INTRODUCTION: We tested the association of brain artery diameters with dementia and stroke risk in three distinct population-based studies using conventional T2-weighted brainmagnetic resonance imaging (MRI) images. METHODS: We included 8420 adults > 40 years old from three longitudinal population-based studies with brain MRI scans. We estimated and meta-analyzed the hazard ratios (HRs) of the brain and carotids and basilar diameters associated with dementia and stroke. RESULT: Overall and carotid artery diameters > 95th percentile increased the risk for dementia by 1.74 (95% confidence interval [CI], 1.13-2.68) and 1.48 (95% CI, 1.12-1.96) fold, respectively. For stroke, meta-analyses yielded HRs of 1.59 (95% CI, 1.04-2.42) for overall arteries and 2.11 (95% CI, 1.45-3.08) for basilar artery diameters > 95th percentile. DISCUSSION: Individuals with dilated brain arteries are at higher risk for dementia and stroke, across distinct populations. Our findings underline the potential value of T2-weighted brain MRI-based brain diameter assessment in estimating the risk of dementia and stroke.

The primary purpose of this study was to identify the association between common infectious disease exposures and radiographic features of brain aging in a community-dwelling sample of older adults.

Objective: Determine whether markers of carotid atherosclerosis are associated with cognitive function through the burden of white matter disease. Background: Atherosclerosis is a risk factor for cognitive decline. Ultrasonographic measures of carotid atherosclerosis (plaque and intima-media thickness) and MRI measures of small vessel disease (white matter hyperintensity volume) are subclinical markers of cerebrovascular disease that are associated with cognitive dysfunction. Design/Methods: We included 1290 subjects from the racially and ethnically diverse Northern Manhattan Study (age 64+/−8years, 60% women, 67% Hispanic, 18% Black, 15% White, education 10+/−5years). We assessed total plaque area (TPA) and intima-media thickness (cIMT) measures on carotid ultrasound and measures of white matter hyperintensity volume (WMHV) on MRI. Participants underwent neurocognitive evaluation to estimate global cognitive performance and domains of episodic memory, executive function, semantic memory, and processing speed. Associative mediation models were employed to determine if WMHV mediates the association of TPA and cIMT on global and domain-specific cognitive performance adjusting for age, sex, race, ethnicity, education, ApoE4 status, hypertension, hypercholesteremia, diabetes, and smoking. Results: Of the 1290 participants, 675 had carotid plaque (TPA 21+/−22mm2, cIMT 0.95+/−0.09mm, and WMHV 0.77+/−0.93% TIV). WMHV(log) mediated the association of TPA on global cognition [b(indirect-effect)=−0.001, p<0.05], episodic memory [b(indirect-effect)=−0.001, p<0.05], and processing speed [b(indirect-effect)=−0.001, p<0.05)] after adjustment. WMHV(log) volume mediated the association of cIMT on global cognition [b(indirect-effect)=−0.073, p<0.05], episodic memory [b(indirect-effect)=−0.112, p<0.05], and processing speed [b(indirect-effect)=−0.097, p<0.05] after adjustment. No associations were present for executive function and semantic memory. Conclusions: Ultrasound measures of extracranial carotid arteriosclerosis are related to intracranial MRI measures of small vessel disease and associated with cognitive performance. White matter hyperintensity volume may be an important factor in understanding the biological link between atherosclerosis and cognitive dysfunction in middle to older age population. More research is needed to better understand vascular imaging biomarkers of age-related cognitive dysfunction. Disclosure: Ms. Ariko has nothing to disclose. Ms. Aimagambetova has nothing to disclose. Ms. Gardener has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Intersocietal Accreditation Commission. Ms. Gardener has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ellipse Analytics. Ms. Gardener has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Baum Hedlund. Ms. Gardener has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant with A Green Slate Consulting. Bonnie Levin has nothing to disclose. Dr. Sun has nothing to disclose. Ms. Cabral has nothing to disclose. Carolina Gutierrez has nothing to disclose. Prof. Zhao has nothing to disclose. Noam Alperin has nothing to disclose. Dr. Elkind has received personal compensation for serving as an employee of American Heart Association. Dr. Elkind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Atria Academy. The institution of Dr. Elkind has received research support from BMS-Pfizer Alliance for Eliquis. The institution of Dr. Elkind has received research support from Roche. Dr. Elkind has received publishing royalties from a publication relating to health care. Dr. Elkind has a non-compensated relationship as a Officer with American Heart Association that is relevant to AAN interests or activities. Dr. Elkind has received personal compensation for serving as an employee of American Heart Association. Dr. Elkind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Atria Academy. The institution of Dr. Elkind has received research support from BMS-Pfizer Alliance for Eliquis. The institution of Dr. Elkind has received research support from Roche. Dr. Elkind has received publishing royalties from a publication relating to health care. Dr. Elkind has a non-compensated relationship as a Officer with American Heart Association that is relevant to AAN interests or activities. Dr. Gutierrez has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Roetzel & Andress, JOHN ASTUNO, JR. L.L.C.. The institution of Dr. Gutierrez has received research support from NIH. Dr. Gutierrez has received publishing royalties from a publication relating to health care. Dr. Gutierrez has received publishing royalties from a publication relating to health care. An immediate family member of Dr. Wright has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. An immediate family member of Dr. Wright has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for MARSHALL DENNEHY. The institution of an immediate family member of Dr. Wright has received research support from Oncospace. Dr. Wright has received publishing royalties from a publication relating to health care. An immediate family member of Dr. Wright has received personal compensation in the range of $500-$4,999 for serving as a surveyor with ASTRO. Dr. Sacco has received personal compensation in the range of $100,000-$499,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association. The institution of Dr. Sacco has received research support from NIH, NINDS, NCATS, NIMHD. The institution of Dr. Sacco has received research support from FL Department of Health. Dr. Sacco has received research support from University of Washington, Seattle. Dr. Sacco has received publishing royalties from a publication relating to health care. The institution of Dr. Rundek has received research support from NIH.

