The Association between Race and Extended Length of Stay in Low-energy Proximal Humerus Fractures in Elderly Patients.

INTRODUCTION: Proximal humerus fractures (PHFs) are one of the most common fractures among patients aged 65 years and older, commonly due to low-energy mechanisms. It is essential to identify drivers of increased healthcare utilization in geriatric PHF patients and bring awareness to any disparities in care. Here, we identify factors associated with the likelihood of inpatient admission and prolonged hospital stay among patients aged 65 years and older who sustain PHF due to falls. METHODS: A national database was used to identify patients aged 65 years and older who suffered proximal humeral fractures due to a fall. Patient factors were analyzed for association with the likelihood of admission and odds of prolonged stay (≥5 days). RESULTS: In the study period, 75,385 PHF patients who met our inclusion criteria presented to the emergency department and 14,118 (18.7%) were admitted. Black race was significantly associated with decreased odds of admission (P < 0.001) and increased likelihood of prolonged stay (P = 0.007) compared with White patients. Patients aged 75 to 84 and 85+ were both more likely to be admitted (P < 0.001) and experienced a prolonged hospital stay (P = 0.015). Patients undergoing surgical intervention with reverse total shoulder arthroplasty were associated with admission and prolonged length of stay (P < 0.001). Hospitals in Midwestern (P < 0.001) and Western (P < 0.001) regions exhibited lower rates of admission and Northeastern hospitals were associated with prolonged stays (P = 0.001). Finally, trauma and nonmetropolitan (P < 0.001) centers were associated with admission. CONCLUSION: Our study highlights the notable influence of age and race on the likelihood of hospital admission and prolonged hospital stay. Specifically, Black patients exhibited prolonged hospital stay, which has been associated with lower-quality care, warranting additional exploration. Understanding these demographic and hospital-related factors is essential for optimizing resource allocation and reducing healthcare disparities in the care of PHF patients, especially as the population ages and the incidence of PHF continues to rise.

Unveiling the evolving landscape of stroke care costs: A time-driven analysis.

INTRODUCTION: Stroke is a common cause of mortality in the United States. However, the economic burden of stroke on the healthcare system is not well known. In this study, we aim to calculate the annual cumulative and per-patient cost of stroke. METHODS: We conducted a retrospective analysis of Nationwide Emergency Department Sample (NEDS). We calculate annual trends in cost for stroke patients from 2006 to 2019. A multivariate linear regression with patient characteristics (e.g. age, sex, Charlson Comorbidity Index) as covariates was used to identify factors for higher costs. RESULTS: In this study time-period, 2,998,237 stroke patients presented to the ED and 2,481,171 (83 %) were admitted. From 2006 to 2019, the cumulative ED cost increased by a factor of 7.0 from 0.49 ± 0.03 to 3.91 ± 0.16 billion dollars (p < 0.001). The cumulative inpatient (IP) cost increased by a factor of 2.7 from 14.42 ± 0.78 to 37.06 ± 2.26 billion dollars (p < 0.001. Per-patient ED charges increased by a factor of 3.0 from 1950 ± 64 to 7818 ± 260 dollars (p < 0.001). Per-patient IP charges increased by 89 % from 40.22 +/- 1.12 to 76.06 ± 3.18 thousand dollars (p < 0.001). CONCLUSION: Strokes place an increasing financial burden on the US healthcare system. Certain patient demographics including age, male gender, more comorbidities, and insurance type were significantly associated with increased cost of care.

Trends in Volume and Charges of Retinal Tear Patients in the Emergency Department.

PURPOSE: To characterize retinal tears (RTs) and calculate the economic burden of RTs that present to the emergency department (ED) in the US. METHODS: We used a large national ED database to retrospectively analyze RTs that presented to the ED from 2006 to 2019. Using extrapolation methods, national of the RT patient ED volume, demographics, comorbidities, disposition, inpatient (IP) charges, and ED charges were calculated. RESULTS: During the period between 2006 and 2019, 15841 ED encounters had RT listed as the primary diagnosis. The average annual RT ED encounters was 2,640 ± 856 and comprised an average of 6.4 × 10-5% of all ED visits annually. The number and ED percentage of RT encounters did not change during this time period (p = .22, p = .67, respectively). Most patients were males, Caucasian, paid with private insurance, and admitted to EDs in the Northeast. The most common comorbidities were hypertension (19%), a history of cataracts (15%), and diabetes (7.2%). During this time period, RTs charges added up to more than $79 million and $33 million in the ED and IP settings, respectively. Mean per-encounter ED and IP charges increased by 145% (p = .0008) and 86% (p = .0047), respectively. CONCLUSION: Despite the stable number of RT patients presenting to the ED, RTs place a significant economic burden to the healthcare system, which increases yearly. We recommend physicians and policy makers to work together to pass laws that could prevent the increasing healthcare charges.

