Larger Ventricular Volumes Research Articles

Distinguishing athletic heart adaptations from cardiomyopathy using myocardial work: new kid on the block

Abstract Background Studying the athlete's heart is challenging due to the overlap between physiological adaptations from exercise and cardiomyopathies. Initially, deformation analysis was promising for differentiation, but it became clear that larger ventricular volumes in athletes result in low strain due to chamber geometry. Recently, a non-invasive myocardial work study tool has emerged, integrating load and deformation. Aim to determine the additional value of the Myocardial Work (MW) indices determined by echocardiography in the study of the athlete's heart. Methods A retrospective analysis of echocardiographic parameters was carried out, measuring myocardial work non-invasively among a group of male athletes (football players - class IC of Mitchell classification), compared with a control group composed of healthy young men. A GE Vivid E95 echocardiographic ultrasound system and EchoPAC V.206 software (GE Vingmed Ultrasound AS, Horten, Norway) were used. Results The athletes' group consisted of 121 males with a median age of 24 years (range 21-31), while the control group included 77 healthy individuals with a median age of 26 years (range 23-31). Refer to Table 1 for the descriptive analysis. Compared to the control group, the athletes had significantly lower blood pressure (p = 0.001), larger left ventricular volumes (p < 0.001), and higher left ventricular ejection fractions (p <0.001). Although there was a trend toward lower GLS in the athletes' group, it was not statistically significant (p = 0.203). GWI, GCW, and GWE were similar between the two groups, with GCW being significantly higher in the athletes (p = 0.01). Conclusion In our study, myocardial work indices in athletes were comparable to those in healthy individuals. Myocardial work is an intuitive and comprehensive variable that shows promise as a tool to differentiate between normal physiological adaptations to exercise and pathology in athletes. Descriptive analysis MW example

Continuous β-Amyloid CSF/PET Imbalance Model to Capture Alzheimer Disease Heterogeneity.

Discordance between CSF and PET biomarkers of β-amyloid (Aβ) might reflect an imbalance between soluble and aggregated species, possibly reflecting disease heterogeneity. Previous studies generally used binary cutoffs to assess discrepancies in CSF/PET biomarkers, resulting in a loss of information on the extent of discordance. In this study, we (1) jointly modeled Aβ-CSF/PET data to derive a continuous measure of the imbalance between soluble and fibrillar pools of Aβ, (2) investigated factors contributing to this imbalance, and (3) examined associations with cognitive trajectories. Across 822 cognitively unimpaired (n = 261) and cognitively impaired (n = 561) Alzheimer's Disease Neuroimaging Initiative individuals (384 [46.7%] females, mean age 73.0 ± 7.4 years), we fitted baseline CSF-Aβ42 and global Aβ-PET to a hyperbolic regression model, deriving a participant-specific Aβ-aggregation score (standardized residuals); negative values represent more soluble relative to aggregated Aβ and positive values more aggregated relative to soluble Aβ. Using linear models, we investigated whether methodological factors, demographics, CSF biomarkers, and vascular burden contributed to Aβ-aggregation scores. With linear mixed models, we assessed whether Aβ-aggregation scores were predictive of cognitive functioning. Analyses were repeated in an early independent validation cohort of 383 Amyloid Imaging to Prevent Alzheimer's Disease Prognostic and Natural History Study individuals (224 [58.5%] females, mean age 65.2 ± 6.9 years). The imbalance model could be fit (pseudo-R2 = 0.94) in both cohorts, across CSF kits and PET tracers. Although no associations were observed with the main methodological factors, lower Aβ-aggregation scores were associated with larger ventricular volume (β = 0.13, p < 0.001), male sex (β = -0.18, p = 0.019), and homozygous APOE-ε4 carriership (β = -0.56, p < 0.001), whereas higher scores were associated with increased uncorrected CSF p-tau (β = 0.17, p < 0.001) and t-tau (β = 0.16, p < 0.001), better baseline executive functioning (β = 0.12, p < 0.001), and slower global cognitive decline (β = 0.14, p = 0.006). In the validation cohort, we replicated the associations with APOE-ε4, CSF t-tau, and, although modestly, with cognition. We propose a novel continuous model of Aβ CSF/PET biomarker imbalance, accurately describing heterogeneity in soluble vs aggregated Aβ pools in 2 independent cohorts across the full Aβ continuum. Aβ-aggregation scores were consistently associated with genetic and AD-associated CSF biomarkers, possibly reflecting disease heterogeneity beyond methodological influences.

