Cellas Ari'ka Hayes

All Publications

• Contrasting associations of diastolic blood pressure with plasma amyloid, tau, and neurodegeneration biomarkers in the Health and Aging Brain Study-Health Disparities (HABS-HD). Journal of Alzheimer's disease : JAD Hayes, C. A., Agwu, C., Dharmapuri, A., Contreas, J. A. 2026: 13872877261427706

  Abstract

  BackgroundBlood pressure is a major modifiable risk factor for both cardiovascular disease and dementia, yet its relationship with blood-based biomarkers of Alzheimer's disease (AD) and neurodegeneration remains unclear.ObjectiveTo evaluate associations of systolic blood pressure, diastolic blood pressure (DBP), and pulse pressure with plasma biomarkers of AD and neurodegeneration, and to examine whether these associations differ across Non-Hispanic White, Non-Hispanic Black, and Hispanic participants.MethodsParticipants were 2636 cognitively normal older adults enrolled in the Health and Aging Brain Study-Health Disparities. Participants with hypotension or hypertensive crisis were excluded. The outcomes were plasma biomarkers including phosphorylated Tau181, phosphorylated tau217 (p-Tau217), amyloid-β 42 to 40 ratio, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Adjusted multivariable linear regression models evaluated associations between blood pressure measures and log transformed plasma biomarker concentrations. Additional models examined the American Heart Association blood pressure categories as a predictor.ResultsHigher DBP was associated with lower concentrations of neurodegeneration related plasma biomarkers, including p-Tau217, NfL, and GFAP, after correction for multiple comparisons. Analyses using American Heart Association blood pressure categories demonstrated that stage 1 and stage 2 hypertension were associated with lower GFAP concentrations compared with normal blood pressure, with patterns that were broadly consistent across racial and ethnic subgroups.ConclusionsIn this multi-racial ethnic cohort of cognitively normal older adults without hypotension or hypertensive crisis, higher DBP and clinical blood pressure categories were associated with lower levels of select plasma biomarkers of neurodegeneration (NfL and GFAP).

  View details for DOI 10.1177/13872877261427706

  View details for PubMedID 41823011

• Sex differences in blood pressure hemodynamics and white matter hyperintensity volume across racial ethnic groups-HABS-HD. Alzheimer's & dementia (New York, N. Y.) Hayes, C. A., Briggs, A. Q., Gills, J. L. 2026; 12 (1): e70214

  Abstract

  It remains unclear whether specific blood pressure components-systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), or mean arterial pressure (MAP)-are similarly associated with white matter hyperintensity (WMH) burden across sexes within racial and ethnic groups.Participants were drawn from the Health and Aging Brain Study-Health Disparities (HABS-HD) and included non-Hispanic White (NHW; n = 1318), non-Hispanic Black (NHB; n = 1009), and Hispanic (n = 1307) adults. Linear regression models examined associations between SBP, DBP, PP, and MAP with log-transformed WMH volume normalized to intracranial volume. Analyses were stratified by race and ethnic group and included sex × blood pressure interaction terms. Models adjusted for age, education, neuroimaging scanner, diabetes, dyslipidemia, obesity, and tobacco use.Among NHW participants, higher SBP and PP were more strongly associated with greater WMH volume in females compared to males. Among NHB participants, blood pressure-WMH associations did not differ by sex. Among Hispanic participants, females exhibited greater WMH volume in DBP- and MAP-adjusted models, although blood pressure-WMH associations were stronger in males.Blood pressure-WMH associations differ by sex within racial and ethnic groups. These findings highlight intersectional heterogeneity in cerebrovascular vulnerability and suggest that sex-specific blood pressure-related pathways to small-vessel injury vary across racial and ethnic contexts.Non-Hispanic White (NHW) females showed stronger systolic blood pressure (SBP)- and pulse pressure (PP)-white matter hyperintensity (WMH) associations than NHW males.Blood pressure (BP)-WMH associations did not differ by sex among non-Hispanic Black participants.Among Hispanic adults, BP-WMH associations were stronger in males than females.Antihypertensive use was associated with higher WMHs across race and ethnic groups.BP-related WMH vulnerability varies by sex and race and ethnic context.

  View details for DOI 10.1002/trc2.70214

  View details for PubMedID 41816360

  View details for PubMedCentralID PMC12971287

• Projected Cognitive and Brain Aging Benefits of Eliminating Cardiometabolic Risks in Non-Hispanic White and Black Males - HABS-HD. Journal of racial and ethnic health disparities Hayes, C. A., Dharmapuri, A., Odden, M. C., Thorpe, R. J. 2026

  View details for DOI 10.1007/s40615-026-02864-9

  View details for PubMedID 41784903

  View details for PubMedCentralID 8493439

• Examining APOE ε4 and Longitudinal Vascular Brain Injury: The Strong Heart Study. Neurology open access Hayes, C. A., Odden, M. C., Levendovszky, S. R., Buchwald, D. S., Verney, S., Shibata, D. K., Zhang, Y., Ali, T., Suchy-Dicey, A. M. 2026; 2 (1)

