Publications by authors named "Clinton B Wright"

203 Publications

Pre-Statistical Considerations for Harmonization of Cognitive Instruments: Harmonization of ARIC, CARDIA, CHS, FHS, MESA, and NOMAS.

J Alzheimers Dis 2021 Aug 24. Epub 2021 Aug 24.

Cognitive Health Services Research Program, University of Michigan Medical School, Ann Arbor, MI, USA.

Background: Meta-analyses of individuals' cognitive data are increasing to investigate the biomedical, lifestyle, and sociocultural factors that influence cognitive decline and dementia risk. Pre-statistical harmonization of cognitive instruments is a critical methodological step for accurate cognitive data harmonization, yet specific approaches for this process are unclear.

Objective: To describe pre-statistical harmonization of cognitive instruments for an individual-level meta-analysis in the blood pressure and cognition (BP COG) study.

Methods: We identified cognitive instruments from six cohorts (the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Coronary Artery Risk Development in Young Adults study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study) and conducted an extensive review of each item's administration and scoring procedures, and score distributions.

Results: We included 153 cognitive instrument items from 34 instruments across the six cohorts. Of these items, 42%were common across ≥2 cohorts. 86%of common items showed differences across cohorts. We found administration, scoring, and coding differences for seemingly equivalent items. These differences corresponded to variability across cohorts in score distributions and ranges. We performed data augmentation to adjust for differences.

Conclusion: Cross-cohort administration, scoring, and procedural differences for cognitive instruments are frequent and need to be assessed to address potential impact on meta-analyses and cognitive data interpretation. Detecting and accounting for these differences is critical for accurate attributions of cognitive health across cohort studies.
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http://dx.doi.org/10.3233/JAD-210459DOI Listing
August 2021

Determinants and Outcomes of Asymptomatic Intracranial Atherosclerotic Stenosis.

J Am Coll Cardiol 2021 Aug;78(6):562-571

Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, New York, USA.

Background: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and confers a high risk of stroke recurrence, despite aggressive management of risk factors.

Objectives: This study identified the role of risk factors and risk of vascular events in subjects with asymptomatic ICAS for improved risk stratification.

Methods: Stroke-free participants in the NOMAS (Northern Manhattan Study) trial, prospectively followed since 1993, underwent a brain magnetic resonance angiogram from 2003 to 2008. The study rated stenosis in 11 brain arteries as: 0: no stenosis; 1: <50% or luminal irregularities; 2: 50%-69%; and 3: ≥70% stenosis or flow gap. The study ascertained vascular events during the post-magnetic resonance imaging (MRI) period. Proportional odds regression quantified the association of pre-MRI exposures, and proportional hazard adjusted models were built to identify the risk of events in the post-MRI period.

Results: The included sample included 1,211 participants from NOMAS (mean age: 71 ± 9 years; 59% women; 65% Hispanic; 45% had any stenosis). Older age (OR: 1.02 per year; 95% CI: 1.01 to 1.04), hypertension duration (OR: 1.01 per year; 95% CI: 1.00 to 1.02), higher number of glucose-lowering drugs (OR: 1.64 per each medication; 95% CI: 1.24 to 2.15), and high-density lipoprotein (OR: 0.96 per mg/dL; 95% CI: 0.92 to 0.99) were associated with ICAS. The highest event risk was noted among participants with ICAS ≥70% (5.5% annual risk of vascular events; HR: 2.1; 95% CI:1.4 to 3.2; compared with those with no ICAS).

Conclusions: ICAS is an imaging marker of established atherosclerotic disease in stroke-free subjects, and incidental diagnosis of ICAS should trigger a thorough assessment of vascular health.
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http://dx.doi.org/10.1016/j.jacc.2021.05.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352282PMC
August 2021

Immune markers are associated with cognitive performance in a multiethnic cohort: The Northern Manhattan Study.

Brain Behav Immun 2021 10 25;97:186-192. Epub 2021 Jul 25.

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.

Objective: To determine whether immune protein panels add significant information to correlates of cognition.

Background: Immune mechanisms in vascular cognitive aging are incompletely characterized.

Design/methods: A subsample of the prospective Northern Manhattan Study underwent detailed neuropsychological testing. Cognitive scores were converted into Z-scores and categorized into four domains (memory, language, processing speed, and executive function) based on factor analysis. Blood samples were analyzed using a 60-plex immunoassay. We used least absolute shrinkage and selection operator (LASSO) procedures to select markers and their interactions independently associated with cognitive scores. Linear regression models assessed cross-sectional associations of known correlates of cognition with cognitive scores, and assessed model fit before and after addition of LASSO-selected immune markers.

Results: Among 1179 participants (mean age 70 ± 8.9 years, 60% women, 68% Hispanic), inclusion of LASSO-selected immune markers improved model fit above age, education, and other risk factors (p for likelihood ratio test < 0.005 for all domains). C-C Motif Chemokine Ligand 11 (CCL 11, eotaxin), C-X-C Motif Chemokine Ligand 9 (CXCL9), hepatocyte growth factor (HGF), and serpin E1 (plasminogen activator inhibitor-1) were associated with each of the domains and with overall cognitive function. Immune marker effects were comparable to conventional risk factors: for executive function, each standard deviation (SD) increase in CCL11 was associated with an effect equivalent to aging three years; for memory, HGF had twice the effect of aging.

Conclusions: Immune markers associate with cognitive function in a multi-ethnic cohort. Further work is needed to validate these findings and determine optimal treatment targets.
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http://dx.doi.org/10.1016/j.bbi.2021.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453105PMC
October 2021

Fluid-Attenuated Inversion Recovery Hyperintense Ischemic Stroke Predicts Less Favorable 90-Day Outcome after Intravenous Thrombolysis.

