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The Performance Index (P-Index) is a measure for evaluating mobility-related dual-task performance in older adults. The identification of specific clinicodemographic factors predictive of P-Index scores, however, remains unclear. This cross-sectional study analyzed data from 120 community-dwelling older adults (average age 71.3 ± 11.23 years) to explore clinicodemographic variables that influence P-Index scores during the instrumented timed up and go test. Unadjusted analyses suggested several factors, including age, gender, body mass index, Mini-Mental Status Examination scores, functional reach test performance, history of falls, ethnicity, Geriatric Depression Scale scores, alcohol consumption, and educational levels, as potential predictors of P-Index. However, adjusted multinomial multiple regression analysis revealed Geriatric Depression Scale and Mini-Mental Status Examination scores as the exclusive independent predictors of P-Index classifications, segmented into high, intermediate, or low (percentiles ≤ 25, 26–74, or ≥ 75, respectively). A significant association was observed between the manifestation of depressive symptoms, lower Mini-Mental Status Examination scores, and reduced cognitive–motor performance. The findings implicate depressive symptoms and low cognitive performance as substantial impediments to optimal dual-task mobility within this cohort. Further studies are warranted to examine the efficacy of cognitive stimulation and antidepressant therapy, in augmenting mobility-related dual-task performance among older adults. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the effects of multicomponent training on adropin, endothelial function, insulin resistance, and sleep quality in overweight older adults. In this randomized controlled study, 40 overweight older adults were randomly divided into training and control groups. The multicomponent training program including aerobic, resistance, and balance exercise was followed for 8 weeks, 3 days a week. Study variables were measured 48 hr before and after the intervention. After 8 weeks of multicomponent training, adropin (p =.01), nitric oxide (p =.01), and maximal oxygen uptake (VO2max; p =.002) increased, and glucose (p =.001), insulin (p =.001), insulin resistance (p =.01), systolic blood pressure (p =.01), and sleep disorders (p =.01) decreased significantly. Also, Pearson's test results showed a significant inverse relationship between adropin level (p =.01 and r = −.55) and glucose (p =.01 and r = −.51) with sleep disorders. It seems that multicomponent training increases adropin and improves insulin resistance, endothelial function, and sleep quality in older adults. [ABSTRACT FROM AUTHOR]

Background: Pickleball has grown tremendously in recent years, yet little evidence exists regarding pickleball-related injuries. This scoping review extends current work on pickleball participation by identifying positive and negative health effects associated with the sport. We summarize how pickleball impacts the health and well-being of adult participants. Methods: Searches were conducted on MEDLINE, CINAHL, ProQuest Nursing, ERIC, SPORTDiscus, PsycINFO, Scopus, CBCA Complete, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ProQuest Dissertations and Theses. Selected studies considered aspects of health and/or well-being of adult pickleball participants. Using the population/concept/context framework, participants were healthy, able-bodied adults 18 years of age or over, who had played pickleball at least once. The positive and negative outcomes of pickleball on participants' health and well-being (concept) within the context of pickleball participation were examined. Full-text articles written in English since 2013 were included. Extracted data were tabulated, and a descriptive summary with thematic analysis was completed. Results: This scoping review comprised 27 articles that met the inclusion criteria. Pickleball is promising as an exercise intervention for all adults, and there is evidence of positive social and psychological effects, and health and fitness benefits to participating in pickleball by older adults. Conclusions: Although we are still in the early stages of studying pickleball, there have been some documented health benefits of using the sport as a physical exercise intervention for adults. More research is needed on the types, prevalence, and severity of pickleball injuries and the sport's impact on younger players. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the behavior of hybrid abutment crowns fabricated from monolithic lithium disilicate ceramic (LDC) and to compare the influence of different in vitro ar>ficial aging protocols. Materials and Methods: A total of 32 monolithic hybrid abutment crowns of monolithic LDC were fabricated. Of these, 24 were ar>ficially aged using three different protocols up to a 20 year simula>on (1.2 × 106, 2.4 × 106, 4.8 × 106 chewing cycles, thermocycling), a control group underwent no ar>ficial aging (n = 8, N = 32). Load-to-failure tests were conducted for all specimens, and failure values were compared (P < .05). Results: All specimens passed in vitro aging. Mean failure load values between 532.6 and 562.8 N were found but did neither differ significantly among the test groups nor from the control group. Conclusions: Within the limita>ons of this in vitro pilot study, hybrid abutment crowns manufactured from monolithic LDC seem to offer appropriate long-las>ng mechanical stability over a simula>on period up to 20 years. The failure values and complica>on paTern seem to b e independent of several aging protocols in this test set-up. [ABSTRACT FROM AUTHOR]

Purpose: Loss of muscle power has a significant impact on mobility in geriatric populations, so this study sought to determine the extent and time course of performance decline in power-centric events throughout the life span via retrospective analyses of masters and elite track-and-field data. Methods: Four track-and-field events were selected based on maximal power output: the 100-m dash, long jump, high jump, and triple jump. Elite and masters athlete data were gathered from the World Masters Outdoor Championships and the International Amateur Athletic Federation World Athletics Championships (17,945 individual results). Data were analyzed by fitting individual and group results to quadratic and linear models. Results: Average age of peak performance in all events was 27.8 (0.8) years for men and 28.3 (0.8) years for women. Athlete performance decline best matched a linear model for the 5 years following peak performance (mean R2 =.68 [.20]) and for ages 35–60, but best matched a quadratic model for ages 60–90 and 35–90 (mean R2 =.75 [.12]). The average rate of decline for the masters data ages 35–60 ranged from 0.55% per year for men's 100-m dash to 1.04% per year for women's long jump. A significant age × sex interaction existed between men and women, with men declining faster throughout life in all events except the 100-m dash. Conclusions: Performance decline begins in the early 30s and is linear through middle age. This pattern of decline provides a basis for further research on power-decline pathophysiology and preventive measures starting in the 30s. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the influence of knee joint range of motion (RoM) on the torque–velocity relationship and fatigue in the knee extensor muscles of 7 young (median = 26 y) and 7 older (68 y) adults. Each leg was assigned a RoM (35° or 75°) over which to perform a torque–velocity protocol (maximal isokinetic contractions, 60–300°·s−1) and a fatigue protocol (120 maximal contractions at 120°·s−1, 0.5 Hz). Six older participants were unable to reach 300°·s−1 over 35°. Therefore, the velocity eliciting 75% of peak torque at 60°·s−1 (V75, °·s−1) was calculated for each RoM from a fit of individual torque–velocity curves (60–240°·s−1), and ΔV75 (35°–75°) was determined. Fatigue (final torque/initial torque) was used to calculate Δfatigue (35°–75°). ΔV75 was not different from 0 in young (−28.3°·s−1 [−158.6 to 55.7], median [range], P =.091) or older (−18.5°·s−1 [−95.0 to 23.9], P =.128), with no difference by age (P =.710). In contrast, fatigue was greater for 75° in young (Δfatigue = 25.9% [17.5–30.3], P =.018) and older (17.2% [11.9–52.9], P =.018), with no effect of age (P =.710). These data indicate that, regardless of age, RoM did not alter the torque–velocity relationship between 60 and 240°·s−1, and fatigue was greater with a larger RoM. [ABSTRACT FROM AUTHOR]

Resistance training is used to combat skeletal muscle function decline in older adults. Few studies have been designed specific for females, resulting in very limited treatment options for skeletal muscle atrophy in aging women. Here, we analyzed the gene expression profiles of skeletal muscle samples from sedentary young women, sedentary older women, and resistance-trained older women, using microarray data from public database. A total of 45 genes that were differentially expressed during female muscle aging and reversed by resistance training were identified. Functional and pathway enrichment analysis, protein–protein interaction network analysis, and receiver operating characteristic analysis were performed to reveal the key genes and pathways involved in the effects of resistance training on female muscle aging. The collagen genes COL1A1, COL3A1, and COL4A1 were identified important regulators of female muscle aging and resistance training, by modulating multiple signaling pathways, such as PI3 kinase-Akt signaling, focal adhesions, extracellular matrix-receptor interactions, and relaxin signaling. Interestingly, the expression of CDKN1A and TP63 were increased during aging, and further upregulated by resistance training in older women, suggesting they may negatively affect resistance training outcomes. Our findings provide novel insights into the molecular mechanisms of resistance training on female muscle aging and identify potential biomarkers and targets for clinical intervention. [ABSTRACT FROM AUTHOR]