  Abstract

  American Indians have a high population risk for cerebrovascular disease, vascular brain injury (VBI), and dementia. The apolipoprotein (APOE) ε4 allele is a strong risk factor for Alzheimer's disease but is also associated with white matter hyperintensities (WMH) and VBI. However, these association have not been thoroughly examined in the American Indian population. Our objective was to determine whether APOE ε4 carriers exhibited greater longitudinal changes in WMH or if the previously reported null effect from cross-sectional findings extended over time in American Indians.We analyzed data from a population-based, longitudinal cohort of American Indians aged 64-95 years from the Strong Heart Study recruited from Northern Plains, Southern Plains, and Southwest regions. Magnetic resonance imaging markers included infarcts, lacunes, hemorrhages, and WMH. APOE genotype was determined through serum analysis and dichotomized based on the presence of the ε4 allele. Covariates included age, sex, education, hypertension, diabetes, stroke history, body mass index, low-density lipoprotein cholesterol, and study site. We used Poisson regression for binary VBI outcomes, linear mixed-effects models to assess longitudinal WMH changes, and Cox regression to analyze incident VBI.The sample size was 395 participants with a mean age of 71.3 (4.7) years and was comprised of 313 non-ε4-carriers and 82 ε4-carriers, predominantly female (70.1%). Cross-sectional analyses indicated no significant associations between APOE ε4 and lacunes (RR=1.03, 95% CI: 0.42-2.57), infarcts (RR =1.28, 95% CI: 0.81-2.02), or hemorrhages (RR = 1.73, 95% CI: 0.60-4.99). Longitudinal analyses revealed no significant associations between APOE ε4 and changes in WMH volume (β = 0.00, 95% CI: -0.02-0.03). APOE ε4 was not associated with overall VBI incidence in fully adjusted models (HR = 2.84, 95% CI: 0.17-48.59).Our findings echo previous work that APOE e4 does not appear to have specificity as a risk factor WMH in American Indians. Further research in a larger sample size and as well as how modifiable environmental factors might modify the biological effects of APOE ε4 on brain aging in American Indians is required to validate these findings.

  View details for DOI 10.1212/wn9.0000000000000059

  View details for PubMedID 41497781

  View details for PubMedCentralID PMC12768527

• Plasma p-tau217 and cognitive impairment: Evaluating biomarker equity across racial/ethnic groups in HABS-HD. Alzheimer's & dementia (Amsterdam, Netherlands) Hayes, C. A., Najmi, Z., Contreras, J. A., Dharmapuri, A., Winston, C. N. 2026; 18 (1): e70269

  Abstract

  Plasma phosphorylated tau 217 (p-tau217) is a leading blood-based biomarker of Alzheimer's disease. Its performance in underrepresented racial/ethnic groups remains insufficiently characterized.We analyzed 2798 participants from the Health and Aging Brain Study-Health Disparities, including non-Hispanic White, non-Hispanic Black, and Hispanic adults. Multivariable logistic regression and receiver operating characteristic analyses assessed associations and discriminative accuracy between plasma p-tau217 and clinical cognitive impairment with racial/ethnic-specific thresholds.Across all groups, p-tau217 levels were higher in cognitively impaired than unimpaired participants. Elevated p-tau217 was associated with greater odds of cognitive impairment in all racial and ethnic groups. Discriminative accuracy was modest but significant (area under the curve 0.65-0.72), with highest performance in non-Hispanic Black and lowest in Hispanic participants.Plasma p-tau217 is robustly associated with cognitive impairment across diverse populations with varying thresholds, highlighting the need for population-specific calibration to support equitable biomarker implementation.

  View details for DOI 10.1002/dad2.70269

  View details for PubMedID 41767155

  View details for PubMedCentralID PMC12935564

• Independent associations of phosphorylated tau181 and neurofilament light with cognitive outcomes in the Health and Aging Brain Study-Health Disparities (HABS-HD). Journal of Alzheimer's disease : JAD Housini, M., Contreras, J. A., Hayes, C. A. 2026: 13872877251415367

  Abstract

  BackgroundThe extent to which plasma biomarkers of Alzheimer's disease and neurodegeneration capture domain-specific cognitive performance across diverse populations remains unclear.ObjectiveTo determine whether plasma phosphorylated tau181 (p-tau181) and neurofilament light (NfL) are independently associated with cognitive domains, and whether associations differ across non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic participants.MethodsWe analyzed 3023 community-dwelling older adults from the Health and Aging Brain Study-Health Disparities (38.4% NHW, 22.6% NHW, 38.9% Hispanic). We used linear regressions to test associations between plasma biomarkers and cognitive domains (memory, executive function, processing speed, language), adjusting for age, sex, education, and apolipoprotein ε4 carriership. We fit models including both p-tau181 and NfL to assess their independent associations, evaluate biomarker × racial/ethnic interactions, and test p-tau181 × NfL interactions within each racial/ethnic group.ResultsAmong NHW participants, higher p-tau181 and NfL were associated with poorer memory, executive function, processing speed, and language. In NHB participants, p-tau181 was associated with memory, showed attenuated associations for language, and demonstrated similar associations with executive function and processing speed as observed in NHW participants. In Hispanic participants, p-tau181 was associated with memory and processing speed but was nonsignificant for executive function and language, and NfL showed significant but attenuated associations across all domains. Higher p-tau181 and NfL were jointly associated with slower processing speed only in NHW and NHB participants.ConclusionsPlasma p-tau181 and NfL were associated with multiple cognitive domains, with the strongest effects in NHW participants and attenuated associations in NHB and Hispanic individuals.