Cerebral oxygen extraction fraction declines with ventricular enlargement in patients with normal pressure hydrocephalus

Normal pressure hydrocephalus (NPH) is a neurodegenerative disease that is potentially reversible by shunt surgery in approximately 60% of patients. Imaging may provide a means to investigate brain tissue viability and oxygen metabolism in NPH patients. Oxygen extraction fraction (OEF) mapping was generated from 3D multi-echo gradient echo MRI (mGRE) data using QQ-CCTV algorithm and cerebral blood flow (CBF) using 3D arterial spin labeling (ASL) MRI data, thereby calculating the cerebral metabolic rate of oxygen (CMRO2=CBF×OEF×[H]a) in 16 NPH patients. Regression analyses using cortical gray matter and deep gray matter regions were conducted with age, gender, CSF stroke volume and normalized ventricular volume as independent variables. OEF showed significant negative correlations with normalized brain ventricular volumes in the whole brain (p=0.004, q=0.01), cortical gray matter (p=0.004, q=0.01), caudate (p=0.02, q=0.04), and pallidum (p=0.03, q=0.04), but no significant correlation with CSF stroke volume (q>0.05). There was no significant finding with CBF or CMRO2. In NPH patients, low OEF in several regions was significantly correlated with large ventricular volumes, indicating decreased tissue oxygen metabolism with increased NPH severity. OEF mapping may provide a functional understanding of neurodegeneration in NPH and may improve monitoring of disease course and treatment outcomes.

Ventricular dyssynchrony late after the Fontan operation is associated with decreased survival

BackgroundVentricular dyssynchrony and its relationship to clinical outcomes is not well characterized in patients following Fontan palliation.MethodsSingle-center retrospective analysis of cardiac magnetic resonance (CMR) imaging of patients with a Fontan circulation and an age-matched healthy comparison cohort as controls. Feature tracking was performed on all slices of a ventricular short-axis cine stack. Circumferential and radial strain, strain rate, and displacement were measured; and multiple dyssynchrony metrics were calculated based on timing of these measurements (including standard deviation of time-to-peak, maximum opposing wall delay, and maximum base-to-apex delay). Primary endpoint was a composite measure including time to death, heart transplant or heart transplant listing (D/HTx).ResultsA total of 503 cases (15 y; IQR 10, 21) and 42 controls (16 y; IQR 11, 20) were analyzed. Compared to controls, Fontan patients had increased dyssynchrony metrics, longer QRS duration, larger ventricular volumes, and worse systolic function. Dyssynchrony metrics were higher in patients with right ventricular (RV) or mixed morphology compared to those with LV morphology. At median follow-up of 4.3 years, 11% had D/HTx. Multiple risk factors for D/HTx were identified, including RV morphology, ventricular dilation, dysfunction, QRS prolongation, and dyssynchrony. Ventricular dilation and RV morphology were independently associated with D/HTx.ConclusionsCompared to control LVs, single right and mixed morphology ventricles in the Fontan circulation exhibit a higher degree of mechanical dyssynchrony as evaluated by CMR-FT. Dyssynchrony indices correlate with ventricular size and function and are associated with death or need for heart transplantation. These data add to the growing understanding regarding factors that can be used to risk-stratify patients with the Fontan circulation.

Circulating Angiokines Are Associated With Reverse Remodeling and Outcomes in Chronic Heart Failure

We sought to determine whether circulating modifiers of endothelial function are associated with cardiac structure and clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). We measured 25 proteins related to endothelial function in 99 patients from the GUIDE-IT study. Protein levels were evaluated for association with echocardiographic parameters and the incidence of all-cause death and hospitalization for heart failure (HHF). Higher concentrations of angiopoietin 2 (ANGPT2), vascular endothelial growth factor receptor 1 (VEGFR1) and hepatocyte growth factor (HGF) were significantly associated with worse function and larger ventricular volumes. Over time, decreases in ANGPT2 and, to a lesser extent, VEGFR1 and HGF, were associated with improvements in cardiac size and function. Individuals with higher concentrations of ANGPT2, VEGFR1 or HGF had increased risks for a composite of death and HHF in the following year (HR 2.76 (95% CI 1.73-4.40) per 2-fold change in ANGPT2; HR 1.76 (95% CI 1.11-2.79) for VEGFR1; and HR 4.04 (95% CI 2.19-7.44) for HGF). Proteins related to endothelial function associate with cardiac size, cardiac function and clinical outcomes in patients with HFrEF. These results support the concept that endothelial function may be an important contributor to the progression to and the recovery from HFrEF.

