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Introduction: Chronic musculoskeletal (MSK) pain is prevalent in older adults and confers significant risk for loss of independence and low quality of life. While obesity is considered a risk factor for developing chronic MSK pain, both high and low body mass index (BMI) have been associated with greater pain reporting in older adults. Measures of body composition that distinguish between fat mass and lean mass may help to clarify the seemingly contradictory associations between BMI and MSK pain in this at-risk group. Methods: Twenty-four older adults (mean age: 78.08 ± 5.1 years) completed dual-energy x-ray absorptiometry (DEXA), and pain measures (Graded Chronic Pain Scale, number of anatomical pain sites, pressure pain threshold, mechanical temporal summation). Pearson correlations and multiple liner regression examined associations between body mass index (BMI), body composition indices, and pain. Results: Significant positive associations were found between number of pain sites and BMI (b = 0.37) and total fat mass (b = 0.42), accounting for age and sex. Total body lean mass was associated with pressure pain sensitivity (b = 0.65), suggesting greater lean mass is associated with less mechanical pain sensitivity. Discussion: The results from this exploratory pilot study indicate lean mass may provide additional resilience to maladaptive changes in pain processing in older adults, and highlights the importance of distinguishing body composition indices from overall body mass index to better understand the complex relationship between obesity and MSK pain in older adults.
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BACKGROUND: Chronic pain has been associated with accelerated biological aging, which may be related to epigenetic alterations. We evaluated the association of high-impact pain (ie, pain that limits activities and function) with epigenetic aging, a measure of biological aging, in a nationally representative sample of middle-aged and older adults in the United States. METHODS: Cross-sectional analysis of adults 50 years of age and older from the 2016 Health and Retirement Study. Epigenetic aging was derived from 13 epigenetic clocks based on DNA methylation patterns that predict aging correlates of morbidity and mortality. Ordinary least squares regressions were performed to test for differences in the epigenetic clocks, adjusting for the complex survey design, as well as biological, social, and behavioral factors. RESULTS: The analysis consisted of 3 855 adults with mean age of 68.5 years, including 59.8% with no pain and 25.8% with high-impact pain. Consistent with its operational definition, high-impact pain was associated with greater functional and activity limitations. High-impact pain was associated with accelerated epigenetic aging compared to no pain, as measured via second (Zhang, PhenoAge, GrimAge) and third (DunedinPoAm) generation epigenetic clocks. Additionally, GrimAge was accelerated in high-impact pain as compared to low-impact pain. CONCLUSIONS: High-impact pain is associated with accelerated epigenetic aging among middle-aged and older adults in the United States. These findings highlight aging-associated epigenetic alterations in high-impact chronic pain and suggest a potential for epigenetic therapeutic approaches for pain management and the preservation of physical function in older adults.
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Envejecimiento , Dolor Crónico , Metilación de ADN , Epigénesis Genética , Humanos , Anciano , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Envejecimiento/genética , Envejecimiento/fisiología , Dolor Crónico/genética , Estados Unidos/epidemiología , Metilación de ADN/genéticaRESUMEN
BACKGROUND: Food insecurity is recognized as a key social determinant of health for older adults. While food insecurity has been associated with morbidity and mortality, few studies have examined how it may contribute to accelerated biological aging. A potential mechanism by which food insecurity may contribute to aging is via epigenetic alterations. We examined the relationship between food insecurity and epigenetic aging, a novel measure of biological aging, in a nationally representative sample of middle-aged and older adults in the United States. METHODS: Cross-sectional analysis of adults 50 years of age and older from the 2016 Health and Retirement Study (HRS). Financial food insecurity was self-reported via two questions that ascertained having enough money for food or eating less than they felt they should. Epigenetic aging was measured via epigenetic clocks based on DNA methylation patterns that predict aging correlates of morbidity and mortality. Linear regressions were performed to test for differences in the epigenetic clocks, adjusting for biological, socioeconomic, and behavioral factors. RESULTS: The analysis consisted of 3875 adults with mean age of 68.5 years. A total of 8.1% reported food insecurity. Food insecurity was associated with several characteristics, including younger age, race/ethnic minority, lower income, total wealth, and educational attainment, higher BMI, and less physical activity. Food insecurity was associated with accelerated epigenetic aging compared to food security, as measured via second (Zhang, PhenoAge, GrimAge) and third (DunedinPoAm) generation epigenetic clocks. In particular, food insecurity remained significantly associated with accelerated Zhang (B = 0.09, SE = 0.03, p = 0.011) and GrimAge (B = 0.57, SE = 0.24, p = 0.022) in the fully adjusted models. CONCLUSIONS: Food insecurity is associated with accelerated epigenetic aging among middle-aged and older adults in the United States. Food insecurity may contribute to DNA methylation alterations across the genome and biological age acceleration. These findings add to a growing understanding of the influence of socioeconomic status on the epigenome and health in aging.