  View details for DOI 10.1177/13872877251415367

  View details for PubMedID 41603391

• STROKE INCIDENCE AND HIGH-SENSITIVITY C-REACTIVE PROTEIN AMONG AFRICAN AMERICANS: THE JACKSON HEART STUDY ETHNICITY & DISEASE Hayes, C. A., Thorpe, R. J., Dhamoon, M., Heitman, E., Norris, K. C., Beech, B. M., Bruce, M., Walker, B., Reneker, J. C. 2025; 35 (1): 1-7

  View details for Web of Science ID 001502076000001

• Public Health. Alzheimer's & dementia : the journal of the Alzheimer's Association Hayes, C. A., Abdullah, L. B., Gills, J. L., Odden, M. C. 2025; 21 Suppl 6 (Suppl 6): e099530

  Abstract

  Black individuals have a higher overall dementia risk than Non-Hispanic Whites (NHW), potentially driven by a greater prevalence of vascular risk factors. This study examines the independent and interactive effects of race and cardiometabolic risk factors on cognitive performance and estimates the population-level impact of hypothetical interventions using causal inference methods among Black and NHW participants.Data from 1,098 NHW and 616 Black participants in the Health and Aging Brain Study: Health Disparities were analyzed. Multivariable regression models assessed interactions between race and cardiometabolic risk factors across four cognitive domains, controlling for demographics. Population intervention measures estimated the reduction in cognitive performance outcomes under the hypothetical elimination of risk factors, stratified by race. This method is similar to population attributable fraction calculations but allows for more flexible modeling.Diabetes and hypertension were more prevalent among Black participants (26.3% and 80.4%) compared to NHW (13.5% and 58.7%, p < 0.001). Black participants consistently scored lower across all cognitive domains (-0.34 to -0.57 points, p < 0.001). There were no significant interactions between race and diabetes or hypertension for any cognitive domain (p > 0.05). Hypothetical elimination of hypertension and diabetes was associated with larger improvements in cognitive performance for Black participants compared to NHW. For executive function, eliminating hypertension would increase scores by 0.07 points (95% CI: 0.01-0.13) for Black participants and 0.05 (95% CI: 0.01-0.09) for NHW. Language function could increase by 0.08 points (95% CI: 0.01-0.14) among Black participants and 0.06 (95% CI: 0.01-0.10) for NHW. Diabetes showed similar but more modest trends.Hypertension and diabetes disproportionately impact cognitive outcomes in Black participants, emphasizing their higher prevalence as key contributors to observed disparities in cognitive aging.

  View details for DOI 10.1002/alz70860_099530

  View details for PubMedID 41435200

  View details for PubMedCentralID PMC12726196

• Discontinuation of Anticholinergic Medications Among VA Nursing Home Residents With and Without Dementia Hayes, C. OXFORD UNIV PRESS. 2025

  View details for DOI 10.1093/geroni/igaf122.357

  View details for Web of Science ID 001652738000001

• Population intervention models of racial ethnic disparities in cognitive outcomes from cardiometabolic risk factors - HABS-HD. Alzheimer's research & therapy Hayes, C. A., Abdullah, L., Gills, J., Odden, M. C., Health and Aging Brain Study (HABS-HD) Study Team 2025; 17 (1): 217

  Abstract

  BACKGROUND: Alzheimer's disease and related dementias are major public health challenges, with the apolipoprotein (APOE) epsilon4 allele being a significant genetic risk factor. Cardiometabolic risk factors such as diabetes, hypertension, dyslipidemia, obesity, and tobacco use are also linked to cognitive impairment. The objective of this study was to (1) characterize both independent and interactive associations of racial/ethnic group (Non-Hispanic White (NHW), Non-Hispanic Black (NHB) and Hispanic), APOE epsilon4 genotype, and multiple cardiometabolic risk factors with performance across four cognitive domains. Secondarily, we aimed to quantify the hypothetical population-level cognitive gains that could result from eliminating each modifiable risk factor within each racial/ethnic group.METHODS: We analyzed baseline data from 3,833 HABS-HD participants (1,348 NHW; 1,065 NHB; 1,420 Hispanic; mean age 65.3±8.6years; 62.0% female). APOE genotype, consensus-determined cardiometabolic status, and harmonized cognitive domain scores (episodic memory, executive function, processing speed, language) were obtained. Multivariable linear regressions assessed independent effects of race/ethnicity, APOE epsilon4 carriage, and each cardiometabolic factor on domain-specificz-scores, adjusting for age, sex, and education (Bonferroni-corrected). Interaction terms tested effect modification by race/ethnicity. Counterfactual population intervention models estimated the mean cognitive gain from hypothetically eliminating each modifiable risk factor within each racial/ethnic group.RESULTS: NHB Hispanic, and NHW participants prevalences wereAPOE epsilon4 (32.2%, 27.4%, 17.6%), diabetes (26.1%, 35.0%, 13.9%), hypertension (79.0%, 63.6%,58.2%), obesity (56.8%, 50.3%,38.5%), and tobacco dependence (12.9%, 7.5%, 3.9%). In adjusted models, NHB and Hispanic ethnicity, APOE epsilon4, diabetes, hypertension, and tobacco dependence each independently predicted lower performance across all four cognitive domains (adjusted p<.001), whereas obesity showed domain-specific positive associations. No race*risk-factor interactions remained significant after correction. In intervention models, hypothetically eliminating diabetes and hypertension yielded the largest predicted improvements, especially in executive function and language, with the greatest gains projected among NHB and Hispanic racial ethnic group.CONCLUSIONS: Cardiometabolic health markedly contributes to racial ethnic differences in cognitive aging beyond APOE epsilon4 effects. Population-level interventions targeting diabetes and hypertension could narrow NHB and Hispanic cognitive deficits, informing precision public-health strategies for dementia prevention.

