The Burden of Sickle Cell Disease on Children and Their Caregivers: Caregiver Reports of Children's Health-Related Quality of Life and School Experiences, Caregiver Burden, and Their Association with Frequency of Vaso-Occlusive Crises.

Background: Children with sickle cell disease (SCD) experience a multiplex of disease-related symptoms and complications, including vaso-occlusive crises (VOCs), episodes characterized by extreme pain. Methods: A cross-sectional observational survey examined the health-related quality of life (HRQoL) and school experiences of children with SCD 2 months-11 years, burden experienced by their caregivers, and associations between these outcomes and VOC frequency. Caregivers (N=167) of children with SCD in the US completed the Infant-Toddler Quality of Life-Short Form 47 (ITQoL-SF47) for children 2 months-4 years, the Child Health Questionnaire-Parent Form 50 (CHQ-PF50) and PROMIS Pain Interference and Sleep Disturbance Parent Proxy short forms for children 5-11 years, and a study-specific survey of school experiences. Results: Children with SCD 2 months-4 years had lower ITQoL-SF47 scores (ie, worse HRQoL, p<0.001) than a normative sample of children; across domains, differences ranged from 18.73-45.03 points and exceeded minimal important difference (MID) thresholds. Except for the behavior domain, children with SCD 5-11 years had lower scores on all CHQ-PF50 domains than the normative sample (p<0.001); differences ranged from 6.78-36.37 points and exceeded MID thresholds. Children with more frequent VOCs had lower HRQoL and worse school experiences than children with less frequent VOCs (p<0.05, except for behavior domains). The largest differences based on VOC frequency were observed for overall health and bodily pain/discomfort among children 2 months-4 years (differences=40.88 and 32.50 points, respectively), and bodily pain and role/social limitations due to physical health among children 5-11 years (differences=38.99 and 37.80, respectively). Caregivers of children with more frequent VOCs experienced greater burden than caregivers of children with less frequent VOCs, though specific areas of impact (eg, caregiver emotions, time) differed across child age groups. Conclusion: VOC frequency is negatively associated with HRQoL, highlighting the burden experienced by children with SCD and their caregivers.

Association Between Hematologic Response and Change in Health-Related Quality of Life Among Patients with Light-Chain (AL) Amyloidosis.

Purpose: The purpose of this secondary data analysis was to examine the association between hematologic response and health-related quality of life (HRQoL) among patients with light-chain (AL) amyloidosis. Patients and Methods: Data for this secondary analysis were collected through a non-interventional, longitudinal, online self-report survey of patients with AL amyloidosis. Patients completed an initial online survey, with follow-up surveys administered 1, 6, 12, 18, and 24 months after completion of the initial survey. The online survey included an assessment of patients' most recent self-reported hematologic response status. Eight domains and 2 summary components of HRQoL were evaluated with the SF-36v2® Health Survey. A series of logistic regression models were used to examine the association between self-reported hematologic response at 24 months (dichotomized as new or maintained complete hematologic response; less than a complete response) and change in HRQoL from baseline to 24 months (dichotomized as meaningful worsening; improvement or preservation). Results: For all measured domains of HRQoL except physical functioning, there was no statistically significant relationship between meaningful worsening in HRQoL and hematologic response status at 24 months. Patients without a complete hematologic response had an odds of experiencing meaningful worsening of HRQoL that was similar to that of patients with a complete hematologic response. Conclusion: Among patients with AL amyloidosis, change in HRQoL was generally not associated with hematologic response. Achieving a complete hematologic response does not necessarily mean that a patient will experience increased or stable HRQoL. When defining treatment success, it is important to recognize that clinical markers such as hematologic response may not fully encapsulate the patient experience.

Health-Related Quality of Life Instruments for Clinical Trials in AL Amyloidosis: Report from the Amyloidosis Forum HRQOL Working Group.

