Hearing Loss and Sociodemographic Barriers to Health Care Access Using the All of Us Research Program.

OBJECTIVE: To explore how gender and low-income status independently influence general health care access in patients with hearing loss. STUDY DESIGN: Cross-sectional study. SETTING: National database. METHODS: Patients with a diagnosis of sensorineural hearing loss from the National Institutes of Health All of Us database were included. Data entered from May 2018 to November 2022 was analyzed. Patient demographics such as age, gender, educational level, and insurance status were assessed. Multivariate logistic regressions were performed for statistical evaluation. RESULTS: A subset of 8875 patients (48.3% male, mean age 69) were evaluated. After multivariate analysis, female participants were more likely than male participants to report difficulty affording prescribed medications (odds ratio [OR]: 1.7, p < .0005) and specialists (OR: 1.4, p < 0.005). Female patients were also more likely to delay care due to elder care responsibilities (OR: 2.6, p < .0005), employment obligations (OR: 1.7, p < .0005), and feelings of apprehension in seeing a provider (OR: 1.7, p < .0005). Finally, female participants reported feeling less likely to be involved in their own medical care compared to males (OR: 1.2, p < .005). Low-income (<$25,000) participants reported less likely to feel respected (OR: 3.2, p < .0005) and delivered understandable health information (OR: 2.3, p < .0005) by providers compared to participants of higher income. CONCLUSION: This work suggests that patients with hearing loss, female gender, and lower socioeconomic status independently introduce barriers to health care access and utilization. These factors should be considered in efforts to promote equity in the care of patients with hearing loss.

Predictors of multiple dilations and functional outcomes after total laryngectomy and laryngopharyngectomy.

BACKGROUND: Following total laryngectomy (TL) or laryngopharyngectomy (TLP), patients may develop strictures that require multiple dilations to treat. However, the risk factors associated with dysphagia refractory to a single dilation are unknown. METHODS: Single-institution retrospective review of patients who underwent at least one stricture dilation after TL/TLP between March 2013 and March 2022. RESULTS: A total of 49 patients underwent stricture dilation after TL/TLP. Thirty-five (71%) underwent multiple dilations. Pharyngocutaneous fistula, primary chemoradiation therapy, and a shorter time interval from TL/TLP to first dilation were independently associated with dysphagia requiring multiple dilations. Patients in the multiple dilations group had a higher rate of limited diet and G-tube dependence compared to patients in the single dilation group. CONCLUSIONS: Shorter time interval to stricture formation is a prognostic indicator of the need for multiple dilations following TL/TLP. Patients requiring multiple dilations are at increased risk of persistent dysphagia long-term.

Functional considerations between flap and non-flap reconstruction in oral tongue cancer: A systematic review.

This systematic review aims to provide insight into the ideal reconstructive approach of the oral tongue in oral tongue cancer (OTC) by investigating the relationship between functional outcomes and the extent of tongue resection. A structured search was performed in Ovid MEDLINE, EMBASE, and Web of Science. Studies comparing patient-reported and objective measurements of the oral tongue function between flap vs. non-flap reconstruction were included. Functional outcomes of interest were speech production, deglutition efficiency, tongue mobility, overall quality of life, and postoperative complications. A total of nine studies were retrieved and critically appraised. Patients with 20 % or less of oral tongue resected had superior swallowing efficiency and speech intelligibility with a non-flap reconstruction while patients with a tongue defect of 40-50 % self-reported or demonstrated better swallowing function with a flap repair. The data in intermediate tongue defects (20-40 % tongue resected) was inconclusive, with several studies reporting comparable functional outcomes between approaches. A longitudinal multi-institutional prospective study that rigidly controls the extent of tongue resected and subsites involved is needed to determine the percentage of tongue resected at which a flap reconstruction yields a superior functional result in OTC.

Depth of resection predicts loss of tongue tip sensation after partial glossectomy in oral tongue cancer: A pilot study.