Neural correlates of digital measures shown by structural MRI: a post-hoc analysis of a smartphone-based remote assessment feasibility study in multiple sclerosis

BackgroundA study was undertaken to evaluate remote monitoring via smartphone sensor-based tests in people with multiple sclerosis (PwMS). This analysis aimed to explore regional neural correlates of digital measures derived from these tests.MethodsIn a 24-week, non-randomized, interventional, feasibility study (NCT02952911), sensor-based tests on the Floodlight Proof-of-Concept app were used to assess cognition (smartphone-based electronic Symbol Digit Modalities Test), upper extremity function (Draw a Shape Test, Pinching Test), and gait and balance (Static Balance Test, Two-Minute Walk Test, U-Turn Test). In this post-hoc analysis, digital measures and standard clinical measures (e.g., Nine-Hole Peg Test [9HPT]) were correlated against regional structural magnetic resonance imaging outcomes. Seventy-six PwMS aged 18–55 years with an Expanded Disability Status Scale score of 0.0–5.5 were enrolled from two different sites (USA and Spain). Sixty-two PwMS were included in this analysis.ResultsWorse performance on digital and clinical measures was associated with smaller regional brain volumes and larger ventricular volumes. Whereas digital and clinical measures had many neural correlates in common (e.g., putamen, globus pallidus, caudate nucleus, lateral occipital cortex), some were observed only for digital measures. For example, Draw a Shape Test and Pinching Test measures, but not 9HPT score, correlated with volume of the hippocampus (r = 0.37 [drawing accuracy over time on the Draw a Shape Test]/ − 0.45 [touching asynchrony on the Pinching Test]), thalamus (r = 0.38/ − 0.41), and pons (r = 0.35/ − 0.35).ConclusionsMultiple neural correlates were identified for the digital measures in a cohort of people with early MS. Digital measures showed associations with brain regions that clinical measures were unable to demonstrate, thus providing potential novel information on functional ability compared with standard clinical assessments.

Right Ventricular Function Improves Early After Percutaneous Mitral Valve Repair in Patients Suffering From Severe Mitral Regurgitation.

BackgroundPercutaneous mitral valve edge-to-edge procedure (PMVR) using the MitraClip® system (Abbot Vascular, CA) is an established therapy for severe mitral regurgitation (MR) in patients judged inoperable or at high surgical risk. Besides determining exercise capacity, right ventricular (RV) function has prognostic value in heart failure and after cardiac surgery. We therefore investigated the impact of PMVR on RV function in patients with severe MR.Methods and ResultsSixty-three patients undergoing PMVR at our department were prospectively enrolled. Transthoracic echocardiography was performed before, early (2–12d) after PMVR and after 3 months, including advanced echocardiographic analyses such as 3D imaging and strain analyses. At baseline, all patients presented with advanced heart failure symptoms. Etiology of MR was more often secondary and, if present, left ventricular (LV) dysfunction was predominantly caused by ischemic cardiomyopathy. PMVR substantially reduced MR to a grade ≤ 2 in most patients. Echocardiographic assessment revealed a largely unchanged LV systolic function early after PMVR, while in contrast RV function substantially improved after PMVR [3D RV EF (%): pre 33.7% [27.4; 39.6], post 40.0% [34.5; 46.0] (p < 0.01 vs. pre), 3 months 42.8% [38.3; 48.1] (p < 0.01 vs. pre); 2D RV GLS (%): pre −12.9% [−14.5; −10.5], post −16.0% [−17.9; −12.6] (p < 0.01 vs. pre), 3 months −17.2% [−21.7; −14.9] (p < 0.01 vs. pre)]. Factors that attenuated RV improvement were larger ventricular volumes, lower LV function, secondary MR, and a higher STS score (all p < 0.05).ConclusionBy using advanced echocardiographic parameters, we discovered an early improvement of RV function after PMVR that is preserved for months, independent from changes in LV function. Improvement of RV function was less pronounced in patients presenting with an advanced stage of heart failure and a higher burden of comorbidities reflected by the STS score.