BACKGROUND AND PURPOSE: The Systolic Blood Pressure Intervention (SPRINT) randomized trial demonstrated that intensive blood pressure management resulted in slower progression of cerebral white matter hyperintensities, compared with standard therapy. We assessed longitudinal changes in brain functional connectivity to determine whether intensive treatment results in less decline in functional connectivity and how changes in brain functional connectivity relate to changes in brain structure. MATERIALS AND METHODS: Five hundred forty-eight participants completed longitudinal brain MR imaging, including resting-state fMRI, during a median follow-up of 3.84 years. Functional brain networks were identified using independent component analysis, and a mean connectivity score was calculated for each network. Longitudinal changes in mean connectivity score were compared between treatment groups using a 2-sample t test, followed by a voxelwise t test. In the full cohort, adjusted linear regression analysis was performed between changes in the mean connectivity score and changes in structural MR imaging metrics. RESULTS: Four hundred six participants had longitudinal imaging that passed quality control. The auditory-salience-language network demonstrated a significantly larger decline in the mean connectivity score in the standard treatment group relative to the intensive treatment group (P = .014), with regions of significant difference between treatment groups in the cingulate and right temporal/insular regions. There was no treatment group difference in other networks. Longitudinal changes in mean connectivity score of the default mode network but not the auditory-salience-language network demonstrated a significant correlation with longitudinal changes in white matter hyperintensities (P = .013). CONCLUSIONS: Intensive treatment was associated with preservation of functional connectivity of the auditory-salience-language network, while mean network connectivity in other networks was not significantly different between intensive and standard therapy. A longitudinal increase in the white matter hyperintensity burden is associated with a decline in mean connectivity of the default mode network.

