Systematic review and meta-analysis of the effects of menopause hormone therapy on cognition.

Introduction: Despite evidence from preclinical studies suggesting estrogen's neuroprotective effects, the use of menopausal hormone therapy (MHT) to support cognitive function remains controversial. Methods: We used random-effect meta-analysis and multi-level meta-regression to derive pooled standardized mean difference (SMD) and 95% confidence intervals (C.I.) from 34 randomized controlled trials, including 14,914 treated and 12,679 placebo participants. Results: Associations between MHT and cognitive function in some domains and tests of interest varied by formulation and treatment timing. While MHT had no overall effects on cognitive domain scores, treatment for surgical menopause, mostly estrogen-only therapy, improved global cognition (SMD=1.575, 95% CI 0.228, 2.921; P=0.043) compared to placebo. When initiated specifically in midlife or close to menopause onset, estrogen therapy was associated with improved verbal memory (SMD=0.394, 95% CI 0.014, 0.774; P=0.046), while late-life initiation had no effects. Overall, estrogen-progestogen therapy for spontaneous menopause was associated with a decline in Mini Mental State Exam (MMSE) scores as compared to placebo, with most studies administering treatment in a late-life population (SMD=-1.853, 95% CI -2.974, -0.733; P = 0.030). In analysis of timing of initiation, estrogen-progestogen therapy had no significant effects in midlife but was associated with improved verbal memory in late-life (P = 0.049). Duration of treatment >1 year was associated with worsening in visual memory as compared to shorter duration. Analysis of individual cognitive tests yielded more variable results of positive and negative effects associated with MHT. Discussion: These findings suggest time-dependent effects of MHT on certain aspects of cognition, with variations based on formulation and timing of initiation, underscoring the need for further research with larger samples and more homogeneous study designs.

Impact of a Best Practices Program in Patients with Relapsed/Refractory Multiple Myeloma Receiving Selinexor.

Best practice (BP) in cancer care consists of a multifaceted approach comprising individualized treatment plans, evidence-based medicine, the optimal use of supportive care and patient education. We investigated the impact of a BP program in patients with relapsed/refractory multiple myeloma (RRMM) receiving selinexor. Features of the BP program that were specific to selinexor were initiating selinexor at doses ≤80 mg once weekly and the upfront use of standardized antiemetics. Study endpoints included time to treatment failure (TTF), duration of therapy, dose limiting toxicities and overall survival. Comparative analysis on TTF and duration of therapy was conducted using a log-rank test and multivariate Cox proportional hazard regression. Over the ensuing 12-month post-BP period, 41 patients received selinexor-based therapy compared to 68 patients who received selinexor-based therapy pre-BP implementation. Patients treated in the post-BP period had reductions in TTF (hazard ratio [HR] = 0.50; 95% CI: 0.27 to 0.92). Patients in the pre-BP period were four times more likely to stop therapy than those in the post-period (odds ratio [OR] = 4.0, 95% CI: 1.75 to 9.3). The findings suggest a BP program tailored to selinexor could increase the time to treatment failure, increase treatment duration and lower the incidence of drug limiting toxicities.

Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer's disease and dementia.

