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Background: Coronary CT angiography (CCTA) and contrast-enhanced thoracic CT (CECT) are distinctly different diagnostic procedures that involve intravenous contrast-enhanced CT of the chest. The technical component of these procedures is reimbursed at the same rate by the Centers for Medicare and Medicaid Services (CMS). This study tests the hypothesis that the direct costs of performing these exams are significantly different., Methods: Direct costs for both procedures were measured using a time-driven activity-based costing (TDABC) model. The exams were segmented into four phases: preparation, scanning, post-scan monitoring, and image processing. Room occupancy and direct labor times were collected for scans of 54 patients (28 CCTA and 26 CECT studies), in seven medical facilities within the USA and used to impute labor and equipment cost. Contrast material costs were measured directly. Cost differences between the exams were analyzed for significance and variability., Results: Mean CCTA duration was 3.2 times longer than CECT (121 and 37 ​min, respectively. p ​< ​0.01). Mean CCTA direct costs were 3.4 times those of CECT ($189.52 and $55.28, respectively, p ​< ​0.01). Both labor and capital equipment costs for CCTA were significantly more expensive (6.5 and 1.8-fold greater, respectively, p ​< ​0.001). Segmented by procedural phase, CCTA was both longer and more expensive for each (p ​< ​0.01). Mean direct costs for CCTA exceeded the standard CMS technical reimbursement of $182.25 without accounting for indirect or overhead costs., Conclusion: The direct cost of performing CCTA is significantly higher than CECT, and thus reimbursement schedules that treat these procedures similarly undervalue the resources required to perform CCTA and possibly decrease access to the procedure., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:G.D.R. is an advisor to HeartFlow, outside the submitted work. C. B. gave a lecture in 2019 for HeartFlow, outside the submitted work. B.B.G. is supported by institutional grants to his institution from Siemens Healthineers and the NIH, outside the submitted work. No interests or disclosures declared for M.E.Z., J.C.B., M.G.R., R.B., G.E.W., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Mutations in the glucocerebrosidase (GBA) gene are a strong genetic risk factor for the development of Parkinson's disease and dementia with Lewy Bodies. However the penetrance of GBA mutations is low for these diseases in heterozygous carriers. The aim of this study was to examine the relationship between mutation status and cognitive and motor functioning in a sample of community-dwelling older adults. Using linear mixed effects models, we examined the effect of heterozygous mutation status on 736 community-dwelling older adults (≥70 years) without dementia or Parkinson's disease assessed over an average of 6 years, 28 of whom had a single GBA mutation (primarily N370S). Verbal memory was measured using the picture version of the Free and Cued Selective Reminding Test, and carriers showed significantly (p < 0.05) greater decline in verbal memory over time. There was no difference in motor function or any other cognitive domain. Taken together, these results suggest an effect, but an overall limited burden, of harboring a single GBA mutation in aging mutation carriers., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Apolipoprotein ε4 (ApoE4) is a strong genetic risk factor for sporadic Alzheimer's disease and memory decline in older adults. A single-nucleotide polymorphism in the cholesteryl ester transfer protein (CETP) gene (isoleucine to valine; V405) is associated with slower memory decline and a lower risk of Alzheimer's disease. As both genes regulate cholesterol, we hypothesized that the favorable CETPV405 allele may buffer the effect of ApoE4 on memory decline in older adults. Using linear regression, we examined the interactive effect of ApoE4 by CETPV405 on memory decline among 909 community-dwelling, nondemented, older adults (≥70 years) from the Einstein Aging Study. Episodic memory was measured using the picture version of the Free and Cued Selective Reminding Test with immediate recall (pFCSRT+IR). There was a significant ApoE × CETP interaction on decline in pFCSRT+IR scores (p = 0.01). ApoE4 carriers experienced faster decline than noncarriers among CETPI405I homozygotes (p = 0.007) and in CETPI405V heterozygotes (p = 0.015) but not in CETPV405V homozygotes (p = 0.614). Results suggest that the CETPV405 allele buffers ApoE4-associated memory decline in a gene dose-dependent manner., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The retrogenesis hypothesis postulates that late-myelinated white matter fibers are most vulnerable to age- and disease-related degeneration, which in turn mediate cognitive decline. While recent evidence supports this hypothesis in the context of Alzheimer's disease, it has not been tested systematically in normal cognitive aging. In the current study, we examined the retrogenesis hypothesis in a group (n = 282) of cognitively normal individuals, ranging in age from 7 to 87 years, from the Brain Resource International Database. Participants were evaluated with a comprehensive neuropsychological battery and were imaged with diffusion tensor imaging. Fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (DA), measures of white matter coherence, were computed in 2 prototypical early-myelinated fiber tracts (posterior limb of the internal capsule, cerebral peduncles) and 2 prototypical late-myelinated fiber tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus) chosen to parallel previous studies; mean summary values were also computed for other early- and late-myelinated fiber tracts. We examined age-associated differences in FA, RD, and DA in the developmental trajectory (ages 7-30 years) and degenerative trajectory (ages 31-87 years), and tested whether the measures of white matter coherence mediated age-related cognitive decline in the older group. FA and DA values were greater for early-myelinated fibers than for late-myelinated fibers, and RD values were lower for early-myelinated than late-myelinated fibers. There were age-associated differences in FA, RD, and DA across early- and late-myelinated fiber tracts in the younger group, but the magnitude of differences did not vary as a function of early or late myelinating status. FA and RD in most fiber tracts showed reliable age-associated differences in the older age group, but the magnitudes were greatest for the late-myelinated tract summary measure, inferior longitudinal fasciculus (late fiber tract), and cerebral peduncles (early fiber tract). Finally, FA in the inferior longitudinal fasciculus and cerebral peduncles and RD in the cerebral peduncles mediated age-associated differences in an executive functioning factor. Taken together, the findings highlight the importance of white matter coherence in cognitive aging and provide some, but not complete, support for the white matter retrogenesis hypothesis in normal cognitive aging., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Although the treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) has been shown to be effective, nightly adherence to treatment remains poor. The objective of this study was to examine the degree to which various levels of PAP therapy adherence normalized verbal memory function after 3 months of therapy in patients with OSA who were memory-impaired prior to the initiation of PAP therapy., Methods: Participants were administered neuropsychological testing prior to the initiation of PAP treatment and at a 3-month follow-up visit. Fifty-eight memory-impaired participants were categorized into the following three groups based on 3 months of adherence to PAP therapy: (1) poor users (n = 14), participants who averaged < 2 h of PAP use per night; (2) moderate users (n = 25), participants who averaged 2 to 6 h of PAP use per night; and (3) optimal users (n = 19), participants who averaged > 6 h of PAP use per night., Results: Logistic regression analyses revealed that the odds of optimal users exhibiting normalization of memory function following 3 months of PAP therapy were 7.9 times (p = 0.01) the odds of poor users exhibiting normalization of memory abilities. Overall, 21% of poor users, 44% of moderate users, and 68% of optimal users exhibited memory performance in the clinically normal range following 3 months of PAP use (chi(2) = 7.27; p = 0.03)., Conclusions: These preliminary findings indicate that impaired verbal memory performance in patients with OSA may be reversible with optimal levels of PAP treatment. OSA patients exhibiting verbal memory impairments may experience a clinically meaningful benefit in their memory abilities when they use PAP for at least 6 h per night.