Longitudinal Association Between Perceived Fatigability and Brain Volumes in Community-Dwelling Older Adults

Perceived fatigability is linked to declining physical and cognitive performance, yet whether fatigability reflects early subclinical change in brain structure is unknown. Using mixed effects models, we assessed the longitudinal association of 3T MRI-derived brain volumes with perceived fatigability after a 5-min treadmill walk (0.67 m/s, 0% grade) using the Borg Rating of Perceived Exertion scale (range 6-20) in 802 BLSA participants (age 68.2+/-12.4 years, 45% men 66% White). In models adjusted for intracranial volume, demographics, chronic conditions, and CESD score, declining gray matter volumes in the frontal (β=-0.01) and temporal (β=-0.02) lobes, as well as the hippocampus (β=-0.25), precuneus (β=-0.10) and thalamus (β=-0.19) were associated with higher fatigability. Larger ventricular volumes were also associated with higher fatigability (β=0.02). Brain atrophy, particularly in gray matter and the hippocampal region, is longitudinally associated with increased fatigability in cognitively normal older adults, making it a potential marker of brain atrophy.

Energetic Cost of Walking and Brain Atrophy in Mid-to-Late Life.

Higher energetic costs for mobility are associated with declining gait speed, and slow gait is linked to cognitive decline and Alzheimer's disease. However, the physiological underpinnings of gait and brain health have not been well explored. We examined the associations of the energetic cost of walking with brain volume in cognitively unimpaired adults from the Baltimore Longitudinal Study of Aging. We used brain magnetic resonance imaging (MRI) data from 850 participants (mean baseline age 66.3 ± 14.5 years), of whom 451 had longitudinal MRI data (2.8 ± 1.0 MRI scans over 4.0 ± 2.0 years). The energetic cost of walking was assessed as the average energy expended (V̇O2) during 2.5 minutes of customary-paced overground walking. Multivariable linear mixed-effects models examined the associations between baseline energetic cost of walking and regional brain volumes adjusting for covariates. At baseline, higher energetic cost of walking was cross-sectionally associated with lower gray and white matter volumes within the frontal, parietal, and temporal lobes, as well as hippocampal, total brain, and larger ventricular volumes (all false-discovery rate [FDR] p < .05). A baseline energetic cost of walking × time interaction demonstrated that participants with higher energetic cost of walking had faster annual decline in hippocampal volume (FDR p = .02) and accelerated annual increase in ventricular volumes (FDR p = .02). The energetic cost of walking is associated with gray and white matter volumes and subsequent hippocampal atrophy and ventricular enlargement. Collectively, these data suggest the energetic cost of walking may be an early marker of neurodegeneration that contributes to the gait brain connection.

Cognitive dysfunction and cerebral volumetric deficits in individuals with Alzheimer's disease, alcohol use disorder, and dual diagnosis

Epidemiological surveys suggest that excessive drinking is associated with higher risk of Alzheimer's disease (AD). The present study utilized data from the National Alzheimer's Coordinating Center to examine cognition as well as gray/white matter and ventricular volumes among participants with AD and alcohol use disorder (AD/AUD, n=52), AD only (n=701), AUD only (n=67), and controls (n=1283). AUD diagnosis was associated with higher Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) in AD than in non-AD. AD performed worse on semantic fluency and Trail Making Test A+B (TMT A+B) and showed smaller total GMV, WMV, and larger ventricular volume than non-AD. AD had smaller regional GMV in the inferior/superior parietal cortex, hippocampal formation, occipital cortex, inferior frontal gyrus, posterior cingulate cortex, and isthmus cingulate cortex than non-AD. AUD had significantly smaller somatomotor cortical GMV and showed a trend towards smaller volume in the hippocampal formation, relative to non-AUD participants. Misuse of alcohol has an additive effect on dementia severity among AD participants. Smaller hippocampal volume is a common feature of both AD and AUD. Although AD is associated with more volumetric deficits overall, AD and AUD are associated with atrophy in largely distinct brain regions.