Cerebrovasc Dis 2021 Jul 20:1-8. Epub 2021 Jul 20.

Stroke Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland, USA.

Introduction: The absence of an ischemic lesion on MRI fluid-attenuated inversion recovery (FLAIR) is helpful in predicting stroke onset within 4.5 h. However, some ischemic strokes become visible on FLAIR within 4.5 h. We hypothesized that the early lesion visibility on FLAIR may predict stroke outcome 90 days after intravenous (IV) thrombolysis, independent of time.

Materials And Methods: We analyzed data from acute ischemic stroke patients presenting over the last 10 years who were screened with MRI and treated with IV thrombolysis within 4.5 h from onset. Three independent readers assessed whether ischemic lesions seen on diffusion-weighted imaging were also FLAIR positive based on visual inspection. Multivariable regression analyses were used to obtain an adjusted odds ratio of favorable clinical and radiological outcomes based on FLAIR positivity.

Results: Of 297 ischemic stroke patients, 25% had lesion visibility on initial FLAIR. The interrater agreement for the FLAIR positivity assessment was 84% (κ = 0.604, 95% CI: 0.557-0.652). Patients with FLAIR-positive lesions had more right hemispheric strokes (57 vs. 41%, p = 0.045), were imaged later (129 vs. 104 min, p = 0.036), and had less frequent favorable 90-day functional outcome (49 vs. 63%, p = 0.028), less frequent early neurologic improvement (30 vs. 58%, p = 0.001), and more frequent contrast extravasation to the cerebrospinal fluid space (44 vs. 26%, p = 0.008).

Conclusions: Early development of stroke lesion on FLAIR within 4.5 h of onset is associated with reduced likelihood of favorable 90-day outcome after IV thrombolysis.
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http://dx.doi.org/10.1159/000517241DOI Listing
July 2021

Systemic Arterial Correlates of Cervical Carotid Artery Tortuosity : The Northern Manhattan Study.

Clin Neuroradiol 2021 Jun 16. Epub 2021 Jun 16.

Department of Neurology, Columbia University, New York, NY, USA.

Introduction: The association between cervical internal carotid artery (cICA) tortuosity and atherosclerosis is a matter of debate. Additionally, some genetic syndromes characterized by connective tissue remodeling are associated with arterial tortuosity, raising the possibility that cICA tortuosity may not only be atherosclerotic. In this study, we hypothesized that cICA tortuosity is not associated with imaging biomarkers of atherosclerosis.

Methods: The Northern Manhattan Study (NOMAS) was a prospective, multiethnic cohort of stroke-free individuals who underwent brain MRA, carotid ultrasound and transthoracic echocardiogram from 2003-2008. The cICA tortuosity was scored in each carotid as 0 = no tortuosity, 1 = tortuosity <90°, 2 = tortuosity ≥90°. A summary cICA tortuosity score (possible range 0-4) was created by adding up the tortuosity score from each carotid. Participants were assessed for atherosclerotic markers by using B‑mode carotid sonography and transthoracic echocardiography.

Results: Of 558 participants 178 (31.9%) had any cervical ICA tortuosity (tortuosity score >0). The cICA tortuosity score was higher in women and was associated with diastolic and systolic blood pressures and height (all P < 0.05). In models adjusted for demographics and risk factors, only the association with diastolic blood pressure remained significant (β = 0.002, P = 0.02). Similarly, cICA tortuosity was associated with larger aortic root diameter (B = 1.03 ± 0.36, P = 0.004) but not with other markers of carotid or aortic atherosclerosis.

Conclusion: Cervical ICA tortuosity is associated with a higher diastolic blood pressure and larger aortic root diameter but not with other measures of atherosclerosis. Determining the risks of vascular events associated with this non-atherosclerotic phenotype may help for a better risk stratification for individuals with cICA tortuosity.
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http://dx.doi.org/10.1007/s00062-021-01044-yDOI Listing
June 2021

Gut permeability and cognitive decline: A pilot investigation in the Northern Manhattan Study.

Brain Behav Immun Health 2021 Mar 29;12. Epub 2021 Jan 29.

Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.

Background: Gut microbiota may impact cognitive function and decline, though data are limited. This pilot study examines the associations between gut dysbiosis products, plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14), with cognitive decline and immune molecule activation among 40 participants in the longitudinal population-based Northern Manhattan Study.

Methods: We selected stroke- and dementia-free participants at baseline with high activation levels of core components of the immune signaling pathways underlying microbiota metabolite-cognitive associations (IL-1, IL-17, TNF). Participants were followed with up to three complete neuropsychological assessments, at least 5 years apart.

Results: Elevated sCD14 was associated with high levels of IL-1 pathway activation (p < 0.05), whereas in samples where only those molecules within the IL-17 and TNF pathways were increased, LPS and sCD14 levels were not elevated. LPS was associated with decline in global cognitive performance over 2-3 assessments (adjusted β = -0.023 per SD per year, 95% CI:-0.036, -0.010). The association between sCD14 and cognitive decline was marginal (adjusted β = -0.018 per SD per year, 95% CI:-0.040, 0.004).

Conclusions: These preliminary data support the hypothesis that gut dysbiosis leads to systemic and neuro-inflammation, and subsequently cognitive decline. Further large targeted and untargeted gut microbiota-derived metabolomic studies are needed.
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http://dx.doi.org/10.1016/j.bbih.2021.100214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186438PMC
March 2021

Systolic Blood Pressure and Cognition in the Elderly: The Northern Manhattan Study.

J Alzheimers Dis 2021 ;82(2):689-699

Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.

Background: Increasing evidence suggests that hypertension is a risk factor for cognitive impairment and dementia. The relationship between blood pressure and cognition in a racially and ethnically diverse population remains unclear.

