least one plaque. ICA angle was not associated with cIMT or plaque presence. Unfavorable left and right ICA angles were associated with advanced age (per 10-year increase ß=-1.6; p=0.01, and -1.3; p=0.03, respectively) and being Black participant (ß=-4.6; p<0.01 and -2.9; p=0.04, respectively), while unfavorable left ICA angle was associated with being female (ß=-2.8; p=0.03) and increased diastolic blood pressure (per 10 mmHg increase ß=-2.1; p<0.01). Overall, studied factors explained less than 10% of the variance in ICA angle (left R2=0.07; right R2=0.05). CONCLUSION: Only a small portion of ICA angle variation were explained by demographics, vascular risk factors and arterial wall changes. Whether ICA angle is determined by other environmental or genetic factors, and is an independent risk factor for atherogenesis, requires further investigation.

Prevalence and Clinical Correlates of Intracranial Dolichoectasia in Individuals With Ischemic Stroke.

Background and Purpose: Acute ischemic stroke is a known complication of intracranial dolichoectasia (IDE). However, the frequency of IDE causing brain infarction is unknown. We aim to determine the prevalence and clinical correlates of IDE in acute ischemic stroke by employing an objective IDE definition for major intracranial arteries of the anterior and posterior circulation. Methods: Consecutive patients with acute ischemic stroke admitted to a tertiary-care hospital during a 4-month period were analyzed. Intracranial arterial diameter, length, and tortuosity were determined by semiautomatic vessel segmentation and considered abnormal if ≥2 SDs from the study population mean. Either ectasia (increased diameter) or dolichosis (increased length or tortuosity) of at least one proximal intracranial artery defined IDE. Symptomatic IDE was considered when the infarct was located in the territory supplied by an affected artery in the absence of any alternative pathogenic explanation. Multivariate models were fitted to determine IDE clinical correlates. Results: Among 211 cases screened, 200 patients (mean age 67±14 years, 47.5% men) with available intracranial vessel imaging were included. IDE was identified in 24% cases (5% with isolated ectasia, 9.5% with isolated dolichosis, and 9.5% with both ectasia and dolichosis). IDE was considered the most likely pathogenic mechanism in 12 cases (6% of the entire cohort), which represented 23.5% of strokes initially categorized as undetermined cause. In addition, 21% of small-artery occlusion strokes had the infarct territory supplied by a dolichoectatic vessel (3% of the entire cohort). IDE was independently associated with male sex (odds ratio, 4.2 [95% CI, 1.7­10.6]) and its component of ectasia was associated with advanced age (odds ratio, 3.5 [95% CI, 1.3­9.5]). Vascular risk profile was similar across patients with stroke with and without IDE. Conclusions: Our findings suggest that IDE is an arteriopathy frequently found in patients with acute ischemic stroke and is likely responsible for a sizable fraction of strokes initially categorized as of undetermined cause and perhaps also in those with small-artery occlusion.

Risk Factors Control and Early Recurrent Cerebral Infarction in Patients with Symptomatic Intracranial Atherosclerotic Disease.

BACKGROUND: The risk of early recurrent cerebral infarction (RCI) is high in patients with symptomatic intracranial atherosclerotic disease (IAD). We sought to determine the relationship between risk factor control and early RCI risk among patients with symptomatic IAD. METHODS: We analyzed participants with symptomatic IAD in the multi-center prospective observational MYRIAD study. Risk factor control was assessed at 6-8-week follow-up. Optimal risk factor control was defined by target systolic blood pressure, being non-smoker, target physical activity, and antiplatelet and antilipidemic therapy compliance. Age-adjusted associations were calculated between risk factor control and RCI determined by MRI-evident new infarcts in the territory of the stenotic vessel at 6-8 weeks from the index event. RESULTS: Among 82 participants with clinical and brain MRI information available 6-8 weeks after the index event (mean age 63.5 ±12.5 years, 62.2% men), RCI occurred in 21 (25.6%) cases. At 6-8-week follow-up, 37.8% had target systolic blood pressure, 92.7% were non-smokers, 51.2% had target physical activity, and 98.8% and 86.6% were compliant with antiplatelet and antilipidemic therapy, respectively. Optimal risk factor control increased from 4.9% at baseline to 19.5% at 6-8-week follow-up (p=0.01). None of the participants with optimal risk factor control at follow-up had RCI (0% vs. 31.8%, p<0.01). CONCLUSIONS: Only one-fifth of MYRIAD participants had optimal risk factor control during early follow-up. Approximately half and two-thirds had physical inactivity and uncontrolled systolic blood pressure, respectively. These risk factors may represent important therapeutic targets to prevent early RCI in patients with symptomatic IAD.