Systemic AL (light chain) amyloidosis is a rare protein misfolding disorder associated with plasma cell dyscrasia affecting various organs leading to organ dysfunction and failure. The Amyloidosis Forum is a public-private partnership between the Amyloidosis Research Consortium and the US Food and Drug Administration Center for Drug Evaluation and Research with the goal of accelerating the development of effective treatments for AL amyloidosis. In recognition of this goal, 6 individual working groups were formed to identify and/or provide recommendations related to various aspects of patient-relevant clinical trial endpoints. This review summarizes the methods, findings, and recommendations of the Health-Related Quality of Life (HRQOL) Working Group. The HRQOL Working Group sought to identify existing patient-reported outcome (PRO) assessments of HRQOL for use in clinical trials and practice deemed relevant across a broad spectrum of patients with AL amyloidosis. A systematic review of the AL amyloidosis literature identified 1) additional signs/symptoms not currently part of an existing conceptual model, and 2) relevant PRO instruments used to measure HRQOL. The Working Group mapped content from each identified instrument to areas of impact in the conceptual model to determine which instrument(s) provide coverage of relevant concepts. The SF-36v2® Health Survey (SF-36v2; QualityMetric Incorporated, LLC) and Patient-Reported Outcomes Measurement Information System-29 Profile (PROMIS-29; HealthMeasures) were identified as instruments relevant to patients with AL amyloidosis. Existing evidence of reliability and validity was evaluated with a recommendation for future work focused on estimating clinically meaningful within-patient change thresholds for these instruments. For sponsors, the context of use-including specific research objectives, trial population, and investigational product under study-should inherently drive selection of the appropriate PRO instrument and endpoint definitions to detect meaningful change and enable patient-focused drug development.

A structured review evaluating content validity of the Asthma Control Test, and its consistency with U.S. guidelines and patient expectations for asthma control.

OBJECTIVE: To assess whether the content of the Asthma Control Test (ACT) served as a valid measure of asthma control (i.e., content validity) by mapping ACT items to the National Heart, Lung and Blood Institute (NHLBI) guideline asthma control definitions, and to language used by patients to describe their asthma. DATA SOURCES: PubMed and EMBASE databases were used for a structured literature analysis. STUDY SELECTIONS: Full-text, English-language articles that reported findings from qualitative studies conducted in adults, focusing on patient descriptors of asthma symptoms, impacts, or severity, were included. Pediatric studies, studies conducted in patients without asthma, and studies that did not contain qualitative data were excluded. RESULTS: ACT items reflected all domains of asthma impairment described in the NHLBI guidelines, except pulmonary function. Following the literature review, 28 full-text publications were identified that included patient descriptors that could be mapped to ACT items. For example, per ACT Item 1, patients described having trouble at work, school, and completing household chores; and, per ACT Item 2, patients used the phrase "short of breath" to describe asthma-associated symptoms. CONCLUSION: ACT item content corresponded well with the NHLBI guideline definitions of the impairment domain of asthma control (focused on asthma symptoms and impact), and we identified numerous examples in the literature indicating that ACT concepts and item content mirror the language patients use when discussing asthma symptoms and impact, and their degree of asthma control. This provides further evidence to support content validity of the ACT as a measure of asthma control.

Work Outcomes Among Patients with Light Chain (AL) Amyloidosis: Findings from Three Patient Cohorts.

BACKGROUND: Light chain (AL) amyloidosis is a rare and progressive disease that affects myriad organs and systems. Patients with cardiac involvement have the highest risk of death. This report compiles findings across three cohorts of patients with AL amyloidosis to understand patterns of employment and work impacts. METHODS: Data came from three cohorts recruited through patient advocacy organizations in the US. Patients in Cohort 1 completed the SF-36v2® Health Survey (SF-36v2), the Work Productivity and Activity Impairments - Specific Health Problem (WPAI) questionnaire, and the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). The relationship between work impacts (WPAI scores) and HRQoL (SF-36v2 scores) was investigated using multivariable logistic regression and summarized according to cardiac severity using New York Heart Association (NYHA) classes estimated from KCCQ-12 scores. Changes in employment, days of missed work, and long-term disability due to AL amyloidosis were summarized for patients diagnosed in the past 24 months and stratified by NYHA class (Cohort 2). Findings were contextualized using patient interviews (Cohort 3). RESULTS: Work-related impacts, especially reduced productivity, were common among patients with AL amyloidosis. WPAI scores were significantly related to HRQoL (p<0.05 for all models). Among patients with cardiac involvement, the greatest degree of work impacts was observed for those in NYHA class 3 or 4. Changes in employment, missed work, and long-term disability were common among newly diagnosed patients, especially among those in NYHA class 3 or 4. Patient interviews supported the survey findings; patients described absences, reduced productivity at work, and loss of employment due to the disease and its treatment. CONCLUSION: Patients with AL amyloidosis, particularly those with more advanced disease, experience impacts across a range of employment-related outcomes. These findings highlight the need for more effective treatments and interventions which may improve functioning and patient outcomes, while reducing indirect costs associated with the disease.

