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Background and Purpose High-grade carotid artery stenosis may alter hemodynamics in the ipsilateral hemisphere, but consequences of this effect are poorly understood. Cortical thinning is associated with cognitive impairment in dementia, head trauma, demyelination, and stroke. We hypothesized that hemodynamic impairment, as represented by a relative time-to-peak (TTP) delay on MRI in the hemisphere ipsilateral to the stenosis, would be associated with relative cortical thinning in that hemisphere.Methods We used baseline MRI data from the NINDS-funded Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis–Hemodynamics (CREST-H) study. Dynamic contrast susceptibility MR perfusion-weighted images were post-processed with quantitative perfusion maps using deconvolution of tissue and arterial signals. The protocol derived a hemispheric TTP delay, calculated by subtraction of voxel values in the hemisphere ipsilateral minus those contralateral to the stenosis.Results Among 110 consecutive patients enrolled in CREST-H to date, 45 (41%) had TTP delay of at least 0.5 seconds and 9 (8.3%) subjects had TTP delay of at least 2.0 seconds, the maximum delay measured. For every 0.25-second increase in TTP delay above 0.5 seconds, there was a 0.006-mm (6 micron) increase in cortical thickness asymmetry. Across the range of hemodynamic impairment, TTP delay independently predicted relative cortical thinning on the side of stenosis, adjusting for age, sex, hypertension, hemisphere, smoking history, low-density lipoprotein cholesterol, and preexisting infarction (P=0.032).Conclusions Our findings suggest that hemodynamic impairment from high-grade asymptomatic carotid stenosis may structurally alter the cortex supplied by the stenotic carotid artery.

Background and Purpose: Studies of carotid artery disease have suggested that high-grade stenosis can affect cognition, even without stroke. The presence and degree of cognitive impairment in such patients have not been reported and compared with a demographically matched population-based cohort. Methods: We studied cognition in 1000 consecutive CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) patients, a treatment trial for asymptomatic carotid disease. Cognitive assessment was after randomization but before assigned treatment. The cognitive battery was developed in the general population REGARDS Study (Reasons for Geographic and Racial Differences in Stroke), involving Word List Learning Sum, Word List Recall, and Word List fluency for animal names and the letter F. The carotid stenosis patients were >45 years old with ≥70% asymptomatic carotid stenosis and no history of prevalent stroke. The distribution of cognitive performance for the patients was standardized, accounting for age, race, and education using performance from REGARDS, and after further adjustment for hypertension, diabetes, dyslipidemia, and smoking. Using the Wald Test, we tabulated the proportion of Z scores less than the anticipated deviate for the population-based cohort for representative percentiles. Results: There were 786 baseline assessments. Mean age was 70 years, 58% men, and 52% right-sided stenosis. The overall Z score for patients was significantly below expected for higher percentiles ( P P =0.015). Lower performance was attributed largely to Word List Recall ( P P ≤0.01). The scores for left versus right carotid disease were similar. Conclusions: Baseline cognition of patients with severe carotid stenosis showed below normal cognition compared to the population-based cohort, controlling for demographic and cardiovascular risk factors. This cohort represents the largest group to date to demonstrate that poorer cognition, especially memory, in this disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02089217.

Neuropsychologists evaluate patients for cognitive decline and dementia, using validated psychometric tests, along with behavioral observation, record review, clinical interview, and information about psychological functioning, to evaluate brain-behavior relationships and aid in differential diagnosis and treatment planning. Also considered are premorbid functioning, education, sex, socioeconomic status, primary language, culture, and race-related health disparities when selecting tests, interpreting performance, and providing a diagnostic impression. Neuropsychologists provide diagnostic clarity, explain symptoms and likely disease course to patients and family members, and assist the family with future planning, behavioral management strategies, and ways to mitigate caregiver burden.

ImportanceIncident stroke is associated with accelerated cognitive decline. Whether poststroke vascular risk factor levels are associated with faster cognitive decline is uncertain.ObjectiveTo evaluate associations of poststroke systolic blood pressure (SBP), glucose, and low-density lipoprotein (LDL) cholesterol levels with cognitive decline.Design, Setting, and ParticipantsIndividual participant data meta-analysis of 4 US cohort studies (conducted 1971-2019). Linear mixed-effects models estimated changes in cognition after incident stroke. Median (IQR) follow-up was 4.7 (2.6-7.9) years. Analysis began August 2021 and was completed March 2023.ExposuresTime-dependent cumulative mean poststroke SBP, glucose, and LDL cholesterol levels.Main Outcomes and MeasuresThe primary outcome was change in global cognition. Secondary outcomes were change in executive function and memory. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition.ResultsA total of 1120 eligible dementia-free individuals with incident stroke were identified; 982 (87.7%) had available covariate data and 138 (12.3%) were excluded for missing covariate data. Of the 982, 480 (48.9%) were female individuals, and 289 (29.4%) were Black individuals. The median age at incident stroke was 74.6 (IQR, 69.1-79.8; range, 44.1-96.4) years. Cumulative mean poststroke SBP and LDL cholesterol levels were not associated with any cognitive outcome. However, after accounting for cumulative mean poststroke SBP and LDL cholesterol levels, higher cumulative mean poststroke glucose level was associated with faster decline in global cognition (−0.04 points/y faster per each 10–mg/dL increase [95% CI, −0.08 to −0.001 points/y]; P = .046) but not executive function or memory. After restricting to 798 participants with apolipoprotein E4 (APOE4) data and controlling for APOE4 and APOE4 × time, higher cumulative mean poststroke glucose level was associated with a faster decline in global cognition in models without and with adjustment for cumulative mean poststroke SBP and LDL cholesterol levels (−0.05 points/y faster per 10–mg/dL increase [95% CI, −0.09 to −0.01 points/y]; P = .01; −0.07 points/y faster per 10–mg/dL increase [95% CI, −0.11 to −0.03 points/y]; P = .002) but not executive function or memory declines.Conclusions and RelevanceIn this cohort study, higher poststroke glucose levels were associated with faster global cognitive decline. We found no evidence that poststroke LDL cholesterol and SBP levels were associated with cognitive decline.