Differential thrombectomy utilization across hospital classifications in the United States.

OBJECTIVES: To determine hospital-level factors associated with thrombectomy uptake. MATERIALS AND METHODS: The Nationwide Emergency Department Sample was retrospectively queried to determine the total number of thrombectomies performed based on different hospital characteristics. Joint point analysis was used to determine which years were associated with significant increases in the number of high-volume thrombectomy centers (ostensibly defined as >50 thrombectomies/year), thrombectomy-capable centers (>15 thrombectomies/year), and total number of thrombectomies performed. Multivariable logistic regression was used to determine hospital factors associated with having an increased odds of performing thrombectomies, and of being classified as a high-volume thrombectomy or a thrombectomy-capable center. RESULTS: Between 2007-2020 there was a stepwise increase in the number of thrombectomy-capable and high-volume thrombectomy centers in the United States. In 2020, there were a total of 15,705 thrombectomies performed, with 89 high-volume thrombectomy centers, and 359 thrombectomy-capable centers. The number of thrombectomy-capable centers significantly increased after 2011. After 2013 and 2016 there was a significant change in the growth rate of high-volume thrombectomy centers. There was also a significant increase in the total number of thrombectomies performed after 2016. Hospital characteristics that were associated with an increased likelihood of being classified as thrombectomy-capable or high-volume included trauma level 1 and 2 hospitals. CONCLUSIONS: Between 2007 and 2020, there was a marked growth in thrombectomy utilization for acute ischemic stroke. This growth outpaced new diagnoses of ischemic stroke, and was driven largely by certain hospital types, with the greatest rises following seminal publications of positive randomized thrombectomy trials.

Factors associated with discharge against medical advice among acute stroke patients: Analysis of the Nationwide Emergency Department Sample.

BACKGROUND: Patients discharged against medical advice have been shown to have worse outcomes across a host of different conditions. However, risk factors related to an increased odds of discharge against medical advice remain understudied in patients who suffer from acute cerebral infarction. METHODS: We retrospectively examined the 2019 National Emergency Department Sample Database for stroke patients. Multivariable logistic regression was used to estimate associations between patient- and hospital-level factors and the outcome of discharge against medical advice. RESULTS: Of the 603,623 encounters for acute ischemic stroke, 8858 (1.5%) were discharged against medical advice. Predictors of discharge against medical advice were lower income quartile and having either Medicaid insurance (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.10-1.58) or being uninsured (OR 1.28, 95% CI 1.03-1.58). Vascular comorbidities associated with discharge against medical advice included prior tobacco use (OR 1.60, 95%CI 1.45-1.78) and coronary artery disease (OR 1.19, 95% CI 1.04-1.35). Treatment with thrombectomy (OR 0.33, 95% CI 0.13-0.78) or systemic thrombolysis (OR 0.39, 95% CI 0.23-0.66) was inversely associated with discharge against medical advice. A high modified Charlson Comorbidity Index (3+ vs. 0, OR 0.49, 95% CI 0.42-0.56) was also associated with a lower odds of discharge against medical advice. Presenting to a Northeastern hospital had the highest rate of discharge against medical advice, when compared to other regions (p<0.05). CONCLUSIONS: Certain patient-level, socioeconomic, and regional factors were associated with discharge against medical advice following acute stroke. These patient and systems-level factors warrant heightened attention in order to optimize acute care and secondary prevention strategies.

The validity and applications of the analgesia nociception index: a narrative review.