Qualitative and psychometric approaches to evaluate the PROMIS pain interference and sleep disturbance item banks for use in patients with rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) commonly experience pain despite the availability of disease-modifying treatments. Sleep disturbances are frequently reported in RA, with pain often a contributing factor. The Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference and Sleep Disturbance item banks were initially developed to provide insights into the patient experience of pain and sleep, respectively, though they were not specifically intended for use in RA populations. This study evaluated the content validity of the PROMIS Pain Interference and Sleep Disturbance item banks in RA and identified relevant content for short forms for patients with RA that achieved high measurement precision across a broad range of health. METHODS: A qualitative approach consisting of hybrid concept elicitation and cognitive debriefing interviews was used to evaluate the content validity of the item banks in RA. Interviews were semi-structured and open-ended, allowing a range of concepts and responses to be captured. Findings from the qualitative interviews were used to select the most relevant items for the short forms, and psychometric evaluation, using existing item-response theory (IRT) item parameters, was used to evaluate the marginal reliability and measurement precision of the short forms across the range of the latent variables (i.e. pain interference and sleep disturbance). RESULTS: Thirty-two participants were interviewed. Participants reported that RA-related pain and sleep disturbances have substantial impacts on their daily lives, particularly with physical functioning. The PROMIS Pain Interference and Sleep Disturbance item banks were easy to understand and mostly relevant to their RA experiences, and the 7-day recall period was deemed appropriate. Qualitative and IRT-based approaches identified short forms for Pain Interference (11 items) and Sleep Disturbance (7 items) that had high relevance and measurement precision, with good coverage of the concepts identified by participants during concept elicitation. CONCLUSION: Pain and sleep disturbances affect many aspects of daily life in patients with RA and should be considered when novel treatments are developed. This study supports the use of the PROMIS Pain Interference and Sleep Disturbance item banks in RA, and the short forms developed herein have the potential to be used in clinical studies of RA.

The impact of vaso-occlusive crises and disease severity on quality of life and productivity among patients with sickle cell disease in the US.

AIM: Sickle cell disease (SCD) is a lifelong blood disorder affecting approximately 100,000 individuals in the United States (US). A number of new treatments have recently become available to improve SCD clinical outcomes, but it is unclear how treatment innovations that reduce disease severity could affect patients' humanistic and economic outcomes. METHODS AND MATERIALS: To answer this question, an online survey of US adult residents with a self-reported SCD diagnosis was conducted. Humanistic outcomes based on health-related quality of life (HRQoL)) were assessed during and outside of vaso-occlusive crises (VOCs). Economic outcomes were measured by annual household income and whether the respondent received disability insurance. RESULTS: Among the 301 respondents completing the survey, average age was 34.4 years and 73.4% were female. Average HRQoL, measured using health utilities, were 0.311 (95% CI: 0.286, 0.337) during a VOC and 0.738 (0.720, 0.756) not during a VOC. The likelihood of claiming disability insurance was correlated with more frequent VOCs (0 VOCs: 12% vs. ≥4 VOCs: 47%, p = .002) and disease severity (Severity Class II: 16% vs. Severity Class III: 39%, p = .03). There was a weak relationship between VOC frequency and household income (0 VOCs: $47,488 vs. ≥4 VOCs: $34,569, p = .06) and no evidence of a relationship between disease severity class and income (Severity Class II: $42,443 vs. Severity Class III: $36,842, p = .29). CONCLUSION: In conclusion, disease severity, strongly predicted worse self-reported HRQoL, moderately predicted increased likelihood of collecting disability insurance, and weakly predicted lower household income levels.