Introduction: Cognitive decline and dementia after stroke is a major public healthcare problem, with dementia risk doubling over time, affecting more than 2M people in the US, with no current treatment. Silent brain infarction has been associated with cognitive decline, especially among those at risk for cardio-embolism. The therapeutic challenge is to prevent the occurrence of silent infarction to mitigate proactively the loss of cognitive function. Methods: The NINDS-funded ARCADIA-CSI is an ancillary study to ARCADIA, a randomized trial comparing apixaban vs aspirin to prevent recurrent clinical stroke in patients with cryptogenic stroke and left atrial cardiopathy. The aim of ARCADIA-CSI is to address whether apixaban might also reduce the incidence of silent infarction and be associated with better cognitive function over time compared to aspirin. Five hundred patients will be enrolled at least 90 days after the ARCADIA index stroke and undergo cognitive assessments at baseline and yearly thereafter using a telephone-based cognitive battery. We are testing the hypothesis that the slope of change in cognitive function is less steep during the follow-up period in patients on apixaban compared to patients on aspirin therapy. We will also collect an initial MRI around the time of the qualifying stroke and a follow-up MRI at the time that the subject completes participation in the ARCADIA parent study to assess the occurrence of new silent infarction. Results: As of August 12, 2021, the study has enrolled 188 subjects from 78 ARCADIA sites which have been green-lighted for enrollment in ARCADIA-CSI. A total of 61 sites have enrolled at least one subject. To date, there is a 95% completion of baseline cognitive exams and 98% completion at the 1-yr follow-up. We have obtained 91% of the clinical scans of the index stroke of which 95% have undergone central reading and interpretation. Conclusion: ARCADIA-CSI is designed to identify the most favorable medical approach to prevent the occurrence of silent infarction and cognitive decline in the setting of secondary stroke prevention. An update will be provided regarding the number of patients enrolled, centers green-lighted, and the completion rates of cognitive assessments, and MRIs obtained and interpreted.

Introduction: Associations between post-stroke vascular risk factors levels with post-stroke cognitive decline are uncertain. We determined associations between systolic blood pressure (BP), glucose, and low-density lipoprotein (LDL) cholesterol levels with post-stroke cognitive decline. Hypothesis: Higher post-stroke systolic BP, glucose, and LDL cholesterol levels are associated with faster post-stroke cognitive decline. Methods: This cohort study pooled data from 832 participants 18 and older with incident stroke and free of dementia before stroke (50% women and 32% Black) from 4 cohort studies from 1971-2019: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Offspring Study, and REasons for Geographic and Racial Differences in Stroke Study. Linear mixed-effects models were used to estimate longitudinal changes in cognition after incident stroke. The primary outcome was change in global cognition. Global cognition was harmonized across studies and standardized as T-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Median (IQR) follow-up was 5.5 (3.3-8.3) years. Results: In separate models, higher post-stroke glucose and LDL levels, but not systolic BP, were associated with faster declines in global cognition (Models M1a, M1b, and M1c, Table 1). In a model with all three vascular risk factors, higher post-stroke mean glucose and LDL levels were associated with faster global cognition decline, though not to traditional levels of statistical significance; however, post-stroke mean systolic BP was not associated with global cognition decline (Model M2, Table 1). Older age was associated with faster cognitive decline in all models. Conclusions: Our results suggest that higher post-stroke glucose and LDL levels are associated with faster post-stroke cognitive decline. We found no evidence that post-stroke BP levels are associated with post-stroke cognitive decline.

Introduction: Low cerebral blood flow can affect cognition in patients with high-grade asymptomatic internal carotid artery stenosis. Current clinical algorithms use stroke risk to determine which patients should undergo revascularization without considering cognitive decline. Although correlations between low-flow and cognitive impairment have been reported, it is not known whether a threshold exists below which such a correlation expresses itself. Such information would be critical in treatment decisions about whether to intervene in patients with high-grade carotid artery stenosis who are at risk for cognitive decline. Objective: To determine how reduced blood flow correlates with lower cognitive scores. Methods: Patients with ≥80% unilateral internal carotid artery stenosis with no history of stroke were recruited from inpatient and outpatient practices at a single, large, comprehensive stroke center. Patients underwent bilateral insonation of middle cerebral arteries with standard 2-Hz probes over the temporal windows with transcranial Doppler. Cognitive assessments were performed by an experienced neuropsychologist using a cognitive battery comprising 14 standardized tests with normative samples grouped by age. Z-scores were generated for each test and averaged to obtain a composite Z-score for each patient. Multivariable linear regression examined associations between mean flow velocity (MFV) and composite Z-score, adjusting for age, education, and depression. The Davies test was used to determine if there was a breakpoint for a non-zero difference in slope of a segmented relationship over the range of composite Z-score values. Results: Forty-two patients with unilateral high-grade internal carotid artery stenosis without stroke were enrolled (26 males, age = 74 ± 9 years, education = 16 ± 3 years). Average composite Z-score was –0.31 SD below the age-specific normative mean (range –2.8 to +1.2 SD). In linear regression adjusted for age, education, and depression, MFV correlated with cognitive Z-score (β = 0.308, p = 0.043). A single breakpoint in the range of composite Z-scores was identified at 45 cm/s. For MFV 45 cm/s, Z-score change was nonsignificant (95% CI: –0.07 to 0.05). Conclusions: In high-grade, asymptomatic carotid artery stenosis, cognitive impairment correlated linearly with lower flow in the hemisphere fed by the occluded internal carotid artery, but only below a threshold of MFV = 45 cm/s. Identifying a hemodynamic threshold for cognitive decline using a simple, noninvasive method may influence revascularization decision-making in otherwise “asymptomatic” carotid disease.