Background: Retirement transition has been shown to associate with changes in physical activity (PA) and self-rated health (SRH), but their interrelationship is less studied. The aim was to investigate changes in accelerometer-measured total PA, moderate to vigorous PA (MVPA), and sedentary time across retirement transition as a predictor of SRH. Methods: Data from the Swedish Retirement Study and the Finnish Retirement and Aging study were harmonized and pooled. Data from 3 waves (about 12 mo apart) were included: 1 preretirement (wave 1) and 2 postretirement follow-ups (wave 2–3). A totally of 245 participants (27% men) were included. Thigh-worn accelerometers were used to collect data for PA variables (wave 1–2), and SRH was obtained from the questionnaire (wave 1–3). Results: Between wave 1 and 2, total PA decreased with 11 (CI, −22 to −1) minutes per day, MVPA was stable (0 [CI, −3 to 3] min), and sedentary time decreased nonsignificantly with 9 (CI, −20 to 1) minutes. SRH changed between all 3 waves (all P <.001). At preretirement, 10 more minutes of MVPA was associated with greater odds of better SRH when adjusting for accelerometer wear-time, cohort, sex, age, and occupational status (odds ratio: 1.11 [95% CI, 1.02–1.22]). This association was no longer statistically significant when additionally adjusting for marital status, body mass index, and smoking. No significant associations were observed between changes in the PA variables during retirement transition and SRH at postretirement follow-ups. Conclusions: This study showed a cross-sectional association between MVPA and greater odds of reporting better SRH before retirement. No longitudinal associations were observed between changes in the PA variables from before to after retirement and later changes in SRH. [ABSTRACT FROM AUTHOR]

Large-amplitude thermal excursions imposed on deeply supercooled liquids modulate the nonlinear time evolution of their structural rearrangements. The consequent aftereffects are treated within a Wiener–Volterra expansion in laboratory time that allows one to calculate the associated physical-aging and thermal response functions. These responses and the corresponding higher-harmonic susceptibilities are illustrated using calculations based on the Tool–Narayanaswamy–Moynihan (TNM) model. The conversion from laboratory to material time is thoroughly discussed. Similarities and differences to field-induced higher-harmonic susceptibilities are illustrated using Lissajous and Cole–Cole plots and discussed in terms of aging nonlinearity parameters. For the Lissajous plots, banana-type shapes emerge, while the Cole–Cole plots display cardioidic and other visually appealing patterns. For application beyond the regime in which conventional single-parameter aging concepts work, the Wiener–Volterra material-time-series is introduced as the central tool. Calculations and analyses within this general framework in conjunction with suitable choices of higher-order memory kernels and employing correspondingly extended TNM models yield at least qualitative agreement with recent large-perturbation physical aging experiments. Implications for differential scanning calorimetry and related methods are discussed. The introduced concepts and analyses provide a solid foundation for a generalized description of nonlinear thermal out-of-equilibrium dynamics of glass forming materials, differing from the nonlinear responses known from rheology and dielectric spectroscopy. [ABSTRACT FROM AUTHOR]

This study evaluated physical activity interventions designed for individuals with visual impairments and sought to guide health intervention scientists aiming to promote physical activity in this demographic. We delved into the specifics of participants' visual impairments, intervention features, accommodation approaches, and replicability prospects. The search spanned four databases, namely PubMed, CINAHL, SportDiscus, and Scopus, providing a wide scope and diversity of potential studies. There were no restrictions on publication years. We reviewed 13 studies, totaling 15 interventions. A consensus on visual-impairment definitions remains elusive, and the intervention dosages displayed variability. Notably, 66.7% (n = 7) integrated behavior-change techniques to amplify physical activity levels. Multiple studies employed audio descriptions as an accommodation method. While most studies provided adequate information for potential replication, detailed study protocols were frequently absent. It is essential for developed interventions to be persistently evaluated and fine-tuned to optimize results. [ABSTRACT FROM AUTHOR]

This case study assessed body composition, muscle strength, cardiorespiratory fitness, and metabolic health of the present female world champion powerlifter in the 70+ age category who started resistance exercise training at 63 years of age with no prior experience with structured exercise training. Measures of body composition (magnetic resonance imaging, computed tomography, and dual-energy X-ray absorptiometry scanning, leg volume); strength (one-repetition maximum leg press and extension, maximum voluntary contraction, and handgrip strength); physical function (short physical performance battery); cardiorespiratory fitness (peak oxygen consumption); and metabolic health (oral glucose tolerance test) were assessed. In addition, a muscle biopsy was collected to assess muscle fiber type distribution and cross-sectional area (CSA). Where possible, data were compared with previously (un)published sex- and age-matched data using z scores. Skeletal muscle mass index was calculated by dividing limb muscle mass by height squared. Data from the control groups are expressed as mean ± 95% confidence interval. Our participant (age: 71 years; body mass: 64.5 kg; body mass index: 27.6 kg/m2) reported a good bone mineral density of 1.09 g/cm2 (T score between −1 and +1) and very low values of abdominal and organ body fat (i.e., between 20% and 70% lower compared with a reference group of postmenopausal women). In addition, she showed a 33% greater skeletal muscle mass index when compared with healthy, older female control subjects (7.9 vs. 5.9 [5.7–6.2] kg/m2; n = 61) as well as 37% greater muscle quadriceps CSA (63.8 vs. 46.6 [44.5–48.7] cm2; n = 48) and 46% greater Type II muscle fiber CSA (4,536 vs. 3,097 [2,707–3,488] μm2; n = 19). Absolute leg press muscle strength was 36% greater (190 vs. 140 [132–147] kg; n = 30) and handgrip strength was 33% greater (33 vs. 25 [23–26] kg; n = 48) when compared with healthy, age-matched controls. In conclusion, even for resistance exercise naïve individuals, starting exercise at an advanced age can lead to improvements in body composition and muscle strength allowing older adults to reduce the risk for developing metabolic syndrome, live independently, and even compete at a world class level. [ABSTRACT FROM AUTHOR]

Background: Walking activity has been associated with reduction in the development of chronic disease, cognitive and physical function impairment, disability, and mortality. The objective of this study was to examine the relationship between walking activity and physical function over 9 years of follow-up among Mexican Americans aged 78 years and older. Methods: Participants (N = 998) were from the Hispanic Established Population for the Epidemiologic Study of the Elderly (2007–2016). Measures included walking activity duration and frequency, socio-demographics, body mass index, medical conditions, pain, depressive symptoms, limitation in activities of daily living, and the Mini-Mental State Examination. Low physical function was defined as scoring <7 on the Short Physical Performance Battery. At baseline, participants were grouped into nonwalkers (n = 653), walked <150 minutes/week (n = 144), and walked 150 minutes/week or more (n = 201). A Generalized Estimating Equation model was used to estimate the odds ratio and 95% CI of low physical performance as a function of walking activity status. Results: Compared with nonwalkers, participants walking < 150 minutes/week had lower odds (odds ratio = 0.66, 95% CI, 0.51–0.86) of low physical function over time, after controlling for all covariates, as did those walking ≥ 150 minutes/week (odds ratio = 0.54, 95% CI, 0.41–0.71). Conclusions: Mexican American older adults who engage in any walking activity are at reduced risk of low physical function, even those with disability. Interventions at the individual and community level are recommended to reduce physical function impairment, even in those with preexisting medical conditions or disability. [ABSTRACT FROM AUTHOR]