Content Validation of the ATTR Amyloidosis Patient Symptom Survey: Findings from Patient and Clinician Cognitive Debriefing Interviews.

PURPOSE: Amyloid transthyretin (ATTR) amyloidosis is a rare, progressive, and fatal disease. The ATTR Patient Symptom Survey (ATTR-PSS) was previously developed through literature review and concept elicitation input from clinicians and patients and revised after evaluation by a patient focus group. This study further evaluated the content validity of the ATTR-PSS through qualitative cognitive debriefing interviews with clinicians and patients. METHODS: Seven clinicians and 10 patients with ATTR amyloidosis were interviewed individually regarding their overall impressions, the clarity and appropriateness of the survey, relevance of concepts measured, and comprehensiveness and comprehensibility of items and response choice sets. RESULTS: Clinicians acknowledged the usefulness of the ATTR-PSS in research and clinical settings. They suggested minor modifications to the survey instructions, the addition of 3 symptoms, and the transfer of 10 conditions from the symptom list to 2 separate items. Patients found the ATTR-PSS to be easy to complete and relevant to their experiences. Their feedback resulted in modification to instruction text, edits to the description of 4 symptoms, removal of 1 symptom, and addition of 2 diagnoses. CONCLUSION: The findings support the content validity of the ATTR-PSS as an appropriate measure of symptom frequency, severity, and impact in patients with wild-type and hereditary ATTR amyloidosis.

The relationship between frequency and severity of vaso-occlusive crises and health-related quality of life and work productivity in adults with sickle cell disease.

PURPOSE: Patients with sickle cell disease (SCD) may experience sickle cell-related pain crises, also referred to as vaso-occlusive crises (VOCs), which are a substantial cause of morbidity and mortality. The study explored how VOC frequency and severity impacts health-related quality of life (HRQoL) and work productivity. METHODS: Three hundred and three adults with SCD who completed an online survey were included in the analysis. Patients answered questions regarding their experience with SCD and VOCs, and completed the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) and the Workplace Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP). Differences in ASCQ-Me and WPAI:SHP domains were assessed according to VOC frequency and severity. RESULTS: Nearly half of the patient sample (47.2%) experienced ≥ 4 VOCs in the past 12 months. The most commonly reported barriers to receiving care for SCD included discrimination by or trouble trusting healthcare professionals (39.6%, 33.3%, respectively), limited access to treatment centers (38.9%), and difficulty affording services (29.4%). Patients with more frequent VOCs reported greater impacts on emotion, social functioning, stiffness, sleep and pain, and greater absenteeism, overall productivity loss, and activity impairment than patients with less frequent VOCs (P < 0.05). Significant impacts on HRQoL and work productivity were also observed when stratifying by VOC severity (P < 0.05 for all ASCQ-Me and WPAI domains, except for presenteeism). CONCLUSIONS: Results from the survey indicated that patients with SCD who had more frequent or severe VOCs experienced deficits in multiple domains of HRQoL and work productivity. Future research should examine the longitudinal relationship between these outcomes.

Effect of tardive dyskinesia on quality of life in patients with bipolar disorder, major depressive disorder, and schizophrenia.