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Envejecimiento , Inseguridad Alimentaria , Humanos , Anciano , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Estados Unidos/epidemiología , Epigénesis Genética , Factores Socioeconómicos , Metilación de ADN , Anciano de 80 o más AñosRESUMEN
Chronic pain has negative physical and cognitive consequences in older adults and may lead to a poorer quality of life. Mediterranean ketogenic nutrition (MKN) is a promising nonpharmacological intervention for pain management, but long-term adherence is challenging due to the carbohydrate restrictive diet regimen. The main objective of this study was to evaluate the effects of the pilot MKN Adherence (MKNA) Program on pain in older adults with mild cognitive impairment and to assess whether improvements in self-reported pain were associated with adherence to MKN. Older adults (N = 58) aged 60-85 with possible mild cognitive impairment were randomized to a 6-week MKNA arm or an MKN Education (MKNE) program arm. Both arms received the same nutrition education and group format; however, the MKNA arm received additional motivational interviewing and cognitive behavioral skills to enhance adherence. Changes in self-reported pain (Brief Pain Inventory, Roland Morris, Patient's Global Impression of Change) and adherence to MKN (ketone levels, self-reported adherence) were assessed at baseline, 6-weeks, and 3-months post intervention. Both arms showed clinically significant reductions in pain. Greater adherence to MKN across the 6-week intervention was associated with higher ratings of pain-related changes on the Patient's Global Impression of Change scale. Based on these findings, adherence to MKN may promote improvements in self-reported pain in older adults with mild cognitive impairment and findings support the need for future full-scale randomized clinical trials evaluating MKN programs on pain. Trial Registration: Clinicaltrials.gov ID: NCT04817176.
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This article investigates the benefits of adopting qualitative and quantitative sensory testing (QQST) in sensory assessment, with a focus on understanding neuropathic pain. The innovative QQST method combines participant qualitative experiences with quantitative psychophysical measurements, offering a more varied interpretation of sensory abnormalities and normal sensory function. This article also explores the steps for the optimization of the method by identifying qualitative signs of sensory abnormalities and standardizing data collection. By leveraging the inherent subjectivity in the test design and participant responses, the QQST method contributes to a more holistic exploration of both normal and abnormal sensory experiences. This article positions the QQST approach as a foundational element within the Sensory Evaluation Network, uniting international experts to harmonize qualitative and quantitative sensory evaluation methods.
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OBJECTIVE: Knee osteoarthritis (OA) is a leading cause of chronic pain in adults and shows wide interindividual variability, with peripheral and central factors contributing to the pain experience. Periarticular factors, such as muscle quality (eg, echo intensity [EI] and shear wave velocity [SWV]), may contribute to knee OA pain; however, the role of muscle quality in OA symptoms has yet to be fully established. METHODS: Twenty-six adults (age >50 years) meeting clinical criteria for knee OA were included in this cross-sectional study. Quantitative ultrasound imaging was used to quantify EI and SWV in the rectus femoris of the index leg. Pearson correlations followed by multiple linear regression was used to determine associations between muscle quality and pain, controlling for strength, age, sex, and body mass index. RESULTS: EI and SWV were significantly associated with movement-evoked pain (b = 0.452-0.839, P = 0.024-0.029). Clinical pain intensity was significantly associated with SWV (b = 0.45, P = 0.034), as were pressure pain thresholds at the medial (b = -0.41, P = 0.025) and lateral (b = -0.54, P = 0.009) index knee joint line, adjusting for all covariates. Pain interference was significantly associated with knee extension strength (b = -0.51, P = 0.041). CONCLUSION: These preliminary findings suggest that EI and SWV may impact knee OA pain and could serve as malleable treatment targets. Findings also demonstrate that muscle quality is a unique construct, distinct from muscle strength, which may impact pain and treatment outcomes. More research is needed to fully understand the role of muscle quality in knee OA.