Pain refers to the subjective, unpleasant experience that is related to illness or injury. In contrast to pain, nociception refers to the physiological neural processing of noxious stimuli, such as intra-operative surgical stimuli. One novel device, the Analgesia Nociception Index (ANI), aims to objectively measure intra-operative nociception by analyzing the heart rate variability in patients undergoing surgery. Through this method of nociceptive monitoring, the ANI device aims to provide an objective, continuous evaluation of patient comfort levels and allow anesthesiologists to better manage surgical stress and patient analgesia, perhaps with even better efficacy than current practices used to assess nociception. Additionally, ANI may have clinical application in settings outside of the operating room, such as in the intensive care unit. In this narrative review, we compiled and summarized the findings of many studies that have investigated ANI's validity and applications in different clinical settings. Currently, the literature appears mostly supportive of ANI's ability to detect nociception in both surgical and non-surgical settings. However, the ability for ANI to provide clinical benefits, such as decreased intra-operative opioid use, post-operative opioid use, and post-operative pain compared to standard practices appear controversial. Because of the wide variety of methodology, clinical settings, patient populations, and limitations in these studies, more investigation of ANI is needed before any firm conclusions can be drawn on its clinical benefits.

Nanoparticle-Based Treatment Approaches for Skin Cancer: A Systematic Review.

Nanoparticles have shown marked promise as both antineoplastic agents and drug carriers. Despite strides made in immunomodulation, low success rates and toxicity remain limitations within the clinical oncology setting. In the present review, we assess advances in drug delivery nanoparticles, for systemic and topical use, in skin cancer treatment. A systematic review of controlled trials, meta-analyses, and Cochrane review articles was conducted. Eligibility criteria included: (1) a primary focus on nanoparticle utility for skin cancer; (2) available metrics on prevention and treatment outcomes; (3) detailed subject population; (4) English language; (5) archived as full-text journal articles. A total of 43 articles were selected for review. Qualitative analysis revealed that nanoscale systems demonstrate significant antineoplastic and anti-metastasis properties: increased drug bioavailability, reduced toxicity, enhanced permeability and retention effect, as well as tumor growth inhibition, among others. Nanoformulations for skin cancers have largely lagged behind those tested in other cancers-several of which have commercialized formulae. However, emerging evidence has indicated a powerful role for these carriers in targeting primary and metastatic skin cancers.

Regulatory miRNAs and lncRNAs in Skin Cancer: A Narrative Review.

Non-coding RNAs (ncRNAs) have a significant regulatory role in the pathogenesis of skin cancer, despite the fact that protein-coding genes have generally been the focus of research efforts in the field. We comment on the actions of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the current review with an eye toward potential therapeutic treatments. LncRNAs are remarkably adaptable, acting as scaffolding, guides, or decoys to modify key signaling pathways (i.e., the Wnt/ß-catenin pathway) and gene expression. As post-transcriptional gatekeepers, miRNAs control gene expression by attaching to messenger RNAs and causing their degradation or suppression during translation. Cell cycle regulation, cellular differentiation, and immunological responses are all affected by the dysregulation of miRNAs observed in skin cancer. NcRNAs also show promise as diagnostic biomarkers and prognostic indicators. Unraveling the complexity of the regulatory networks governed by ncRNAs in skin cancer offers unprecedented opportunities for groundbreaking targeted therapies, revolutionizing the landscape of dermatologic care.

Evidence-Based Utility of Adjunct Antioxidant Supplementation for the Prevention and Treatment of Dermatologic Diseases: A Comprehensive Systematic Review.

Skin conditions are a significant cause of fatal and nonfatal disease burdens globally, ranging from mild irritations to debilitating diseases. Oxidative stress, which is an imbalance between reactive oxygen species and the cells' ability to repair damage, is implicated in various skin diseases. Antioxidants have been studied for their potential benefits in dermatologic health, but the evidence is limited and conflicting. Herein, we conducted a systematic review of controlled trials, meta-analyses, and Cochrane review articles to evaluate the current evidence on the utility of antioxidant supplementation for adjunct prevention and treatment of skin disease and to provide a comprehensive assessment of their role in promoting dermatologic health. The Cochrane Library, PubMed, EMBASE, and Epistemonikos databases were queried. Eligibility criteria included (1) primary focus on nanoparticle utility for skin cancer; (2) includes measurable outcomes data with robust comparators; (3) includes a number of human subjects or cell-line types, where applicable; (4) English language; and (5) archived as full-text journal articles. A total of 55 articles met the eligibility criteria for the present review. Qualitative analysis revealed that topical and oral antioxidant supplementation has demonstrated preliminary efficacy in reducing sunburns, depigmentation, and photoaging. Dietary exogenous antioxidants (namely vitamins A, C, and E) have shown chemopreventive effects against skin cancer. Antioxidant supplementation has also shown efficacy in treating non-cancer dermatoses, including rosacea, psoriasis, atopic dermatitis, and acne vulgaris. While further studies are needed to validate these findings on a larger scale, antioxidant supplementation holds promise for improving skin health and preventing skin diseases.