Falls are very serious health concerns among older adults. Providing additional cutaneous and proprioceptive feedback to older adults may enhance their balance control and therefore reduce the incidents of falls. This study aimed to investigate the acute and acclimated effect of wearing waist-to-above-ankle compression garments (CGs) on balance control in community-dwelling older adults. Thirty-one older adults participated in the study. The Timed Up and Go, Berg Balance Scale, and the Fall Risk Test of the Biodex Balance System were used in a random order to examine balance control in three testing sessions 1 week apart. Results indicated wearing CGs had a significant impact on the Timed Up and Go test (p <.001), Berg Balance Scale (p =.001), and the Fall Risk Test (p =.001). For the Timed Up and Go test, participants exhibited significant improvement in both the acute (8.68 vs. 7.91 s) and acclimated effect (7.91 vs. 7.41 s) of wearing CGs. For the Berg Balance Scale, participants showed significant improvement after wearing CGs for 1 week in comparison to the no CGs condition (55.77 vs. 55.39 points). For the Fall Risk Test, participants showed a significant improvement in the acute effect of wearing CGs in comparison to the no CGs condition (1.55° vs. 1.31°). This exploratory study showed that wearing waist-to-above-ankle CGs provided a positive impact on balance control in healthy community-dwelling older adults. It lays the foundation for future studies with a larger sample size to investigate the potential benefits of wearing CGs in individuals with balance control deficits and/or other comorbidities. [ABSTRACT FROM AUTHOR]

The present paper explores how aging bodies of middle-aged women can enable and constrain participation in physical activity. The study is inspired by the process sociology of Norbert Elias and builds on qualitative empirical material from passive observations (N = 57), focus groups (N = 51), and individual follow-up interviews (N = 21) with middle-aged Danish women who participated in a 3-month research project with exercise intervention. The qualitative study found that awareness of bodily aging enabled the taking up of exercise in the intervention. Additionally, taking up regular exercise in midlife can be understood as a highly rationalized leisure-time activity in relation to societal moral norms of self-responsibility for own physiological health. Furthermore, the qualitative material indicates that participation enabled a self-realization among the middle-aged women, as strong and capable bodies counter to the biomedical view of decline in the aging body. [ABSTRACT FROM AUTHOR]

Manipulating the amount of muscle mass engaged during exercise can noninvasively inform the contribution of central cardiovascular and peripheral vascular-oxidative functions to endurance performance. To better understand the factors contributing to exercise limitation in older and younger individuals, exercise performance was assessed during single-leg and double-leg cycling. 16 older (67 ± 5 years) and 14 younger (35 ± 5 years) individuals performed a maximal exercise using single-leg and double-leg cycling. The ratio of single-leg to double-leg cycling power (RatioPower SL/DL) was compared between age groups. The association between fitness (peak oxygen consumption, peak power output, and physical activity levels) and RatioPower SL/DL was explored. The RatioPower SL/DL was greater in older compared with younger individuals (1.14 ± 0.11 vs. 1.06 ± 0.08, p =.041). The RatioPower SL/DL was correlated with peak oxygen consumption (r =.886, p <.001), peak power output relative to body mass (r =.854, p <.001), and levels of physical activity (r =.728, p =.003) in the younger but not older subgroup. Reducing the amount of muscle mass engaged during exercise improved exercise capacity to a greater extent in older versus younger population and may reflect a greater reduction in central cardiovascular function compared with peripheral vascular-oxidative function with aging. [ABSTRACT FROM AUTHOR]

PurposeTo investigate sex-based differences in inflammation-related biomarkers on spectral-domain OCT.DesignCross-sectional study.ParticipantsPatients with diabetic macular edema (DME) between February 1, 2019, and March 31, 2023, without intravitreal anti-VEGF injection within the previous 6 months.MethodsWe reviewed each patient's medical record for age, biological sex, race and ethnicity, most recent glycated hemoglobin A1c (HbA1c) level, visual acuity (VA), and central macular thickness (CMT). OCT biomarkers that have been found in literature to be associated with inflammation, including disorganization of retinal inner layers (DRIL), retinal hyperreflective retinal foci (HRFs), hyperreflective choroidal foci (HCFs), subfoveal neuroretinal detachment (SND), and perturbation in retinal nerve fiber layer thickness, ganglion cell layer thickness, and inner nuclear layer (INL) thickness were evaluated by graders masked to the clinical characteristics of the patients. We performed multivariable regression analyses with the OCT biomarkers as the outcome variables and sex, age, HbA1c, and CMT as independent variables.Main outcome measuresOCT inflammation-related biomarkers, as listed above.ResultsFemale patients were, on average, 2 years older than male patients (P = 0.041). There were no significant differences in race and ethnicity, HbA1c, VA, or CMT between male and female patients. After controlling for age, HbA1c, and CMT, we found male sex to be associated with more HRF (incidence rate ratio [IRR] = 1.19; 95% confidence interval [CI] = 1.10-1.29), more HCF (odds ratio = 2.01; 95% CI = 1.12-3.64), and thicker INL (7 μm thicker in males; 95% CI = 2-12). Sex was not a significant predictor for either DRIL or SND in the multivariable regression models. Patients with higher HbA1c were more likely to have more HRF (IRR = 1.02 per 1 point increase; 95% CI = 1.00-1.04) after controlling for other factors.ConclusionsMale sex was correlated with more inflammation-related biomarkers on OCT including more HRF, more HCF, and thicker INL, after accounting for age, glycemic control, and amount of DME. Further studies are needed to evaluate the potential implications of these sex-based differences for individualized treatment.Financial disclosuresProprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

BackgroundChronic pain leads to tau accumulation and hippocampal atrophy, which may be moderated through inflammation. In older men, we examined associations of chronic pain with Alzheimer's disease (AD)-related plasma biomarkers and hippocampal volume as moderated by systemic inflammation.MethodsParticipants were men without dementia. Chronic pain was defined as moderate-to-severe pain in 2+ study waves at average ages 56, 62, and 68. At age 68, we measured plasma amyloid-beta (Aβ42, n = 871), Aβ40 (n = 887), total tau (t-tau, n = 841), and neurofilament light chain (NfL, n = 915), and serum high-sensitivity C-reactive protein (hs-CRP, n = 968), a marker of systemic inflammation. A subgroup underwent structural MRI to measure hippocampal volume (n = 385). Analyses adjusted for medical morbidities, depressive symptoms, and opioid use.ResultsChronic pain was related to higher Aβ40 (β = 0.25, p = .009), but hs-CRP was unrelated to AD-related biomarkers (ps > .05). There was a significant interaction such that older men with both chronic pain and higher levels of hs-CRP had higher levels of Aβ42 (β = 0.36, p = .001) and Aβ40 (β = 0.29, p = .003). Chronic pain and hs-CRP did not interact to predict levels of Aβ42/Aβ40, t-tau, or NfL. Furthermore, there were significant interactions such that Aβ42 and Aβ40 were associated with lower hippocampal volume, particularly when levels of hs-CRP were elevated (hs-CRP × Aβ42: β = -0.19, p = .002; hs-CRP × Aβ40: β = -0.21, p = .001), regardless of chronic pain status.ConclusionsChronic pain was associated with higher plasma Aβ, especially when hs-CRP was also elevated. Higher hs-CRP and Aβ levels were both related to smaller hippocampal volumes. Chronic pain, when accompanied by systemic inflammation, may elevate the risk of neurodegeneration in AD-vulnerable regions.