Hypertension has been linked with peripheral and central reductions in vascular density, and with devastating effects on brain function. However, the underlying mechanisms in the relationship between blood pressure and cognitive impairment have yet to be fully elucidated. Here, we review compelling evidence from two lines of inquiry: one that links microvascular rarefaction with insulin-like growth factor 1 (IGF-1) deficiencies, and another which posits that vascular dysfunction precedes hypertension. Based on the findings from experimental and clinical studies, we propose that these lines of evidence converge, and suggest that age-related declines in IGF-1 concentrations precede microvascular rarefaction, initiate an increase in vascular resistance, and therefore are causally linked to onset of hypertension. Physical exercise provides a relevant model for supporting our premise, given the well-established effects of exercise in attenuating vascular dysfunction, hypertension, IGF-1 deficiency, and cognitive decline. We highlight here the role of exercise-induced increases in blood flow in improving vascular integrity and enhancing angiogenesis via the actions of IGF-1, resulting in reversal of rarefaction and hypertension, and enhancement of cerebral blood flow and cognition.

Silent brain infarctions (SBIs) are brain lesions noted on neuroimaging that are not associated with clinical symptoms. SBIs are associated with a number of vascular risk factors and are common following invasive cardiovascular procedures such as atrial fibrillation (AF) ablation, coronary artery bypass graft (CABG), and transcatheter aortic valve replacement (TAVR). Although not eliciting signs of clinical stroke, SBIs are associated with increased frailty, and motor and mood features. Less is known, however, about the relationship between SBI, cognition, and delirium following invasive cardiac procedures and most investigations into these relationships have been reported in large-scale epidemiological studies. In the current paper, we conducted a systematic review to evaluate evidence of a relationship between SBI, delirium, and cognitive decline following CABG, AF ablation, and TAVR. Twenty studies met inclusion criteria. In general, our review identified conflicting results for each cardiac procedure, with some studies suggesting a relationship between SBI, cognitive impairment, and delirium, whereas others showed no relationship between SBI, cognitive impairment, and delirium. Potential reasons for this discrepancy as well as suggestions for future research are discussed.

Objective: Describe those with persistent neuropsychiatric symptoms seeking treatment for Post-Acute Sequelae of COVID-19 (PASC). Method: Patients were referred for neuropsychological evaluation from the University of Alabama at Birmingham (UAB) Post-COVID Treatment Program. Ninety-seven patients completed a comprehensive set of self-report questionnaires. Results: Patients were 49 years old (range: 18 to 74), had 15.49 years (SD = 2.43) of education, and identified as female (77%), married (51%), and White/Caucasian (73%) or Black/AA (25%). Reported annual income ranged from ≤ $20,000 (11%) to ≥ $100,000 (32%), with 75% currently employed. Confirmed positive test result for COVID-19 was reported in 88%, with 87% having the original virus and 13% the Delta variant, based on estimated dates of infection. Symptoms during the acute illness included: headache (76%), fever (51%), cough (57%), shortness of breath (56%), and loss of smell or taste (54%). Most of the participants were not hospitalized (76%) nor required oxygen therapy (78%). Persistent symptoms included: headache (55%), shortness of breath (53%), muscle and joint pain (53%), cough (17%), congestion (40%) and loss of smell or taste (25%). Of these participants, 87% reported they had not returned to their baseline health because of COVID-19 and most indicated impaired job performance following COVID-19 infection. Conclusion: Those who sought treatment for persistent neuropsychiatric symptoms following a symptomatic course of COVID-19 were commonly middle aged, White, women, with at least a high school education. “Brain fog” secondary to PASC can result in reported persistent health and neuropsychiatric issues that can impact ability to work.

Objective: To investigate the relationship between systematic inflammatory biomarkers and cognition in patients with Multiple Sclerosis (MS). Method: We recruited 36 patients diagnosed with MS (31 with relapsing-remitting and 5 with progressive) who presented for treatment at the University of Alabama at Birmingham (UAB). Patients underwent a comprehensive neuropsychological battery, and serum blood samples were collected. Cognitive data was divided into an overall Cognitive Composite score and seven cognitive domains (i.e., Attention, Verbal Memory, Visual Memory, Visuospatial Ability, Language, Processing Speed, and Executive Function) using z-score averages. Pearson's product-moment correlations were conducted to determine the relationship between cognitive performance and 14 inflammatory biomarkers specifically chosen for their potential role in MS. Results: Matrix Metalloproteinase-9 (MMP-9) was significantly correlated with Visual Memory (r= -.424; p=.01), Language (r= -.425; p= .01), and Cognitive Composite (r= -.380; p= .022) scores. Additionally, Insulin-like Growth Factor-1 (IGF-1) was significantly correlated with the overall Cognitive Composite (r= -.346; p= .039) score. Conclusions: Studies investigating associations between inflammation and cognition in MS are lacking. In our sample of persons with Multiple Sclerosis, serum IGF-1 and MMP-9 biomarkers were moderately negatively correlated with the overall Cognitive Composite scores. MMP-9 was negatively correlated with Visual Memory and Language cognitive domain scores. These findings in a representative sample of patients with MS highlight the need for further research exploring the relationship between systematic inflammatory biomarkers and cognition in MS.

Objective: To determine if an 8-week HIIT exercise intervention would improve VO2max and cognitive function in older sedentary women. Method: Eleven women between the ages of 60 and 75 participated in an 8-week HIIT exercise intervention. At baseline, participants were administered a VO2max test and a neuropsychological battery, which assessed both global functioning as well as specific domains of processing speed, visual memory, attention, language and executive function. Composite scores for each domain were calculated using average z-scores. Procedures performed at baseline were conducted again following intervention. Results: Following the intervention, there was a mean VO2max increase of 3.89 ml/kg/min (p Conclusions: We found that 8-weeks of HIIT was sufficient to increase VO2max in older sedentary women. Total composite z-scores and specific domains of visual memory and language also showed significant improvement after intervention. Total cognitive composite scores and visual memory were also correlated with VO2max. These findings highlight the need to explore further the mechanisms that drive exercise effects on cognition across diverse populations.