OBJECTIVE(S): To characterize the change in sensory function following partial glossectomy for oral tongue cancer (OTC) and to identify predictors of loss of tongue-tip sensation (LoTTS). MATERIALS AND METHODS: Patients with at least three months follow-up after partial glossectomy for primary OTC were included. All patients underwent a qualitative tongue sensation assessment and an objective tongue sensory exam of the native tongue tip. Additional details regarding the oncologic resection, surgical reconstruction, and pathological stage were collected. Multiple linear and logistic regressions were used for statistical analysis. RESULTS: Sixty-four patients were enrolled, including 34 (53%) men with a median age of 65 at enrollment. Ten (15%) patients reported LoTTS. Increased depth of resection (DOR) was an independent predictor of LoTTS on multivariate analysis, with an increased risk at a threshold of 1.3 cm. LoTTS was also associated with worse subjective quality of life and perceptive speech performance in our qualitative tongue assessment. CONCLUSIONS: In this pilot study, we found that DOR is a critical prognostic factor in predicting post treatment function. Patients with an increased DOR, particularly above 1.3 cm, are at greatest risk of LoTTS and associated morbidity. These findings may be used to predict post-operative sensory deficits, manage patients' expectations, and optimize the reconstructive approach. Future studies are needed to validate and replicate our results.

C-NODDI: a constrained NODDI model for axonal density and orientation determinations in cerebral white matter.

Purpose: Neurite orientation dispersion and density imaging (NODDI) provides measures of neurite density and dispersion through computation of the neurite density index (NDI) and the orientation dispersion index (ODI). However, NODDI overestimates the cerebrospinal fluid water fraction in white matter (WM) and provides physiologically unrealistic high NDI values. Furthermore, derived NDI values are echo-time (TE)-dependent. In this work, we propose a modification of NODDI, named constrained NODDI (C-NODDI), for NDI and ODI mapping in WM. Methods: Using NODDI and C-NODDI, we investigated age-related alterations in WM in a cohort of 58 cognitively unimpaired adults. Further, NDI values derived using NODDI or C-NODDI were correlated with the neurofilament light chain (NfL) concentration levels, a plasma biomarker of axonal degeneration. Finally, we investigated the TE dependence of NODDI or C-NODDI derived NDI and ODI. Results: ODI derived values using both approaches were virtually identical, exhibiting constant trends with age. Further, our results indicated a quadratic relationship between NDI and age suggesting that axonal maturation continues until middle age followed by a decrease. This quadratic association was notably significant in several WM regions using C-NODDI, while limited to a few regions using NODDI. Further, C-NODDI-NDI values exhibited a stronger correlation with NfL concentration levels as compared to NODDI-NDI, with lower NDI values corresponding to higher levels of NfL. Finally, we confirmed the previous finding that NDI estimation using NODDI was dependent on TE, while NDI derived values using C-NODDI exhibited lower sensitivity to TE in WM. Conclusion: C-NODDI provides a complementary method to NODDI for determination of NDI in white matter.

Cerebral aggregate g-ratio mapping using magnetic resonance relaxometry and diffusion tensor imaging to investigate sex and age-related differences in white matter microstructure.

Axonal demyelination is a cardinal feature of aging and age-related diseases. The g-ratio, mathematically defined as the inner-to-outer diameter of a myelinated axon, is used as a structural index of optimal axonal myelination and has been shown to represent a sensitive imaging biomarker of microstructural integrity. Several magnetic resonance imaging (MRI) methods for whole-brain mapping of aggregate g-ratio have been introduced. Computation of the aggerate g-ratio requires estimates of the myelin volume fraction (MVF) and the axonal volume fraction (AVF). While accurate determinations of MVF and AVF can be obtained through multicomponent relaxometry or diffusion analyses, respectively, these methods require lengthy acquisition times making their implementation challenging in a clinical context. Therefore, any attempt to overcome this drawback is needed. Expanding on our previous work, we introduced a new MRI method for whole-brain mapping of aggregate g-ratio. This new approach is based on the use of a single-shell diffusion for AVF determination, reducing the acquisition time by approximately ~10 min from our recently introduced approach, while offering the possibility to investigate g-ratio differences in previous studies with existing data for MVF mapping and single-shell diffusion data for AVF mapping. Our comparison analysis indicates that our newly derived aggregate g-ratio values were similar to those derived from our previous method, which requires a longer acquisition time. Further, in agreement with our previous observations, we found quadratic U-shaped relationships between aggregate g-ratio and age in this much larger study cohort. However, our results show that sexual dimorphism in g-ratio was not significant in any brain region investigated.