BackgroundBreast arterial calcification (BAC) on mammograms has emerged as a biomarker of women's cardiovascular disease (CVD) risk, but there is a lack of quantification tools and clinical outcomes studies.ObjectivesThis study assessed the association of BAC (both presence and quantity) with CVD outcomes.MethodsThis single-center, retrospective study included women with a screening mammogram from 2007 to 2016. BAC was quantified using an artificial intelligence-generated score, which was assessed as both a binary and continuous variable. Regression analyses evaluated the association between BAC and mortality and a composite of acute myocardial infarction, heart failure, stroke, and mortality. Analyses were adjusted for age, race, diabetes, smoking, blood pressure, cholesterol, and history of CVD and chronic kidney disease.ResultsA total of 18,092 women were included in this study (mean age 56.8 ± 11.0 years; diabetes [13%], hypertension [36%], hyperlipidemia [40%], and smoking [5%]). BAC was present in 4,223 (23%). Over a median follow-up of 6 years, death occurred in 7.8% and 2.3% of women with and without BAC, respectively. The composite occurred in 12.4% and 4.3% of women with and without BAC, respectively. Compared to those without, women with BAC had adjusted HRs of 1.49 (95% CI: 1.33-1.67) for mortality and 1.56 (95% CI: 1.41-1.72) for the composite. Each 10-point increase in the BAC score was associated with higher risk of mortality (HR: 1.08 [95% CI: 1.06-1.11]) and the composite (HR: 1.08 [95% CI: 1.06-1.10]). BAC was especially predictive of future events among younger women.ConclusionsBAC is independently associated with mortality and CVD, especially among younger women. Measurement of BAC beyond presence adds incremental risk stratification. Quantifying BAC using an artificial intelligence algorithm is feasible, clinically relevant, and may improve personalized CVD risk stratification.

Adverse early life experiences are strongly associated with reduced cognitive function throughout life. The link is strong in many human studies, but these do not enable assigning causality, and the limited access to the live human brain can impede establishing the mechanisms by which early-life adversity (ELA) may induce cognitive problems. In experimental models, artificially imposed chronic ELA/stress results in deficits in hippocampus dependent memory as well as increased vulnerability to the deleterious effects of adult stress on memory. This causal relation of ELA and life-long memory impairments provides a framework to probe the mechanisms by which ELA may lead to human cognitive problems. Here we focus on the consequences of a one-week exposure to adversity during early postnatal life in the rodent, the spectrum of the ensuing memory deficits, and the mechanisms responsible. We highlight molecular, cellular and circuit mechanisms using convergent trans-disciplinary approaches aiming to enable translation of the discoveries in experimental models to the clinic.

Coronary artery calcium (CAC) scans contain valuable information beyond the Agatston Score which is currently reported for predicting coronary heart disease (CHD) only. We examined whether new artificial intelligence (AI) applied to CAC scans can predict non-CHD events, including heart failure, atrial fibrillation, and stroke. We applied AI-enabled automated cardiac chambers volumetry and calcified plaque characterization to CAC scans (AI-CAC) of 5830 asymptomatic individuals (52.2% women, age 61.7 ± 10.2 years) in the multi-ethnic study of atherosclerosis during 15 years of follow-up, 1773 CVD events accrued. The AUC at 1-, 5-, 10-, and 15-year follow-up for AI-CAC vs. Agatston score was (0.784 vs. 0.701), (0.771 vs. 0.709), (0.789 vs. 0.712) and (0.816 vs. 0.729) (p

Subjective well-being (SWB) is often described as being U-shaped over adulthood, declining to a midlife slump and then improving thereafter. Improved SWB in later adulthood has been considered a paradox given age-related declines in health and social losses. While SWB has mostly been studied in high-income countries, it remains largely unexplored in rural subsistence populations lacking formal institutions that reliably promote social welfare. Here, we evaluate the age profile of SWB among three small-scale subsistence societies (n = 468; study 1), forest users from 23 low-income countries (n = 6987; study 2), and Tsimane horticulturalists (n = 1872; study 3). Across multiple specifications, we find variability in SWB age profiles. In some cases, we find no age-related differences in SWB or even inverted U-shapes. Adjusting for confounders reduces observed age effects. Our findings highlight variability in average well-being trajectories over the life course. Ensuring successful aging will require a greater focus on cultural and socioecological determinants of individual trajectories.

The Resource Centers for Minority Aging Research (RCMAR) is a flagship education, training, and development program of the National Institute of Health (NIH), and the National Institute on Aging (NIA) focused on increasing the number and diversity of researchers in aging. We sought to assess the program's contributions to geriatric and gerontology education by examining the scientific productivity of 294 RCMAR scientists who received pilot funding from the program during the last complete grant cycle, 2018 to 2023. Across the 18 funded sites, the scientists obtained 53 NIH grants and 29 NIA-specific grants. They published 281 manuscripts, of which 141 were noted as direct outcomes of the pilot funding and support received through the program. Findings indicated that the RCMAR program in its last cycle succeeded in promoting education and scientific career development of researchers from diverse backgrounds and researchers focused on health disparities to conduct transdisciplinary social and behavioral aging research.

IntroductionBlood-brain barrier (BBB) dysfunction occurs in Alzheimer's disease (AD). Yet, the stage at which it appears along the AD time course and whether it contributes to neurodegeneration remain unclear.MethodsOlder adults (61 to 90 years) from cognitively normal (CN) to mildly cognitively impaired (CI), enriched for APOE ?4 and amyloid positivity, underwent dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and diffusion MRI to measure BBB permeability and brain microstructure. Analysis of variance compared BBB permeability according to cognitive status, amyloid beta (Aβ), and APOE4. Linear regressions assessed associations of BBB permeability with brain microstructure and interactions with Aβ and APOE4.ResultsBBB permeability was elevated for APOE4 carriers across the cortical gray matter, with the strongest differences among CN amyloid-negative individuals. Associations between entorhinal BBB permeability and microstructure interacted with Aβ and APOE4, with the strongest relationships in amyloid-positive individuals and APOE4 carriers.DiscussionAPOE4 may drive widespread BBB dysfunction in preclinical AD, which may contribute to neurodegenerative changes early along the AD cascade.HighlightsGray matter blood-brain barrier (BBB) permeability is elevated for APOE4 carriers. APOE4-related BBB breakdown appears in the absence of cognitive decline or amyloid. BBB leakage correlates with entorhinal cortex microstructural injury. Associations with microstructure are strongest for amyloid-positive APOE4 carriers.

Early stages of Alzheimer's disease (AD) are associated with volume reductions in specific subregions of the medial temporal lobe (MTL). Using a manual segmentation method-the Olsen-Amaral-Palombo (OAP) protocol-previous work in healthy older adults showed that reductions in grey matter volumes in MTL subregions were associated with lower scores on the Montreal Cognitive Assessment (MoCA), suggesting atrophy may occur prior to diagnosis of mild cognitive impairment, a condition that often progresses to AD. However, current "gold standard" manual segmentation methods are labour intensive and time consuming. Here, we examined the utility of Automatic Segmentation of Hippocampal Subfields (ASHS) to detect volumetric differences in MTL subregions of healthy older adults who varied in cognitive status as determined by the MoCA. We trained ASHS on the OAP protocol to create the ASHS-OAP atlas and then examined how well automated segmentation replicated manual segmentation. Volumetric measures obtained from the ASHS-OAP atlas were also contrasted against those from the ASHS-PMC atlas, a widely used atlas provided by the ASHS team. The pattern of volumetric results was similar between the ASHS-OAP atlas and manual segmentation for anterolateral entorhinal cortex and perirhinal cortex, suggesting that ASHS-OAP is a viable alternative to current manual segmentation methods for detecting group differences based on cognitive status. Although ASHS-OAP and ASHS-PMC produced varying volumes for most regions of interest, they both identified early signs of neurodegeneration in CA2/CA3/DG and identified marginal differences in entorhinal cortex. Our findings highlight the utility of automated segmentation methods but still underscore the need for a unified and harmonized MTL segmentation atlas.

Protein aggregation is involved in many human diseases, but characterizing the sizes and shapes of intermediate oligomers (∼10-100 nm) that are important to the formation of macroscale aggregates like amyloid fibrils is a significant analytical challenge. Here, charge detection mass spectrometry (CDMS) is used to characterize individual conformational states of bovine serum albumin oligomers with up to ∼225 molecules (15 MDa). Elongated, partially folded, and globular conformational families for each oligomer can be readily distinguished based on the extent of charging. The abundances of individual conformers vary with changes in the monomer concentration or by adding aggregation inhibitors, such as SDS, heparin, or MgCl2. These results show the potential of CDMS for investigating intermediate oligomers in protein aggregation processes that are important for understanding aggregate formation and inhibition mechanisms and could accelerate formulation buffer development to prevent the aggregation of biotherapeutics.