Objective: To describe psychiatric symptoms in a sample of patients seeking treatment for “brain fog” due to Post-Acute Sequelae of COVID-19 (PASC). Method: Patients were referred for a neuropsychological evaluation from the University of Alabama at Birmingham (UAB) Post-COVID Treatment Program. Ninety-two patients completed a battery of self-report questionnaires to measure mood symptoms and behavior. Patients were on average 49 years of age (range: 18 to 74), female (77%), and White/Caucasian (73%)/Black/African American (25%), with 15.49 years of education (SD = 2.43). Results: On average, patients who sought treatment for PASC reported mild to moderate anxiety (Generalized Anxiety Disorder Assessment [GAD-7]; M = 9.83, SD = 6.07), moderate depression (Patient Health Questionnaire [PHQ-8]; M = 13.23, SD = 5.81), moderate stress levels (Perceived Stress Scale [PSS]; M = 22.97, SD = 7.99). They also reported overall functional impairment in activities of daily living (Functional Assessment Questionnaire [FAQ]; M = 9.57, SD = 8.29) and perceived cognitive impairment (Cognitive Failures Questionnaire [CFQ]; M = 55.22, SD = 18.66). Additionally, patients endorsed several somatic symptoms (PHQ-15; M = 13.90, SD = 5.16), mild insomnia (Insomnia Severity Index [ISI]; M = 14.80, SD = 6.85), and severe fatigue (Chalder’s Fatigue Scale [CFS]; M = 25.53, SD = 5.72). Conclusion: Patients seeking treatment for “long-COVID” report a variety of clinically significant psychiatric symptoms, suggesting the need for incorporating behavioral, lifestyle, and psychological interventions in the treatment of this population.

Objective: Describe cognitive function in patients seeking treatment for Post-Acute Sequelae of COVID-19 (PASC). Method: Ninety-two patients underwent neuropsychological evaluation secondary to reported “brain fog” following COVID-19 infection. Patients were referred from the University of Alabama at Birmingham (UAB) Post-COVID Treatment Program. Patients were on average 49 years of age (range: 18-74), female (77%), and White/Caucasian (73%)/Black/AA (25%), with 15.49 years of education (SD = 2.43). Results: Overall, many patients demonstrated mild impairment on a brief global cognitive screener (MoCA; M = 24.78, SD = 3.46). On specific tasks of cognitive abilities, processing speed was variable; ranging from low average (Oral TMT Part A; M = 88.31, SD = 28.78) to below average (Oral SDMT; M = 72.80, SD = 20.37). Memory for immediate recall was low average (CVLT3-Brief Form (BF) Trials 1-4, M = 88.01, SD = 17.11), while delayed recall was average (CVLT3-BF, M = 94.17, SD = 19.11). Performances on measures of attention/working memory (WAIS-IV Digit Span; M = 96.75, SD = 12.54), executive functioning (Oral TMT Part B; M = 92.71, SD = 28.48), language (COWAT; M = 92.03, SD = 14.19) and visuospatial abilities (RBANS Figure Copy M = 104.04, SD = 16.08) were intact. Performance on embedded validity measures was also intact (RDS [95% valid]; CVLT-3 FC [93% valid]). Conclusion: Overall, patients with “brain fog” following COVID-19 infection experience difficulties in specific domains of cognitive functioning. Further investigation of neuropsychological profiles associated with PASC is warranted to inform diagnosis, neurocognitive trajectory, and treatment planning.

A healthy brain is critical for living a longer and fuller life. The projected aging of the population, however, raises new challenges in maintaining quality of life. As we age, there is increasing compromise of neuronal activity that affects functions such as cognition, also making the brain vulnerable to disease. Once pathology-induced decline begins, few therapeutic options are available. Prevention is therefore paramount, and primary care can play a critical role. The purpose of this American Heart Association scientific statement is to provide an up-to-date summary for primary care providers in the assessment and modification of risk factors at the individual level that maintain brain health and prevent cognitive impairment. Building on the 2017 American Heart Association/American Stroke Association presidential advisory on defining brain health that included “Life’s Simple 7,” we describe here modifiable risk factors for cognitive decline, including depression, hypertension, physical inactivity, diabetes, obesity, hyperlipidemia, poor diet, smoking, social isolation, excessive alcohol use, sleep disorders, and hearing loss. These risk factors include behaviors, conditions, and lifestyles that can emerge before adulthood and can be routinely identified and managed by primary care clinicians.

Objective: To review the research literature pertaining to post-stroke language recovery, and to discuss neurocognitive assessment in patients in the context of aphasia, time course of language recovery, factors associated with language recovery, and therapeutic techniques designed to facilitate language recovery. Method: Articles were identified through PubMed, MEDLINE, PsychINFO, and Google Scholar searches. Examples of utilized keywords include "post-stroke aphasia," "post-stroke language recovery," "post-stroke neurocognitive assessment," and "neuropsychology and aphasia." Results: Most language recovery occurs in the first few weeks following stroke, but residual recovery may occur for many years. Although initial aphasia severity is the single largest determinant of post-stroke language recovery, a number of other variables also contribute. Several techniques have been developed to aid in the recovery process including speech-language therapy and noninvasive brain stimulation, although the effectiveness of acute and subacute treatment remains unclear. Some degree of valid neurocognitive assessment is possible in patients with aphasia, and the information gained from such an evaluation can aid the rehabilitative process Conclusions: Significant recovery of language function is possible following a stroke, but prediction of level of recovery in an individual patient is difficult. Information about initial aphasia severity and the integrity of cognitive domains other than language can help guide the rehabilitation team, as well as manage expectations for recovery.