Real-World Outcomes for Basilar Artery Occlusion Thrombectomy With Mild Deficits: The National Inpatient Sample.

BACKGROUND: Thrombectomy for basilar artery occlusion (BAO) has proven efficacy in patients with moderate-to-severe deficits, but has unclear benefits for those with mild symptoms. METHODS: Using an observational cohort design, the US National Inpatient Sample (2018-2020) was queried for adult patients with basilar artery occlusion and National Institutes of Health Stroke Scale (NIHSS) <10 for patients treated with thrombectomy versus medical management. The primary outcome of routine discharge (to home or self-care) was evaluated using multivariable logistic regression and propensity score matching, adjusted for baseline characteristics, stroke severity, and treatment with thrombolysis. RESULTS: Of 17 019 with basilar artery occlusion, 5795 patients met the criteria for inclusion criteria for our study, and 880 (15.4%) were treated with endovascular thrombectomy. In the propensity score-matched cohort, 880 patients were treated with medical management and endovascular thrombectomy, respectively. In multivariable regression, endovascular thrombectomy was associated with both an increased odds of routine discharge (odds ratio, 1.95 [95% CI, 1.31-2.90]; P=0.001) and a decreased length of hospital stay (B, -0.74 [95% CI, -1.36 to -0.11]; P=0.02) compared with medical management. In the propensity score matched cohort, endovascular thrombectomy remained associated with greater odds of routine discharge (2.01 [95% CI, 1.21-3.34]; P=0.007) but no difference in length of hospital stay (B, -0.22 [95% CI, -0.90 to 0.46]; P=0.53). CONCLUSIONS: Routine discharge was more common in this representative US cohort of patients with basilar artery occlusion and National Institutes of Health Stroke Scale <10 who underwent thrombectomy compared to conventional medical management. These findings suggest thrombectomy may be associated with better functional outcomes despite lower National Institutes of Health Stroke Scale and should be validated in a clinical trial setting.

Spatial Mapping of Genes Implicated in SARS-CoV-2 Neuroinvasion to Dorsolateral Prefrontal Cortex Gray Matter.

Introduction: SARS-CoV-2 is the newest beta coronavirus family member to demonstrate neuroinvasive capability in severe cases of infection. Despite much research activity in the SARS-CoV-2/COVID-19 space, the gene-level biology of this phenomenon remains poorly understood. In the present analysis, we leveraged spatial transcriptomics methodologies to examine relevant gene heterogeneity in tissue retrieved from the human prefrontal cortex. Methods: Expression profiles of genes with established relations to the SARS-CoV-2 neuroinvasion process were spatially resolved in dorsolateral prefrontal cortex tissue (N = 4). Spotplots were generated with mapping to six (6) previously defined gray matter layers. Results: Docking gene BSG, processing gene CTSB, and viral defense gene LY6E demonstrated similar spatial enrichment. Docking gene ACE2 and transmembrane series proteases involved in spike protein processing were lowly expressed across DLPFC samples. Numerous other findings were obtained. Conclusion: Efforts to spatially represent expression levels of key SARS-CoV-2 brain infiltration genes remain paltry to date. Understanding the sobering history of beta coronavirus neuroinvasion represents a weak point in viral research. Here we provide the first efforts to characterize a motley of such genes in the dorsolateral prefrontal cortex.

Predictors of inpatient admission likelihood and prolonged length of stay among cerebrovascular disease patients: A nationwide emergency department sample analysis.