Introduction: Despite a large preclinical literature demonstrating neuroprotective effects of estrogen, use of menopausal hormone therapy (HT) for Alzheimer's disease (AD) risk reduction has been controversial. Herein, we conducted a systematic review and meta-analysis of HT effects on AD and dementia risk. Methods: Our systematic search yielded 6 RCT reports (21,065 treated and 20,997 placebo participants) and 45 observational reports (768,866 patient cases and 5.5 million controls). We used fixed and random effect meta-analysis to derive pooled relative risk (RR) and 95% confidence intervals (C.I.) from these studies. Results: Randomized controlled trials conducted in postmenopausal women ages 65 and older show an increased risk of dementia with HT use compared with placebo [RR = 1.38, 95% C.I. 1.16-1.64, p < 0.001], driven by estrogen-plus-progestogen therapy (EPT) [RR = 1.64, 95% C.I. 1.20-2.25, p = 0.002] and no significant effects of estrogen-only therapy (ET) [RR = 1.19, 95% C.I. 0.92-1.54, p = 0.18]. Conversely, observational studies indicate a reduced risk of AD [RR = 0.78, 95% C.I. 0.64-0.95, p = 0.013] and all-cause dementia [RR = .81, 95% C.I. 0.70-0.94, p = 0.007] with HT use, with protective effects noted with ET [RR = 0.86, 95% C.I. 0.77-0.95, p = 0.002] but not with EPT [RR = 0.910, 95% C.I. 0.775-1.069, p = 0.251]. Stratified analysis of pooled estimates indicates a 32% reduced risk of dementia with midlife ET [RR = 0.685, 95% C.I. 0.513-0.915, p = 0.010] and non-significant reductions with midlife EPT [RR = 0.775, 95% C.I. 0.474-1.266, p = 0.309]. Late-life HT use was associated with increased risk, albeit not significant [EPT: RR = 1.323, 95% C.I. 0.979-1.789, p = 0.069; ET: RR = 1.066, 95% C.I. 0.996-1.140, p = 0.066]. Discussion: These findings support renewed research interest in evaluating midlife estrogen therapy for AD risk reduction.

Outcomes of patients with pre-existing disability managed by mobile stroke units: A sub-analysis of the BEST-MSU study.

BACKGROUND: Few data exist on acute stroke treatment in patients with pre-existing disability (PD) since they are usually excluded from clinical trials. A recent trial of mobile stroke units (MSUs) demonstrated faster treatment and improved outcomes, and included PD patients. AIM: To determine outcomes with tissue plasminogen activator (tPA), and benefit of MSU versus management by emergency medical services (EMS), for PD patients. METHODS: Primary outcomes were utility-weighted modified Rankin Scale (uw-mRS). Linear and logistic regression models compared outcomes in patients with versus without PD, and PD patients treated by MSU versus standard management by EMS. Time metrics, safety, quality of life, and health-care utilization were compared. RESULTS: Of the 1047 tPA-eligible ischemic stroke patients, 254 were with PD (baseline mRS 2-5) and 793 were without PD (baseline mRS 0-1). Although PD patients had worse 90-day uw-mRS, higher mortality, more health-care utilization, and worse quality of life than non-disabled patients, 53% returned to at least their baseline mRS, those treated faster had better outcome, and there was no increased bleeding risk. Comparing PD patients treated by MSU versus EMS, 90-day uw-mRS was 0.42 versus 0.36 (p = 0.07) and 57% versus 46% returned to at least their baseline mRS. There was no interaction between disability status and MSU versus EMS group assignment (p = 0.67) for 90-day uw-mRS. CONCLUSION: PD did not prevent the benefit of faster treatment with tPA in the BEST-MSU study. Our data support inclusion of PD patients in the MSU management paradigm.

In vivo Brain Estrogen Receptor Expression By Neuroendocrine Aging And Relationships With Gray Matter Volume, Bio-Energetics, and Clinical Symptomatology.

17ß-estradiol,the most biologically active estrogen, exerts wide-ranging effects in brain through its action on estrogen receptors (ERs), influencing higher-order cognitive function and neurobiological aging. However, our knowledge of ER expression and regulation by neuroendocrine aging in the living human brain is limited. This in vivo multi-modality neuroimaging study of healthy midlife women reveals progressively higher ER density over the menopause transition in estrogen-regulated networks. Effects were independent of age and plasma estradiol levels, and were highly consistent, correctly classifying all women as being post-menopausal or not. Higher ER density was generally associated with lower gray matter volume and blood flow, and with higher mitochondria ATP production, possibly reflecting compensatory mechanisms. Additionally, ER density predicted changes in thermoregulation, mood, cognition, and libido. Our data provide evidence that ER density impacts brainstructure, perfusion and energy production during female endocrine aging, with clinical implications for women's health.

Elevated gonadotropin levels are associated with increased biomarker risk of Alzheimer's disease in midlife women.