Dawson Fingers in Older Adults with Cerebral Small Vessel Disease: A Population Study.

Dawson fingers are used to differentiate multiple sclerosis (MS) from other conditions that affect the subcortical white matter. However, there are no studies evaluating the presence of Dawson fingers in subjects with cerebral small vessel disease (cSVD). We aimed to assess prevalence and -correlates of Dawson fingers in older adults with cSVD-related moderate-to-severe white matter hyperintensities (WMH). Community-dwelling older adults residing in rural Ecuador - identified by means of door-to-door surveys - underwent a brain MRI. Exams of individuals with cSVD-related moderate-to-severe WMH were reviewed with attention to the presence of Dawson fingers. Of 590 enrolled individuals, 172 (29%) had moderate-to-severe WMH. Of these, 18 (10.5%) had Dawson fingers. None had neurological manifestations suggestive of MS. Increasing age was independently associated with Dawson fingers (p = 0.017). Dawson fingers may be less specific for MS than previously thought. Concomitant damage of deep medullary veins may explain the presence of Dawson fingers in cSVD.

The association between aortic arterial stiffness, carotid intima-media thickness and carotid plaques in community-dwelling older adults: A population-based study.

OBJECTIVE: Information on the associations among arterial stiffness, carotid intima-media thickness (cIMT) and carotid plaques as biomarkers of atherosclerosis is limited in diverse populations. We aimed to assess whether aortic pulse wave velocity (aPWV) - as a surrogate of arterial stiffness - is associated with increased cIMT and the presence of carotid plaques in a cohort of older adults of Amerindian ancestry. METHODS: Atahualpa residents aged ≥60 years (n = 320) underwent aPWV determinations, and carotid ultrasounds for cIMT and plaque assessment. Multivariate models were fitted to assess the independent association between the aPWV, and cIMT and carotid plaques, after adjusting for relevant confounders. Differences in risk factors across these biomarkers were investigated. RESULTS: Mean values of aPWV were 10.3 ± 1.8 m/s, and those of cIMT were 0.91 ± 0.21 mm (24% had a cIMT >1 mm). Carotid plaques were observed in 118 (37%) subjects. In univariate analyses, risk factors associated with an increased aPWV included age, female gender, poor physical activity and high blood pressure. An increased cIMT was associated with age, male gender, a poor diet, high blood pressure and severe tooth loss. The presence of carotid plaques was associated with increasing age, poor physical activity and high blood pressure. Multivariate models showed a significant association between aPWV and cIMT (ß: 0.028; 95% C.I.: 0.001-0.056; p = 0.047) but not between aPWV and carotid plaques (OR: 1.14; 95% C.I.: 0.83-1.56; p = 0.423). CONCLUSIONS: This study shows an independent association between aPWV and cIMT but not with carotid plaques. These biomarkers may indicate distinct phenotypes for atherosclerosis.

Intracranial Hemorrhage in Hospitalized Patients: An Infrequently Studied Condition with High Mortality.

BACKGROUND: Intracranial hemorrhage (ICH) may occur in patients admitted to the hospital for unrelated medical conditions, resulting in prolonged hospitalization and worse prognosis. We aim to assess the clinical presentation and outcomes of in-hospital ICH compared to patients with ICH presenting from the community. METHODS: We conducted a retrospective analysis of all acute stroke alerts diagnosed with ICH in an urban academic hospital over a 4-year period. Demographics, clinical presentation, use of antithrombotic therapy, and presence of coagulopathy were recorded. ICH score and a sequential organ failure assessment score were calculated during the initial assessment. Initial head computed tomography was reviewed to determine ICH subtype, location, and volume of the hematoma. In-hospital mortality and discharge disposition were used as surrogate of clinical outcome. RESULTS: From the 1965 stroke alert cases analyzed over the studied years, 145 (7.4%) were diagnosed with ICH. Overall, the mean age was 62.9 ± 13.9 and 53.7% were women. Thirty-two patients (22%) developed ICH in the inpatient setting and 113 (78%) presented from the community. Systolic blood pressure at presentation was lower in the in-hospital group (p < 0.01). Inpatients who developed ICH were more likely than community ICH patients to be on combination of antiplatelet agents (21.9% vs. 5.3%, p < 0.05) or therapeutic heparinoids (21.9% vs. 0.9%, p < 0.01). Also, In-hospital ICH patients had a higher rate of spontaneous or iatrogenic coagulopathy (65.6% vs. 10.6%, p < 0.01) and thrombocytopenia (31.3% vs. 1.8%, p < 0.01). Lobar hemorrhages were more prevalent in the in-hospital group (82.6% vs. 39.1%, p < 0.01) and the mean hematoma volume was higher (40.9 ± 43.1 mL vs. 24.1 ± 30.4 mL; p < 0.02). Median ICH score in the in-hospital group was not statistically different from the emergency department group: 2 (IQR: 0-3) versus 1 (IQR: 0-3). When comparing patients with in-hospital ICH and those from the community, the short-term mortality was higher in the former group (81% vs. 31%, p < 0.01). The incidence of withdrawal of life-sustaining therapies as a proximate mechanism of death was higher, but not statistically significant, in the in-hospital group (86% vs. 61%). CONCLUSION: ICH is a critical complication in the inpatient setting, predominantly occurring in already ill patients with underlying spontaneous or iatrogenic coagulopathy. Large volume lobar intraparenchymal hemorrhage is a common radiographic finding. ICH is frequently a catastrophic event and powerfully weighs in with end-of-life discussion, resulting in high short-term mortality rate.