Introduction: Hematocrit at both low and high extremes can result in both hypoxia and thrombosis respectively. While both scenarios may predispose to ischemia, it is unclear whether hematocrit associates with small vessel cerebrovascular lacunar infarcts. Hypothesis: Hematocrit levels will associate with both asymptomatic and symptomatic cerebrovascular lacunar infarcts in stroke-free participants and ischemic stroke patients, respectively. Methods: A cross sectional observational analysis of a prospective, population-based cohort study of stroke-free, older adult (>50) participants from the Northern Manhattan study (NOMAS) receiving baseline hematocrit testing and MRI between 2003-2008 were analyzed. A second, single center prospective cohort of admitted adult ischemic stroke patients receiving baseline hematocrit testing and MRI between 2005-2018 was evaluated. Associations of hematocrit with covert, asymptomatic chronic lacunar infarcts from stroke-free participants in NOMAS were assessed using general additive models after adjusting for relevant covariates. Separate analyses were performed to assess associations of hematocrit with symptomatic acute lacunar infarct stroke etiology using similar adjusted models for patients admitted and enrolled into the ischemic stroke registry. Results: Of 1218 NOMAS participants analyzed, 6% had covert chronic lacunar infarcts. The association between hematocrit and covert chronic lacunar infarcts was U-shaped (X2: 9.21; p-value: 0.03). In the 1489 patients from the ischemic stroke registry, 23% were identified to have symptomatic acute lacunar infarcts. Linear relationships were identified with higher hematocrit and symptomatic acute lacunar infarct etiology (adjusted coefficient beta: 0.020; standard error: 0.009; p=0.03). Conclusions: We identified relationships of hematocrit with both asymptomatic and symptomatic lacunar infarcts in both stroke-free and ischemic stroke cohorts, respectively. There may be a relevant role of red blood cell volumes with ischemic cerebral small vessel disease pathophysiology. However, further studies are required to clarify the mechanisms behind these relationships.

Table S1. Trial Characteristics and Time to Publication Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

The authors regret that Deborah J. Culley and Catherine C. Price were omitted from the author list of the article. The full list of authors and their affiliations appears above. The authors would like to apologise for any inconvenience caused. State of the clinical science of perioperative brain health: report from the American Society of Anesthesiologists Brain Health Initiative Summit 2018British Journal of AnaesthesiaVol. 123Issue 4PreviewCognitive recovery after anaesthesia and surgery is a concern for older adults, their families, and caregivers. Reports of patients who were ‘never the same’ prompted a scientific inquiry into the nature of what patients have experienced. In June 2018, the ASA Brain Health Initiative held a summit to discuss the state of the science on perioperative cognition, and to create an implementation plan for patients and providers leveraging the current evidence. This group included representatives from the AARP (formerly the American Association of Retired Persons), American College of Surgeons, American Heart Association, and Alzheimer's Association Perioperative Cognition and Delirium Professional Interest Area. Full-Text PDF Open Archive

The authors regret that Deborah J. Culley and Catherine C. Price were omitted from the author list of the article. The full list of authors and their affiliations appears above. The authors would like to apologise for any inconvenience caused.

Cognitive recovery after anaesthesia and surgery is a concern for older adults, their families, and caregivers. Reports of patients who were 'never the same' prompted a scientific inquiry into the nature of what patients have experienced. In June 2018, the ASA Brain Health Initiative held a summit to discuss the state of the science on perioperative cognition, and to create an implementation plan for patients and providers leveraging the current evidence. This group included representatives from the AARP (formerly the American Association of Retired Persons), American College of Surgeons, American Heart Association, and Alzheimer's Association Perioperative Cognition and Delirium Professional Interest Area. This paper summarises the state of the relevant clinical science, including risk factors, identification and diagnosis, prognosis, disparities, outcomes, and treatment of perioperative neurocognitive disorders. Finally, we discuss gaps in current knowledge with suggestions for future directions and opportunities for clinical and translational projects.