  View details for DOI 10.1186/s13195-025-01866-9

  View details for PubMedID 41035086

• Micro infarcts are associated with cognitive impairment in neurofibrillary tangle predominant decedents: evidence from the NACC autopsy cohort. Alzheimer's research & therapy Martinez, N., Bharani, K. L., Hasan, S., Hayes, C. A. 2025; 17 (1): 216

  Abstract

  BACKGROUND: A subset of older adults develops high neurofibrillary tangle burden with minimal amyloid, a biomarker profile consistent with suspected non-Alzheimer's pathophysiology or primary age-related tauopathy. Yet its cognitive correlates are unclear, particularly when vascular neuropathologies coexist. We examined whether vascular neuropathologies are linked to cognitive impairment proximate to death and pre-mortem cognitive decline among decedents with intermediate-to-high Braak stage (III-VI) and absent/low neuritic plaques.METHODS: In 579 autopsied participants from the National Alzheimer's Coordinating Center cohort (Braak III-VI; CERAD C0-C1), we evaluated arteriolosclerosis, atherosclerosis of the circle of Willis, cerebral amyloid angiopathy, gross infarcts/lacunes, and microinfarcts effect on harmonized memory, executive function, and language z-scores proximate to death using multivariable linear regression (adjusted for age, sex, education, APOE epsilon4 status). Linear mixed-effects models assessed interactions between each vascular neuropathology and years-to-death on pre-mortem longitudinal decline.RESULTS: At the last assessment, microinfarcts were associated with lower memory (beta=-0.28, 95% CI -0.51 - -0.05; p=0.02), executive function (beta=-0.24, 95% CI -0.44 - -0.04; p=0.02), and language (beta=-0.21, 95% CI -0.38 - -0.04; p=0.02). These associations remained after controlling for cardiovascular risk, neuritic plaques and Braak stage, last assessment and death interval, and co-existing vascular neuropathologies. Microinfarcts were not associated with the rates of pre-mortem cognitive decline.CONCLUSIONS: Microinfarcts are contributors to domain-specific cognitive deficits in tangle-predominant, low-amyloid older adults. These findings underscore a vascular-neurodegenerative pathway distinct from classic Alzheimer's disease. Thus, targeting microvascular injury may mitigate impairment in this underrecognized phenotype.

  View details for DOI 10.1186/s13195-025-01863-y

  View details for PubMedID 41035071

• Application of modified Poisson regression for risk estimation of major neuropathology outcomes: National Alzheimer's coordinating center. Journal of Alzheimer's disease : JAD Hayes, C. A., Odden, M. C., Thorpe, R. J. 2025: 13872877251375099

  Abstract

  Odds ratios (OR) can overestimate risk when the prevalence of outcomes is more than 10%. We compared logistic and modified Poisson models in 5843 National Alzheimer's Coordinating Center decedents to examine associations of apolipoprotein (APOE) ε4, age at death, sex, and education with 7 neuropathologies. OR for neuritic plaques (6.28) and Braak stage (4.90) attenuated to prevalence rate ratios of 1.38 and 1.08; similar attenuation occurred for Lewy body disease, arteriolosclerosis, cerebral amyloid angiopathy, and infarcts. Modified Poisson regression is critical for valid risk estimation, reliable interpretations, and accurate risk stratification in non-rare outcome studies.

  View details for DOI 10.1177/13872877251375099

  View details for PubMedID 40924589

• Targeting the cardiometabolic bottleneck to slow polypathology and cognitive decline. Alzheimer's & dementia : the journal of the Alzheimer's Association Hayes, C. A., Younes, K. 2025; 21 (9): e70684

  View details for DOI 10.1002/alz.70684

  View details for PubMedID 40916741

  View details for PubMedCentralID PMC12415439

• Sex differences in the association of cardiometabolic risk scores and blood pressure measurements with white matter hyperintensities in diverse older adults-HABS-HD. Frontiers in aging neuroscience Hayes, C. A., Vintimilla, R., Chaudhuri, S., Odden, M. C. 2025; 17: 1607646