PURPOSE: Tardive dyskinesia (TD) is a common but serious hyperkinetic movement disorder and side effect of antipsychotic medications used to treat bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ). The purpose of this study was to evaluate health-related quality of life (HRQoL) in a population with diagnoses for BD, MDD, or SZ by comparing patients with TD (n = 197) with those without TD (n = 219). HRQoL in each group was also compared with HRQoL of the general population. METHODS: This study employed a cross-sectional web-based survey. HRQoL was assessed by four instruments: the SF-12 Health Survey, Version 2 (SF-12v2), the Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF), the Social Withdrawal subscale of the Internalized Stigma of Mental Illness Scale (SW-ISMI); and two questions on movement disorders. RESULTS: Patients with TD had significantly worse HRQoL and social withdrawal than those without. The differences were more pronounced for physical HRQoL domains than for mental health domains. Patients with more-severe TD, assessed through either self-rating or clinician rating, experienced significantly worse HRQoL than did those with less-severe TD. The impact of TD was substantially greater in patients with SZ than in those with BD or MDD. Compared with the general population, patients with BD, MDD, or SZ experienced significantly worse HRQoL regardless of TD status, although this deficit in HRQoL was greater among those with TD. CONCLUSIONS: The presence of TD is associated with worse HRQoL and social withdrawal. The most severe impact of TD is on physical aspects of patients' HRQoL.

Associations between Health-Related Quality of Life and Self-Reported Emergency Room Department Visits and Inpatient Hospitalizations: Insights from a Secondary Data Analysis of Patients with Light-Chain (AL) Amyloidosis.

INTRODUCTION: Light-chain (AL) amyloidosis is a rare, progressive, and typically fatal disease. Health-related quality of life (HRQoL) has been shown to be a significant prognostic factor associated with clinical outcomes such as survival and response to treatment. A better understanding of how patterns of HRQoL may be prospectively associated with costly healthcare resource utilization, such as emergency department (ED) visits and inpatient hospitalizations, is warranted. METHODS: A secondary data analysis of a non-interventional, longitudinal online study of patients with AL amyloidosis (n = 224) was conducted. Negative binomial regression models were used to examine whether initial HRQoL scores (as measured by the SF-36v2® Health Survey [SF-36v2], where higher scores reflect better HRQoL) and changes in HRQoL were associated with the number of ED visits and inpatient hospitalizations during a 12-month period. Incidence rate ratios were interpreted by 5-point decrements in initial HRQoL scores and minimally important changes in HRQoL change scores. RESULTS: There were significant inverse associations between initial SF-36v2 scores and subsequent rates of ED visits and inpatient hospitalizations across all domains and summary components (p < 0.05 for all). In contrast, changes in physical, but not mental, functioning were associated with rates of ED visits and inpatient hospitalizations during a 12-month period of observation. CONCLUSION: Scores from patient-reported HRQoL surveys may be helpful in identifying patients at risk of future ED visits and hospital admissions, and may serve as a proxy for disease severity. Such information can provide stakeholders with insight into the humanistic and societal cost associated with AL amyloidosis.

A meta-analytic review of measurement equivalence study findings of the SF-36® and SF-12® Health Surveys across electronic modes compared to paper administration.

PURPOSE: Patient-reported outcome (PRO) measures originally developed for paper administration are increasingly being administered electronically in clinical trials and other health research studies. Three published meta-analyses of measurement equivalence among paper and electronic modes aggregated findings across hundreds of PROs, but there has not been a similar meta-analysis that addresses a single PRO, partly because there are not enough published measurement equivalence studies using the same PRO. Because the SF-36(R) Health Survey (SF-36) is a widely used PRO, the aim of this study was to conduct a meta-analysis of measurement equivalence studies of this survey. METHODS: A literature search of several medical databases used search terms for variations of "SF-36" or "SF-12" and "equivalence" in the title or abstract of English language publications. The eight scale scores and two summary measures of the SF-36 and SF-12 were transformed to norm-based scores (NBS) using developer guidelines. A threshold of within ± 2 NBS points was set as the margin of equivalence. Comprehensive meta-analysis software was used. RESULTS: Twenty-five studies were included in the meta-analysis. Results indicated that mean differences across domains and summary scores ranged from 0.01 to 0.39 while estimates of agreement ranged from 0.76 to 0.91, all well within the equivalence threshold. Moderator analyses showed that time between administration, survey language, and type of electronic device did not influence equivalence. CONCLUSIONS: The results of the meta-analysis support equivalence of paper-based and electronic versions of the SF-36 and SF-12 across a variety of disease populations, countries, and electronic modes.

Treatment Tolerability in Patients with Immunoglobulin Light-Chain Amyloidosis.