Objective: Age-associated decline in gray matter brain volume and cognitive function in healthy adults has been reported in the literature. The goal of the current study is to examine the relationship between age-related changes in regional gray matter volumes and cognitive function in a large, cross-sectional sample of healthy adults across the lifespan., Methods: Magnetic resonance imaging and cognitive assessment were conducted on 148 adults aged 21-76 years. Multiple regression analyses examining the effect of age were performed on magnetic resonance image-derived gray matter brain volumes and standardized cognitive summary scores of attention and executive function. Regression was also performed to test the effect of age, gray matter volumes, and their interaction on the prediction of cognitive performance., Results: Age significantly predicted performance on tests of attention (F [1, 146]=50.97, p <0.01, R2=0.26) and executive function (F [1, 146]=126.19, p <0.01, R2=0.46) and gray matter volumes for frontal subregions (lateral, medial, orbital), hippocampus, amygdala, and putamen (F [2, 145]=45.34-23.96, p <0.01-0.02). Lateral frontal (beta=-1.53, t=-2.16, df=131, p <0.03) and orbital frontal (beta=1.24, t=2.08, df=131, p <0.04) regions significantly predicted performance on tests of attention. Lateral frontal (beta=-1.69, t=-2.83, df=131, p <0.01) and the interaction between age and lateral frontal volume (beta=3.76, t=2.49, df=131, p <0.02) significantly predicted executive function., Conclusions: The findings confirm age-associated decline in cognitive function and gray matter volumes, particularly in anterior cortical brain regions. Furthermore, the association between lateral frontal gray matter volume and the ability to successfully plan, organize, and execute strategies varies as a function of age across the healthy adult lifespan.

Background: The current study utilized magnetic resonance imaging (MRI) to more fully elucidate the relationship among age, regional white matter, and neuropsychological functioning., Methods: One hundred ninety-nine neurologically healthy adults received MRI and standardized neuropsychological assessment. MR images were spatially normalized and segmented by tissue type; relative white matter values in each of the four cerebral lobes in each hemisphere were computed. Subjects were divided into Younger (ages 21-30), Middle (ages 31-54), and Older (ages 55-79) age groups., Results: The Older group had significantly less overall relative white matter than the Middle group, who had significantly less overall relative white matter than the Younger participants (F (2, 193) = 5.42, p = 0.005). Differences in frontal lobe white matter were of largest magnitude, followed by temporal lobe (F (6, 579) = 3.32, p = 0.003). Age and frontal and temporal lobe white matter were primarily associated with performance on neuropsychological tests of executive functioning and memory. Mediational analysis suggested that frontal lobe white matter mediated the relationship between age and performance on tasks of executive functioning and memory., Conclusions: The results confirm age-associated decline in frontal and temporal white matter, and age-related cognitive decline in several domains. Decline in neuropsychological functioning is, in part, mediated by a relative age-related reduction in frontal white matter.

Background: Previous magnetic resonance imaging (MRI) studies indicate that compared with healthy volunteers, patients with bipolar disorder have structural and functional abnormalities in the prefrontal cortex. The aim of this study was to investigate differences in prefrontal subregions between bipolar patients and healthy subjects., Methods: Bipolar patients hospitalized for a manic episode (n = 17), and demographically matched healthy volunteers (n = 12) were recruited. Contiguous 1-mm coronal T1-weighted MRI slices were obtained using a Picker 1.5 Tesla scanner. The gray and white matter volumes of five prefrontal subregions of interest were measured: superior, middle, inferior, cingulate, and orbital., Results: Bipolar patients had smaller left prefrontal gray matter volumes, specifically in the middle and superior subregions and smaller right prefrontal gray matter volumes, specifically in the inferior and middle subregions. White matter differences were not observed in any of the prefrontal subregions., Conclusions: The results suggest that bipolar patients have subregion-specific gray matter volume reductions in the prefrontal cortex as compared to healthy subjects. Further investigations into the role of specific prefrontal subregions in bipolar disorder are warranted.