Objective: To study association of blood pressure with cognition cross-sectionally and longitudinally in the elderly.

Methods: Participants are stroke-free individuals from the racially and ethnically diverse Northern Manhattan Study (NOMAS) (n = 1215). General linear models are constructed to examine blood pressure in relation to cognition cross-sectionally and longitudinally at a five-year follow-up.

Results: We found a cross-sectional association of systolic blood pressure (SBP) with word fluency/semantic memory, executive function, and processing speed/visual motor integration (VMI) function. This association was independent of demographics, vascular risk factors, white matter hyperintensity volume (WMHV), and carotid intima-media thickness (cIMT). The cross-sectional association of SBP with processing speed/VMI and executive function was attenuated after adjusting anti-hypertension medications in the models. Baseline SBP was associated with the change of processing speed/VMI function after adjusting vascular risk factors, WMHV, and cIMT at a 5-year follow-up. This longitudinal association was not found after adjusting anti-hypertension medications in the models. Further analyses revealed that individuals with category SBP from < 120 mmHg to≥140 mmHg had a linear decline in processing speed/VMI function at a 5-year follow-up.

Conclusion: We show that SBP is negatively associated with cognition cross-sectionally and longitudinally in the elderly. Anti-hypertension treatment eliminates the negative association of SBP with processing speed/VMI function longitudinally. Our findings support the treatment of stage 1 systolic hypertension in the elderly.
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http://dx.doi.org/10.3233/JAD-210252DOI Listing
September 2021

Association of Intensive vs Standard Blood Pressure Control With Magnetic Resonance Imaging Biomarkers of Alzheimer Disease: Secondary Analysis of the SPRINT MIND Randomized Trial.

JAMA Neurol 2021 May;78(5):568-577

Department of Diagnostic Medicine, Dell Medical School, University of Texas at Austin, Austin.

Importance: Meta-analyses of randomized clinical trials have indicated that improved hypertension control reduces the risk for cognitive impairment and dementia. However, it is unclear to what extent pathways reflective of Alzheimer disease (AD) pathology are affected by hypertension control.

Objective: To evaluate the association of intensive blood pressure control on AD-related brain biomarkers.

Design, Setting, And Participants: This is a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT MIND), a multicenter randomized clinical trial that compared the efficacy of 2 different blood pressure-lowering strategies. Potential participants (n = 1267) 50 years or older with hypertension and without a history of diabetes or stroke were approached for a brain magnetic resonance imaging (MRI) study. Of these, 205 participants were deemed ineligible and 269 did not agree to participate; 673 and 454 participants completed brain MRI at baseline and at 4-year follow-up, respectively; the final follow-up date was July 1, 2016. Analysis began September 2019 and ended November 2020.

Interventions: Participants were randomized to either a systolic blood pressure goal of less than 120 mm Hg (intensive treatment: n = 356) or less than 140 mm Hg (standard treatment: n = 317).

Main Outcomes And Measures: Changes in hippocampal volume, measures of AD regional atrophy, posterior cingulate cerebral blood flow, and mean fractional anisotropy in the cingulum bundle.

Results: Among 673 recruited patients who had baseline MRI (mean [SD] age, 67.3 [8.2] years; 271 women [40.3%]), 454 completed the follow-up MRI at a median (interquartile range) of 3.98 (3.7-4.1) years after randomization. In the intensive treatment group, mean hippocampal volume decreased from 7.45 cm3 to 7.39 cm3 (difference, -0.06 cm3; 95% CI, -0.08 to -0.04) vs a decrease from 7.48 cm3 to 7.46 cm3 (difference, -0.02 cm3; 95% CI, -0.05 to -0.003) in the standard treatment group (between-group difference in change, -0.033 cm3; 95% CI, -0.062 to -0.003; P = .03). There were no significant treatment group differences for measures of AD regional atrophy, cerebral blood flow, or mean fractional anisotropy.

Conclusions And Relevance: Intensive treatment was associated with a small but statistically significant greater decrease in hippocampal volume compared with standard treatment, consistent with the observation that intensive treatment is associated with greater decreases in total brain volume. However, intensive treatment was not associated with changes in any of the other MRI biomarkers of AD compared with standard treatment.

Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.
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http://dx.doi.org/10.1001/jamaneurol.2021.0178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941253PMC
May 2021

Race/Ethnic Disparities in Mild Cognitive Impairment and Dementia: The Northern Manhattan Study.

J Alzheimers Dis 2021 ;80(3):1129-1138

Evelyn F McKnight Brain Institute, University of Miami Miller School of Medicine, Miami, FL, USA.

Background: Variability in dementia rates across racial and ethnic groups has been estimated at 60%. Studies suggest disparities in Caribbean Hispanic and Black populations, but community-based data are limited.

Objective: Estimate the prevalence of mild cognitive impairment (MCI) and dementia in the racially and ethnically diverse community-based Northern Manhattan Study cohort and examine sociodemographic, vascular risk factor, and brain imaging correlates.

Methods: Cases of MCI and dementia were adjudicated by a team of neuropsychologists and neurologists and prevalence was estimated across race/ethnic groups. Ordinal proportional odds models were used to estimate race/ethnic differences in the prevalence of MCI or dementia adjusting for sociodemographic variables (model 1), model 1 plus potentially modifiable vascular risk factors (model 2), and model 1 plus structural imaging markers of brain integrity (model 3).

Results: There were 989 participants with cognitive outcome determinations (mean age 69±9 years; 68% Hispanic, 16% Black, 14% White; 62% women; mean (±SD) follow-up five (±0.6) years). Hispanic and Black participants had greater likelihood of MCI (20%) and dementia (5%) than White participants accounting for age and education differences. Hispanic participants had greater odds of MCI or dementia than both White and Black participants adjusting for sociodemographic variables, vascular risk factors, and brain imaging factors. White matter hyperintensity burden was significantly associated with greater odds of MCI or dementia (OR = 1.3, 1.1 to 1.6), but there was no significant interaction by race/ethnicity.