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Fuerza Muscular , Osteoartritis de la Rodilla , Músculo Cuádriceps , Ultrasonografía , Humanos , Osteoartritis de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/diagnóstico por imagen , Femenino , Masculino , Estudios Transversales , Persona de Mediana Edad , Fuerza Muscular/fisiología , Anciano , Músculo Cuádriceps/fisiopatología , Músculo Cuádriceps/diagnóstico por imagen , Dimensión del Dolor , Artralgia/fisiopatología , Artralgia/etiología , Articulación de la Rodilla/fisiopatología , Articulación de la Rodilla/diagnóstico por imagenRESUMEN
Chronic musculoskeletal pain is often associated with lower socioeconomic status (SES). SES correlates with psychological and environmental conditions that could contribute to the disproportionate burden of chronic stress. Chronic stress can induce changes in global DNA methylation and gene expression, which increases risk of chronic pain. We aimed to explore the association of epigenetic aging and SES in middle-to-older age individuals with varying degrees of knee pain. Participants completed self-reported pain, a blood draw, and answered demographic questions pertaining to SES. We used an epigenetic clock previously associated with knee pain (DNAmGrimAge) and the subsequent difference of predicted epigenetic age (DNAmGrimAge-Diff). Overall, the mean DNAmGrimAge was 60.3 (±7.6), and the average DNAmGrimAge-diff was 2.4 years (±5.6 years). Those experiencing high-impact pain earned less income and had lower education levels compared to both low-impact and no pain groups. Differences in DNAmGrimAge-diff across pain groups were found, whereby individuals with high-impact pain had accelerated epigenetic aging (â¼5 years) compared to low-impact pain and no pain control groups (both â¼1 year). Our main finding was that epigenetic aging mediated the associations of income and education with pain impact, as such the relationship between SES and pain outcomes may occur through potential interactions with the epigenome reflective of accelerated cellular aging. PERSPECTIVE: Socioeconomic status (SES) has previously been implicated in the pain experience. The present manuscript aims to present a potential social-biological link between SES and pain via accelerated epigenetic aging.
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Dolor Crónico , Vida Independiente , Adulto , Humanos , Anciano , Factores Socioeconómicos , Clase Social , Dolor Crónico/epidemiología , Dolor Crónico/genética , Epigénesis Genética/genéticaRESUMEN
ABSTRACT: Significant progress has been made in linking measures of individual alpha frequency (IAF) and pain. A lower IAF has been associated with chronic neuropathic pain and with an increased sensitivity to pain in healthy young adults. However, the translation of these findings to chronic low back pain (cLBP) are sparse and inconsistent. To address this limitation, we assessed IAFs in a cohort of 70 individuals with cLBP, implemented 3 different IAF calculations, and separated cLBP subjects based on psychological variables. We hypothesized that a higher fear movement in cLBP is associated with a lower IAF at rest. A total of 10 minutes of resting data were collected from 128 electroencephalography channels. Our results offer 3 novel contributions to the literature. First, the high fear group had a significantly lower peak alpha frequency. The high fear group also reported higher pain and higher disability. Second, we calculated individual alpha frequency using 3 different but established methods; the effect of fear on individual alpha frequency was robust across all methods. Third, fear of movement, pain intensity, and disability highly correlated with each other and together significantly predicted IAF. Our findings are the first to show that individuals with cLBP and high fear have a lower peak alpha frequency.