OBJECTIVES: In the United States, Black individuals have higher stroke incidence and mortality when compared to white individuals and are also at risk of having lower stroke knowledge and awareness. With the need to implement focused interventions to decrease stroke disparities, the objective of this study is to evaluate the feasibility and efficacy of an emergency department-based educational intervention aimed at increasing stroke awareness and preparedness among a disproportionately high-risk group. MATERIALS AND METHODS: Over a three-month timeframe, an emergency department-based, prospective educational intervention was implemented for Black patients in an urban, academic emergency department. All participants received stroke education in the forms of a video, written brochure and verbal counseling. Stroke knowledge was assessed pre-intervention, immediately post-intervention, and at one-month post-intervention. RESULTS: One hundred eighty-five patients were approached for enrollment, of whom 100 participants completed the educational intervention as well as the pre- and immediate post- intervention knowledge assessments. Participants demonstrated increased stroke knowledge from baseline knowledge assessment (5.35 ± 1.97) at both immediate post-intervention (7.66 ± 2.42, p

Background: Data from the CDC show that approximately one-quarter of adults have elevated triglyceride (TG) levels. Recent trials have demonstrated that pharmacologic treatment of high TG levels, in patients already on statin therapy, reduces the rate of major vascular events such as myocardial infarction and stroke (REDUCE-IT trial). We sought to assess how often patients with asymptomatic carotid stenosis (CS) have elevated TG levels and factors associated with high TG values. Methods: Patients enrolled in the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST 2) were analyzed. Baseline lipid profiles were evaluated to determine high TG treatment eligibility as per the REDUCE-IT trial. We also evaluated baseline use of pharmacologic treatment for high TG levels. Demographic factors and baseline medical conditions were studied in relation to high (>150 mg/dl) TG values. Chi square and t tests were used to assess baseline factors and abnormal TG values. Results: As of August 10, 2020, 1655 of 1689 randomized patients (mean age 69.7 years, 61% men) had baseline lipid profiles suitable for analysis. Treatment eligibility according to REDUCE-IT (LDL 41-100 mg/dl, TG>150 mg/dl) was present in 21% (345) of subjects. In these patients, the median TG value was 205 (IQR 93) mg/dl. Fibrate medications were used at baseline in 4.5% of patients. Analysis of demographic and medical history factors and TG values greater than 150 mg/dl is found in the Table. There was significant positive correlation between baseline hemoglobin A1C and triglyceride values (p Conclusions: One in five patients in CREST 2 has TG values that potentially justify pharmacologic treatment. Elevated TG levels are most correlated with diabetes, hypertension, obesity, decreased physical activity, and heart disease. Clinicians should investigate treatment of elevated TG levels as a component of intensive medical therapy for stroke prevention.

Background: Cognition has been found to influence risk of stroke and death for a variety of patient groups but this association has not been examined in heart failure (HF) patients undergoing left ventricular assist device (LVAD) implant. We aimed to study the relationship between cognition, stroke, and death in a cohort of patients who received LVAD therapy. It was hypothesized that cognitive test results obtained prior to LVAD placement would predict stroke and death after surgery. Methods: We retrospectively identified 59 HF patients who had cognitive assessment prior to LVAD placement. Cognitive assessment included measures of attention, memory, language, and visualmotor speed and were averaged to produce one z-score variable per patient. Survival analyses, censored for transplant, evaluated predictors for stroke and death within a follow-up period of 900 days. Results: For patients with stroke or death during the follow up period, the average cognitive z-score predicted post-LVAD stroke (HR = 0.513, 95% CI = 0.31–0.86, p = 0.012) and death (HR = 0.166, 95% CI = 0.06–0.47, p = 0.001). Cognitive performances were worse in the patients who suffered stroke or died. No other variable predicted stroke and death within the follow up period when the cognitive variable was in the model. Conclusion: Cognitive performance was predictive of post-LVAD risk of stroke and death. Results are consistent with findings from other studies in non-LVAD samples and may reflect early signs of neurologic vulnerability. Further studies are needed to clarify the relationship between cognition and LVAD outcomes in order to optimize patient selection, management, and advanced care planning.

BACKGROUND: Ischemic stroke can impact a patient’s quality of life, but the extent is unknown. OBJECTIVE: To evaluate the association between gait measures during inpatient rehabilitation with quality-of-life scores and function at 3 months in patients with stroke. SETTING: Single-Center inpatient rehabilitation facility. PARTICIPANTS: Eight five patients with ischemic stroke. METHODS: A 6-Minute Walk Test and a 10-Meter Walk Test were recorded on admission to rehabilitation. We analyzed the association between gait function at rehabilitation and 3-month quality of life and poor functional outcome (modified Rankin Scale score >2) using multivariable logistic regression. MAIN OUTCOME: Measures 3-month health related quality of life. RESULTS: Eighty-five patients (mean age 68.3 14.9 years; 54.3% male) were enrolled. In adjusted analyses, an increase of 0.31 m/s (ie, 1 SD) on the 10-meter walk test was linked with a decreased odds of impaired lower extremity quality of life by 94% (odds ratio [OR] 0.06, 95% confidence interval [CI] 0.01–0.52; P =.01), and decreased odds of poor functional outcome by 98% (OR 0.02, 95% CI

Introduction: The Emergency Medical Stroke Assessment (EMSA) is a six point stroke severity scale with one point each for gaze preference, facial droop, arm drift, leg drift, abnormal naming, and abnormal repetition that was developed to help emergency medical services (EMS) providers identify acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). We hypothesized that the EMSA would detect left hemisphere LVO with a higher sensitivity than right hemisphere LVO. Methods: We trained 24 trauma system-based emergency communication center (ECC) paramedics in the EMSA. ECC-guided EMS in performance of the EMSA on patients with suspected stroke. We compared the sensitivity, specificity, area under the curve (AUC), and 95% confidence interval (CI) of ECC-guided prehospital EMSA for right versus left hemisphere ICA or M1 occlusion. Results: We enrolled 569 patients from September 2016 through February 2018, out of which 236 had a discharge diagnosis of stroke and 173 had a diagnosis of AIS. We excluded patients with bilateral (n=21) and brainstem (n=21) AIS. There were 64 patients with left hemisphere AIS including 19 with LVO. There were 67 patients with right hemisphere AIS including 22 with LVO. A score of ≥ 4 points yielded a sensitivity of 84.2 (95% CI = 60.4-96.6) and specificity of 66.7 (51.1-80.0) for left hemisphere LVO compared to a sensitivity of 68.2 (45.1-86.1) and specificity of 73.9 (58.9-85.7) for right hemisphere LVO. For predicting a left hemisphere LVO, the AUC was 0.77 (0.65-0.90) compared to 0.66 (0.50-0.82) for right-sided LVO. Assigning 2 points for abnormal gaze yielded an AUC of 0.78 (0.66-0.91) versus 0.67 (0.52-0.83) for left and right hemisphere LVO, respectively. Conclusions: The EMSA, like the National Institutes of Health Stroke Scale (NIHSS) upon which it is based, is more sensitive to left compared to right hemisphere LVO. More heavily weighting abnormal gaze did not improve the sensitivity of the EMSA for right hemisphere LVO. There is no comparable data on the right versus left hemisphere performance of other prehospital scales. There is a need to develop sensitive tests of right hemisphere dysfunction that are suitable for use in the field.