Conclusion: In this diverse community-based cohort, cross-sectional data revealed significant race/ethnic disparities in the prevalence of MCI and dementia. Longer follow-up and incidence data are needed to further clarify these relationships.
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http://dx.doi.org/10.3233/JAD-201370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150441PMC
September 2021

Sex Differences in Cognitive Decline Among US Adults.

JAMA Netw Open 2021 02 1;4(2):e210169. Epub 2021 Feb 1.

Cognitive Health Services Research Program, Department of Internal Medicine, University of Michigan, Ann Arbor.

Importance: Sex differences in dementia risk are unclear, but some studies have found greater risk for women.

Objective: To determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk.

Design, Setting, And Participants: This cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020.

Exposure: Sex.

Main Outcomes And Measures: The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition.

Results: Among 34 349 participants, 26 088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11 775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14 313 women (median [interquartile range] age, 58 [51-67] years at first cognitive assessment; 3636 [25.4%] Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95% CI, 2.04 to 2.35 points; P < .001), executive function (2.13 points higher; 95% CI, 1.98 to 2.29 points; P < .001), and memory (1.89 points higher; 95% CI, 1.72 to 2.06 points; P < .001). Compared with men, women had significantly faster declines in global cognition (-0.07 points/y faster; 95% CI, -0.08 to -0.05 points/y; P < .001) and executive function (-0.06 points/y faster; 95% CI, -0.07 to -0.05 points/y; P < .001). Men and women had similar declines in memory (-0.004 points/y faster; 95% CI, -0.023 to 0.014; P = .61).

Conclusions And Relevance: The results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.0169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907956PMC
February 2021

Show Me Your White Matter, I Will Tell You Who You Are ….

Stroke 2021 Jan 7;52(2):631-633. Epub 2021 Jan 7.

National Institute of Neurological Disorders and Stroke, Bethesda, MD (C.B.W.).

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http://dx.doi.org/10.1161/STROKEAHA.120.033225DOI Listing
January 2021

Organizational Update: NINDS Stroke Research Strategies for Large Vessel Occlusion and Neuroprotection.

Stroke 2021 01 28;52(1):e1-e2. Epub 2020 Dec 28.

National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.

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http://dx.doi.org/10.1161/STROKEAHA.120.029977DOI Listing
January 2021

FGF23, Frailty, and Falls in SPRINT.

J Am Geriatr Soc 2021 02 1;69(2):467-473. Epub 2020 Dec 1.

University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Background/objectives: Chronic kidney disease (CKD) is associated with frailty. Fibroblast growth factor 23 (FGF23) is elevated in CKD and associated with frailty among non-CKD older adults and individuals with human immunodeficiency virus. Whether FGF23 is associated with frailty and falls in CKD is unknown.

Design: Cross-sectional and longitudinal observational study.

Setting: Systolic Blood Pressure Intervention Trial (SPRINT), a randomized trial evaluating standard (systolic blood pressure [SBP] <140 mm Hg) versus intensive (SBP <120 mm Hg) blood pressure lowering on cardiovascular and cognitive outcomes among older adults without diabetes mellitus.

Participants: A total of 2,376 participants with CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m ).

Measurements: The exposure variable was intact FGF23. We used multinomial logistic regression to determine the cross-sectional association of intact FGF23 with frailty and Cox proportional hazards analysis to determine the longitudinal association with incident falls. Models were adjusted for demographics, comorbidities, randomization group, antihypertensives, eGFR, mineral metabolism markers, and frailty.

Results: After adjustment, the odds ratio for prevalent frailty versus non-frailty per twofold higher FGF23 was 1.34 (95% confidence interval [CI] = 1.01-1.77). FGF23 levels in the highest quartile versus the lowest quartile demonstrated more than a twofold increased fall risk (hazard ratio [HR] = 2.32; 95% CI = 1.26-4.26), and the HR per twofold higher FGF23 was 1.99 (95% CI = 1.48-2.68).

Conclusion: Among SPRINT participants with CKD, FGF23 was associated with prevalent frailty and falls.
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http://dx.doi.org/10.1111/jgs.16895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031468PMC
February 2021

Obesity Measures in Relation to Cognition in the Northern Manhattan Study.

J Alzheimers Dis 2020 ;78(4):1653-1660

Department of Neurology, University of Miami, Miller School of Medicine, Miami, FL, USA.

Background: Mid-life obesity is associated with cognitive impairment, though the relationship for late-life obesity is equivocal, and may depend on the anthropometric measure.

Objective: We examined the relationship between adiposity and cognition across age categories, cognitive domains, and by measures of obesity in a multi-ethnic population-based cohort.

Methods: The study included 1,179 Northern Manhattan Study participants with obesity measures at baseline (44% overweight, 30% obese), an initial neuropsychological assessment conducted within 7 years (mean age = 70), and a second cognitive assessment conducted on average 6 years later. Z-scores were derived for cognitive domains (episodic and semantic memory, executive function, processing speed) and averaged to calculate global cognition. Body mass index (BMI) and waist:hip ratio (WHR) were examined in relation to cognitive performance and change over time, stratified by age, using linear regression models adjusting for vascular risk factors.

Results: Among those age<65 years at baseline, greater WHR was associated with worse global cognitive performance at initial assessment and directly associated with decline in performance between assessments. The association with initial performance was strongest for non-Hispanic Whites (beta = -0.155/standard deviation, p = 0.04), followed by non-Hispanic Black/African Americans (beta = -0.079/standard deviation, p = 0.07), and Hispanics (beta = -0.055/standard deviation, p = 0.03). The associations were most apparent for the domains of processing speed and executive function. There was no association for BMI among those <65 years. Among those age ≥65, there was no association for BMI or WHR with cognitive performance at initial assessment nor decline over time.