Plasma volume status in patients after Fontan operation: Prognostic value and the associations with Fontan pathophysiology

Assessment of plasma volume status (PVS) is essential for the management of patients with heart failure (HF). We aimed to elucidate the clinical features of PVS in patients with Fontan circulation (FC). Plasma volume (PV) was measured via pulse dye densitometry (icg-PV) and compared with the calculated PV (c-PV) in 114 patients with FC and 32 with biventricular circulation (BVC). We derived the PVS (%) [{(c-PV－ideal-PV)/ideal-PV} ​× ​100] and elucidated its clinical associations in 275 consecutive patients with FC and 493 with BVC. The c-PV correlated with the icg-PV in FC (r ​= ​0.70) and BVC (r ​= ​0.67) ( p ​< ​0.0001 for each). Compared with BVC, FC exhibited contracted c-PV (37 ​± ​5 vs. 39 ​± ​4 ​mL/kg) and the PVS was lower (−4.7% ​± ​11.5% vs. −1.3% ​± ​9.8%), although the circulating blood volume (BV) was greater (69 ​± ​6 vs. 66 ​± ​5 ​mL/kg) ( p ​< ​0.0001 for all). Increased PVS was independently associated with HF-associated hospitalization and all-cause mortality in both groups ( p ​< ​0.05) with a cutoff value of 3.0% for FC. FC with PVS ≥3.0% (n ​= ​59) was characterized by low aortic pressure, high cardiac index, and large ventricular volume with a high prevalence of protein-losing enteropathy ( p ​< ​0.05–0.0001). Compared with BVC, FC was associated with increased BV but contracted PV. Regarding Fontan, a higher PVS is associated with a phenotype of high output HF and higher risk of adverse outcomes.

Outcomes of Venus P-valve for dysfunctional right ventricular outflow tracts from Indian Venus P-valve database.

Background :Balloon-expandable pulmonary valves are usually not suitable for dilated native outflow tracts.Methods :Indian Venus P-valve registry was retrospectively analyzed for efficacy, complications, and midterm outcomes. Straight valve was used in prestented conduits in patients with right ventricular pressure above two-thirds systemic pressure and/or right ventricular dysfunction. Flared valve 1–4 mm larger than balloon waist was used in native outflow in symptomatic patients, large ventricular volumes, and ventricular dysfunction.Objectives :A self-expanding porcine pericardial Venus P-valve is available in straight and flared designs..Results :Twenty-nine patients were included. Straight valve was successful in all seven conduits, reducing gradients significantly, including one patient with left pulmonary artery (LPA) stent. Flared valve was successfully implanted in 20 out of 22 native outflow tracts. Sharp edges of the older design contributed to two failures. Complications included two migrations with one needing surgery, endocarditis in one, insignificant wire-frame fractures in three, and groin vascular complication in one patient. There were no deaths or valve-related reinterventions at a mean follow-up of 47.8 ± 24.5 months (1–85 months). Modifications of technique succeeded in three patients with narrow LPA. There was significant improvement in symptoms, right ventricular volume, and pulmonary regurgitant fraction.Conclusion :Straight and flared Venus P-valves are safe and effective in appropriate outflow tracts. Straight valve is an alternative to balloon-expandable valves in stenosed conduits. Flared valve is suitable for large outflows up to 34 mm, including patients with LPA stenosis. Recent design modifications may correct previous technical failures. Studies should focus on durability and late complications.

Association of Cerebral Ischemia With Corneal Nerve Loss and Brain Atrophy in MCI and Dementia.

IntroductionThis study assessed the association of cerebral ischemia with neurodegeneration in mild cognitive impairment (MCI) and dementia.MethodsSubjects with MCI, dementia and controls underwent assessment of cognitive function, severity of brain ischemia, MRI brain volumetry and corneal confocal microscopy.ResultsOf 63 subjects with MCI (n = 44) and dementia (n = 19), 11 had no ischemia, 32 had subcortical ischemia and 20 had both subcortical and cortical ischemia. Brain volume and corneal nerve measures were comparable between subjects with subcortical ischemia and no ischemia. However, subjects with subcortical and cortical ischemia had a lower hippocampal volume (P < 0.01), corneal nerve fiber length (P < 0.05) and larger ventricular volume (P < 0.05) compared to those with subcortical ischemia and lower corneal nerve fiber density (P < 0.05) compared to those without ischemia.DiscussionCerebral ischemia was associated with cognitive impairment, brain atrophy and corneal nerve loss in MCI and dementia.