Lack of Association between Periodic Limb Movements during Sleep and Neuroimaging Signatures of Cerebral Small Vessel Disease in Stroke-Free Community-Dwelling Older Adults. The Atahualpa Project.

BACKGROUND: Evidence of the relationship between periodic limb movements during sleep (PLMS) and cerebral small vessel disease (cSVD) is limited and inconsistent. Here, we aimed to assess the independent association between PLMS and the different neuroimaging signatures of cSVD. METHODS: Atahualpa residents aged more than or equal to 60 years enrolled in the Atahualpa Project undergoing polysomnography and MRI with time intervals less than or equal to 6 months were included. MRI readings focused on white matter hyperintensities (WMH) of presumed vascular origin, deep cerebral microbleeds (CMB), silent lacunar infarcts (LI), and more than 10 enlarged basal ganglia-perivascular spaces (BG-PVS). Data from single-night polysomnograms were interpreted according to recommendations of the American Academy of Sleep Medicine. Associations between the PLMS index and neuroimaging signatures of cSVD (as dependent variables) were assessed by means of logistic regression models, adjusted for relevant confounders. RESULTS: A total of 146 individuals (mean age: 71.4 ± 7.5 years; 64% women) were included. A PLMS index more than or equal to 15 per hour were noted in 48 (33%) participants. Moderate-to-severe WMH were present in 33 individuals (23%), deep CMB in 9 (6%), silent LI in 16 (11%), and more than 10 BG-PVS in 44 (30%). In univariate analyses, silent LI (P = .035) and the presence of more than 10 enlarged BG-PVS (P = .034) were significantly higher among participants with a PLMS index more than or equal to 15 per hour. However, fully-adjusted multivariate models showed no significant association between PLMS index more than or equal to 15 per hour and any of the neuroimaging signatures of cSVD. CONCLUSIONS: This study shows no independent association between the PLMS index and neuroimaging signatures of cSVD in stroke-free community-dwelling older adults.

Carotid Intima-media Thickness, Cognitive Performance and Cognitive Decline in Stroke-free Middle-aged and Older Adults. The Atahualpa Project.

BACKGROUND: Little is known on factors influencing cognitive function in rural communities. Using the Atahualpa Project cohort, we aimed to assess whether the carotid intima-media thickness (cIMT) - used as a surrogate of extracranial carotid atherosclerosis - is associated with cognitive performance and further decline in community-dwelling adults living in a rural setting. METHODS: The study included Atahualpa residents aged greater than or equal to 40 years who had ultrasound examination of the extracranial carotid arteries and a baseline Montreal Cognitive Assessment (MoCA), as well as the subset of individuals who also had a follow-up MoCA at least 1 year after baseline. Relationship between cIMT and cognitive function was assessed by means of generalized linear and longitudinal models, adjusted for relevant covariates. Mediation analysis was utilized to establish the proportion of the effect between increased cIMT and cognitive performance, which is mediated by age. RESULTS: A total of 561 individuals were included for the cross-sectional study, and 510 of them were assessed for the prospective cohort. Univariate analysis showed a significant association between increased cIMT and worse cognitive performance (P < .001), which vanishes after considering the effect of age and low scholarity. Causal mediation analysis confirms that age captures 82.6% (95% C.I.: 63.9% to 100%) of the effect of this association. There was no relationship between increased cIMT and cognitive decline in the follow-up. CONCLUSIONS: In this rural population, the association between increased cIMT and cognitive dysfunction is mostly mediated by increasing age.