Objective: To determine if aortic stenosis (AS) is associated with altered cerebral hemodynamics and impaired neurocognition, and whether TAVR improves hemodynamics and cognition. Background: AS results in higher systolic pressure to overcome resistance from the stenotic valve, leading to heart failure and decline in cardiac output. There has been no baseline assessment of CBF with neurocognition in AS, or the effects of valve replacement. Methods: In 40 patients with planned TAVR, transcranial Doppler (TCD) assessed bilateral MCA mean flow velocity (MFV); abnormality was < 30cc/sec. The neurocognitive battery assessed memory, language, attention, visual-spatial skills, and executive function, yielding an average Z-score. Impairment was < 1.5 SD’s below the normative mean. Results: The mean age was 78 years, 59% male, and the mean valve gradient was 46.87%. Mean follow-up was 36 days post-TAVR (range 27 - 55). Before TAVR, the average MFV was 42 cc/sec (SD=10.22), and the mean cognitive score was -0.22 SD’s (range -1.99 to 1.08) below the normative mean. Of the 5 with abnormal MFV’s, none had abnormal cognition (average=0.19 SD’s above the normative mean). After TAVR, the MFV was 43 cc/sec, not different from baseline (p=0.56). The post-TAVR average Z-score was 0.01 SD’s above the normative mean, also not different from baseline (p=0.29). There was no correlation between the change scores in MFV and in neurocognition (r = 0.08, p= 0.69). Conclusions: Among patients with severe AS, there was no correlation at baseline between abnormal MFV’s on TCD and abnormal neurocognition. It was therefore unsurprising that there was little impact of valve replacement on these measures of cerebral blood flow and brain function. Prior assumptions about diminished CBF and the relationship to cognitive function may not be supported.

Background: Presence of atherosclerotic disease in more than one vascular bed (polyvascular disease) is associated with an increased risk of long-term vascular events. In the setting of asymptomatic carotid stenosis, the predictors of disease in other vascular beds is not well delineated. Objective: To identify the frequency and predictors of disease in other vascular beds the CREST 2 randomized trial population with hemodynamically significant stenosis. Methods: Recorded baseline characteristics among CREST 2 participants included: demographics, past medical history, lifestyle factors, and laboratory studies. Each variable was tested against three potential definitions of disease in other beds (cardiac, peripheral arterial disease (PAD) or disease in cardiac + PAD). Statistical analysis was done with Chi square and t tests as appropriate. Results: Data from 1447 patients were available for analysis. In these subjects with carotid disease, 51% also had cardiac disease, 24% also had PAD, and 16% had disease in in both cardiac and PAD. There was no relationship between age or race and presence of disease in other beds. Those with cardiac disease were more likely to be male. Diabetes, hypertension, hypercholesterolemia, and former history of smoking were all more common in those with either cardiac and PAD (TABLE). Elevated triglyceride and low HDL levels were also associated with all three definitions of disease in other beds. Those with either PAD or cardiac + PAD were more likely to be current smokers. Conclusions: Among CREST 2 participants, several medical conditions and lifestyle factors were associated with an increased frequency of disease in other vascular beds. Smoking, in particular, appears to be more common in those with PAD. Future analyses will address whether those with disease in other beds have higher rates of stroke or death.

Background: Perfusion weighted imaging on MRI (MRP) and computerized tomography perfusion (CTP) are increasingly required to manage large vessel disease. Computerized algorithms can quantify perfusion data, but the programs are expensive and not widely used outside acute stroke evaluation. We aimed to determine how well human observers can identify asymmetries in cerebral perfusion images compared with an automated computer algorithm. Methods: Ten clinicians experienced in treating carotid artery disease (4 vascular neurologists, 3 neuroradiologists, 1 vascular surgeon, 1 neurosurgeon, 1 interventional radiologist) were given 28 post-processed, color-coded, axial-slice MRP scans from patients in the Carotid Revascularization Endovascular versus Stenting Trial - Hemodynamics (CREST-H) study. All patients had >70%, unilateral, asymptomatic carotid artery stenosis and had varying degrees of time-to-peak (TTP) delay on the side of stenosis, ranging from 0 to 2 secs, quantified by a semi-automated system that computes quantitative perfusion maps, using deconvolution of tissue and arterial signals (Olea, Cambridge, MA). A minimum volume of 10cc was required for a given TTP delay. Clinicians were asked to determine asymmetry (y/n) and side of occlusion for each case. Number of correct responses that matched the computer output were tallied. Results: We averaged correct responses by the 10 clinicians for cases at each increment of TTP delay; (Figure). At TTP delays ≥1.5 seconds, accuracy was ≥80%. At 1.25 sec accuracy fell to 60%, and at ≤ 1 sec, accuracy was ≤50%. For TTP=0 (no asymmetry), accuracy was 71%. Conclusions: Visual impression of hemodynamic asymmetry among experienced clinicians was reasonably accurate for TTP delays ≥1.5 seconds, but declined with more subtle asymmetries. Depending on the clinical impact of TTP delays (for CREST-H: correlation with cognitive decline), experienced clinicians may perform as well as an automated algorithm.