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Dolor Crónico , Dolor de la Región Lumbar , Trastornos Fóbicos , Adulto Joven , Humanos , Dolor de la Región Lumbar/psicología , Kinesiofobia , Miedo/psicología , Movimiento , Trastornos Fóbicos/psicología , Evaluación de la DiscapacidadRESUMEN
Purpose: Evaluate sensory and psychological differences in individuals with thumb carpometacarpal (CMC) and/or knee osteoarthritis (OA) pain. This secondary analysis focuses on comparing the effects of OA at large and small joints in community-dwelling adults. Patients and Methods: A total of 434 individuals were recruited from communities in Gainesville, FL and Birmingham, AL. Each participant completed health and clinical history questionnaires, quantitative sensory testing, and physical functional tests. Participants were divided into four groups based on their pain ("CMC pain" (n = 33), "knee pain" (n = 71), "CMC + knee pain" (n = 81), and "pain-free" controls (n = 60)). ANCOVAs were performed to identify significant differences in experimental pain and psychological variables across groups. Results: The "CMC + knee pain" group had lower pressure pain thresholds (lateral knee site, p < 0.01) and higher temporal summation of mechanical pain (knee, p < 0.01) when compared to "CMC pain" and "pain-free" groups. The "knee pain" group had lower heat pain tolerance at the forearm site (p = 0.02) and higher mechanical pain (p < 0.01) at both tested sites in comparison to the "CMC pain" group. Lastly, the "CMC + knee pain" group had the highest self-reported pain (p < 0.01) and disability (p < 0.01) compared to all other groups. Conclusion: Results suggest knee OA compounded with CMC OA increases disease impact and decreases emotional health compared to OA at either the CMC or knee joint alone. Results also support a relationship between the number of painful joints and enhanced widespread pain sensitivity. Measuring pain at sites other than the primary OA location is important and could contribute to more holistic treatment and prevention of OA progression.
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Chronic pain disproportionately affects middle-aged and older adults in the United States. Everyday discrimination is associated with worse pain outcomes and is more prevalent among adults from racial/ethnic minoritized groups. Yet, there is limited evidence on relationships between everyday discrimination and chronic pain among middle-aged and older adults, as well as how discrimination and racial/ethnic identity may interact to influence this relationship. We used the 2018 Health and Retirement study to evaluate associations between exposure to everyday discrimination and odds to experience any, severe, and high-impact chronic pain among 5,314 Hispanic, non-Hispanic Black, and non-Hispanic White adults over the age of 50. Logistic regression was used to evaluate the main and interaction effects of everyday discrimination on the odds of chronic pain (any, severe, and high-impact) across racial/ethnic groups. Results showed that Hispanic and non-Hispanic Black middle-aged and older adults had a higher, unadjusted prevalence of severe and high-impact chronic pain and reported more exposure to everyday discrimination compared to non-Hispanic White middle-aged and older adults. In fully adjusted models, exposure to everyday discrimination predicted higher odds to experience each type of chronic pain. In addition, study findings showed that exposure to everyday discrimination significantly raised pain risk among Hispanic and non-Hispanic White, but not non-Hispanic Black, middle-aged, and older adults. Findings underscore the influential role of everyday discrimination on the chronic pain experiences of middle-aged and older adults, as well as differential effects across racial/ethnic groups. PERSPECTIVE: Using national data, we examined associations between discrimination and chronic pain among middle-aged and older adults, including interactions between discrimination and race/ethnicity. Exposure to discrimination predicted a higher chronic pain burden, overall. Differential effects within racial/ethnic groups underscored a need for more nuanced investigations into pain disparities among this population.
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OBJECTIVE: This study evaluated whether food insecurity (US Adult Food Security Survey) was associated with chronic pain (≥ 3 months) and high-impact chronic pain (i.e. pain that limits work and life) among US adults. DESIGN: Cross-sectional analysis. SETTING: Nationally representative sample of non-institutionalised adults in the USA. PARTICIPANTS: 79 686 adults from the National Health Interview Survey (2019-2021). RESULTS: Marginal, low and very low food security were associated with increased prevalence odds of chronic pain (OR: 1·58 (95 % CI 1·44, 1·72), 2·28 (95 % CI 2·06, 2·52) and 3·37 (95 % CI 3·01, 3·78), respectively) and high-impact chronic pain (OR: 1·28 (95 % CI 1·14, 1·42), 1·55 (95 % CI 1·37, 1·75) and 1·90 (95 % CI 1·65, 2·18), respectively) in a dose-response fashion (P-trend < 0·0001 for both), adjusted for sociodemographic, socio-economic and clinically relevant factors. Participation in Supplemental Nutrition Assistance Program (SNAP) and age modified the association between food insecurity and chronic pain. CONCLUSIONS: These findings illustrate the impact of socio-economic factors on chronic pain and suggest that food insecurity may be a social determinant of chronic pain. Further research is needed to better understand the complex relationship between food insecurity and chronic pain and to identify targets for interventions. Moreover, the consideration of food insecurity in the clinical assessment of pain and pain-related conditions among socio-economically disadvantaged adults may be warranted.