Advances in antiretroviral therapy (ART) have made it possible for persons with human immunodeficiency virus (HIV) to live a lifespan approaching that of people without HIV, without progressing to AIDS or transmitting HIV to sexual partners or infants. There is, therefore, increasing emphasis on maintaining health throughout the lifespan. To receive optimal medical care and achieve desired outcomes, persons with HIV must be consistently engaged in care and able to access uninterrupted treatment, including ART. Comprehensive evidence-based HIV primary care guidance is, therefore, more important than ever. Creating a patient-centered, stigma-free care environment is essential for care engagement. Barriers to care must be decreased at the societal, health system, clinic, and individual levels. As the population ages and noncommunicable diseases arise, providing comprehensive health care for persons with HIV becomes increasingly complex, including management of multiple comorbidities and the associated challenges of polypharmacy, while also attending to HIV-specific health concerns. Clinicians must address issues specific to preventive health, including cancer screening, providing recommended vaccinations, as well as promoting sexual health, including sexually transmitted infection diagnosis, treatment, and prevention. Clinicians also must address issues for specific populations, including persons of childbearing potential, including during preconception and pregnancy; children; adolescents; and transgender and gender-diverse individuals. This guidance from an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America updates the previous 2020 HIV Primary Care Guidance.

Study objectivesInsomnia symptoms are prevalent along the trajectory of Alzheimer's disease (AD), but the neurobiological underpinning of their interaction is poorly understood. Here, we assessed structural and functional brain measures within and between the default mode network (DMN), salience network, and central executive network (CEN).MethodsWe selected 320 participants from the ADNI database and divided them by their diagnosis: cognitively normal (CN), Mild Cognitive Impairment (MCI), and AD, with and without self-reported insomnia symptoms. We measured the gray matter volume (GMV), structural covariance (SC), degrees centrality (DC), and functional connectivity (FC), testing the effect and interaction of insomnia symptoms and diagnosis on each index. Subsequently, we performed a within-group linear regression across each network and ROI. Finally, we correlated observed abnormalities with changes in cognitive and affective scores.ResultsInsomnia symptoms were associated with FC alterations across all groups. The AD group also demonstrated an interaction between insomnia and diagnosis. Within-group analyses revealed that in CN and MCI, insomnia symptoms were characterized by within-network hyperconnectivity, while in AD, within- and between-network hypoconnectivity was ubiquitous. SC and GMV alterations were nonsignificant in the presence of insomnia symptoms, and DC indices only showed network-level alterations in the CEN of AD individuals. Abnormal FC within and between DMN and CEN hubs was additionally associated with reduced cognitive function across all groups, and increased depressive symptoms in AD.ConclusionsWe conclude that patients with clinical AD present with a unique pattern of insomnia-related functional alterations, highlighting the profound interaction between both conditions.

Pulmonary veno-occlusive disease (PVOD) is a rare but severe form of pulmonary hypertension characterized by the obstruction of pulmonary arteries and veins, causing increased pulmonary artery pressure and leading to right ventricular (RV) heart failure. PVOD is often resistant to conventional pulmonary arterial hypertension (PAH) treatments and has a poor prognosis, with a median survival time of 2-3 years after diagnosis. We previously showed that the administration of a chemotherapy agent mitomycin C (MMC) in rats mediates PVOD through the activation of the eukaryotic initiation factor 2 (eIF2) kinase protein kinase R (PKR) and the integrated stress response (ISR), resulting in the impairment of vascular endothelial junctional structure and barrier function. Here, we demonstrate that aged rats over 1 year exhibit more severe vascular remodeling and RV hypertrophy than young adult rats following MMC treatment. This is attributed to an age-associated elevation of basal ISR activity and depletion of protein phosphatase 1, leading to prolonged eIF2 phosphorylation and sustained ISR activation. Pharmacological blockade of PKR or ISR mitigates PVOD phenotypes in both age groups, suggesting that targeting the PKR/ISR axis could be a potential therapeutic strategy for PVOD.

Alterations in the nuclear envelope are linked to a variety of rare diseases termed laminopathies. A single amino acid substitution at position 12 (A12T) of the human nuclear envelope protein BAF (Barrier to Autointegration Factor) causes Néstor-Guillermo Progeria Syndrome (NGPS). This premature ageing condition leads to growth retardation and severe skeletal defects, but the underlying mechanisms are unknown. Here, we have generated a novel in vivo model for NGPS by modifying the baf-1 locus in C. elegans to mimic the human NGPS mutation. These baf-1(G12T) mutant worms displayed multiple phenotypes related to fertility, lifespan, and stress resistance. Importantly, nuclear morphology deteriorated faster during aging in baf-1(G12T) compared to wild-type animals, recapitulating an important hallmark of cells from progeria patients. Although localization of BAF-1(G12T) was similar to wild-type BAF-1, lamin accumulation at the nuclear envelope was reduced in mutant worms. Tissue-specific chromatin binding and transcriptome analyses showed reduced BAF-1 association in most genes deregulated by the baf-1(G12T) mutation, suggesting that altered BAF chromatin association induces NGPS phenotypes via altered gene expression.

IntroductionCardiovascular health is important for brain aging, yet its role in the clinical manifestation of autosomal dominant or atypical forms of dementia has not been fully elucidated. We examined relationships between Life's Simple 7 (LS7) and clinical trajectories in individuals with autosomal dominant frontotemporal lobar degeneration (FTLD).MethodsTwo hundred forty-seven adults carrying FTLD pathogenic genetic variants (53% asymptomatic) and 189 non-carrier controls completed baseline LS7, and longitudinal neuroimaging and neuropsychological testing.ResultsAmong variant carriers, higher baseline LS7 is associated with slower accumulation of frontal white matter hyperintensities (WMHs), as well as slower memory and language declines. Higher baseline LS7 associated with larger baseline frontotemporal volume, but not frontotemporal volume trajectories.DiscussionBetter baseline cardiovascular health related to slower cognitive decline and accumulation of frontal WMHs in autosomal dominant FTLD. Optimizing cardiovascular health may be an important modifiable approach to bolster cognitive health and brain integrity in FTLD.HighlightsBetter cardiovascular health associates with slower cognitive decline in frontotemporal lobar degeneration (FTLD). Lifestyle relates to the accumulation of frontal white matter hyperintensities in FTLD. More optimal cardiovascular health associates with greater baseline frontotemporal lobe volume. Optimized cardiovascular health relates to more favorable outcomes in genetic dementia.

Type 2 diabetes mellitus (T2DM) increases the risk of neurological diseases, yet how brain oscillations change as age and T2DM interact is not well characterized. To delineate the age and diabetic effect on neurophysiology, we recorded local field potentials with multichannel electrodes spanning the somatosensory cortex and hippocampus (HPC) under urethane anesthesia in diabetic and normoglycemic control mice, at 200 and 400 days of age. We analyzed the signal power of brain oscillations, brain state, sharp wave associate ripples (SPW-Rs), and functional connectivity between the cortex and HPC. We found that while both age and T2DM were correlated with a breakdown in long-range functional connectivity and reduced neurogenesis in the dentate gyrus and subventricular zone, T2DM further slowed brain oscillations and reduced theta-gamma coupling. Age and T2DM also prolonged the duration of SPW-Rs and increased gamma power during SPW-R phase. Our results have identified potential electrophysiological substrates of hippocampal changes associated with T2DM and age. The perturbed brain oscillation features and diminished neurogenesis may underlie T2DM-accelerated cognitive impairment.