Atherosclerosis with carotid plaque-induced luminal narrowing causes asymptomatic carotid artery stenosis (ACAS) in ~10% of older adults and the vast majority remain undetected (de Weerd et al., Stroke 40(4):1105–1113, 2009; O’Leary et al., Stroke 23(12):1752–1760, 1992). Medical advancements in recent decades have increased life expectancy substantially, leading to an increased incidence of carotid disease, since the prevalence of carotid stenosis increases steeply with advanced age (Fairhead and Rothwell, Br Med J 333(7567):525–527, 2006). The advent of new imaging modalities such as computed tomography angiography (CTA), magnetic resonance angiography (MRA), cerebral angiography, and carotid Doppler ultrasound (CDUS) made it possible to diagnose patients with carotid disease prior to the onset of symptoms.

Objectives The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging. Background TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease. Methods SENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤−1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared the percentage of subjects below −1.5 SD. Correlation and regression analyses assessed the relationship between neurocognitive z-scores and T2 lesion volume. Results Among 234 patients tested, the mean composite z-score was −0.65 SD below the normative mean. Domain scores ranged from −0.15 SD for attention to −1.32 SD for executive function. On the basis of the ≥1.5 SD normative reference, there were significantly greater percentages of impaired scores in the composite z-score (13.2%; p = 0.019), executive function (41.9%; p Conclusions There was a significant proportion of aortic stenosis patients with impaired cognition before TAVR, with a relationship between baseline cognitive function and lesion burden likely attributable to longstanding cerebrovascular disease. These findings underscore the importance of pre-interventional testing and magnetic resonance imaging in any research investigating post-surgical cognitive outcomes in patients with cardiovascular disease.

Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies.

Stroke is the second leading cause of death and the third leading cause of disability-adjusted life years worldwide. Although numerous therapies have been developed over the past 10 years to treat acute ischemic stroke, the stark reality remains that only 5% of these patients are so treated in the United States,1 in part, because of treatment window times 7 million stroke survivors …

BACKGROUND Prior studies have shown a correlation between the National Institutes of Health Stroke Scale (NIHSS) and stroke volume on diffusion weighted imaging (DWI); data are more limited in patients with minor stroke. We sought to determine the association between DWI lesion(s) volume and the (1) total NIHSS score and (2) NIHSS component scores in patients with minor stroke. METHODS We included all patients with minor stroke (NIHSS 0-5) enrolled in the Stroke Warning Information and Faster Treatment study. We calculated lesion(s) volume (cm3 ) on the DWI sequence using Medical Image Processing, Analysis, and Visualization (MIPAV, NIH, Version 7.1.1). We used nonparametric tests to study the association between the primary outcome, DWI lesion(s) volume, and the predictors (NIHSS score and its components). RESULTS We identified 894 patients with a discharge diagnosis of minor stroke; 709 underwent magnetic resonance imaging and 510 were DWI positive. There was a graded relationship between the NIHSS score and median DWI lesion volume in cm3 : (NIHSS 0: 7.1, NIHSS 1: 8.0, NIHSS 2: 17.1, NIHSS 3: 11.6, NIHSS 4: 19.0, and NIHSS 5: 23.6, P < .01). The median lesion volume was significantly higher in patients with neglect (105.6 vs. 12.5, P = .025), language disorder (34.6 vs. 11.9, P < .001), and visual field impairment (185.6 vs. 11.6, P < .001). Other components of the NIHSS were not associated with lesion volume. CONCLUSION In patients with minor stroke, the nature of deficit when used with the NIHSS score can improve prediction of infarct volume. This may have clinical and therapeutic implications.

Neurological complications after transcatheter aortic valve replacement (TAVR) may be reduced with transcatheter cerebral embolic protection (TCEP).This study evaluated the safety and efficacy of TCEP during TAVR.Nineteen centers randomized 363 patients undergoing TAVR to a safety arm (n = 123), device imaging (n = 121), and control imaging (n = 119). The primary safety endpoint consisted of major adverse cardiac and cerebrovascular events (MACCE) at 30 days, and the primary efficacy endpoint was reduction in new lesion volume in protected brain territories on magnetic resonance imaging scans at 2 to 7 days. Patients underwent neurocognitive assessments, and the debris captured was analyzed.The rate of MACCE (7.3%) was noninferior to the performance goal (18.3%, pTCEP was safe, captured embolic debris in 99% of patients, and did not change neurocognitive function. Reduction in new lesion volume on magnetic resonance scans was not statistically significant. (Cerebral Protection in Transcatheter Aortic Valve Replacement [SENTINEL]; NCT02214277).

The ability of neuropsychological tests to predict rehabilitation outcome is unclear, particularly when other ratings of cognition are available. Neuropsychological test scores and functional ratings of cognition (Functional Independence Measure (FIM) Cognition score) were used to predict improvement in patient mobility and self-care skill, as measured by the FIM Motor score. Regression models used both raw neuropsychology test scores and age-adjusted scores. Retrospective chart review was performed for patients on an inpatient rehabilitation unit and referred for neuropsychological assessment. The group included 126 subjects (average age 64.2 ± 17.1 years) and a variety of medical diagnoses. Neuropsychological tests included the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). After forcing the Admission FIM Cognition score into the model, RBANS scores and duration of rehabilitation predicted FIM Motor improvements (F=11.42,p<0.0001). Raw neuropsychological test scores performed better than the model with age-adjusted test scores. FIM Cognition alone did not predict FIM Motor improvements. Neuropsychological tests, combined with duration of rehabilitation, predicted mobility gains for patients undergoing inpatient rehabilitation beyond what was predicted by another, readily available, assessment of cognition. Neuropsychology raw scores performed better than age-adjusted scores, raising questions about the standard use of demographic adjustments for predicting real-world function.