Introduction: In preclinical studies, menopausal elevations in pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), trigger Alzheimer's disease (AD) pathology and synaptic loss in female animals. Herein, we took a translational approach to test whether gonadotropin elevations are linked to AD pathophysiology in women. Methods: We examined 191 women ages 40-65 years, carrying risk factors for late-onset AD, including 45 premenopausal, 67 perimenopausal, and 79 postmenopausal participants with clinical, laboratory, cognitive exams, and volumetric MRI scans. Half of the cohort completed 11C-Pittsburgh Compound B (PiB) amyloid-ß (Aß) PET scans. Associations between serum FSH, LH and biomarkers were examined using voxel-based analysis, overall and stratified by menopause status. Associations with region-of-interest (ROI) hippocampal volume, plasma estradiol levels, APOE-4 status, and cognition were assessed in sensitivity analyses. Results: FSH levels were positively associated with Aß load in frontal cortex (multivariable adjusted P≤0.05, corrected for family wise type error, FWE), an effect that was driven by the postmenopausal group (multivariable adjusted PFWE ≤ 0.044). LH levels were also associated with Aß load in frontal cortex, which did not survive multivariable adjustment. FSH and LH were negatively associated with gray matter volume (GMV) in frontal cortex, overall and in each menopausal group (multivariable adjusted PFWE ≤ 0.040), and FSH was marginally associated with ROI hippocampal volume (multivariable adjusted P = 0.058). Associations were independent of age, clinical confounders, menopause type, hormone therapy status, history of depression, APOE-4 status, and regional effects of estradiol. There were no significant associations with cognitive scores. Discussion: Increasing serum gonadotropin levels, especially FSH, are associated with higher Aß load and lower GMV in some AD-vulnerable regions of midlife women at risk for AD. These findings are consistent with preclinical work and provide exploratory hormonal targets for precision medicine strategies for AD risk reduction.

Progressive superficial siderosis from Chronic CSF leak as a long-term complication of cervical anterior corpectomy: A case report and review of the literature.

Background: Superficial siderosis of the central nervous system (SSCNS) is a rare progressive neurological disorder resulting from chronic subarachnoid hemorrhage and subsequent subpial hemosiderin deposition. A prolonged cerebrospinal fluid (CSF) leak is a known cause of SSCNS. We present a novel case where progressive SSCNS resulted from a chronic CSF leak related to an anterior cervical corpectomy. Case Description: A 73-year-old man presented with gait ataxia and progressive hearing loss. Thirteen years before, he had undergone a combined anterior-posterior cervical decompression for symptomatic ossification of the posterior longitudinal ligament (OPLL). The presenting MR imaging showed extensive superficial siderosis and focal spinal cord herniation at the site of a ventral dural defect at the corpectomy site. A CT myelogram showed extensive CSF leakage into the corpectomy surgical site and a communicating pseudomeningocele in the anterior neck. Conclusion: This is the first reported case of progressive SSCNS as a long-term complication of an anterior cervical corpectomy for OPLL. Clinicians should be aware of SSCNS secondary to a chronic CSF leak in patients with a prior corpectomy.

Comparing hematoma characteristics in primary intracerebral hemorrhage versus intracerebral hemorrhage caused by structural vascular lesions.

Intracerebral hemorrhage (ICH) caused by structural vascular lesions is associated with better outcomes than primary ICH, but this relationship is poorly understood. We tested the hypothesis that ICH from a vascular lesion has more benign hematoma characteristics compared to primary ICH. We performed a retrospective study using data from our medical center. The SMASH-U criteria were used to adjudicate the etiology of ICH. The co-primary outcomes were admission parenchymal hematoma volume and hematoma expansion at 24 h. Linear and logistic regression analyses were performed to test associations. A total of 231 patients were included of whom 42 (18%) had a vascular lesion. Compared to primary ICH patients, those with structural vascular lesions were younger (49 vs. 68 years, p < 0.001), less likely to have hypertension (29% vs. 74%, p < 0.001), had lower mean admission systolic blood pressure (140 ± 23 vs. 164 ± 35, p < 0.001), less frequently had IVH (26% vs. 44%, p = 0.03), and had mostly lobar or infratentorial hemorrhages. The median admission hematoma volume was smaller with vascular lesions (5.9 vs. 9.7 mL, p = 0.01). In regression models, ICH from a vascular lesion was associated with smaller admission hematoma volume (beta, -0.67, 95% CI, -1.29 to -0.05, p = 0.03), but no association with hematoma expansion was detected when assessed as a continuous (OR, 0.93; 95% CI, -4.46 to 6.30, p = 0.73) or dichotomous exposure (OR, 1.86; 95% CI, 0.40 to 8.51, p = 0.42). In a single-center cohort, patients with ICH from vascular lesions had smaller hematoma volumes than patients with primary ICH.