  Abstract

  We aimed to determine whether cardiometabolic risk factors and blood-pressure (BP) metrics were differentially associated with white matter hyperintensities volume (WMHV) in males versus females in the Health and Aging Brain Study-Health Disparities.We analyzed 3,585 community-dwelling adults (2,207 females) from non-Hispanic White, non-Hispanic Black, and Hispanic groups who underwent BP measurement and WMHV quantification. Linear regression models assessed (i) individual risk factors (diabetes, hypertension, dyslipidemia, obesity, tobacco dependence), (ii) a composite risk score, and (iii) four BP metrics (systolic, diastolic, pulse pressure, mean arterial pressure), each including a sex-interaction term and adjusting for age, education, race/ethnicity, and scanner. A second BP model also controlled for all five risk factors.Diabetes (β = 0.46, 95% CI 0.28-0.64), hypertension (β = 0.47, 0.30-0.64), and higher composite risk (β = 0.19, 0.12-0.26) were associated with greater WMHV. Diastolic BP (β = 0.18, 0.11-0.26) and mean arterial pressure (β = 0.14, 0.07-0.21) related to larger WMHV, with diastolic BP remaining significant after full adjustment (β = 0.14, 0.07-0.22). No sex interactions survived correction.These findings underscore the importance of aggressive cardiometabolic and BP control, particularly diastolic BP, to mitigate WMHV in both sexes.

  View details for DOI 10.3389/fnagi.2025.1607646

  View details for PubMedID 40831584

  View details for PubMedCentralID PMC12358495

• Racial and ethnic differences in cardiometabolic predictors of white matter hyperintensities burden among males: The HABS-HD study. Journal of Alzheimer's disease : JAD Hayes, C. A., Jones, R., Thorpe, R. J. 2025: 13872877251365128

  Abstract

  Background: Cardiometabolic conditions accelerate white-matter hyperintensity (WMH) accumulation-a vascular injury marker linked to increased Alzheimer's disease risk-yet how these relationships vary by race and ethnicity in males is poorly understood. Objective: To quantify racial ethnic-specific associations between cardiometabolic risk factors, blood-pressure indices, and WMH volume in Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanic males. Methods: We analyzed 1378 males (558 NHW, 375 NHB, 445 Hispanic) from the Healthy Aging Brain Study-Health Disparities. Five binary exposures (hypertension, diabetes, dyslipidemia, obesity, tobacco dependence), four continuous blood-pressure metrics (systolic, diastolic, pulse, mean arterial pressure), and a principal-component cardiometabolic score were regressed on log-transformed, intracranial volume-adjusted WMH volume in race-stratified models. Results: Hispanic males exhibited the broadest vulnerability: hypertension, diabetes, and tobacco dependence each predicted higher WMH (β range 0.60-0.77, p ≤ 0.002), and the composite score had the strongest association (β = 0.26, 0.13-0.39, p < 0.001). Additionally, every 10-mm Hg rise in systolic, diastolic, pulse, or mean arterial pressure further increased WMH in Hispanic males (e.g., systolic β = 0.18, 0.11-0.26), an effect absent in NHW and NHB males. Conclusions: Cardiometabolic and hemodynamic drivers of WMH differ markedly across racial and ethnic groups of males, with Hispanic males showing the most pervasive risk profile, NHB males selective associations, and NHW males limited links. Tailored vascular-risk interventions may be essential to curb WMH-related pathways to Alzheimer's disease in racially and ethnically diverse male populations.

  View details for DOI 10.1177/13872877251365128

  View details for PubMedID 40760862

• Microinfarcts are Associated with Cognitive Impairment in Neurofibrillary Tangle Predominant Decedents: Evidence from the NACC Autopsy Cohort. Research square Martinez, N. C., Bharani, K. L., Hasan, S., Hayes, C. A. 2025

  Abstract

  Background: A growing number of older adults exhibit neurofibrillary tangle pathology without significant amyloid deposition, a biomarker profile consistent with suspected non-Alzheimer's pathophysiology or primary age-related tauopathy. The cognitive consequences within this subgroup remain poorly characterized, particularly with respect to vascular comorbidity. This study investigates whether vascular neuropathologies are associated with pre-mortem cognitive decline among individuals with predominately neurofibrillary tangles and low to none neuritic plaque pathology detected post-mortem.Methods: The sample included autopsy-confirmed data from 579 participants in the National Alzheimer's Coordinating Center (NACC) cohort with intermediate-to-high Braak stage (B2-B3) and absent or minimal neuritic plaques (C0-C1). Vascular neuropathologies included arteriolosclerosis, atherosclerosis of the circle of Willis, gross infarcts/ lacunes, and microinfarcts were assessed for associations with global cognition (Clinical Dementia Rating Sum of Boxes, CDR-SOB) and harmonized cognitive domain specific performance (memory, executive function, and language) using multivariable regression adjusted for age, sex, education, and apolipoprotein epsilon4 status. Sensitivity analyses further controlled for cardiovascular risk, excluded individuals with any neuritic plaques, and controlling for individual neuritic plaque and Braak staging.Results: Cross-sectionally, microinfarcts were consistently associated with poorer memory (beta = - 0.28, p = 0.02), executive function (beta = - 0.24, p = 0.02), and language (beta = - 0.21, p = 0.02) approximate to death. Gross infarcts were associated with language impairment and higher CDR scores. These associations remained significant after adjusting for cardiovascular risk and were even stronger when restricted to strictly neuritic amyloid negative individuals.Conclusions: Microinfarcts may represent a key driver of cognitive impairment in neurofibrillary tangle predominant individuals. These findings highlight a vascular-neurodegenerative pathway that warrants consideration in non-neuritic plaque models of cognitive decline and may inform targeted prevention strategies.