BACKGROUND: Immunoglobulin light-chain amyloidosis (AL amyloidosis) is a rare and often fatal disease for which there is currently no treatment approved by the US Food and Drug Administration or the European Medicines Agency. Treatment options, which are typically based on therapies for multiple myeloma and are used off-label, are associated with substantial adverse events (AEs). Because the severity of AEs is often determined by clinicians, evaluations of treatment tolerability may not fully consider patients' own experience with treatment. OBJECTIVES: To explore the prevalence of AEs and treatment tolerability problems as reported by patients who received therapies for AL amyloidosis, and to examine the effects of AEs on treatment continuation and on health-related quality of life (HRQOL). METHODS: Patients with AL amyloidosis were recruited for this noninterventional, longitudinal, online survey. The patients responded to survey items regarding demographics, disease characteristics, most recent AL amyloidosis treatment, and HRQOL. The study analyses are based on data collected during the 6-month follow-up survey and are restricted to patients who completed the baseline and 6-month surveys and received treatment for AL amyloidosis within 6 months before the follow-up survey. RESULTS: A total of 100 patients met the inclusion criteria and were included in the study. The patients self-reported having a variety of AEs, which ranged in severity. Overall, 69.4% of patients had problems tolerating their treatment in the past 6 months, of whom 22% discontinued at least 1 therapy. In addition, approximately 33% of patients reduced their AL amyloidosis treatment because of AEs. Most often reported AEs included fatigue (83%), shortness of breath (53%), nausea (52%), and diarrhea (51%). Overall, 50% of the patients reported that their treatment was moderately well-tolerated and 41% said it was very well-tolerated. Those whose treatment was not well-tolerated had significantly worse HRQOL than patients whose treatment was well-tolerated. CONCLUSIONS: Patient-reported experiences should be considered by clinicians when making treatment-related decisions. More research is needed to explore additional factors that may contribute to treatment discontinuation in patients with AL amyloidosis.

Neural evidence for phonologically based language production deficits in older adults: An fMRI investigation of age-related differences in picture-word interference.

INTRODUCTION: Older adults often show declines in phonological aspects of language production, particularly for low-frequency words, but maintain strong semantic systems. However, there are different theories about the mechanism that may underlie such age-related differences in language (e.g., age-related declines in transmission of activation or inhibition). METHODS: This study used fMRI to investigate whether age-related differences in language production are associated with transmission deficits or inhibition deficits. We used the picture-word interference paradigm to examine age-related differences in picture naming as a function of both target frequency and the relationship between the target picture and distractor word. RESULTS: We found that the presence of a categorically related distractor led to greater semantic elaboration by older adults compared to younger adults, as evidenced by older adults' increased recruitment of regions including the left middle frontal gyrus and bilateral precuneus. When presented with a phonologically related distractor, patterns of neural activation are consistent with previously observed age deficits in phonological processing, including age-related reductions in the recruitment of regions such as the left middle temporal gyrus and right supramarginal gyrus. Lastly, older, but not younger, adults show increased brain activation of the pre- and postcentral gyri as a function of decreasing target frequency when target pictures are paired with a phonological distractor, suggesting that cuing the phonology of the target disproportionately aids production of low-frequency items. CONCLUSIONS: Overall, this pattern of results is generally consistent with the transmission deficit hypothesis, illustrating that links within the phonological system, but not the semantic system, are weakened with age.

Recollection after inhibition: The effects of intentional forgetting on the neural correlates of retrieval.

Intentional forgetting is posited to utilize both encoding and inhibition to control what information enters long-term memory. Within the context of the directed forgetting paradigm, evidence for the role of inhibition to support forgetting has been examined primarily during encoding. Specifically, past studies have shown that when encoding processes are intentionally inhibited, information is less likely to be remembered. Despite the recruitment of such inhibitory processes, not all items are successfully forgotten. The current study examined whether items that should have been forgotten (F items), but were ultimately recollected, showed neural evidence at retrieval of having previously undergone attempted inhibition, particularly when compared to items that received "remember" instructions (R items). Results indicate that recollection of F items engaged additional activity in the prefrontal cortex, including the right inferior frontal gyrus and right superior frontal gyrus, suggesting that retrieval of these items required greater effort, most likely due to inhibitory processes that were engaged at encoding. These results suggest that inhibitory processing during attempted but unsuccessful forgetting can result in a more difficult retrieval period.