Evaluation of Transient Ischemic Attack and Minor Stroke: A Rapid Outpatient Model for the COVID-19 Pandemic and Beyond.

The grim circumstances of the COVID-19 pandemic have highlighted the need to refine and adapt stroke systems of care. Patients' care-seeking behaviors have changed due to perceived risks of in-hospital treatment during the pandemic. In response to these challenges, we optimized a recently implemented, novel outpatient approach for the evaluation and management of minor stroke and transient ischemic attack, entitled RESCUE-TIA. This modified approach incorporated telemedicine visits and remote testing, and proved valuable during the pandemic. In this review article, we provide the evidence-based rationale for our approach, describe its operationalization, and provide data from our initial experience.

Feasibility of a wearable biosensor device to characterize exercise and sleep in neurology residents.

BACKGROUND: Research suggests optimizing sleep, exercise and work-life balance may improve resident physician burnout. Wearable biosensors may allow residents to detect and correct poor sleep and exercise habits before burnout develops. Our objectives were to evaluate the feasibility of a wearable biosensor to characterize exercise/sleep in neurology residents and examine its relationship to self-reported, validated survey measures. We also assessed the device's impact on well-being and barriers to use. METHODS: This prospective cohort study evaluated the WHOOP Strap 2.0 in neurology residents. Participants completed regular online surveys, including self-reported hours of sleep/exercise, and validated sleep/exercise scales at 3-month intervals. Autonomic, exercise, and sleep measures were obtained from WHOOP. Changes were evaluated over time via linear regression. Survey and WHOOP metrics were compared using Pearson correlations. RESULTS: Sixteen (72.7%) of 22 eligible participants enrolled. Eleven (68.8%) met the minimum usage requirement (6+ months) and were classified as 'consecutive wearers.' Significant increases were found in sleep duration and exercise intensity. Moderate-to-low correlations were found between survey responses and WHOOP measures. Most (73%) participants reported a positive impact on well-being. Barriers to use included 'Forgetting to wear' (20%) and 'not motivational' (23.3%). CONCLUSION: Wearable biosensors may be a feasible tool to evaluate sleep/exercise in residents.

Prospective, Multicenter, Controlled Trial of Mobile Stroke Units.

BACKGROUND: Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard management by emergency medical services (EMS). Whether and how much MSUs alter outcomes has not been extensively studied. METHODS: In an observational, prospective, multicenter, alternating-week trial, we assessed outcomes from MSU or EMS management within 4.5 hours after onset of acute stroke symptoms. The primary outcome was the score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes according to a patient value system, derived from scores on the modified Rankin scale of 0 to 6, with higher scores indicating more disability). The main analysis involved dichotomized scores on the utility-weighted modified Rankin scale (≥0.91 or <0.91, approximating scores on the modified Rankin scale of ≤1 or >1) at 90 days in patients eligible for t-PA. Analyses were also performed in all enrolled patients. RESULTS: We enrolled 1515 patients, of whom 1047 were eligible to receive t-PA; 617 received care by MSU and 430 by EMS. The median time from onset of stroke to administration of t-PA was 72 minutes in the MSU group and 108 minutes in the EMS group. Of patients eligible for t-PA, 97.1% in the MSU group received t-PA, as compared with 79.5% in the EMS group. The mean score on the utility-weighted modified Rankin scale at 90 days in patients eligible for t-PA was 0.72 in the MSU group and 0.66 in the EMS group (adjusted odds ratio for a score of ≥0.91, 2.43; 95% confidence interval [CI], 1.75 to 3.36; P<0.001). Among the patients eligible for t-PA, 55.0% in the MSU group and 44.4% in the EMS group had a score of 0 or 1 on the modified Rankin scale at 90 days. Among all enrolled patients, the mean score on the utility-weighted modified Rankin scale at discharge was 0.57 in the MSU group and 0.51 in the EMS group (adjusted odds ratio for a score of ≥0.91, 1.82; 95% CI, 1.39 to 2.37; P<0.001). Secondary clinical outcomes generally favored MSUs. Mortality at 90 days was 8.9% in the MSU group and 11.9% in the EMS group. CONCLUSIONS: In patients with acute stroke who were eligible for t-PA, utility-weighted disability outcomes at 90 days were better with MSUs than with EMS. (Funded by the Patient-Centered Outcomes Research Institute; BEST-MSU ClinicalTrials.gov number, NCT02190500.).