  View details for DOI 10.21203/rs.3.rs-7036276/v1

  View details for PubMedID 40709257

• Age-dependent interactions of APOE isoform 4 and Alzheimer's disease neuropathology: findings from the NACC. Acta neuropathologica communications Hayes, C. A., Thorpe, R. J., Odden, M. C. 2025; 13 (1): 102

  Abstract

  Alzheimer's disease related pathologies, neurodegenerative pathologies, and vascular neuropathologies are common in older adults at death. Previous studies using the National Alzheimer's Coordinating Center (NACC) have not investigated the association between age at death and apolipoprotein E (APOE) epsilon4 and the prevalence of neuropathologies found at autopsy. We used autopsy confirmed neuropathology data from the NACC to examine the interactive effects of age and APOE epsilon4 on various neuropathologies (N=5,843) using modified Poisson regression to estimate the prevalence ratios. Significant interactions between APOE epsilon4 and age at death were observed for neuritic plaques, Braak staging, diffuse neuritic plaques, and Lewy body disease pathology, with the effect of APOE epsilon4 decreasing at older ages. In contrast, a significant positive interaction was found for hemorrhages/microbleeds, indicating that the association between APOE epsilon4 and microbleeds strengthens with increasing age. These findings suggest that future therapeutic strategies should consider both genetic risk and age to effectively target AD progression.

  View details for DOI 10.1186/s40478-025-02012-0

  View details for PubMedID 40382659

• Racial ethnic variations in the cardiometabolic determinants and blood pressure of white matter hyperintensities among females-The HABS-HD Study. Alzheimer's & dementia : the journal of the Alzheimer's Association Hayes, C. A., Odden, M. C., Vintimilla, R., Thorpe, R. J. 2025; 21 (5): e70327

  Abstract

  White matter hyperintensity volume (WMH), markers of cerebral small vessel disease, are disproportionately prevalent among Black/African American and Hispanic individuals. While cardiometabolic risk factors contribute to WMHs, their association across racial ethnic groups among females remains unclear. This study examines associations among cardiometabolic risk factors, blood pressure, and WMH volume in non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic females.Using the Health and Aging Brain Study Health Disparities (HABS-HD) cross-sectional visit 1 data (N = 2209), we assessed cardiometabolic risk factors and blood pressure measures in relation to WMH volume via multivariable linear regression models stratified by race/ethnicity.Hypertension was associated with increased WMH volume in NHW females. Diabetes was a significant predictor in Hispanics. Systolic blood pressure and mean arterial pressure were associated with WMH volume in NHB.Findings highlight racial differences in cardiometabolic contributions to WMH burden, emphasizing the need for tailored prevention strategies in racially and ethnically diverse female populations.Overall, there was a main effect of hypertension; however, in stratified analyses hypertension was significantly was associated with greater white matter hyperintensity (WMH) burden in non-Hispanic White females. Non-Hispanic Black females presented with a worse cardiometabolic profile, but this composite was not associated with WMH burden. There was a positive association with the risk composite in non-Hispanic White and Hispanic females. Systolic blood pressure and mean arterial pressure were associated with greater WMH in non-Hispanic Black females, highlighting differential blood pressure contributions to WMH burden.

  View details for DOI 10.1002/alz.70327

  View details for PubMedID 40420353

  View details for PubMedCentralID PMC12106056

• The impact of arteriolosclerosis on cognitive impairment in decedents without severe dementia from the National Alzheimer's Coordinating Center. Alzheimer's & dementia : the journal of the Alzheimer's Association Hayes, C. A., Young, C. B., Abdelnour, C., Reeves, A., Odden, M. C., Nirschl, J., Crane, P. K., Poston, K. L., Mormino, E. C., Younes, K. 2025; 21 (3): e70059

  Abstract

  Alzheimer's disease neuropathologic change (ADNC), Lewy body disease (LBD), and vascular neuropathologies occur together. Previous studies have been limited by a large majority of participants with severe dementia or advanced stages of pathologies, which limits the detectability of cognitive effects from vascular neuropathologies.Using neuropathology data from the National Alzheimer's Coordinating Center, we examined the association of vascular neuropathologies with cognitive scores in participants without severe dementia (N = 1526) using multivariable linear regression.Controlling for age, sex, education, LBD, and ADNC, arteriolosclerosis was associated with lower memory (β = -0.16 ± 0.06, p < 0.001), executive function (β = -0.25 ± 0.05, p < 0.001), and language scores (β = -0.20 ± 0.05, p < 0.001). The effects of arteriolosclerosis remained when controlling for vascular risk factors.Vascular neuropathologies exhibit distinct relationships with cognition. Arteriolosclerosis is an independent contributor to cognition. Further research should be conducted on whether arteriolosclerosis can serve as a surrogate marker for cognitive decline in early disease stages.In individuals who do not have severe dementia, vascular neuropathologies are common, and the combination of pathologies is heterogeneous in a convenience sample from the Alzheimer's Disease Research Center that reported all the neuropathology data elements for this investigation. Arteriolosclerosis is associated with several cognitive domain scores, including memory, executive function, and language when controlling for the effects of Alzheimer's disease neuropathologic change and Lewy body disease. These results reinforce the importance of vascular pathology for cognition among people along the Alzheimer's disease spectrum.