Objective: To determine whether immune protein panels correlate with presence of white matter abnormalities on brain magnetic resonance imaging (MRI). Background: Risk factors for cerebral white matter disease include traditional vascular risk factors. Immune mechanisms in small vessel ischemic injury are less well-characterized. Design/Methods: A subsample of the prospective Northern Manhattan Study underwent brain MRI, and white matter hyperintensity volume (WMHV) was assessed quantitatively and adjusted for head circumference. Contemporaneous blood samples were analyzed using a customized, 60-plex, bead-based immunoassay (Affymetrix, Santa Clara, CA). We used LASSO procedures to select markers and their interactions independently associated with WHMV. We used linear regression models to assess cross-sectional associations of known correlates of WMHV (age, race/ethnicity, socioeconomic status, and vascular risk factors) with WMHV, and assessed model fit before and after addition of LASSO-selected immune markers and their interactions. Results: RESULTS: Participants (n=1179) had mean age 70±8.9 years; 60% were women, and 68% Hispanic. Inclusion of LASSO-selected immune markers and their interactions improved model fit above other risk factors (p for likelihood ratio test Conclusions: Immune markers involved in distinct pathways associate with white matter disease in a multi-ethnic cohort. Further work is needed to determine how immune networks may cause white matter disease, and whether immunotherapies may counter these effects. Disclosure: Dr. Elkind has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbott, Vascular Dynamics, Merck/Organon Auxilium, and Sorin. Dr. Elkind has received research support from BMS-Pfizer Alliance, and Roche. Dr. Moon has nothing to disclose. Dr. DeRosa has nothing to disclose. Dr. Guerrero has nothing to disclose. Dr. Rundek has received research support from Bristol-Myers Squibb, NINDS. Dr. Wright has nothing to disclose. Dr. Sacco has received research support from NIH/NINDS, Boeringher Ingelheim and Bristol-Myers Sqibb. Dr. Hornig has nothing to disclose. Dr. Cheung has nothing to disclose.

Background: Brain arterial dilatation is a core feature of dolichoectasia, and is associated with higher risk of stroke and vascular events. The role of systemic inflammation in brain arterial dilatation is uncertain. Methods: We measured blood levels of lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), and procalcitonin (PCT) in 538 NOMAS participants (mean age 71±8, 42% men, 60% Hispanic) who underwent brain time-of-flight MRA. Brain arterial diameters were normalized and averaged to obtain a global, anterior and posterior circulations measures of dilation. The concentration of each inflammatory biomarker was normalized to facilitate comparison, and to create an inflammation score consisting of the average of the four biomarkers. Generalized linear models were used to assess for main effects and statistical interactions by sex given known differences in arterial size. Results: Greater levels of MPO were associated with global and anterior circulation dilatation whereas greater levels of PCT were associated with posterior circulation dilatation (table 1). A higher inflammation score was associated with global and posterior circulation, but not anterior circulation, dilatation. There was a statistical interaction between MPO and sex (P=0.06). In a stratified model, the association between MPO and global arterial dilatation was significant in men (B=0.164±0.057, P=0.004) but not in women (B=0.053±0.054, P=0.33). There were no sex-based interactions for any of the other three inflammatory biomarkers. Conclusion: The inflammation markers MPO and PCT were associated with global and regional measures of brain arterial dilatation. The strength of the associations with MPO was greatest in men while the association with PCT was greatest for the posterior circulation. Understanding the physiopathology of these associations may uncover novel therapeutic targets for dolichoectasia.

Objective: To examine the association of JNC-8- and SPRINT-defined systolic blood pressure (SBP) levels with regional white matter hyperintensity volume (WMHV). Background: JNC-8 Guidelines recommend SBP Design/Methods: Our sample included participants from the NOMAS MRI Sub-Study aged ≥60 years taking anti-hypertensive medication. An algorithm combining threshold-based analyses of FLAIR images and regional masking using the T1-weighted scan was employed to measure regional WMHV (mL). WMHVs were log-transformed. SBP (mmHg) was categorized as: Results: BP and MRI data were available in 689 participants (mean±SD age=73±8 years, 65% women, 67% Hispanics). About 18% of participants had SBP Conclusions: In this stroke-free sample of participants treated for hypertension, the SPRINT BP goal range was associated with less WM lesion load in specific regions. Further work examining longitudinal associations is warranted. Study Supported by: This study was supported by: NINDS R01 NS 29993 and F30 NS 103462, and the Evelyn F. McKnight Brain Institute. Disclosure: Dr. Caunca has nothing to disclose. Dr. Simonetto has nothing to disclose. Dr. Dong has nothing to disclose. Dr. Gardener has nothing to disclose. Dr. Cheung has nothing to disclose. Dr. Alperin has nothing to disclose. Dr. McLaughlin has nothing to disclose. Dr. Elkind has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbott, Boehringer-Ingelheim, Merck/Organon, Hi-Tech Pharmaceuticals, and Auxilium. . Dr. Rundek has nothing to disclose. Dr. Sacco has nothing to disclose. Dr. Wright has nothing to disclose.