Unusual association of isolation of right pulmonary artery in absent pulmonary valve syndrome.

Absence of arterial duct, a sixth aortic arch derivative, plays an important etiologic role in Tetralogy of Fallot with absent pulmonary valve syndrome. When fetal ductus is absent, the large right ventricular stroke volume dilates the pulmonary trunk leading to pulmonary regurgitation. A proximal extension of the embryonic insult to the entire left sixth arch causes absence of the left pulmonary artery, a common association of absent pulmonary valve syndrome. On the contrary, absence of right pulmonary artery is not reported in absent pulmonary valve syndrome. A rare combination of tetralogy, absent pulmonary valve syndrome and isolation of a hypoplastic right pulmonary artery offered challenges to diagnosis and management.

ALTERAÇÕES MORFOLÓGICAS EM CÉREBROS DE PESSOAS DIAGNOSTICADAS COM DEPRESSÃO: REVISÃO INTEGRATIVA DA LITERATURA

Segundo a Organização mundial da saúde (OMS), a depressão é um transtorno comum que tem crescido exponencialmente em todo o mundo, com uma estimativa de mais de 300 milhões de pessoas acometidas por esta condição, o que a torna um problema de saúde pública. Dentre as consequências, destacase o comprometimento das atividades cotidianas e sociais dos indivíduos em todas as faixas etárias, podendo ocasionar desfechos trágicos e risco de vida. O presente estudo tem como objetivo estudar as alterações morfológicas em cérebros de pessoas diagnosticadas com depressão. Para tanto, foi realizada uma revisão integrativa da literatura nas bases de dados Scielo e Medline. Após leitura criteriosa, foram selecionados cinco artigos que responderam aos critérios de inclusão. A análise dos artigos mostrou que cérebros de pessoas diagnosticadas com depressão apresentam alterações visíveis em exames de neuroimagens, como a ressonância magnética. As alterações identificadas foram volumes subcorticais menores, volumes ventriculares maiores, menor volume da substância cinzenta do córtex orbitofrontal, anormalidade no córtex pré-frontal, perda de diferenciação entre substância branca e cinzenta e envolvimento das estruturas límbicas. O estudo evidenciou, portanto, que os exames de neuroimagem podem apresentar-se como um recurso importante para a obtenção de um diagnóstico mais rápido e preciso dessa patologia.

Ventricular volume, white matter alterations and outcome of major depression and their relationship to endocrine parameters – A pilot study

Objectives Brain morphology and its relation to endocrine parameters were examined, in order to determine the link of these parameters to treatment outcome to psychopharmacological treatment in depressed patients. Methods We examined the potentially predictive value of Magnetic Resonance Imaging (MRI) parameters related to mineralocorticoid receptor (MR) function on the treatment outcome of depression. 16 inpatients with a major depressive episode (MDE) were studied at baseline and 14 of them approximately six weeks later. Physiological biomarkers and 3-T-structural MRI based volume measures, using FreeSurfer 6.0 software, were determined. Results Non-responders (<50% reduction of HAMD-21; n = 6) had a significantly smaller volume of the right anterior cingulate cortex, a significantly larger ventricle to brain ratio (VBR) and third ventricle volume, and smaller volumes of the central and central-anterior corpus callosum (CC) in comparison to responders (n = 7; all p ≤ 0.05). Correlational analysis (Spearman) demonstrated that larger ventricle volume was correlated to a worse treatment outcome, higher body mass index (BMI) and smaller CC segment volume, whereas the total CC volume was negatively correlated to the saliva aldosterone/cortisol concentration ratio (AC-ratio). Conclusion Large ventricular volume may be a predictive marker for worse treatment response to standard antidepressant treatment, potentially via compression of white matter structures. A mediating role of the previously identified markers BMI and the AC-ratio, is suggested.