  View details for DOI 10.1002/alz.70059

  View details for PubMedID 40110658

• Stroke Incidence and High-Sensitivity C-Reactive Protein Among African Americans: The Jackson Heart Study. Ethnicity & disease Hayes, C. A., Thorpe, R. J., Dhamoon, M., Heitman, E., Norris, K. C., Beech, B. M., Bruce, M., Walker, B., Reneker, J. C. 2025; 35 (1): 1-7

  Abstract

  Strokes are a leading cause of death and disability among African Americans in the United States. Biological markers to predict stroke remain elusive; thus, our objective was to investigate whether inflammation, as measured by high-sensitivity C-reactive protein (hs-CRP), was associated with stroke incidence among African Americans enrolled in the Jackson Heart Study (JHS).Baseline hs-CRP levels were categorized in quintiles: quintile 1 (0.0084 mg/L); quintile 2 (0.0085-0.0189 mg/L); quintile 3 (0.0190-0.036 mg/L); quintile 4 (0.037-0.0675 mg/L); quintile 5 (≥0.0676 mg/L). Nonfatal stroke incidence was ascertained from passive community surveillance through annual phone calls and adjudicated via hospital records. At baseline, stroke risk factors/covariates were compared across quintiles using a one-way analysis of variance and a chi-square test. The association between baseline hs-CRP levels and stroke incidence was determined using a Cox regression analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI).In the unadjusted model, hs-CRP levels in quintile 2 (HR, 1.48; 95% CI, 0.96-2.29), quintile 3 (HR, 1.44; 95% CI, 0.93-2.24), and quintile 4 (HR, 1.09; 95% CI, 0.68-1.74) were not associated with stroke incidence when compared with quintile 1 (reference). However, individuals within quintile 5 (HR, 1.78; 95% CI, 1.17-2.72) exhibited a significantly increased risk for stroke compared with those in the reference quintile. This risk persisted after adjusting for stroke risk factors (demographics, anthropometrics, health condition covariates, health behavioral risk factors, and cardiovascular disease history) for quintile 5 (HR, 1.87; 95% CI, 1.17-2.98) compared with reference quintile 1.An increased and independent risk of nonfatal stroke appears at the highest quintile of hs-CRP values (≥0.0676 mg/L) among JHS participants.

  View details for DOI 10.18865/EthnDis-2023-78

  View details for PubMedID 40124641

  View details for PubMedCentralID PMC11928021

• Insulin-like growth factor-1 and cognitive health: Exploring cellular, preclinical, and clinical dimensions. Frontiers in neuroendocrinology Hayes, C. A., Wilson, D., De Leon, M. A., Mustapha, M. J., Morales, S., Odden, M. C., Ashpole, N. 2024: 101161

  Abstract

  Age and insulin-like growth factor-1 (IGF-1) have an inverse association with cognitive decline and dementia. IGF-1 is known to have important pleiotropic functions beginning in neurodevelopment and extending into adulthood such as neurogenesis. At the cellular level, IGF-1 has pleiotropic signaling mechanisms through the IGF-1 receptor on neurons and neuroglia to attenuate inflammation, promote myelination, maintain astrocytic functions for homeostatic balances, and neuronal synaptogenesis. In preclinical rodent models of aging and transgenic models of IGF-1, increased IGF-1 improves cognition in a variety of behavioral paradigms along with reducing IGF-1 via knockout models being able to induce cognitive impairment. At the clinical levels, most studies highlight that increased levels of IGF-1 are associated with better cognition. This review provides a comprehensive and up-to-date evaluation of the association between IGF-1 and cognition at the cellular signaling levels, preclinical, and clinical levels.

  View details for DOI 10.1016/j.yfrne.2024.101161

  View details for PubMedID 39536910

• Empowering Early Career Researchers: The Jackson Heart Study Smith Scholars Program. Journal of racial and ethnic health disparities Hayes, C. A., Jones, R. 2024

  Abstract

  The University of Mississippi Medical Center Graduate Training and Education Center houses the Robert E. Smith, MD, Scholars Program, a two-year certificate program that equips predoctoral trainees from five Mississippi universities with advanced research skills in cardiovascular epidemiology. Funded by the National Heart, Lung, and Blood Institute (NHLBI), the program focuses on addressing health disparities, minority health, and health inequities in underserved communities. Trainees receive mentorship, career coaching, and a $7,500 annual stipend, building a foundation for postdoctoral opportunities and expanding professional networks. The Smith Scholars Program emphasizes population health and provides interdisciplinary training in areas such as biostatistics, scientific communication, and cardiovascular health. It is uniquely positioned to address systemic challenges, particularly in Mississippi, a state with high cardiovascular disease prevalence and limited research funding. The program's regional advantage and its partnership with the Jackson Heart Study offer scholars exposure to health disparities in Black/African American communities, preparing them to contribute to innovative, community-based research. Additionally, it fosters collaborative science, enabling participants to overcome academic barriers and engage with large-scale health equity research efforts. The Smith Scholars Program has been instrumental in shaping the career trajectories of its participants, facilitating their transition to postdoctoral positions and independent research roles.