Insights into human cerebral white matter maturation and degeneration across the adult lifespan.

White matter (WM) microstructural properties change across the adult lifespan and with neuronal diseases. Understanding microstructural changes due to aging is paramount to distinguish them from neuropathological changes. Conducted on a large cohort of 147 cognitively unimpaired subjects, spanning a wide age range of 21 to 94 years, our study evaluated sex- and age-related differences in WM microstructure. Specifically, we used diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) indices, sensitive measures of myelin and axonal density in WM, and myelin water fraction (MWF), a measure of the fraction of the signal of water trapped within the myelin sheets, to probe these differences. Furthermore, we examined regional correlations between MWF and DTI indices to evaluate whether the DTI metrics provide information complementary to MWF. While sexual dimorphism was, overall, nonsignificant, we observed region-dependent differences in MWF, that is, myelin content, and axonal density with age and found that both exhibit nonlinear, but distinct, associations with age. Furthermore, DTI indices were moderately correlated with MWF, indicating their good sensitivity to myelin content as well as to other constituents of WM tissue such as axonal density. The microstructural differences captured by our MRI metrics, along with their weak to moderate associations with MWF, strongly indicate the potential value of combining these outcome measures in a multiparametric approach. Furthermore, our results support the last-in-first-out and the gain-predicts-loss hypotheses of WM maturation and degeneration. Indeed, our results indicate that the posterior WM regions are spared from neurodegeneration as compared to anterior regions, while WM myelination follows a temporally symmetric time course across the adult life span.

Maturation and degeneration of the human brainstem across the adult lifespan.

Brainstem tissue microstructural properties change across the adult lifespan. However, studies elucidating the biological processes that govern brainstem maturation and degeneration in-vivo are lacking. In the present work, conducted on a large cohort of 140 cognitively unimpaired subjects spanning a wide age range of 21 to 94 years, we implemented a multi-parameter approach to characterize the sex- and age differences. In addition, we examined regional correlations between myelin water fraction (MWF), a direct measure of myelin content, and diffusion tensor imaging indices, and transverse and longitudinal relaxation rates to evaluate whether these metrics provide information complementary to MWF. We observed region-dependent differences in myelin content and axonal density with age and found that both exhibit an inverted U-shape association with age in several brainstem substructures. We emphasize that the microstructural differences captured by our distinct MRI metrics, along with their weak associations with MWF, strongly indicate the potential of using these outcome measures in a multi-parametric approach. Furthermore, our results support the gain-predicts-loss hypothesis of tissue maturation and degeneration in the brainstem. Indeed, our results indicate that myelination follows a temporally symmetric time course across the adult life span, while axons appear to degenerate significantly more rapidly than they mature.

Sex and age-related differences in cerebral blood flow investigated using pseudo-continuous arterial spin labeling magnetic resonance imaging.

Adequate cerebral blood flow (CBF) is essential to a healthy central nervous system (CNS). Previous work suggests that CBF differs between men and women, and declines with age and certain pathologies, but a highly controlled systematic study across a wide age range, and incorporating white matter (WM) regions, has not been undertaken. Here, we investigate age- and sex-related differences in CBF in gray matter (GM) and WM regions in a cohort (N = 80) of cognitively unimpaired individuals over a wide age range. In agreement with literature, we find that GM regions exhibited lower CBF with age. In contrast, WM regions exhibited higher CBF with age in various cerebral regions. We attribute this new finding to increased oligodendrocyte metabolism to maintain myelin homeostasis in the setting of increased myelin turnover with age. Further, consistent with prior studies, we found that CBF was higher in women than in men in all brain structures investigated. Our work provides new insights into the effects of age and sex on CBF. In addition, our results provide reference CBF values for the standard ASL protocol recommended by the ISMRM Perfusion Study Group and the European ASL in Dementia consortium. Thus, these results provide a foundation for further investigations of CNS perfusion in a variety of settings, including aging, cerebrovascular diseases, and dementias.