PURPOSE: To examine the hospital- and patient-related factors associated with increased likelihood of inpatient admission and extended hospitalization. METHODS: We applied multivariate logistic regression to a subset of ED hospital and patient characteristics linearly extrapolated from the 2019 National Emergency Department Sample database (n=626,508). Patient characteristics with 10 or fewer ED visits after national extrapolation were not reported in the current study to maintain patient confidentiality, in accordance with the HCUP Data Use Agreement. All selected ED visits represented a primary diagnosis of CVD (ICD-10 codes 160-168). All reported hospital and patient characteristics were subject to adjustment for covariates. P-values < 0.05 were considered statistically significant. MAIN FINDINGS: Medicare beneficiaries report higher inpatient admission rates than uninsured OR 0.81 (0.73-0.91) and privately insured OR 0.86 (0.79-0.94) individuals. Black and Native-American patients were 37% and 55% more likely to be hospitalized long (>75th percentile) (OR 1.37 [1.25-1.50], OR 1.55 [1.14-2.10]). Northeast emergency departments reported an increased odds of admission compared to the Midwest OR (0.40-0.62), South OR 0.79 (0.63-0.98) and West OR 0.52 (0.39-0.69). Patients with multiple comorbidities (mCCI = 3+) were 226% more likely to have a longer stay OR 3.26 (3.09-3.45) than patients presenting with zero or few comorbidities. Level I, II, and III trauma centers report distinctly high odds of inpatient admission (OR 3.54 [2.84-4.42], OR 2.68 [2.14-3.35], OR 1.51 [1.25-1.84]). PRINCIPAL CONCLUSIONS: Likelihoods of inpatient admission and long hospital stays were observably stratified through multiple, independently acting hospital and patient characteristics. Significant associations were stratified by race/ethnicity, location, and clinical presentation, among others. Attention to the factors reported here may serve well to mitigate emergency department crowding and its sobering impact on United States healthcare systems and patients.

Incidence, Characteristics, and Cost of Eyelid Lacerations in the United States from 2006 to 2014.

INTRODUCTION: To report the incidence, demographics, and cost of eyelid lacerations (ELs) in the USA. METHODS: The Nationwide Emergency Department Sample is the largest publicly available emergency department database in the US. We conducted a retrospective longitudinal analysis to identify all emergency department (ED) visits in the sample from 2006 to 2014 with a primary or secondary diagnosis of EL. Descriptive statistics were calculated for hospital characteristics, patient demographics, and inflation-adjusted patient ED and in-patient (IP) charges. RESULTS: The incidence of primary and total ELs from 2006 to 2014 decreased by 50 per million and 7.1 per million, respectively. In the same period, the total ED and average ED charge, corrected for inflation, increased by almost $37 million and $1600 per person, respectively. Motor vehicle accidents (MVAs) were the mechanism of injury (MOI) associated with the highest average ED and IP costs at $5391 and $42,677, respectively. However, object- (42.2%) and fall-related (28.8%) were the most reported MOI overall. Peak months of EL presentations were seen in May and July, and > 90% of primary ELs were classified as periocular. Most ELs occurred in men and children, representing 69% and 44% of all primary EL cases, respectively. CONCLUSION: The incidence of ELs declined from 2006 to 2014. ELs occurred most frequently in children and young adults. The high proportion of object and fall-related injuries in this population highlights an area to develop strategies to reduce the frequency of preventable eye injuries.

Incidence and Characteristics of Orbital Hemorrhages in the United States from 2006 to 2018.

Purpose: To determine the incidence, characteristics, and costs associated with orbital hemorrhages presenting to US EDs. Patients and Methods: This was a retrospective, longitudinal study of the Nationwide Emergency Department Sample, 2006 to 2018. Medical records from patients presenting to participating hospital-owned EDs and diagnosed with primary or secondary orbital hemorrhage were examined to determine incidence, demographics, clinical characteristics, mechanism, disposition and related risk factors, and costs. Results: From 2006 to 2018, an estimated 20,762 US ED visits included an orbital hemorrhage diagnosis. Most primary diagnosis patients were elderly (35%) and male (51%), and incidence increased from 1.1 (95% CI: 0.8-1.4) to 3.1 per million (95% CI: 2.5-3.7, p < 0.0001). Fall was the most common mechanism (21.6%), particularly among the elderly (39.9%). Fall-related diagnoses increased from 0.03 (95% CI: -0.01-0.07) to 1.0 per million (95% CI: 0.7-1.3, p < 0.0001), while overall falls increased by only 7%. Assault-related orbital hemorrhage increased from 0.1 (95% CI: 0.0-0.2) to 0.6 per million (95% CI: 0.4-0.7, p < 0.0001), while overall assaults decreased by 22%. Annual total ED costs increased from $463,220 (95% CI: 233,993-692,446) to $6,117,320 (95% CI: 4,665,403-7,569,237, p < 0.001). Inpatient admission was uncommon (9.0%), but related costs totaled $18.9 million (95% CI: 13.3-24.5). Odds of admission were lower in fall- and objects-related injuries and higher with certain concurrent injuries. Conclusion: Orbital hemorrhages are becoming more frequent and costly. A disproportionately large increase in fall- and assault-related diagnoses highlights the need for targeted injury prevention strategies to reduce cost and morbidity.