Brain aging process is influenced by various lifestyle, environmental and genetic factors, as well as by age-related and often coexisting pathologies. Magnetic resonance imaging and artificial intelligence methods have been instrumental in understanding neuroanatomical changes that occur during aging. Large, diverse population studies enable identifying comprehensive and representative brain change patterns resulting from distinct but overlapping pathological and biological factors, revealing intersections and heterogeneity in affected brain regions and clinical phenotypes. Herein, we leverage a state-of-the-art deep-representation learning method, Surreal-GAN, and present methodological advances and extensive experimental results elucidating brain aging heterogeneity in a cohort of 49,482 individuals from 11 studies. Five dominant patterns of brain atrophy were identified and quantified for each individual by respective measures, R-indices. Their associations with biomedical, lifestyle and genetic factors provide insights into the etiology of observed variances, suggesting their potential as brain endophenotypes for genetic and lifestyle risks. Furthermore, baseline R-indices predict disease progression and mortality, capturing early changes as supplementary prognostic markers. These R-indices establish a dimensional approach to measuring aging trajectories and related brain changes. They hold promise for precise diagnostics, especially at preclinical stages, facilitating personalized patient management and targeted clinical trial recruitment based on specific brain endophenotypic expression and prognosis.

The magnetic resonance imaging (MRI) Core has been operating since Alzheimer's Disease Neuroimaging Initiative's (ADNI) inception, providing 20 years of data including reliable, multi-platform standardized protocols, carefully curated image data, and quantitative measures provided by expert investigators. The overarching purposes of the MRI Core include: (1) optimizing and standardizing MRI acquisition methods, which have been adopted by many multicenter studies and trials worldwide and (2) providing curated images and numeric summary values from relevant MRI sequences/contrasts to the scientific community. Over time, ADNI MRI has become increasingly complex. To remain technically current, the ADNI MRI protocol has changed substantially over the past two decades. The ADNI 4 protocol contains nine different imaging types (e.g., three dimensional [3D] T1-weighted and fluid-attenuated inversion recovery [FLAIR]). Our view is that the ADNI MRI data are a greatly underutilized resource. The purpose of this paper is to educate the scientific community on ADNI MRI methods and content to promote greater awareness, accessibility, and use. HIGHLIGHTS: The MRI Core provides multi-platform standardized protocols, carefully curated image data, and quantitative analysis by expert groups. The ADNI MRI protocol has undergone major changes over the past two decades to remain technically current. As of April 25, 2024, the following numbers of image series are available: 17,141 3D T1w; 6877 FLAIR; 3140 T2/PD; 6623 GRE; 3237 dMRI; 2846 ASL; 2968 TF-fMRI; and 2861 HighResHippo (see Table 1 for abbreviations). As of April 25, 2024, the following numbers of quantitative analyses are available: FreeSurfer 10,997; BSI 6120; tensor based morphometry (TBM) and TBM-SYN 12,019; WMH 9944; dMRI 1913; ASL 925; TF-fMRI NFQ 2992; and medial temporal subregion volumes 2726 (see Table 4 for abbreviations). ADNI MRI is an underutilized resource that could be more useful to the research community.

Glaucoma, an optic neuropathy with the loss of retinal ganglion cells (RGCs), is a leading cause of irreversible vision loss. Oxidative stress and mitochondrial dysfunction have a significant role in triggering glia-driven neuroinflammation and subsequent glaucomatous RGC degeneration in the context of glaucoma. It has previously been shown that apolipoprotein A-I binding protein (APOA1BP or AIBP) has an anti-inflammatory function. Moreover, Apoa1bp-/- mice are characterized by retinal neuroinflammation and RGC loss. In this study, we found that AIBP deficiency exacerbated the oxidative stress-induced disruption of mitochondrial dynamics and function in the retina, leading to a further decline in visual function. Mechanistically, AIBP deficiency-induced oxidative stress triggered a reduction in glycogen synthase kinase 3β and dynamin-related protein 1 phosphorylation, optic atrophy type 1 and mitofusin 1 and 2 expression, and oxidative phosphorylation, as well as the activation of mitogen-activated protein kinase (MAPK) in Müller glia dysfunction, leading to cell death and inflammatory responses. In vivo, the administration of recombinant AIBP (rAIBP) effectively protected the structural and functional integrity of retinal mitochondria under oxidative stress conditions and prevented vision loss. In vitro, incubation with rAIBP safeguarded the structural integrity and bioenergetic performance of mitochondria and concurrently suppressed MAPK activation, apoptotic cell death, and inflammatory response in Müller glia. These findings support the possibility that AIBP promotes RGC survival and restores visual function in glaucomatous mice by ameliorating glia-driven mitochondrial dysfunction and neuroinflammation.

BackgroundDigital cognitive assessments, particularly those that can be done at home, present as low-burden biomarkers for participants and patients alike, but their effectiveness in the diagnosis of Alzheimer's disease (AD) or predicting its trajectory is still unclear. Here, we assessed what utility or added value these digital cognitive assessments provide for identifying those at high risk of cognitive decline.MethodsWe analyzed >500 Alzheimer's Disease Neuroimaging Initiative participants who underwent a brief digital cognitive assessment and amyloid beta (Aβ)/tau positron emission tomography scans, examining their ability to distinguish cognitive status and predict cognitive decline.ResultsPerformance on the digital cognitive assessment was superior to both cortical Aβ and entorhinal tau in detecting mild cognitive impairment and future cognitive decline, with mnemonic discrimination deficits emerging as the most critical measure for predicting decline and future tau accumulation.DiscussionDigital assessments are effective at identifying at-risk individuals, supporting their utility as low-burden tools for early AD detection and monitoring.HighlightsPerformance on digital cognitive assessments predicts progression to mild cognitive impairment at a higher proficiency compared to amyloid beta and tau. Deficits in mnemonic discrimination are indicative of future cognitive decline. Impaired mnemonic discrimination predicts future entorhinal and inferior temporal tau.

Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes.

UNLABELLED: Our study examined associations of the CXC motif chemokine ligand 9 (CXCL9), a pro-inflammatory protein implicated in age-related inflammation, with musculoskeletal function in elderly men. We found in certain outcomes both cross-sectional and longitudinal significant associations of CXCL9 with poorer musculoskeletal function and increased mortality in older men. This requires further investigation. PURPOSE: We aim to determine the relationship of (CXCL9), a pro-inflammatory protein implicated in age-related inflammation, with both cross-sectional and longitudinal musculoskeletal outcomes and mortality in older men. METHODS: A random sample from the Osteoporotic Fractures in Men (MrOS) Study cohort (N = 300) was chosen for study subjects that had attended the third and fourth clinic visits, and data was available for major musculoskeletal outcomes (6 m walking speed, chair stands), hip bone mineral density (BMD), major osteoporotic fracture, mortality, and serum inflammatory markers. Serum levels of CXCL9 were measured by ELISA, and the associations with musculoskeletal outcomes were assessed by linear regression and fractures and mortality with Cox proportional hazards models. RESULTS: The mean CXCL9 level of study participants (79.1 ± 5.3 years) was 196.9 ± 135.2 pg/ml. There were significant differences for 6 m walking speed, chair stands, physical activity scores, and history of falls in the past year across the quartiles of CXCL9. However, higher CXCL9 was only significantly associated with changes in chair stands (β =  - 1.098, p

IntroductionAlzheimer's disease (AD) disproportionately affects minoritized populations who remain underrepresented in AD trials.MethodsWe partnered with local nursing community-based organizations to implement a culturally tailored educational intervention and recruit Hispanic/Latino American, Filipino American, and Korean American adults aged 55 to 80 for the AHEAD study, a preclinical AD trial, at the University of California, Irvine.ResultsWe engaged 654 individuals across 21 events, leading to 71 prescreenings: 21.1% Filipino, 11.2% Hispanic/Latino, and 67.6% Korean adults. Ineligibility due to age and language barriers was common among Hispanic/Latino and Korean adults, respectively. Filipino adults often withdrew interest or were lost to follow-up. Ultimately, 25 participants enrolled: eight Filipino, two Hispanic/Latino, and 15 Korean adults. Tailored, culturally relevant content significantly contributed to the engagement success.DiscussionThis study demonstrates the value and impact of novel partnerships with health-related provider organizations that provide trusted care and access to underrepresented communities.HighlightsSix hundred and fifty four underrepresented individuals were reached, and 25 enrolled in the AHEAD 3-45 trial. Twenty-one community events were held via partnerships with nursing and community organizations. The study engaged 21% Filipino, 11% Hispanic/Latino, 68% Korean adults. Community-Based Participatory Research (CBPR) principles enhanced the recruitment process. Transparent communication and joint planning were key.