Conclusion: Our results support the detrimental effect of mid-life rather than later life obesity, particularly abdominal adiposity, on cognitive impairment and decline.
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http://dx.doi.org/10.3233/JAD-201071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902200PMC
January 2020

Inaugural Health Equity and Actionable Disparities in Stroke: Understanding and Problem-Solving Symposium.

Stroke 2020 11 26;51(11):3382-3391. Epub 2020 Oct 26.

Department of Neurology, University of California, San Francisco, CA (B.O.).

Race/ethnic minorities face significant inequities in stroke incidence, prevalence, care, and outcomes. The Health Equity and Actionable Disparities in Stroke: Understanding and Problem-solving symposium, a collaborative initiative of the American Heart Association and National Institute of Neurological Disorders and Stroke, was the first-ever annual multidisciplinary scientific forum focused on race/ethnic inequities in cerebrovascular disease, with the overarching goal of reducing inequities in stroke and accelerating the translation of research findings to improve outcomes for race/ethnic minorities. The symposium featured esteemed invited plenary speakers, lecturing on determinants of race/ethnic inequities in stroke and interventions aimed at redressing the inequities. The Edgar J. Kenton III Award recognized Ralph Sacco, MD, MS, for his lifetime contributions to investigation, management, mentorship, and community service in the field of stroke inequities. Early career investigators were provided with travel awards to attend the symposium; presented their research at moderated poster and Think Tank sessions; received career development advice at the Building Momentum session; and networked with experienced stroke inequities researchers. Future conferences-The Health Equity and Actionable Disparities in Stroke: Understanding and Problem-solving 2021 to 2024-will broaden the focus to include 5 major persistent inequities (race/ethnic, sex, geographic, socioeconomic, and global). Each year will focus on a different theme (community and stakeholder engagement; clinical trials; implementation science; and policy and dissemination). By fostering a community of stroke inequities researchers, we hope to highlight promising work, illuminate research gaps, facilitate networking, inform policy makers, recognize achievement, inspire greater interest among junior investigators to pursue careers in this field, and provide networking opportunities for underrepresented minority scientists.
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http://dx.doi.org/10.1161/STROKEAHA.120.030423DOI Listing
November 2020

Critical NIH Resources to Advance Therapies for Pain: Preclinical Screening Program and Phase II Human Clinical Trial Network.

Neurotherapeutics 2020 07;17(3):932-934

Division of Clinical Research, National Institutes of Health, National Institute of Neurological Disorders and Stroke, 6001 Executive Blvd, Bethesda, MD, 20852-9535, USA.

Opioid-related death and overdose have now reached epidemic proportions. In response to this public health crisis, the National Institutes of Health (NIH) launched the Helping to End Addiction Long-term Initiative, or NIH HEAL Initiative, an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis. Herein, we describe two NIH HEAL Initiative programs to accelerate development of non-opioid, non-addictive pain treatments: The Preclinical Screening Platform for Pain (PSPP) and Early Phase Pain Investigation Clinical Network (EPPIC-Net). These resources are provided at no cost to investigators, whether in academia or industry and whether within the USA or internationally. Both programs consider small molecules, biologics, devices, and natural products for acute and chronic pain, including repurposed and combination drugs. Importantly, confidentiality and intellectual property are protected. The PSPP provides a rigorous platform to identify and profile non-opioid, non-addictive therapeutics for pain. Accepted assets are evaluated in in vitro functional assays to rule out opioid receptor activity and to assess abuse liability. In vivo pharmacokinetic studies measure plasma and brain exposure to guide the dose range and pretreatment times for the side effect profile, efficacy, and abuse liability. Studies are conducted in accordance with published rigor criteria. EPPIC-Net provides academic and industry investigators with expert infrastructure for phase II testing of pain therapeutics across populations and the lifespan. For assets accepted after a rigorous, objective scientific review process, EPPIC-Net provides clinical trial design, management, implementation, and analysis.
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http://dx.doi.org/10.1007/s13311-020-00918-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609631PMC
July 2020

Machine learning-based estimation of cognitive performance using regional brain MRI markers: the Northern Manhattan Study.

Brain Imaging Behav 2021 Jun;15(3):1270-1278

Evelyn F. McKnight Brain Institute, University of Miami, Miami, FL, USA.

High dimensional neuroimaging datasets and machine learning have been used to estimate and predict domain-specific cognition, but comparisons with simpler models composed of easy-to-measure variables are limited. Regularization methods in particular may help identify regions-of-interest related to domain-specific cognition. Using data from the Northern Manhattan Study, a cohort study of mostly Hispanic older adults, we compared three models estimating domain-specific cognitive performance: sociodemographics and APOE ε4 allele status (basic model), the basic model and MRI markers, and a model with only MRI markers. We used several machine learning methods to fit our regression models: elastic net, support vector regression, random forest, and principal components regression. Model performance was assessed with the RMSE, MAE, and R statistics using 5-fold cross-validation. To assess whether prediction models with imaging biomarkers were more predictive than prediction models built with randomly generated biomarkers, we refit the elastic net models using 1000 datasets with random biomarkers and compared the distribution of the RMSE and R in models using these random biomarkers to the RMSE and R from observed models. Basic models explained ~ 31-38% of the variance in domain-specific cognition. Addition of MRI markers did not improve estimation. However, elastic net models with only MRI markers performed significantly better than random MRI markers (one-sided P < .05) and yielded regions-of-interest consistent with previous literature and others not previously explored. Therefore, structural brain MRI markers may be more useful for etiological than predictive modeling.
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http://dx.doi.org/10.1007/s11682-020-00325-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854979PMC
June 2021

Genome-wide association study of cognitive function in diverse Hispanics/Latinos: results from the Hispanic Community Health Study/Study of Latinos.