Walking Efficiency as a Predictor of Brain Atrophy with Aging

PURPOSE: Emerging evidence suggests decreasing gait speed may precede declining cognitive function with age. Rising energetic costs of walking precede age-related declines in gait speed, making poor walking efficiency a potential early marker of changes in brain structure and function. The purpose of this study was to examine whether diminished walking efficiency precedes aging-related changes in brain structure. METHODS: Longitudinal data from 767 participants (mean age 64.8 + 14.8 years, 51% women) enrolled in the Baltimore Longitudinal Study of Aging neuroimaging substudy over up to 7 years (range 1-7) were examined using linear mixed models to estimate the effects of baseline walking efficiency on brain volumes at the most recent visit. Energy expended during 2.5 minutes of usual paced overground walking was assessed using a portable, indirect calorimeter and standardized per meter walked to derive walking efficiency (ml/kg/m). Using MRI scans, brain volume measurements (cm3) were derived with semi-automated region-of-interest algorithms. RESULTS: In models adjusted for baseline age, sex, time since baseline, race, education, BMI, intracranial volume, and mild cognitive impairment/dementia status, a 0.01 ml/kg/m higher baseline cost of walking was associated with lower total brain volumes (β= -1.2 cm3), white matter (β= -0.9 cm3), gray matter (β= -0.7 cm3), and larger ventricular volumes (β= 0.4 cm3) at follow-up (p<0.03 for all). Standardized coefficients indicated these associations tended to be strongest for white matter, particularly in the frontal and temporal lobes. CONCLUSION: As walking efficiency declines with age, there is associated brain atrophy explained by an observed increase in ventricle volume and shrinkage of total brain, gray and white matter, independent of cognitive impairment and dementia. These findings suggest that rising inefficiencies related to mobility may precede brain atrophy that occurs with aging and serve as novel targets for future interventions that may improve brain health through adaptive motor learning and/or skill development.

Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients With Alzheimer Disease

Plasma neurofilament light (NfL) has been suggested as a noninvasive biomarker to monitor neurodegeneration in Alzheimer disease (AD), but studies are lacking. To examine whether longitudinal plasma NfL levels are associated with other hallmarks of AD. This North American cohort study used data from 1583 individuals in the multicenter Alzheimer's Disease Neuroimaging Initiative study from September 7, 2005, through June 16, 2016. Patients were eligible for inclusion if they had NfL measurements. Annual plasma NfL samples were collected for up to 11 years and were analyzed in 2018. Clinical diagnosis, Aβ and tau cerebrospinal fluid (CSF) biomarkers, imaging measures (magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography), and tests on cognitive scores. The primary outcome was the association between baseline exposures (diagnosis, CSF biomarkers, imaging measures, and cognition) and longitudinal plasma NfL levels, analyzed by an ultrasensitive assay. The secondary outcomes were the associations between a multimodal classification scheme with Aβ, tau, and neurodegeneration (ie, the ATN system) and plasma NfL levels and between longitudinal changes in plasma NfL levels and changes in the other measures. Of the included 1583 participants, 716 (45.2%) were women, and the mean (SD) age was 72.9 (7.1) years; 401 had no cognitive impairment, 855 had mild cognitive impairment, and 327 had AD dementia. The NfL level was increased at baseline in patients with mild cognitive impairment and AD dementia (mean levels: cognitive unimpairment, 32.1 ng/L; mild cognitive impairment, 37.9 ng/L; and AD dementia, 45.9 ng/L; P < .001) and increased in all diagnostic groups, with the greatest increase in patients with AD dementia. A longitudinal increase in NfL level correlated with baseline CSF biomarkers (low Aβ42 [P = .001], high total tau [P = .02], and high phosphorylated tau levels [P = .02]), magnetic resonance imaging measures (small hippocampal volumes [P < .001], thin regional cortices [P = .009], and large ventricular volumes [P = .002]), low fluorodeoxyglucose-positron emission tomography uptake (P = .01), and poor cognitive performance (P < .001) for a global cognitive score. With use of the ATN system, increased baseline NfL levels were seen in A-T+N+ (P < .001), A+T-N+ (P < .001), and A+T+N+ (P < .001), and increased rates of NfL levels were seen in A-T+N- (P = .009), A-T+N+ (P = .02), A+T-N+ (P = .04), and A+T+N+ (P = .002). Faster increase in NfL levels correlated with faster increase in CSF biomarkers of neuronal injury, faster rates of atrophy and hypometabolism, and faster worsening in global cognition (all P < .05 in patients with mild cognitive impairment; associations differed slightly in cognitively unimpaired controls and patients with AD dementia). The findings suggest that plasma NfL can be used as a noninvasive biomarker associated with neurodegeneration in patients with AD and may be useful to monitor effects in trials of disease-modifying drugs.