Cerebrovascular Correlates of Dementia in Community-Dwelling Older Adults Living in Rural Communities - The Three Villages Study. Rationale and Protocol of a Population-Based Prospective Cohort Study.

BACKGROUND: Despite the assumption that dementia is increasing in rural areas of Latin America, there is no information on the burden and risk factors leading to dementia in these settings. AIMS: To assess prevalence and incidence of dementia, and its cerebrovascular correlates in an established cohort of community-dwelling older adults living in rural Ecuador, and to explore the impact of dementia on functional disability and the role of the social determinants of health in the above-mentioned relationships. DESIGN: Population-based, cohort study with cross-sectional and longitudinal components. Baseline clinical interviews will focus on the assessment of cognitive performance and dementia by means of the clinical dementia rating scale (CDRS). Functional disability and social determinants of health will be correlated with CDRS scores. In addition, participants will undergo interviews and procedures to assess cardiovascular risk factors and signatures of brain damage, cerebral small vessel disease, and other stroke subtypes. The CDRS and the Functional Activities Questionnaire will be administered every year to assess the rate of incident dementia and the severity of functional disability. Neuroimaging studies will be repeated at the end of the study (5 years) to assess the impact of newly appeared cerebral and vascular lesions on cognitive decline. COMMENT: This study will allow determine whether cerebrovascular diseases are in the path of dementia development in these rural settings. This may prove cost-effective for the development of preventive strategies aimed to control modifiable factors and reduce disability in patients with dementia living in underserved populations.

Prevalence and Correlates of Intracranial Atherosclerotic Disease Among Community-Dwelling Older Adults of Amerindian Ancestry. The Three Villages Study.

BACKGROUND: Knowledge on the prevalence and correlates of intracranial atherosclerotic disease (ICAD) is limited. We aimed to assess prevalence, clinical and neuroimaging correlates of ICAD in a cohort of older adults of Amerindian ancestry. METHODS: The study included 581 community-dwellers aged ≥60 years (mean age 71 ± 8.4 years; 57% women) living in rural Ecuadorian villages. ICAD was identified by means of CT determinations of carotid siphon calcifications (CSC) or MRA findings of significant stenosis of intracranial arteries. Fully-adjusted logistic regression models were fitted with biomarkers of ICAD as the dependent variables. RESULTS: A total of 205 (35%) of 581 participants had ICAD, including 185 with high calcium content in the carotid siphons and 40 with significant stenosis of at least one intracranial artery (20 subjects had both biomarkers). Increasing age, high fasting blood glucose, >10 enlarged basal ganglia-perivascular spaces and non-lacunar strokes were associated with high calcium content in the carotid siphons. In contrast, male gender, moderate-to-severe white matter hyperintensities, lacunar and non-lacunar strokes were associated with significant stenosis of intracranial arteries. Stroke was more common among subjects with any biomarker of ICAD than in those with no biomarkers (29% versus 9%, p < 0.001). Significant stenosis of intracranial arteries was more often associated with stroke than high calcium content in the carotid siphons, suggesting that CSC are more likely an ICAD biomarker than causally related to stroke. CONCLUSIONS: ICAD prevalence in Amerindians is high, and is significantly associated with stroke. CSC and significant stenosis of intracranial arteries may represent different phenotypes of ICAD.

BE-FAST: A Sensitive Screening Tool to Identify In-Hospital Acute Ischemic Stroke.