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Dolor Crónico , Asistencia Alimentaria , Adulto , Humanos , Estados Unidos/epidemiología , Dolor Crónico/epidemiología , Dolor Crónico/etiología , Pobreza , Estudios Transversales , Abastecimiento de Alimentos , Inseguridad AlimentariaRESUMEN
The difference between the estimated brain age and the chronological age ('brain-PAD') could become a clinical biomarker. However, most brain age models were developed for research-grade high-resolution T1-weighted MRIs, limiting their applicability to clinical-grade MRIs from various protocols. We adopted a dual-transfer learning strategy to develop a model agnostic to modality, resolution, or slice orientation. We retrained a convolutional neural network (CNN) using 6281 clinical MRIs from 1559 patients, among 7 modalities and 8 scanner models. The CNN was trained to estimate brain age from synthetic research-grade magnetization-prepared rapid gradient-echo MRIs (MPRAGEs) generated by a 'super-resolution' method. The model failed with T2-weighted Gradient-Echo MRIs. The mean absolute error (MAE) was 5.86-8.59 years across the other modalities, still higher than for research-grade MRIs, but comparable between actual and synthetic MPRAGEs for some modalities. We modeled the "regression bias" in brain age, for its correction is crucial for providing unbiased summary statistics of brain age or for personalized brain age-based biomarkers. The bias model was generalizable as its correction eliminated any correlation between brain-PAD and chronological age in new samples. Brain-PAD was reliable across modalities. We demonstrate the feasibility of brain age predictions from arbitrary clinical-grade MRIs, thereby contributing to personalized medicine.
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Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Redes Neurales de la Computación , Encéfalo/diagnóstico por imagenRESUMEN
An individual's brain predicted age minus chronological age (brain-PAD) obtained from MRIs could become a biomarker of disease in research studies. However, brain age reports from clinical MRIs are scant despite the rich clinical information hospitals provide. Since clinical MRI protocols are meant for specific clinical purposes, performance of brain age predictions on clinical data need to be tested. We explored the feasibility of using DeepBrainNet, a deep network previously trained on research-oriented MRIs, to predict the brain ages of 840 patients who visited 15 facilities of a health system in Florida. Anticipating a strong prediction bias in our clinical sample, we characterized it to propose a covariate model in group-level regressions of brain-PAD (recommended to avoid Type I, II errors), and tested its generalizability, a requirement for meaningful brain age predictions in new single clinical cases. The best bias-related covariate model was scanner-independent and linear in age, while the best method to estimate bias-free brain ages was the inverse of a scanner-independent and quadratic in brain age function. We demonstrated the feasibility to detect sex-related differences in brain-PAD using group-level regression accounting for the selected covariate model. These differences were preserved after bias correction. The Mean-Average Error (MAE) of the predictions in independent data was â¼8 years, 2-3 years greater than reports for research-oriented MRIs using DeepBrainNet, whereas an R2 (assuming no bias) was 0.33 and 0.76 for the uncorrected and corrected brain ages, respectively. DeepBrainNet on clinical populations seems feasible, but more accurate algorithms or transfer-learning retraining is needed.