Cell-specific regulation of gene expression using splicing-dependent frameshifting.

Precise and reliable cell-specific gene delivery remains technically challenging. Here we report a splicing-based approach for controlling gene expression whereby separate translational reading frames are coupled to the inclusion or exclusion of mutated, frameshifting cell-specific alternative exons. Candidate exons are identified by analyzing thousands of publicly available RNA sequencing datasets and filtering by cell specificity, conservation, and local intron length. This method, which we denote splicing-linked expression design (SLED), can be combined in a Boolean manner with existing techniques such as minipromoters and viral capsids. SLED can use strong constitutive promoters, without sacrificing precision, by decoupling the tradeoff between promoter strength and selectivity. AAV-packaged SLED vectors can selectively deliver fluorescent reporters and calcium indicators to various neuronal subtypes in vivo. We also demonstrate gene therapy utility by creating SLED vectors that can target PRPH2 and SF3B1 mutations. The flexibility of SLED technology enables creative avenues for basic and translational research.

An Analysis of Epidemiological Factors in Heart Failure Outcomes.

Background Various socioeconomic and demographic factors play a role in determining treatment outcomes across numerous conditions. Different studies have shown that certain demographic factors, such as income status, directly correlate with treatment outcomes. In this study, we analyze the effect of some of these variables, namely, insurance and age, on various endpoints, including length of stay and discharge status, among heart failure patients. Methodology The data used in this project were retrieved from the HealthCare Utilization Project. We sorted the data by insurance, age, length of stay, and discharge status. To compare discharge status between different insurance types and age groups, we used Stata to compute odds ratios and 95% confidence intervals. To compare the length of stay among different age groups and insurance types, we conducted an unpaired two-tailed Student's t-test. Results Across all age groups, we found that younger patients with heart failure are more likely to discharge against medical advice compared to older patients. The average length of stay for heart failure patients was the same across all age groups except those 85 and older. Moreover, patients with a lower socioeconomic status, as determined by insurance type, were more likely to discharge against medical advice and less likely to die within hospitals. Conclusions Our results speak to the socioeconomic inequalities seen in medicine today. Studies have shown that those with a lower socioeconomic status tend to have worse outcomes across various conditions. Our analysis shows this phenomenon holds true for heart failure as well. In addition, our study helps to determine which groups are at higher risk of making medical decisions, such as discharging against medical advice, that will negatively affect their condition. Identifying these high-risk groups is a key first step to counteracting such behavior.

Altered linear coupling between stimulus-evoked blood flow and oxygen metabolism in the aging human brain.

Neural-vascular coupling (NVC) is the process by which oxygen and nutrients are delivered to metabolically active neurons by blood vessels. Murine models of NVC disruption have revealed its critical role in healthy neural function. We hypothesized that, in humans, aging exerts detrimental effects upon the integrity of the neural-glial-vascular system that underlies NVC. To test this hypothesis, calibrated functional magnetic resonance imaging (cfMRI) was used to characterize age-related changes in cerebral blood flow (CBF) and oxygen metabolism during visual cortex stimulation. Thirty-three younger and 27 older participants underwent cfMRI scanning during both an attention-controlled visual stimulation task and a hypercapnia paradigm used to calibrate the blood-oxygen-level-dependent signal. Measurement of stimulus-evoked blood flow and oxygen metabolism permitted calculation of the NVC ratio to assess the integrity of neural-vascular communication. Consistent with our hypothesis, we observed monotonic NVC ratio increases with increasing visual stimulation frequency in younger adults but not in older adults. Age-related changes in stimulus-evoked cerebrovascular and neurometabolic signal could not fully explain this disruption; increases in stimulus-evoked neurometabolic activity elicited corresponding increases in stimulus-evoked CBF in younger but not in older adults. These results implicate age-related, demand-dependent failures of the neural-glial-vascular structures that comprise the NVC system.