BACKGROUND: Development of acute ischemic stroke in hospitalized patients represents a significant proportion of all cerebral ischemia. Several prehospital stroke scales were developed to screen for acute ischemic stroke in the community. Despite the advent of inpatient stroke alert systems, there is a lack of validated screening tools for the inpatient population. This study aims to assess the validity of BE-FAST (Balance, Eyes, Face, Arm, Speech, Time) as a screening tool for acute ischemic stroke among inpatients. METHODS: We retrospectively analyzed all stroke alert activations at a single academic medical center between 2012 and 2016. We classified the triggering symptom as: focal neurologic deficit, aphasia, dysarthria, ataxia/vertigo/dizziness, alteration of consciousness, acute confusion, or headache. BE-FAST was applied retrospectively, and patients were classified as BE-FAST positive or negative. The final diagnosis was classified as acute ischemic stroke, transient ischemic attack , intracranial hemorrhage or noncerebrovascular diagnosis. RESULTS: Of 1965 stroke alerts, 489 were among inpatients. The mean age was 63 ± 16.1 years; 57% of patients were women (n = 1121). Acute ischemic stroke was diagnosed in 29% of all the activations (n = 567), transient ischemic attack in 12% (n = 232), intracranial hemorrhage in 8 % (n = 160) and noncerebrovascular in 51% (n = 1006). When comparing inpatient with community-onset stroke alerts, the sensitivity of BE-FAST for diagnosing acute ischemic stroke was 85% versus 94% (P = .005), with a specificity of 43% versus 23% (P < .001), respectively. However, when evaluating in-patients with an intact level of consciousness separately, BE-FAST sensitivity for diagnosing acute ischemic stroke was 92% compared to 94% in the community (P = .579). Among in-patients with acute ischemic stroke who were (1) candidates for reperfusion therapy and (2) diagnosed with acute large vessel occlusion, the sensitivity of BE-FAST was 83% and 94%, respectively. CONCLUSIONS: This is the first study to analyze the performance of BE-FAST among hospitalized patients evaluated through the inpatient stroke alert system. We found BE-FAST to be a very sensitive tool for screening for all in-hospital acute ischemic strokes, including inpatients that were candidates for acute reperfusion therapy.

Mechanical Thrombectomy for Patients with In-Hospital Ischemic Stroke: A Case-Control Study.

BACKGROUND AND AIM: Patients with in-hospital acute ischemic stroke (AIS) have, in general, worse outcomes compared to those presenting from the community, partly attributed to the numerous contraindications to intravenous thrombolysis. We aimed to identify and analyze a group of patients with in-hospital AIS who remain suitable candidates for acute endovascular therapies. METHODS: A retrospective 6-year data analysis was conducted in patients evaluated through the in-hospital stroke alert protocol in a single tertiary care university hospital to identify those with in-hospital AIS due to acute intracranial large vessel occlusion (ILVO). Feasibility and safety of mechanical thrombectomy for in-hospital AIS was assessed in a case-control study comparing inpatients to those presenting from the community. RESULTS: From 1460 in-hospital stroke alert activations, 11% had a final diagnosis of AIS (n = 167). One hundred and two patients with in-hospital AIS had emergent intracranial vessel imaging and were included in our cohort. Acute ILVO was identified in 27 patients within this cohort. Patients were younger in the ILVO group and had more severe neurologic deficit on presentation. Compared to a matched (1:2) control group of patients presenting from the community, inpatients who underwent mechanical thrombectomy achieved equivalent technical success, safety, and clinical outcomes. CONCLUSIONS: The incidence of acute ILVO in patients with in-hospital AIS who underwent emergent vessel imaging is similar to the reported incidence of ILVO in patients presenting with community-onset AIS. Among patients with in-hospital AIS secondary to ILVO, mechanical thrombectomy is a feasible and safe therapy associated with favorable outcomes.

Clinical and neuroimaging risk factors for cognitive decline in community-dwelling older adults living in rural Ecuador. A population-based prospective cohort study.

OBJECTIVE: There is limited information on factors influencing cognitive decline in rural settings from low- and middle-income countries. Using the Atahualpa Project cohort, we aimed to assess the burden of cognitive decline in older adults living in a rural Ecuadorian village. METHODS: The study included Atahualpa residents aged greater than or equal to 60 years who had a follow-up Montreal Cognitive Assessment (MoCA) repeated at least 1 year after baseline. MoCA decline was assessed by multivariable longitudinal linear models, adjusted for demographics, days between MoCA tests, cardiovascular risk factors, and neuroimaging signatures of structural brain damage. RESULTS: We included 252 individuals who contributed 923.7 person-years of follow-up (mean: 3.7 ± 0.7 years). The mean baseline MoCA was 19.5 ± 4.5 points, and the follow-up MoCA was 18.1 ± 4.9 points (P = 0.001). Overall, 154 individuals (61%) had lower MoCA scores at follow-up. The best fitted longitudinal linear model showed a decline of follow-up MoCA from baseline (ß: 0.14; 95% CI, 0.0-0.21; P < 0.001). High glucose levels, global cortical atrophy, and white matter hyperintensities were independently and significantly associated with greater MoCA decline. CONCLUSION: This study provides evidence of cognitive decline in older adults living in a rural setting. Main targets for prevention should include glucose control and the control of factors that are deleterious for the development of cortical atrophy and white matter hyperintensities.