  View details for DOI 10.1007/s40615-024-02226-3

  View details for PubMedID 39455520

• Revolutionizing Postdoctoral Training Using the Social Ecological Model: Insights and Experiences from the Propel Scholars GEN BIOTECHNOLOGY Hayes, C. A., Headley, C. A., Nava, A. R., Vizcarra, E. A., Garcia, K. C., Mullen, M. M. S., Morales, J., Venida, A. C., Follis, S. 2024

  View details for DOI 10.1089/genbio.2024.0014

  View details for Web of Science ID 001283346900001

• Revolutionizing Postdoctoral Training Using the Social Ecological Model: Insights and Experiences from the Propel Scholars. GEN biotechnology Hayes, C. A., Headley, C. A., Nava, A. R., Vizcarra, E. A., Garcia, K. C., Mullen, M. M., Morales, J. F., Venida, A. C., Follis, S. 2024; 3 (4): 196-206

  Abstract

  The dissatisfaction within the postdoctoral training phase has led to the drastic reduction in the number of U.S. citizens pursuing postdoctoral positions within the biological and biomedical sciences fields. Even more so, there is an obvious disparity in not only the recruitment but the retention among underrepresented groups to pursue careers as academic scientists. The proposed social-ecological model and National Institute of Health advisory committee suggests reforming the postdoctoral training phase to overcome these downward trends and disparities. Importantly, some programs like the Stanford Propel Postdoctoral Program were integrating this framework and recommendations without knowledge that they would be released 2 years later. The goal of the Propel Program is to provide social, cohort, financial, and institutional support to diverse cohorts of postdoctoral trainee to diversify the professoriate. Within this piece, several of the Propel scholars come together to provide their perspectives on how the Propel Program has benefited their postdoctoral training experience.

  View details for DOI 10.1089/genbio.2024.0014

  View details for PubMedID 40709103

  View details for PubMedCentralID PMC12288851

• Unlocking the power of virtual networking for early-career researchers. eLife Hayes, C. A., Moore, J. T., Headley, C. A., Berrios-Negron, A. L., Lambert, W. M. 2024; 13

  Abstract

  Many successful researchers in the biomedical sciences have benefitted from mentors and networks earlier in their career. However, early-career researchers from minoritized and underrepresented groups do not have the same access to potential mentors and networks as many of their peers. In this article we describe how 'cold emails' and social media platforms - notably Twitter/X and LinkedIn - can be used to build virtual networks, and stress the need to invest in maintaining networks once they have been established.

  View details for DOI 10.7554/eLife.96381

  View details for PubMedID 38501601

• Academic ethics of mental health: the national black postdocs framework for the addressment of support for undergraduate and graduate trainees. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Hayes, C. A., Berrios-Negron, A. L., Tamir, T., Hardeman, K. N., Heyward, F. D. 2024

  View details for DOI 10.1038/s41386-023-01787-x

  View details for PubMedID 38191654

  View details for PubMedCentralID 7199285

• Neuronal and Astrocyte Insulin-like Growth Factor-1 Signaling Differentially Modulates Ischemic Stroke Damage. bioRxiv : the preprint server for biology Hayes, C. A., Morgan, N. I., Thomas, K. C., Pushie, M. J., Vijayasankar, A., Ashmore, B. G., Wontor, K., De Leon, M. A., Ashpole, N. M. 2023

  Abstract

  Ischemic stroke is a leading cause of death and disability, as therapeutic options for mitigating the long-term deficits precipitated by the event remain limited. Acute administration of the neuroendocrine modulator insulin-like growth factor-1 (IGF-1) attenuates ischemic stroke damage in preclinical models, and clinical studies suggest IGF-1 can reduce the risk of stroke and improve overall outcomes. The cellular mechanism by which IGF-1 exerts this protection is poorly defined, as all cells within the neurovascular unit express the IGF-1 receptor. We hypothesize that the functional regulation of both neurons and astrocytes by IGF-1 is critical in minimizing damage in ischemic stroke. To test this, we utilized inducible astrocyte-specific or neuron-specific transgenic mouse models to selectively reduce IGF-1R in the adult mouse brain prior to photothrombotic stroke. Acute changes in blood brain barrier permeability, microglial activation, systemic inflammation, and biochemical composition of the brain were assessed 3 hours following photothrombosis, and significant protection was observed in mice deficient in neuronal and astrocytic IGF-1R. When the extent of tissue damage and sensorimotor dysfunction was assessed for 3 days following stroke, only the neurological deficit score continued to show improvements, and the extent of improvement was enhanced with additional IGF-1 supplementation. Overall, results indicate that neuronal and astrocytic IGF-1 signaling influences stroke damage but IGF-1 signaling within these individual cell types is not required for minimizing tissue damage or behavioral outcome.

  View details for DOI 10.1101/2023.04.02.535245

  View details for PubMedID 37034764