Content validation of the SF-36v2® health survey with AL amyloidosis patients.

BACKGROUND: This study examined the content validity of the SF-36v2® Health Survey (SF-36v2) in patients with AL amyloidosis using qualitative interviews with physicians and patients. The study included three distinct phases of qualitative research: concept elicitation interviews among physicians, concept elicitation interviews among patients, and cognitive debriefing interviews among patients. The concept elicitation interviews focused on areas of health-related quality of life that are affected by AL amyloidosis and may be affected by treatment, while patient cognitive debriefings aimed to confirm whether the SF-36v2 instructions, recall period, items, and response choices were comprehensive and understandable to AL amyloidosis patients. RESULTS: Physicians discussed the importance of measuring physical functioning, general health, mental/emotional health, sleep, fatigue, and work impact; though they also reported that they do not routinely use a standard Patient-Reported Outcome (PRO) measure of health-related quality of life. Patients described social, physical, role, and emotional impacts of AL amyloidosis and various treatments. Cognitive debriefing interviews confirmed the relevance of the concepts measured by the SF-36v2 and indicated that patients found the SF-36v2 both easy to understand and complete, that the SF-36v2 instructions and items were comprehensive and understandable without change, and the response choices and recall period were appropriate for use with patients with AL amyloidosis. CONCLUSIONS: The findings support the content validity of the SF-36v2 as an appropriate measure of health-related quality of life in patients with AL amyloidosis.

Language, aging, and cognition: frontal aslant tract and superior longitudinal fasciculus contribute toward working memory performance in older adults.

Previous research has documented change in white matter tract integrity with increasing age. Both interhemispheric and intrahemispheric tracts that underlie language processing are susceptible to these age-related changes. The aim of the current study was to explore age and white matter integrity in language-related tracts as predictors of cognitive task performance in younger and older adults. To this end, we carried out principal component analyses of white matter tracts and confirmatory factor analysis of neuropsychological measures. We next carried out a series of regression analyses that used white matter components to predict scores on each of the neuropsychological components. For both younger and older adults, age was a significant predictor of processing speed and working memory. However, white matter integrity did not contribute independently toward these models. In older adults only, both age and a white matter component that included the bilateral frontal aslant tract and left superior longitudinal fasciculus were significant predictors of working memory. Taken together, these results extend our understanding of the contributions of language-related white matter structure to cognitive processing and highlight the effects of age-related differences in both frontal and dorsal tracts.

The neural language systems that support healthy aging: Integrating function, structure, and behavior.

Although healthy aging is generally characterized by declines in both brain structure and function, there is variability in the extent to which these changes result in observable cognitive decline. Specific to language, age-related differences in language production are observed more frequently than in language comprehension, although both are associated with increased right prefrontal cortex activation in older adults. The current paper explores these differences in the language system, integrating them with theories of behavioral and neural cognitive aging. Overall, data indicate that frontal reorganization of the dorsal language stream in older adults benefits task performance during comprehension, but not always during production. We interpret these results in the CRUNCH framework (compensation-related utilization of neural circuits hypothesis), which suggests that differences in task and process difficulty may underlie older adults' ability to successfully adapt. That is, older adults may be able to neurally adapt to less difficult tasks (i.e., comprehension), but fail to do so successfully as difficulty increases (i.e., production). We hypothesize greater age-related differences in aspects of language that rely more heavily on the dorsal language stream (e.g., syntax and production) and that recruit general cognitive resources that rely on frontal regions (e.g., executive function, working memory, inhibition). Moreover, there should be a relative sparing of tasks that rely predominantly on ventral stream regions. These results are both consistent with patterns of age-related structural decline and retention and with varying levels of difficulty across comprehension and production. This neurocognitive framework for understanding age-related differences in the language system centers on the interaction between prefrontal cortex activation, structural integrity, and task difficulty.