Nonlinear associations of neurite density and myelin content with age revealed using multicomponent diffusion and relaxometry magnetic resonance imaging.

Most magnetic resonance imaging (MRI) studies investigating the relationship between regional brain myelination or axonal density and aging have relied upon nonspecific methods to probe myelin and axonal content, including diffusion tensor imaging and relaxation time mapping. While these studies have provided pivotal insights into changes in cerebral architecture with aging and pathology, details of the underlying microstructural alterations have not been fully elucidated. In the current study, we used the BMC-mcDESPOT analysis, a direct and specific multicomponent relaxometry method for imaging of myelin water fraction (MWF), a marker of myelin content, and NODDI, an emerging multicomponent diffusion technique, for neurite density index (NDI) imaging, a proxy of axonal density. We investigated age-related differences in MWF and NDI in several white matter brain regions in a cohort of cognitively unimpaired participants over a wide age range. Our results indicate a quadratic, inverted U-shape, relationship between MWF and age in all brain regions investigated, suggesting that myelination continues until middle age followed by a decrease at older ages, in agreement with previous work. We found a similarly complex regional association between NDI and age, with several cerebral structures also exhibiting a quadratic, inverted U-shape, relationship. This novel observation suggests an increase in axonal density until the fourth decade of age followed by a rapid loss at older ages. We also observed that these age-related differences in MWF and NDI vary across different brain regions, as expected. Finally, our study indicates no significant association between MWF and NDI in most cerebral structures investigated, although this association approached significance in a limited number of brain regions, indicating the complementary nature of their information and encouraging further investigation. Overall, we find evidence of nonlinear associations between age and myelin or axonal density in a sample of well-characterized adults, using direct myelin and axonal content imaging methods.

Association of cerebral blood flow with myelin content in cognitively unimpaired adults.

BACKGROUND: Myelin loss and cerebral blood flow (CBF) decline are central features of several neurodegenerative diseases. Myelin maintenance through oligodendrocyte metabolism is an energy-demanding process, so that myelin homeostasis is particularly sensitive to hypoxia, hypoperfusion or ischaemia. However, in spite of its central importance, little is known about the association between blood supply and myelin integrity. OBJECTIVE: To assess associations between cortical and subcortical CBF, and subcortical myelin content, in critical brain white matter regions. MATERIALS AND METHODS: MRI was performed on a cohort of 67 cognitively unimpaired adults. Using advanced MRI methodology, we measured whole-brain longitudinal and transverse relaxation rates (R1 and R2 ), sensitive but non-specific markers of myelin content, and myelin water fraction (MWF), a direct surrogate of myelin content, as well as regional CBF, from each of these participants. RESULTS: All quantitative relaxometry metrics were positively associated with CBF in all brain regions evaluated. These associations between MWF or R1 and CBF, and, to a lesser extent, between R2 and CBF, were statistically significant in most brain regions examined, indicating that lower regional cortical or subcortical CBF corresponds to a decrease in local subcortical myelin content. Finally, all relaxometry metrics exhibited a quadratic, inverted U-shaped, association with age; this is attributed to the development of myelination from young to middle age, followed by progressive loss of myelin in later years. CONCLUSIONS: In this first study examining the association between local blood supply and myelin integrity, we found that myelin content declines with CBF across a wide age range of cognitively normal subjects.

Quantitative age-dependent differences in human brainstem myelination assessed using high-resolution magnetic resonance mapping.