BackgroundCompared to normal high-density lipoprotein (HDL) cholesterol values, very high HDL cholesterol is associated with a higher incidence of mortality and atherosclerotic cardiovascular disease (ASCVD). As such, clinical risk stratification among persons with very high HDL cholesterol is challenging.ObjectivesAmong persons with very high HDL cholesterol, the purpose was to determine the prevalence of coronary artery calcium (CAC) and compare the association between traditional risk factors vs CAC for all-cause mortality and ASCVD.MethodsThe primary analysis was completed among 446 participants from the Cedars-Sinai Medical Center of the CAC Consortium with very high HDL cholesterol (≥77 mg/dL in men, ≥97 mg/dL in women). Cox proportional hazards regression assessed the association of CAC and traditional risk factors with all-cause mortality during a median follow-up of 10.7 years. Replication and validation analyses were performed for all-cause mortality among 119 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with very high HDL cholesterol, who also had information on incident ASCVD.ResultsThe mean age was 57.9 years old, 49% were women, and the median HDL cholesterol was 98 mg/dL. One-half of participants (50%) had prevalent CAC, in whom the median CAC score was 118. Prevalent CAC conferred a 3.6-fold higher risk of all-cause mortality (HR: 3.64; 95% CI: 1.21-11.01), which appeared to be a more robust predictor than individual traditional risk factors beyond age. In the validation sample, prevalent CAC but not individual traditional risk factors were associated with all-cause mortality (HR: 2.39; 95% CI: 1.07-5.34) and a 4.0-fold higher risk of ASCVD (HR: 4.06; 95% CI: 1.11-14.84).ConclusionsMeasurement of CAC may facilitate clinical risk assessment among individuals with very high HDL cholesterol.

BackgroundThe Mnemonic Similarity Task (MST) is a popular memory task designed to assess hippocampal integrity. We assessed whether analyzing MST performance using a multinomial processing tree (MPT) cognitive model could detect individuals with elevated Alzheimer's disease (AD) biomarker status prior to cognitive decline.MethodWe analyzed MST data from >200 individuals (young, cognitively healthy older adults and individuals with mild cognitive impairment [MCI]), a subset of which also had existing cerebrospinal fluid (CSF) amyloid beta (Aβ) and phosphorylated tau (pTau) data using both traditional and model-derived approaches. We assessed how well each could predict age group, memory ability, MCI status, Aβ, and pTau status using receiver operating characteristic analyses.ResultsBoth approaches predicted age group membership equally, but MPT-derived metrics exceeded traditional metrics in all other comparisons.DiscussionA MPT model of the MST can detect individuals with AD prior to cognitive decline, making it a potentially useful tool for screening and monitoring older adults during the asymptomatic phase of AD.HighlightsThe MST, along with cognitive modeling, identifies individuals with memory deficits and cognitive impairment. Cognitive modeling of the MST identifies individuals with increased AD biomarkers prior to changes in cognitive function. The MST is a digital biomarker that identifies individuals at high risk of AD.

Dendrite defects and loss are early cellular alterations observed across neurodegenerative diseases that play a role in early disease pathogenesis. Dendrite degeneration can be modeled by expressing pathogenic polyglutamine disease transgenes in Drosophila neurons in vivo. Here, we show that we can protect against dendrite loss in neurons modeling neurodegenerative polyglutamine diseases through injury to a single primary dendrite branch. We find that this neuroprotection is specific to injury-induced activation of dendrite regeneration: neither injury to the axon nor injury just to surrounding tissues induces this response. We show that the mechanism of this regenerative response is stabilization of the actin (but not microtubule) cytoskeleton. We also demonstrate that this regenerative response may extend to other neurodegenerative diseases. Together, we provide evidence that activating dendrite regeneration pathways has the potential to slow-or even reverse-dendrite loss in neurodegenerative disease.

Background and purposeClinicians use reference values to contextualize physical performance scores, but data are sparse in individuals 90 years and older and racial/ethnic diversity is limited in existing studies. Gait speed provides valuable information about an individual's health status. Slow gait speed is associated with falls, cognitive decline, and mortality. Here, we report gait speed reference values in a racially/ethnically diverse oldest-old cohort.MethodsLifeAfter90 is a multiethnic cohort study of individuals 90 years and older. Participants are long-term members of an integrated healthcare delivery system without a dementia diagnosis at enrollment. We assessed gait speed using the 4-m walk test and calculated means, standard deviations, and percentiles by age, sex, assistive device use, and device type. We used linear regression to compare means by sex, age, device use and type, living situation and arrangement, and race/ethnicity.Results and discussionThe mean age of the 502 participants was 92.9 (range 90.1-102.8) years. Of these, 62.6% were women, 34.7% were college educated, 90.8% lived in a private residence, 20.9% self-reported as Asian, 22.5% as Black, 11.8% as Hispanic, 35.7% as White, and 9.2% as multiple, "other," or declined to state. The overall mean gait speed was 0.54 m/s (women = 0.51 m/s, men = 0.58 m/s). Mean gait speeds were 0.58 m/s, 0.53 m/s, and 0.48 m/s in the 90 to 91, 92 to 93, and 94+ age categories, respectively. In those without a device, mean gait speed was 0.63 m/s compared to 0.40 m/s in those with a device (cane = 0.44 m/s, walker = 0.37 m/s). Mean gait speed was significantly slower in women compared to men, age category 94+ compared to 90 to 91, participants with a device compared to those without, participants with a walker compared to a cane, and Black participants compared to Asian and White participants. However, differences by race/ethnicity were attenuated when chronic health conditions were considered.ConclusionsReference values developed from this multiethnic 90+ cohort will help clinicians interpret gait speed measures and tailor recommendations toward a 90+ population that is growing in number and in racial/ethnic diversity.

Lactate, a product of glycolysis, is formed under aerobic conditions. Extensive work has shown lactate flux in young and exercising humans; however, the effect of age is not known. We tested the hypothesis that postprandial lactate shuttling (PLS) would be diminished in older adults. We used [3-13C]lactate and [6,6-2H]glucose tracers, an oral glucose tolerance test (OGTT), and arterialized blood sampling to determine postprandial lactate rates of appearance (Ra), disappearance (Rd), and oxidation (Rox) in 15 young (28.1 ± 1.4 yr) and 13 older (70.6 ± 2.4 yr) healthy men and women. In young participants, fasting blood [lactate] (≈0.5 mM) rose after the glucose challenge, peaked at 15 min, dipped to a nadir at 30 min, and rose again peaking at 60 min (≈1.0 mM). Initial responses in lactate Ra of older participants were delayed and diminished until 90 min rising by 0.83 mg·kg-1·min-1. Lactate Rox was higher throughout the entire trial in young participants by a difference of ∼0.5 mg·kg-1·min-1. Initial peaks in lactate Ra and concentration in all volunteers demonstrated the presence of an enteric PLS following an OGTT. Notably, in the systemic, but not enteric, PLS phase, lactate Ra correlated highly with glucose Rd (r2 = 0.92). Correspondence of second peaks in lactate Ra and concentration and glucose Rd shows dependence of lactate Ra on glucose Rd. Although results show both enteric and systemic PLS phases in young and older study cohorts, metabolic responses were delayed and diminished in healthy older individuals.NEW & NOTEWORTHY We used isotope tracers, an oral glucose tolerance test, and arterialized blood sampling to determine postprandial lactate flux rates in healthy young and older men and women. Lactate rates of appearance and oxidation and the lactate-pyruvate exchange were delayed and diminished in both enteric and systemic postprandial lactate shuttle phases in older participants.