Sarcoid-Associated Bilateral Multifocal Choroiditis Secondary to Adalimumab.

PURPOSE: To report a rare paradoxical development of systemic sarcoidosis in a patient taking adalimumab manifesting as multifocal choroidal infiltrates and seventh nerve palsy. METHODS: This was a single patient case report. RESULTS: A 30-year-old man with a history of psoriatic arthritis on adalimumab presented with intermittent fevers and headaches. Initial infectious serology and initial ophthalmic examination were within normal limits. Over the next month, he developed a seventh nerve palsy, unilateral decreased visual acuity, and bilateral multifocal choroidal infiltrates. The patient was diagnosed with systemic sarcoidosis secondary to tumor necrosis factor alpha (TNFα) inhibitor use after a hilar lymph node biopsy. Upon treatment with high-dose oral corticosteroids, the patient's symptoms and choroidal lesions significantly improved. CONCLUSION: This case report illustrates a rare presentation of ocular, neurologic, and systemic sarcoidosis presenting as a bilateral multifocal choroiditis and seventh nerve paresis in a patient treated with adalimumab. We highlight the importance of obtaining an ophthalmic evaluation in the management of this rare adverse effect of TNFα inhibitors.

Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza.

IMPORTANCE: It is uncertain whether coronavirus disease 2019 (COVID-19) is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection. OBJECTIVE: To compare the rate of ischemic stroke between patients with COVID-19 and patients with influenza, a respiratory viral illness previously associated with stroke. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted at 2 academic hospitals in New York City, New York, and included adult patients with emergency department visits or hospitalizations with COVID-19 from March 4, 2020, through May 2, 2020. The comparison cohort included adults with emergency department visits or hospitalizations with influenza A/B from January 1, 2016, through May 31, 2018 (spanning moderate and severe influenza seasons). EXPOSURES: COVID-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 in the nasopharynx by polymerase chain reaction and laboratory-confirmed influenza A/B. MAIN OUTCOMES AND MEASURES: A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, mechanisms, and outcomes. We used logistic regression to compare the proportion of patients with COVID-19 with ischemic stroke vs the proportion among patients with influenza. RESULTS: Among 1916 patients with emergency department visits or hospitalizations with COVID-19, 31 (1.6%; 95% CI, 1.1%-2.3%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78 years); 18 (58%) were men. Stroke was the reason for hospital presentation in 8 cases (26%). In comparison, 3 of 1486 patients with influenza (0.2%; 95% CI, 0.0%-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was higher with COVID-19 infection than with influenza infection (odds ratio, 7.6; 95% CI, 2.3-25.2). The association persisted across sensitivity analyses adjusting for vascular risk factors, viral symptomatology, and intensive care unit admission. CONCLUSIONS AND RELEVANCE: In this retrospective cohort study from 2 New York City academic hospitals, approximately 1.6% of adults with COVID-19 who visited the emergency department or were hospitalized experienced ischemic stroke, a higher rate of stroke compared with a cohort of patients with influenza. Additional studies are needed to confirm these findings and to investigate possible thrombotic mechanisms associated with COVID-19.

Risk of Ischemic Stroke in Patients with Covid-19 versus Patients with Influenza.