Transl Psychiatry 2020 07 22;10(1):245. Epub 2020 Jul 22.

Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Cognitive function such as reasoning, attention, memory, and language is strongly correlated with brain aging. Compared to non-Hispanic whites, Hispanics/Latinos have a higher risk of cognitive impairment and dementia. The genetic determinants of cognitive function have not been widely explored in this diverse and admixed population. We conducted a genome-wide association analysis of cognitive function in up to 7600 middle aged and older Hispanics/Latinos (mean = 55 years) from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL). Four cognitive measures were examined: the Brief Spanish English Verbal Learning Test (B-SEVLT), the Word Fluency Test (WFT), the Digit Symbol Substitution Test (DSST), the Six-Item Screener (SIS). Four novel loci were identified: one for B-SEVLT at 4p14, two for WFT at 3p14.1 and 6p21.32, and one for DSST at 10p13. These loci implicate genes highly expressed in brain and previously connected to neurological diseases (UBE2K, FRMD4B, the HLA gene complex). By applying tissue-specific gene expression prediction models to our genotype data, additional genes highly expressed in brain showed suggestive associations with cognitive measures possibly indicating novel biological mechanisms, including IFT122 in the hippocampus for SIS, SNX31 in the basal ganglia for B-SEVLT, RPS6KB2 in the frontal cortex for WFT, and CSPG5 in the hypothalamus for DSST. These findings provide new information about the genetic determinants of cognitive function in this unique population. In addition, we derived a measure of general cognitive function based on these cognitive tests and generated genome-wide association summary results, providing a resource to the research community for comparison, replication, and meta-analysis in future genetic studies in Hispanics/Latinos.
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http://dx.doi.org/10.1038/s41398-020-00930-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376098PMC
July 2020

Association between PNPLA3 rs738409 G variant and MRI cerebrovascular disease biomarkers.

J Neurol Sci 2020 Sep 20;416:116981. Epub 2020 Jun 20.

Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Introduction: Nonalcoholic fatty liver disease (NAFLD) has been associated with greater cerebral white matter hyperintensity (WMH) volume and microbleeds. The adiponutrin (PNPLA3) rs738409 G variant, a robust NAFLD susceptibility variant, has been variably associated with carotid atherosclerosis. We hypothesized that this variant is associated with WMH volume, microbleeds, covert brain infarction (CBI), and small perivascular spaces.

Methods: We performed a cross-sectional analysis of the Northern Manhattan Study-MRI Substudy. The associations between the rs738409 G variant allele and outcomes were assessed using linear regression for WMH volume, logistic regression for microbleeds and CBI, and Poisson regression for small perivascular spaces. Models were adjusted for age, sex, principal components, diabetes, and body mass index.

Results: We included 1063 Northern Manhattan Study participants who had brain MRI and genotype data available (mean age 70 ± 9 years, 61% women). The G allele frequency was 24%. The prevalence of any microbleeds and CBI were 8% and 18%, respectively. The median WMH volume and small perivascular space count score were 7.7 mL and 6, respectively. GG homozygosity, but not heterozygosity, was associated with WMH volume (β = 0.27; 95% CI, 0.03, 0.51) compared to non-carriers. Having at least one G allele was associated with the presence of microbleeds (Odds ratio, 1.78; 95% CI, 1.02, 3.12); the association was attenuated in other models. No associations were observed for CBI and small perivascular spaces.

Conclusion: The PNPLA3 rs738409 G allele was associated with greater WMH volume, and inconsistent associations with microbleeds were seen.
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http://dx.doi.org/10.1016/j.jns.2020.116981DOI Listing
September 2020

Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities.

Stroke 2020 07 10;51(7):2111-2121. Epub 2020 Jun 10.

Department of Psychiatry (C.F.-N.), University of California, San Diego, La Jolla, CA.

Background And Purpose: Periventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings.

Methods: Participants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC.

Results: In the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 (), 10q23.1 (), and 10q24.33 ( In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 () and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: (2q32.1), (3q27.1), (5q27.1), and (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype.

Conclusions: Our study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.
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http://dx.doi.org/10.1161/STROKEAHA.119.027544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365038PMC
July 2020

Randomized Trial of Combined Aerobic, Resistance, and Cognitive Training to Improve Recovery From Stroke: Feasibility and Safety.

J Am Heart Assoc 2020 05 12;9(10):e015377. Epub 2020 May 12.

Department of Neurology Miller School of Medicine University of Miami FL.

Background Physical exercise and cognitive training have been recommended to improve cognitive outcomes poststroke, but a multifaceted strategy including aerobic, resistance, and cognitive training to facilitate poststroke recovery has not been investigated. We aimed to assess the feasibility, adherence, and safety of a combined aerobic, resistance, and cognitive training intervention (CARET+CTI) after stroke. Methods and Results We prospectively randomized patients presenting with recent stroke to a comparison of a supervised 12-week CARET+CTI program and a control group receiving sham CARET+CTI. Participants were scheduled for 3 weekly CARET and CTI sessions. All participants underwent pre- and postintervention assessments of strength, endurance, and cognition. The primary outcomes were feasibility and adherence, defined as the ratio of scheduled and observed visits, and safety. We enrolled 131 participants, of whom 37 withdrew from the study. There were 17 (20%) withdrawals in the CARET+CTI and 20 (44%) in the control group. The observed-over-expected visit ratio was significantly higher in the intervention than in the control group (0.74±0.30 versus 0.54±0.38; =0.003). A total of 99 adverse events were reported by 59 participants, none of which were serious and related to the intervention. Greater gains in physical, cognitive, and mood outcomes were found in the CARET+CTI group than in the control group, but were not statistically significant after adjustments. Conclusions A CARET+CTI intervention, after stroke, is safe, feasible, and has satisfactory participant adherence over 12 weeks. REGISTRATION URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT02272426.
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http://dx.doi.org/10.1161/JAHA.119.015377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660866PMC
May 2020

Association Between Blood Pressure and Later-Life Cognition Among Black and White Individuals.