Previous in-vivo magnetic resonance imaging (MRI)-based studies of age-related differences in the human brainstem have focused on volumetric morphometry. These investigations have provided pivotal insights into regional brainstem atrophy but have not addressed microstructural age differences. However, growing evidence indicates the sensitivity of quantitative MRI to microstructural tissue changes in the brain. These studies have largely focused on the cerebrum, with very few MR investigations addressing age-dependent differences in the brainstem, in spite of its central role in the regulation of vital functions. Several studies indicate early brainstem alterations in a myriad of neurodegenerative diseases and dementias. The paucity of MR-focused investigations is likely due in part to the challenges imposed by the small structural scale of the brainstem itself as well as of substructures within, requiring accurate high spatial resolution imaging studies. In this work, we applied our recently developed approach to high-resolution myelin water fraction (MWF) mapping, a proxy for myelin content, to investigate myelin differences with normal aging within the brainstem. In this cross-sectional investigation, we studied a large cohort (n = 125) of cognitively unimpaired participants spanning a wide age range (21-94 years) and found a decrease in myelination with age in most brainstem regions studied, with several regions exhibiting a quadratic association between myelin and age. We believe that this study is the first investigation of MWF differences with normative aging in the adult brainstem. Further, our results provide reference MWF values.

Four-angle method for practical ultra-high-resolution magnetic resonance mapping of brain longitudinal relaxation time and apparent proton density.

Changes in longitudinal relaxation time (T1) and proton density (PD) are sensitive indicators of microstructural alterations associated with various central nervous system diseases as well as brain maturation and aging. In this work, we introduce a new approach for rapid and accurate high-resolution (HR) or ultra HR (UHR) mapping of T1 and apparent PD (APD) of the brain with correction of radiofrequency field, B1, inhomogeneities. The four-angle method (FAM) uses four spoiled-gradient recalled-echo (SPGR) images acquired at different flip angles (FA) and short repetition times (TRs). The first two SPGR images are acquired at low-spatial resolution and used to accurately map the active B1+ field with the recently introduced steady-state double angle method (SS-DAM). The estimated B1+ map is used in conjunction with the two other SPGR images, acquired at HR or UHR, to map T1 and APD. The method is evaluated with numerical, phantom, and in-vivo imaging measurements. Furthermore, we investigated imaging acceleration methods to further shorten the acquisition time. Our results indicate that FAM provides an accurate method for simultaneous HR or UHR mapping of T1 and APD in human brain in clinical high-field MRI. Derived parameter maps without B1+correction suffer from large inaccuracies, but this issue is well-corrected through use of the SS-DAM. Furthermore, the use of SPGR imaging with short TR and phased-array coil acquisition permits substantial imaging acceleration and enables robust HR or UHR T1 and APD mapping in a clinically acceptable time frame, with whole brain coverage obtained in less than 2 min or 5 min, respectively. The method exhibits high reproducibility and benefits from the use of the conventional SPGR sequence, available in all preclinical and clinical MRI machines, and very simple modeling to address a critical outstanding issue in neuroimaging.

Adult brain aging investigated using BMC-mcDESPOT-based myelin water fraction imaging.

The relationship between regional brain myelination and aging has been the subject of intense study, with magnetic resonance imaging perhaps the most effective modality for elucidating this. However, most of these studies have used nonspecific methods to probe myelin content, including diffusion tensor imaging, magnetization transfer ratio, and relaxation times. In the present study, we used the BMC-mcDESPOT analysis, a direct and specific method for imaging of myelin water fraction (MWF), a surrogate of myelin content. We investigated age-related differences in MWF in several brain regions in a large cohort of cognitively unimpaired participants, spanning a wide age range. Our results indicate a quadratic, inverted U-shape, relationship between MWF and age in all brain regions investigated, suggesting that myelination continues until middle age followed by decreases at older ages. We also observed that these age-related differences vary across different brain regions, as expected. Our results provide evidence for nonlinear associations between age and myelin in a large sample of well-characterized adults, using a direct myelin content imaging method.