IMPORTANCE: Case series without control groups suggest that Covid-19 may cause ischemic stroke, but whether Covid-19 is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection is uncertain. OBJECTIVE: To compare the rate of ischemic stroke between patients with Covid-19 and patients with influenza, a respiratory viral illness previously linked to stroke. DESIGN: A retrospective cohort study. SETTING: Two academic hospitals in New York City. PARTICIPANTS: We included adult patients with emergency department visits or hospitalizations with Covid-19 from March 4, 2020 through May 2, 2020. Our comparison cohort included adult patients with emergency department visits or hospitalizations with influenza A or B from January 1, 2016 through May 31, 2018 (calendar years spanning moderate and severe influenza seasons). Exposures: Covid-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the nasopharynx by polymerase chain reaction, and laboratory-confirmed influenza A or B. Main Outcomes and Measures: A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, etiological mechanisms, and outcomes. We used logistic regression to compare the proportion of Covid-19 patients with ischemic stroke versus the proportion among patients with influenza. RESULTS: Among 2,132 patients with emergency department visits or hospitalizations with Covid-19, 31 patients (1.5%; 95% confidence interval [CI], 1.0%-2.1%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78) and 58% were men. Stroke was the reason for hospital presentation in 8 (26%) cases. For our comparison cohort, we identified 1,516 patients with influenza, of whom 0.2% (95% CI, 0.0-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was significantly higher with Covid-19 than with influenza infection (odds ratio, 7.5; 95% CI, 2.3-24.9). CONCLUSIONS AND RELEVANCE: Approximately 1.5% of patients with emergency department visits or hospitalizations with Covid-19 experienced ischemic stroke, a rate 7.5-fold higher than in patients with influenza. Future studies should investigate the thrombotic mechanisms in Covid-19 in order to determine optimal strategies to prevent disabling complications like ischemic stroke.

Association between Pregnancy and Cervical Artery Dissection.

OBJECTIVE: We wanted to determine whether pregnancy is associated with cervical artery dissection. METHODS: We performed a case-control study using claims data from all nonfederal emergency departments and acute care hospitals in New York and Florida between 2005 and 2015. Cases were women 12-42 years of age hospitalized with cervical artery dissection, defined using validated diagnosis codes for carotid/vertebral artery dissection. Controls were women 12-42 years of age with a primary diagnosis of renal colic. Cases and controls were matched 1:1 on age, race, insurance, income, state, and visit year. The exposure variable was pregnancy, defined as labor and delivery within 90 days before or 6 months after the index visit. Logistic regression was used to compare the odds of pregnancy between cases and controls. We performed a secondary cohort-crossover study comparing the risk of cervical artery dissection during pregnancy versus the same time period 1 year later. RESULTS: Pregnancy was twice as common among 826 women with cervical artery dissection compared with the 826 matched controls with renal colic (odds ratio, 2.5; 95% confidence interval [CI], 1.3-4.7). In our secondary analysis, pregnancy was associated with a higher risk of cervical artery dissection (incidence rate ratio [IRR], 2.2; 95% CI, 1.3-3.5), with the heightened risk limited to the postpartum period (IRR, 5.5; 95% CI, 2.6-11.7). INTERPRETATION: Pregnancy, specifically the postpartum period, was associated with hospitalization for cervical artery dissection. Although these findings might in part reflect ascertainment bias, our results suggest that arterial dissection is one mechanism by which pregnancy can lead to stroke. ANN NEUROL 2020;88:596-602.

Differences in Admission Blood Pressure Among Causes of Intracerebral Hemorrhage.