JAMA Neurol 2020 07;77(7):810-819

Cognitive Health Services Research Program, Department of Internal Medicine, University of Michigan, Ann Arbor.

Importance: Black individuals are more likely than white individuals to develop dementia. Whether higher blood pressure (BP) levels in black individuals explain differences between black and white individuals in dementia risk is uncertain.

Objective: To determine whether cumulative BP levels explain racial differences in cognitive decline.

Design, Setting, And Participants: Individual participant data from 5 cohorts (January 1971 to December 2017) were pooled from the Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represented a 0.1-SD difference in cognition. The median (interquartile range) follow-up was 12.4 (5.9-21.0) years. Analysis began September 2018.

Main Outcomes And Measures: The primary outcome was change in global cognition, and secondary outcomes were change in memory and executive function.

Exposures: Race (black vs white).

Results: Among 34 349 participants, 19 378 individuals who were free of stroke and dementia and had longitudinal BP, cognitive, and covariate data were included in the analysis. The mean (SD) age at first cognitive assessment was 59.8 (10.4) years and ranged from 5 to 95 years. Of 19 378 individuals, 10 724 (55.3%) were female and 15 526 (80.1%) were white. Compared with white individuals, black individuals had significantly faster declines in global cognition (-0.03 points per year faster [95% CI, -0.05 to -0.01]; P = .004) and memory (-0.08 points per year faster [95% CI, -0.11 to -0.06]; P < .001) but significantly slower declines in executive function (0.09 points per year slower [95% CI, 0.08-0.10]; P < .001). Time-dependent cumulative mean systolic BP level was associated with significantly faster declines in global cognition (-0.018 points per year faster per each 10-mm Hg increase [95% CI, -0.023 to -0.014]; P < .001), memory (-0.028 points per year faster per each 10-mm Hg increase [95% CI, -0.035 to -0.021]; P < .001), and executive function (-0.01 points per year faster per each 10-mm Hg increase [95% CI, -0.014 to -0.007]; P < .001). After adjusting for cumulative mean systolic BP, differences between black and white individuals in cognitive slopes were attenuated for global cognition (-0.01 points per year [95% CI, -0.03 to 0.01]; P = .56) and memory (-0.06 points per year [95% CI, -0.08 to -0.03]; P < .001) but not executive function (0.10 points per year [95% CI, 0.09-0.11]; P < .001).

Conclusions And Relevance: These results suggest that black individuals' higher cumulative BP levels may contribute to racial differences in later-life cognitive decline.
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http://dx.doi.org/10.1001/jamaneurol.2020.0568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154952PMC
July 2020

Cholinergic White Matter Lesions, AD-Signature Cortical Thickness, and Change in Cognition: The Northern Manhattan Study.

J Gerontol A Biol Sci Med Sci 2020 07;75(8):1508-1515

Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida.

Background: How cerebrovascular disease and neurodegeneration affect each other to impact cognition is not yet known. We aimed to test whether Alzheimer's disease-signature (AD) cortical thickness mediates the association between cholinergic white matter lesion load and change in domain-specific cognition.

Methods: Clinically stroke-free participants from the Northern Manhattan Study with both regional white matter hyperintensity volume (WMHV) and gray matter measurements were included (N = 894). Tract-specific WMHVs were quantified through FSL using the Johns Hopkins University white matter tract atlas. We used Freesurfer 5.1 to estimate regional cortical thickness. We fit structural equation models, including multiple indicator latent change score models, to examine associations between white matter hyperintensity volume (WMHV) in cholinergic tracts, AD-signature region cortical thickness (CT), and domain-specific cognition.

Results: Our sample (N = 894) had a mean (SD) age = 70 (9) years, years of education = 10 (5), 63% women, and 67% Hispanics/Latinos. Greater cholinergic WMHV was significantly related to worse processing speed at baseline (standardized β = -0.17, SE = 0.05, p = .001) and over time (standardized β = -0.28, SE = 0.09, p = .003), with a significant indirect effect of AD-signature region CT (baseline: standardized β = -0.02, SE = 0.01, p = .023; change: standardized β = -0.03, SE = 0.02, p = .040).

Conclusions: Cholinergic tract WMHV is associated with worse processing speed, both directly and indirectly through its effect on AD-signature region CT.
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http://dx.doi.org/10.1093/gerona/glz279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457185PMC
July 2020

Creatinine versus cystatin C for renal function-based mortality prediction in an elderly cohort: The Northern Manhattan Study.

PLoS One 2020 15;15(1):e0226509. Epub 2020 Jan 15.

Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States of America.

Background: Estimated glomerular filtration rate (eGFR) is routinely utilized as a measure of renal function. While creatinine-based eGFR (eGFRcr) is widely used in clinical practice, the use of cystatin-C to estimate GFR (eGFRcys) has demonstrated superior risk prediction in various populations. Prior studies that derived eGFR formulas have infrequently included high proportions of elderly, African-Americans, and Hispanics.

Objective: Our objective as to compare mortality risk prediction using eGFRcr and eGFRcys in an elderly, race/ethnically diverse population.