Coronary artery disease and reasonably incomplete coronary revascularization in high-risk patients undergoing transcatheter aortic valve implantation.

To evaluate the long-term impact of coronary artery disease (CAD) and heart team-guided incomplete coronary revascularization in patients undergoing transcatheter aortic valve implantation (TAVI). Revascularization strategy of CAD diagnosed with routine coronary angiography before TAVI is uncertain. Five hundred and forty consecutive TAVI patients were classified as having CAD or normal coronary arteries (no-CAD). Within the CAD group, patients were further classified as those with complete (CR) versus incomplete revascularization (IR). Revascularization strategy was guided by the Heart Team following an algorithm largely based on current guidelines. Main outcome of interest was the incidence of 5-year cardiovascular (CV) death. Prevalence of CAD was 53.9%. CAD patients showed significantly lower left ventricular ejection fraction (LVEF: 55.8 ± 13.4% CAD vs. 61.4% ± 12.1 no-CAD, p < .0001), lower gradients, and larger ventricular volumes in comparison with the no-CAD group. Within the CAD group, 138 patients (47.4%) received CR and 153 (52.6%) IR. In-hospital mortality was 3.9%, without significant difference between groups (4.0% no-CAD vs. 3.8% CAD, p = .88; 2.9% CR vs. 4.6% IR, p = .45). Median follow-up was 57.8 months. Five-year survival free from CV death was 79.6% in the CAD versus 77.9% in the no-CAD group (p = .98), and 84.3% in the CR versus 74.3% in the IR groups (p = .25). These results were confirmed excluding patients with previous revascularization. At multivariable analyses, presentation with acute coronary syndrome (ACS) was significantly associated with 5-year CV death. CAD is frequent in patients undergoing TAVI but portends an adverse prognosis only when presenting with ACS. Heart-team directed complete or reasonably incomplete revascularization was associated with comparable outcomes.

Assessment of Brain Injury and Brain Volumes after Posthemorrhagic Ventricular Dilatation: A Nested Substudy of the Randomized Controlled ELVIS Trial

To compare the effect of early and late intervention for posthemorrhagic ventricular dilatation on additional brain injury and ventricular volume using term-equivalent age-MRI. In the Early vs Late Ventricular Intervention Study (ELVIS) trial, 126 preterm infants ≤34weeks of gestation with posthemorrhagic ventricular dilatation were randomized to low-threshold (ventricular index>p97 and anterior horn width >6mm) or high-threshold (ventricular index>p97+4mm and anterior horn width >10mm) groups. In 88 of those (80%) with a term-equivalent age-MRI, the Kidokoro Global Brain Abnormality Score and the frontal and occipital horn ratio were measured. Automatic segmentation was used for volumetric analysis. The total Kidokoro score of the infants in the low-threshold group (n=44) was lower than in the high-threshold group (n=44; median, 8 [IQR, 5-12] vs median 12 [IQR, 9-17], respectively; P<.001). More infants in the low-threshold group had a normal or mildly increased score vs more infants in the high-threshold group with a moderately or severely increased score (46% vs 11% and 89% vs 54%, respectively; P=.002). The frontal and occipital horn ratio was lower in the low-threshold group (median, 0.42 [IQR, 0.34-0.63]) than the high-threshold group (median 0.48 [IQR, 0.37-0.68], respectively; P=.001). Ventricular cerebrospinal fluid volumes could be calculated in 47 infants and were smaller in the low-threshold group (P=.03). More brain injury and larger ventricular volumes were demonstrated in the high vs the low-thresholdgroup. These results support the positive effects of early intervention for posthemorrhagic ventricular dilatation. ISRCTN43171322.