Background and Purpose- It is unknown whether admission systolic blood pressure (SBP) differs among causes of intracerebral hemorrhage (ICH). We sought to elucidate an association between admission BP and ICH cause. Methods- We compared admission SBP across ICH causes among patients in the Cornell Acute Stroke Academic Registry, which includes all adults with ICH at our center from 2011 through 2017. Trained analysts prospectively collected demographics, comorbidities, and admission SBP, defined as the first recorded value in the emergency department or on transfer from another hospital. ICH cause was adjudicated by a panel of neurologists using the SMASH-U criteria. We used ANOVA to compare mean admission SBP among ICH causes. We used multiple linear regression to adjust for age, sex, race, Glasgow Coma Scale score, and hematoma size. In secondary analyses, we compared hourly SBP measurements during the first 72 hours after admission, using mixed-effects linear models adjusted for the covariates above plus antihypertensive agents. Results- Among 484 patients with ICH, admission SBP varied significantly across ICH causes, ranging from 138 (±24) mm Hg in those with structural vascular lesions to 167 (±35) mm Hg in those with hypertensive ICH (P<0.001). The mean admission SBP in hypertensive ICH was 17 (95% CI, 11-24) mm Hg higher than in ICH of all other causes combined. These differences remained significant after adjustment for age, sex, race, Glasgow Coma Scale score, and hematoma size (P<0.001), and this persisted throughout the first 72 hours of hospitalization (P<0.001). Conclusions- In a single-center ICH registry, SBP varied significantly among ICH causes, both on admission and during hospitalization. Our results suggest that BP in the acute post-ICH setting is at least partly associated with ICH cause rather than simply representing a physiological reaction to the ICH itself.

Geographic Analysis of Mobile Stroke Unit Treatment in a Dense Urban Area: The New York City METRONOME Registry.

Background Mobile stroke units (MSUs) reduce time to intravenous thrombolysis in acute ischemic stroke. Whether this advantage exists in densely populated urban areas with many proximate hospitals is unclear. Methods and Results We evaluated patients from the METRONOME (Metropolitan New York Mobile Stroke) registry with suspected acute ischemic stroke who were transported by a bi-institutional MSU operating in Manhattan, New York, from October 2016 to September 2017. The comparison group included patients transported to our hospitals via conventional ambulance for acute ischemic stroke during the same hours of MSU operation (Monday to Friday, 9 am to 5 pm). Our exposure was MSU care, and our primary outcome was dispatch-to-thrombolysis time. We estimated mean differences in the primary outcome between both groups, adjusting for clinical, demographic, and geographic factors, including numbers of nearby designated stroke centers and population density. We identified 66 patients treated or transported by MSU and 19 patients transported by conventional ambulance. Patients receiving MSU care had significantly shorter dispatch-to-thrombolysis time than patients receiving conventional care (mean: 61.2 versus 91.6 minutes; P=0.001). Compared with patients receiving conventional care, patients receiving MSU care were significantly more likely to be picked up closer to a higher mean number of designated stroke centers in a 2.0-mile radius (4.8 versus 2.7, P=0.002). In multivariable analysis, MSU care was associated with a mean decrease in dispatch-to-thrombolysis time of 29.7 minutes (95% CI, 6.9-52.5) compared with conventional care. Conclusions In a densely populated urban area with a high number of intermediary stroke centers, MSU care was associated with substantially quicker time to thrombolysis compared with conventional ambulance care.

Individualized clinical management of patients at risk for Alzheimer's dementia.

INTRODUCTION: Multidomain intervention for Alzheimer's disease (AD) risk reduction is an emerging therapeutic paradigm. METHODS: Patients were prescribed individually tailored interventions (education/pharmacologic/nonpharmacologic) and rated on compliance. Normal cognition/subjective cognitive decline/preclinical AD was classified as Prevention. Mild cognitive impairment due to AD/mild-AD was classified as Early Treatment. Change from baseline to 18 months on the modified Alzheimer's Prevention Cognitive Composite (primary outcome) was compared against matched historical control cohorts. Cognitive aging composite (CogAging), AD/cardiovascular risk scales, and serum biomarkers were secondary outcomes. RESULTS: One hundred seventy-four were assigned interventions (age 25-86). Higher-compliance Prevention improved more than both historical cohorts (P = .0012, P < .0001). Lower-compliance Prevention also improved more than both historical cohorts (P = .0088, P < .0055). Higher-compliance Early Treatment improved more than lower compliance (P = .0007). Higher-compliance Early Treatment improved more than historical cohorts (P < .0001, P = .0428). Lower-compliance Early Treatment did not differ (P = .9820, P = .1115). Similar effects occurred for CogAging. AD/cardiovascular risk scales and serum biomarkers improved. DISCUSSION: Individualized multidomain interventions may improve cognition and reduce AD/cardiovascular risk scores in patients at-risk for AD dementia.