PURPOSE: There are cognitive changes in primary hyperparathyroidism (PHPT) that improve with parathyroidectomy but the mechanism of cognitive dysfunction has not been delineated. We assessed if cerebrovascular function is impaired in PHPT, improves post-parathyroidectomy and is associated with PTH level and cognitive dysfunction. METHODS: This is an observational study of 43 patients with mild hypercalcemic or normocalcemic PHPT or goiter. At baseline, cerebrovascular function (dynamic cerebral autoregulation and vasomotor reactivity) by transcranial Doppler and neuropsychological function were compared between all 3 groups. A subset underwent parathyroidectomy or thyroidectomy, and was compared 6 months post-operatively. RESULTS: Mean cerebrovascular and neuropsychological function was normal and no worse in PHPT compared to controls preoperatively. Higher PTH was associated with worse intracerebral autoregulation (r=−0.43, p=0.02) and worse cognitive performance on some tests. Post-parathyroidectomy, mood improved significantly, but changes did not differ compared to those having thyroidectomy (p=0.84). There was no consistent improvement in cognition or change in vascular function in either surgical group. CONCLUSIONS: Although higher PTH was associated with worse intracerebral autoregulation, cerebrovascular function, cognition and mood were normal in mild PHPT. PTX did not improve vascular or cognitive function. The observed improvement in mood cannot be clearly attributed to PTX. Notwithstanding the small sample size, the results do not support changing current criteria for parathyroidectomy to include cognitive complaints. However, the associations between PTH, cognition and cerebral autoregulation merit future studies in those with more severe hyperparathyroidism.

Background: The importance of physical activity in preventing major vascular events has received increased attention in the past decade. Due to the inclusion of the INTERVENT lifestyle modification program, the CREST2 trial provides a unique opportunity to study physical activity profiles in patients with severe asymptomatic extracranial carotid stenosis. Hypothesis: Based on data from a trial of intracranial stenosis patients, we aimed to evaluate the hypothesis that Methods: We analyzed 1087 CREST2 participants with baseline data on physical activity. The Physician-based Assessment and Counseling for Exercise (PACE) score is recorded for each patient and dichotomized as “in target” (4-8 points) or “out of target” ( Results: The mean age of the study population is 69.5±7.8 years (60% male). The median PACE score at baseline is 4.0 (mean 3.8±2.1; IQR 2 to 6). The Table shows baseline characteristics of patients by mean PACE score. Being male, not having diabetes mellitus, having a body mass index Conclusions: We have defined several patient groups with asymptomatic carotid stenosis that have suboptimal physical activity. These results provide opportunities for targeted efforts to improve primary stroke prevention. These baseline data will also allow investigators to determine if trial involvement and the INTERVENT program leads to improvement in the level of physical activity.

PURPOSE OF REVIEW: To review the current literature that supports the notion that cerebral hemodynamic compromise from internal carotid artery stenosis may be a cause of vascular cognitive impairment that is amenable to treatment by revascularization. RECENT FINDINGS: Converging evidence suggests that successful carotid endarterectomy and carotid artery stenting are associated with reversal of cognitive decline in many patients with severe but asymptomatic carotid artery stenosis. Most of these findings have been derived from cohort studies and comparisons with either normal or surgical controls. Failure to find treatment benefit in a number of studies appears to have been the result of patient heterogeneity or confounding from concomitant conditions independently associated with cognitive decline, such as heart failure and other cardiovascular risk factors, or failure to establish pre-procedure hemodynamic failure. SUMMARY: Patients with severe carotid artery stenosis causing cerebral hemodynamic impairment may have a reversible cause of cognitive decline. None of the prior studies, however, were done in the context of a randomized clinical trial with large numbers of participants. The ongoing CREST-2 trial comparing revascularization with medical therapy versus medical therapy alone, and its associated CREST-H study determining whether cognitive decline is reversible among those with hemodynamic compromise may address this question.

The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) involves 123 clinics assessing intensive medical management (IMM) alone compared to either carotid endarterectomy plus IMM or carotid stenting plus IMM. Cognitive function is assessed prior to treatment and yearly thereafter. The neurocognitive battery, administered via telephone by interviewers at a university Survey Research Unit, includes measures administered in identical fashion in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Learning and memory (CERAD Word List Learning-WLL and Word List Delay Recall--WLD) and executive function (animal—AF and letter fluency—LF) are assessed. We compared the baseline assessments of the first 207 CREST-2 participants with normative data drawn from >5000 REGARDS participants without stroke. We compared demographics-adjusted z-scores, as well as observed frequencies and confidence intervals for the 95th, 75th, 50th, 25th and 5th percentiles in each study. CREST-2 participants had a mean age of 69; 59% were men. Their mean scores for WLL, WLD, and LF were significantly lower than those in REGARDS (p values

Objective:To determine the independent effects of aphasia on outcomes during acute stroke admission, controlling for total NIH Stroke Scale (NIHSS) scores and loss of consciousness.Methods:Data from the Tulane Stroke Registry were used from July 2008 to December 2014 for patient demographics, NIHSS scores, length of stay (LOS), complications (sepsis, deep vein thrombosis), and discharge modified Rankin Scale (mRS) score. Aphasia was defined as a score >1 on question 9 on the NIHSS on admission and hemiparesis as >1 on questions 5 or 6.Results:Among 1,847 patients, 866 (46%) had aphasia on admission. Adjusting for NIHSS score and inpatient complications, those with aphasia had a 1.22 day longer LOS than those without aphasia, whereas those with hemiparesis (n = 1,225) did not have any increased LOS compared to those without hemiparesis. Those with aphasia had greater odds of having a complication (odds ratio [OR] 1.44, confidence interval [CI] 1.07–1.93, p = 0.0174) than those without aphasia, which was equivalent to those having hemiparesis (OR 1.47, CI 1.09–1.99, p = 0.0137). Controlling for NIHSS scores, aphasia patients had higher odds of discharge mRS 3–6 (OR 1.42 vs 1.15).Conclusion:Aphasia is independently associated with increased LOS and complications during the acute stroke admission, adding $2.16 billion annually to US acute stroke care. The presence of aphasia was more likely to produce a poor functional outcome than hemiparesis. These data suggest that further research is necessary to determine whether establishing adaptive communication skills can mitigate its consequences in the acute stroke setting.