Design: The Northern Manhattan Study (NOMAS) is a multiethnic prospective cohort of elderly stroke-free individuals consisting of a total of 3,298 participants recruited between 1993 and 2001, with a median follow-up of 18 years.

Participants: We included all Northern Manhattan Study (NOMAS) participants with concurrent measured creatinine and cystatin-C.

Main Measures: The eGFRcr was calculated using the CKD-EPI 2009 equation. eGFRcys was calculated using the CKD-EPI 2012 equations. The performance of each eGFR formula in predicting mortality risk was tested using receiver-operating characteristics, calibration and reclassification. Net reclassification improvement (NRI) was calculated based on the Reynolds 10 year risk score from adjusted Cox models with mortality as an outcome. The primary hypothesis was that eGFRcys would better predict mortality than eGFRcr.

Results: Participants (n = 2988) had a mean age of 69±10.2 years and were predominantly Hispanic (53%), overweight (69%), and current or former smokers (53% combined). The mean eGFRcr (74.68±18.8 ml/min/1.73m2) was higher than eGFRcys (51.72±17.2 ml/min/1.73m2). During a mean of 13.0±5.6 years of follow-up, 53% of the cohort had died. The AUC of eGFRcys (0.73) was greater than for eGFRcr (0.67, p for difference<0.0001). The proportions of correct reclassification (NRI) based on 10 year mortality for the model with eGFRcys compared to the model with eGFRcr were 4.2% (p = 0.002).

Conclusions: In an elderly, race/ethnically diverse cohort low eGFR is associated with risk of all-cause mortality. Estimated GFR based on serum cystatin-C, in comparison to serum creatinine, was a better predictor of all-cause mortality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226509PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961921PMC
April 2020

Diastolic Blood Pressure Is Associated With Regional White Matter Lesion Load: The Northern Manhattan Study.

Stroke 2020 02 8;51(2):372-378. Epub 2020 Jan 8.

National Institute of Neurological Disorders and Stroke, Bethesda, MD (C.B.W.).

Background and Purpose- Few studies have examined the separate contributions of systolic blood pressure and diastolic blood pressures (DBP) on subclinical cerebrovascular disease, especially using the 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines. Furthermore, associations with region-specific white matter hyperintensity volume (WMHV) are underexplored. Methods- Using data from the NOMAS (Northern Manhattan Study), a prospective cohort study of stroke risk and cognitive aging, we examined associations between systolic blood pressure and DBP, defined by the 2017 American College of Cardiology/American Heart Association guidelines, with regional WMHV. We used a linear mixed model approach to account for the correlated nature of regional brain measures. Results- The analytic sample (N=1205; mean age 64±8 years) consisted of 61% women and 66% Hispanics/Latinos. DBP levels were significantly related to WMHV differentially across regions ( for interaction<0.05). Relative to those with DBP 90+ mm Hg, participants with DBP <80 mm Hg had 13% lower WMHV in the frontal lobe (95% CI, -21% to -3%), 11% lower WMHV in the parietal lobe (95% CI, -19% to -1%), 22% lower WMHV in the anterior periventricular region (95% CI, -30% to -14%), and 16% lower WMHV in the posterior periventricular region (95% CI, -24% to -6%). Participants with DBP 80 to 89 mm Hg also exhibited about 12% (95% CI, -20% to -3%) lower WMHV in the anterior periventricular region and 9% (95% CI, -18% to -0.4%) lower WMHV in the posterior periventricular region, relative to participants with DBP 90≥ mm Hg. Post hoc pairwise tests showed that estimates for periventricular WMHV were significantly different from estimates for temporal WMHV (Holms stepdown-adjusted <0.05). Systolic blood pressure was not strongly related to regional WMHV. Conclusions- Lower DBP levels, defined by the 2017 American College of Cardiology/American Heart Association guidelines, were related to lower white matter lesion load, especially in the periventricular regions relative to the temporal region.
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http://dx.doi.org/10.1161/STROKEAHA.119.025139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219602PMC
February 2020

Global Vascular Risk Score and CAIDE Dementia Risk Score Predict Cognitive Function in the Northern Manhattan Study.

J Alzheimers Dis 2020 ;73(3):1221-1231

Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.

Background: Modifiable vascular risk factors (VRF) have been implicated in cognitive impairment.

Objective: We compared the prediction of cognitive performance between the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score, a validated tool to estimate dementia risk using VRF, and the Northern Manhattan Study (NOMAS) global vascular risk score (GVRS), created to predict vascular events.

Methods: The CAIDE and GVRS scores were calculated based on baseline VRF among 1,290 stroke-free participants in the prospective population-based NOMAS MRI cohort (mean age 64±8 years, 60% women; 66% Hispanic, 17% Black, 15% White; 46% completed high school). Domain-specific Z-scores were derived for episodic and semantic memory, executive function, and processing speed, and averaged to calculate global cognition.

Results: The CAIDE score was associated with worse global cognition at initial assessment (Beta per SD = -0.347, p < 0.0001), and with greater decline over time (Beta per SD = -0.033, p = 0.02). These associations were largely due to age and education, and the association with cognitive decline was not significant after adjusting for age, sex, and education. The GVRS was inversely associated with global cognition at initial testing (Beta per SD = -0.247, p < 0.0001) and greater decline over time (Beta per SD = -0.127, p < 0.0001), which persisted after adjusting for sociodemographics. The associations for both scores with initial cognitive performance were driven by executive function and processing speed, and the GVRS was associated with decline in episodic memory and processing speed.

Conclusions: The GVRS was a stronger predictor of cognitive decline than the CAIDE in a multi-ethnic urban cohort. The inclusion of glucose and smoking in the GVRS, which are absent in CAIDE, likely explains the better performance of the GVRS.
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http://dx.doi.org/10.3233/JAD-190925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880168PMC
May 2021
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