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Encéfalo , Imagen por Resonancia Magnética , Humanos , Estudios de Factibilidad , Encéfalo/diagnóstico por imagen , AlgoritmosRESUMEN
Chronic pain is driven by factors across the biopsychosocial spectrum. Previously, we demonstrated that magnetic resonance images (MRI)-based brain-predicted age differences (brain-PAD: brain-predicted age minus chronological age) were significantly associated with pain severity in individuals with chronic knee pain. We also previously identified four distinct, replicable, multidimensional psychological profiles significantly associated with clinical pain. The brain aging-psychological characteristics interface in persons with chronic pain promises elucidating factors contributing to their poor health outcomes, yet this relationship is barely understood. That is why we examined the interplay between the psychological profiles in participants having chronic knee pain impacting function, brain-PAD, and clinical pain severity. Controlling for demographics and MRI scanner, we compared the brain-PAD among psychological profiles at baseline (n = 164) and over two years (n = 90). We also explored whether profile-related differences in pain severity were mediated by brain-PAD. Brain-PAD differed significantly between profiles (ANOVA's omnibus test, P = .039). Specifically, participants in the profile 3 group (high negative/low positive emotions) had an average brain-PAD â¼4 years higher than those in profile- (low somatic reactivity), with P = .047, Bonferroni-corrected, and than those in profile 2 (high coping), with P = .027, uncorrected. Repeated measures ANOVA revealed no significant change in profile-related brain-PAD differences over time, but there was a significant decrease in brain-PAD for profile 4 (high optimism/high positive affect), with P = .045. Moreover, profile-related differences in pain severity at baseline were partly explained by brain-PAD differences between profile 3 and 1, or 2; but brain-PAD did not significantly mediate the influence of variations in profiles on changes in pain severity over time. PERSPECTIVE: Accelerated brain aging could underlie the psychological-pain relationship, and psychological characteristics may predispose individuals with chronic knee pain to worse health outcomes via neuropsychological processes.
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There is a high prevalence of chronic pain among middle-aged and older adults in the United States. Chronic life stressors have been shown to have detrimental consequences for myriad health conditions, including chronic pain. However, there is limited evidence on the types of chronic life stressors that affect middle-aged and older adults and how these stressors influence the chronic pain burden in this population. Moreover, the interaction between chronic life stressors and racial/ethnic identity remains poorly understood as it relates to chronic pain. The current analysis used the 2018 Health and Retirement Study to investigate relationships between chronic life stressors and odds to experience any chronic pain and high-impact chronic pain. Chronic life stressors were characterized, overall and by racial/ethnic identity, and the main and interaction effects were calculated to evaluate relationships between chronic life stressors, racial/ethnic identity, and odds of experiencing any chronic pain and high-impact chronic pain. Results indicate that in 2018, the most common chronic life stressor among middle-aged and older adults was dealing with their own health problems (68%), followed by dealing with the physical or emotional issues affecting a spouse or child (46%). Adjusted analyses showed that a higher total of chronic life stressors increased the odds of middle-aged and older adults experiencing any chronic pain and high-impact chronic pain. There were no significant interactions between the overall chronic life stress burden and racial/ethnic identity as a predictor of odds to experience any chronic pain or high-impact chronic pain, but significant interaction effects were found related to specific chronic life stressors. Findings underscore the significant impact of chronic life stressors on the chronic pain burden among middle-aged and older adults in the United States, which cut across racial/ethnic identity.
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Body weight significantly impacts health and quality of life, and is a leading risk factor for the development of knee osteoarthritis (OA). Weight cycling may have more negative health consequences compared to steady high or low weight. Using the Osteoarthritis Initiative dataset, we investigated the effects of weight cycling on physical function, quality of life, and depression over 72-months compared to stable or unidirectional body weight trajectories. Participants (n = 731) had knee OA and were classified as: (1) stable-low (BMI < 25), (2) stable-overweight (BMI = 25-29.9), and (3) stable-obese (BMI ≥ 30); (4) steady-weight-loss; (5) steady-weight-gain (weight loss/gain ≥ 2.2 kg every 2-years); (6) gain-loss-gain weight cycling, and (7) loss-gain-loss weight cycling (weight loss/gain with return to baseline), based on bi-annual assessments. We compared Knee Injury and Osteoarthritis Outcome Knee-Related Quality of Life, Function in Sports and Recreation, Physical Activity in the Elderly, Short Form SF-12, repeated chair rise, 20-m gait speed, and Center for Epidemiological Studies Depression using repeated-measures ANOVA. The steady weight loss group demonstrated the worst pain, physical function, and depressive symptoms over time (p's < 0.05). More research is needed to confirm these findings, and elucidate the mechanisms by which steady weight loss is associated with functional decline in knee OA.