PURPOSE OF REVIEW: We reviewed recent evidence regarding the impact of climate change (specifically, high ambient temperatures, heatwaves, weather-related disasters, and air pollution) on older adults mental health. We also summarized evidence regarding other medical problems that can occur in aging adults in connection with climate change, resulting in psychiatric manifestations or influencing psychopharmacological management. RECENT FINDINGS: Older adults can experience anxiety, depressive, and/or posttraumatic stress symptoms, as well as sleep disturbances in the aftermath of climate disasters. Cognitive deficits may occur with exposure to air pollutants, heatwaves, or post-disaster. Individuals with major neurocognitive disorders and/or preexisting psychiatric illness have a higher risk of psychiatric hospitalizations after exposure to high temperatures and air pollution. There is a growing body of research regarding psychiatric clinical presentations associated with climate change in older adults. However, there is a paucity of evidence on management strategies. Future research should investigate culturally appropriate, cost-effective psychosocial and pharmacological interventions.

Genetically heterogeneous UM-HET3 mice born in 2020 were used to test possible lifespan effects of alpha-ketoglutarate (AKG), 2,4-dinitrophenol (DNP), hydralazine (HYD), nebivolol (NEBI), 16α-hydroxyestriol (OH_Est), and sodium thiosulfate (THIO), and to evaluate the effects of canagliflozin (Cana) when started at 16 months of age. OH_Est produced a 15% increase (p = 0.0001) in median lifespan in males but led to a significant (7%) decline in female lifespan. Cana, started at 16 months, also led to a significant increase (14%, p = 0.004) in males and a significant decline (6%, p = 0.03) in females. Cana given to mice at 6 months led, as in our previous study, to an increase in male lifespan without any change in female lifespan, suggesting that this agent may lead to female-specific late-life harm. We found that blood levels of Cana were approximately 20-fold higher in aged females than in young males, suggesting a possible mechanism for the sex-specific disparities in its effects. NEBI was also found to produce a female-specific decline (4%, p = 0.03) in lifespan. None of the other tested drugs provided a lifespan benefit in either sex. These data bring to 7 the list of ITP-tested drugs that induce at least a 10% lifespan increase in one or both sexes, add a fourth drug with demonstrated mid-life benefits on lifespan, and provide a testable hypothesis that might explain the sexual dimorphism in lifespan effects of the SGLT2 inhibitor Cana.

PurposeLong COVID-19 syndrome occurs in 10-20 % of people after a confirmed/probable SARS-COV-2 infection; new symptoms begin within three months of COVID-19 diagnosis and last > 8 weeks. Little is known about risk factors for long COVID, particularly in older people who are at greater risk of COVID complications.MethodsData are from Women's Health Initiative (WHI) postmenopausal women who completed COVID surveys that included questions on whether they had ever been diagnosed with COVID and length and nature of symptoms. Long COVID was classified using standard consensus criteria. Using WHI demographic and health data collected at study enrollment (1993-98) through the present day, machine learning identified the top 20 risk factors for long COVID. These variables were tested in logistic regression models.ResultsOf n = 37,280 survey respondents, 1237 (mean age = 83 years) reported a positive COVID-19 test and 425 (30 %) reported long COVID. Symptoms included an array of neurological, cardio-pulmonary, musculoskeletal, and general fatigue, and malaise symptoms. Long COVID risk factors included weight loss, physical and mobility limitations, and specific heath conditions (e.g., history of heart valve procedure, rheumatoid arthritis).ConclusionsKnowledge of risk factors for long COVID may be the first step in understanding the etiology of this complex disease.

BackgroundPain is ubiquitous, yet understudied. The objective of this study was to analyze inequities in pain assessment and management for hospitalized older adults focusing on demographic and geriatric-related variables.MethodsThis was a retrospective cohort study from January 2013 through September 2021 of all adults 65 years or older on the general medicine service at UCSF Medical Center. Primary exposures included (1) demographic variables including race/ethnicity and limited English proficiency (LEP) status and (2) geriatric-related variables including age, dementia or mild cognitive impairment diagnosis, hearing or visual impairment, end-of-life care, and geriatrics consult involvement. Primary outcomes included (1) adjusted odds of numeric pain assessment versus other assessments and (2) adjusted opioids administered, measured by morphine milligram equivalents (MME).ResultsA total of 15,809 patients were included across 27,857 hospitalizations with 1,378,215 pain assessments, with a mean age of 77.8 years old. Patients were 47.4% White, 26.3% with LEP, 49.6% male, and 50.4% female. Asian (OR 0.75, 95% CI 0.70-0.80), Latinx (OR 0.90, 95% CI 0.83-0.99), and Native Hawaiian or Pacific Islander (OR 0.77, 95% CI 0.64-0.93) patients had lower odds of a numeric assessment, compared with White patients. Patients with LEP (OR 0.70, 95% CI 0.66-0.74) had lower odds of a numeric assessment, compared with English-speaking patients. Patients with dementia, hearing impairment, patients 75+, and at end-of-life were all less likely to receive a numeric assessment. Compared with White patients (86 MME, 95% CI 77-96), Asian patients (55 MME, 95% CI 46-65) received fewer opioids. Patients with LEP, dementia, hearing impairment and those 75+ years old also received significantly fewer opioids.ConclusionOlder, hospitalized, general medicine patients from minoritized groups and with geriatric-related conditions are uniquely vulnerable to inequitable pain assessment and management. These findings raise concerns for pain underassessment and undertreatment.

ObjectivesLatinos are about twice as likely to develop cognitive impairment. Culturally, filial support and familismo are expected within Latino families. Yet approximately twenty percent of Latinos live alone in the United States. The purpose of this study is to explore the concerns and priorities of older Latinos living alone with cognitive impairment, using a precarity framework.MethodWe conducted 22 in-home interviews with older Latinos living alone with cognitive impairment, and we supplemented the interviews with interviews with members of the older adults' social circle and providers. Themes influencing the precarity of Latino older adults living alone were organized through the major areas of the precarity lens; 1) Limited awareness of cognitive impairment; 2) Self-management of cognitive impairment; and 3) Lacking tailored services for cognitive impairment.ResultsLatino culture permeated and intersected across the lived experiences of participants living alone with cognitive impairment. Precarity was prevalent in all participants' lives and was exacerbated by familismo combined with cognitive impairment.ConclusionFindings showed precarity in the experiences the participants shared. Participant narratives reveal how the Latino culture intersects with the experience of precarity while living alone with cognitive impairment, especially in reference to the role that family plays through the expectation of familismo. However, given the difficult demands of employment and raising their own families, familismo can become more like a goal than a practice. Further research is needed to better understand how to bridge the gap between the needs of these older Latino adults living alone with cognitive impairment, their families, and formal services.

Developmental myelination is a protracted process in the mammalian brain1. One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age2-4. We tested this theory in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity5. During adolescence, visual experience modulated the rate of oligodendrocyte maturation in visual cortex. To determine whether oligodendrocyte maturation in turn regulates neuronal plasticity, we genetically blocked oligodendrocyte differentiation and myelination in adolescent mice. In adult mice lacking adolescent oligodendrogenesis, a brief period of monocular deprivation led to a significant decrease in visual cortex responses to the deprived eye, reminiscent of the plasticity normally restricted to adolescence. This enhanced functional plasticity was accompanied by a greater turnover of dendritic spines and coordinated reductions in spine size following deprivation. Furthermore, inhibitory synaptic transmission, which gates experience-dependent plasticity at the circuit level, was diminished in the absence of adolescent oligodendrogenesis. These results establish a critical role for oligodendrocytes in shaping the maturation and stabilization of cortical circuits and support the concept of developmental myelination acting as a functional brake on neuronal plasticity.