Significant Interaction Of Age Research Articles

When the Going Gets Tough: Multimorbidity and Heavy and Binge Drinking Among Adults

Multimorbidity, the presence of two or more long-term health conditions in the same individual, is an emerging epidemic associated with increased morbidity and mortality. Continued drinking concurrent with alcohol-related chronic conditions, particularly with multimorbidity, is likely to further elevate health risk. This study aimed to examine the associations of multimorbidity among diabetes, hypertension, heart disease, and cancer with drinking, and moderation of these associations by age. Logistic regression modeling was performed in 2023 using a nationally representative sample of U.S. adults from the 2015-19 National Survey on Drug Use and Health. Multimorbidity was assessed using (1) a count of these conditions and (2) disease-specific categories. The outcomes were past month heavy drinking (7+/14+ drinks weekly) and binge drinking (4+/5+ drinks per occasion) for women and men. A pattern of reduced odds for drinking outcomes associated with a greater degree of multimorbidity was found. This pattern was more apparent in models using the continuous measure of multimorbidity than in those using the categorical measure, and more consistent for binge drinking than for heavy drinking and for women than for men. Significant age interactions were found: the log odds of heavy drinking and binge drinking for both men and women decreased as the number of conditions increased, and more steeply for those ages 50+ than the younger. The log odds of heavy drinking varied little among men under age 50 regardless of multimorbidity. Alcohol interventions to reduce drinking with multimorbidity, particularly among heavy-drinking men under age 50, are warranted.

Clinical characteristics and independent prognostic factors of patients with mantle cell lymphoma over last two decades with a focus on the interaction between tumor stage and age.

e19065 Background: Mantle Cell Lymphoma (MCL) poses challenges in clinical management due to its rarity and aggressiveness. Understanding its epidemiology and outcomes is crucial. This study examines demographic and clinicopathologic profiles of 746 MCL patients in the USA from 2000-2015, focusing on the interplay between age and tumor stage. Methods: Using SEER data, this retrospective study analyzes demographic and clinical variables to assess mortality risks. Univariate and multivariate Cox regression models evaluate overall mortality (OM) and MCL-specific mortality (CSM), identifying independent prognostic factors (HR >1). The study explores age-tumor stage interaction. Results: Multivariate Cox proportional hazard regression analysis revealed age as pivotal, with those ≥80 facing higher risks for overall mortality (HR=3.93) and MCL-related mortality (HR=4.02) . Advanced Ann Arbor staging (II, III, IV) predicts heightened risks for both mortality types. Widowed status significantly influences outcomes ,with widowed individuals facing notably higher risks of overall mortality (HR=1.85) and MCL-related mortality (HR=1.81).Stage II and age groups 60-79 and ≥80 show substantial mortality risks, with similar trends in Stage IV combined with these age groups. Intriguingly, Stage III lacks significant age interactions, suggesting heterogeneous clinical profiles and treatment responses compared to patients in Stages II and IV. Therefore, the influence of age on mortality outcomes may be obscured by the complexities inherent in Stage III disease presentation and management. Conclusions: This study underscores age, staging, and marital status as key factors influencing MCL mortality. Widowed status emerges as notable, emphasizing social support's importance. Integrating these insights into clinical practice can enhance risk stratification and guide tailored interventions for improved outcomes. Our findings, particularly the lack of significant interactions between Stage III and age groups, highlight the intricate interplay between age and disease stage in MCL patients. This observation prompts us to advocate for further research aimed at elucidating the underlying mechanisms driving these complex interactions. Understanding the biological and clinical factors that influence the relationship between age and disease stage could provide valuable insights into MCL pathogenesis and progression. Further research in this area is warranted to inform personalized therapeutic approaches and ultimately enhance patient care and outcomes.

Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Following Prior Infection or Vaccination.

The extent to which infection versus vaccination has conferred similarly durable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity during the Omicron era remains unclear. In a cohort of 4496 adults under continued serological surveillance throughout the first year of Omicron-predominant SARS-CoV-2 transmission, we examined incidence of new infection among individuals whose last known antigenic exposure was either recent (<90 days) or remote (≥90 days) infection or vaccination. We adjudicated 2053 new-onset infections occurring between 15 December 2021 through 22 December 2022. In multivariable-adjusted analyses, compared to individuals whose last known exposure was remote vaccination, those with recent vaccination (odds ratio [OR], 0.82 [95% confidence interval {CI}, .73-.93]; P = .002) or recent infection (OR, 0.14 [95% CI, .05-.45]; P = .001) had lower risk for new infection within the subsequent 90-day period. Given a significant age interaction (P = .004), we found that remote infection compared to remote vaccination was associated with significantly greater new infection risk in persons aged ≥60 years (OR, 1.88 [95% CI, 1.13-3.14]; P = .015) with no difference seen in those <60 years (1.03 [95% CI, .69-1.53]; P = .88). During the initial year of Omicron, prior infection and vaccination both offered protection against new infection. However, remote prior infection was less protective than remote vaccination for individuals aged ≥60 years. In older adults, immunity gained from vaccination appeared more durable than immunity gained from infection.

Ascorbic Acid Infusion Improves Cerebrovascular Reactivity in Middle-Aged and Older Adults

Aging is associated with reductions in cerebrovascular reactivity (CVR) and cerebrovascular conductance (CVC), which may contribute to the development of neurodegenerative disease and stroke. In the peripheral vasculature, increased oxidative stress is linked to vascular dysfunction and is ameliorated following infusion of the antioxidant ascorbic acid (AA). However, oxidative stress’ effect on cerebrovascular function in humans is not entirely understood. PURPOSE: To determine whether oxidative stress reduces CVR and CVC in middle-aged and older adults (MA/O). We hypothesized that AA infusion would increase CVR and CVC in MA/O but not young adults (YA). METHODS: Young (18-29 years) and middle-aged and older (55-79 years) adults were recruited for two identical experimental visits. Each visit consisted of the same measures performed both before and after the infusion of either AA or saline (SAL). Middle cerebral artery blood velocity (MCAv) was recorded using a transcranial Doppler ultrasound probe. CVR was tested using a hypercapnia protocol that was achieved with a computer-based gas blender that increased the subjects’ end-tidal partial pressure of carbon dioxide (PETCO2) 9 mmHg above baseline for a 3-minute period. CVR was defined as the percent change in MCAv during hypercapnia divided by the absolute change in PETCO2. CVC was defined as the percent of CVR normalized for the changes in mean arterial blood pressure. Two-way ANOVAs were used to assess the effects of AA and SAL on CVR and CVC. Fisher’s LSD tests were used to assess main and interaction effects when necessary. RESULTS: 8 YA (25 + 2 years) and 14 MA/O (65 + 6 years) completed the experimental visits. There was a significant main effect of condition (pre/post) on CVR following SAL infusion (p = 0.016), and a significant age x condition interaction effect on CVR following AA infusion (p = 0.016). There were no significant main or interaction effects on CVC following SAL infusion, but there was a significant age x condition interaction effect on CVC following AA infusion (p = 0.012). Post hoc testing indicated that the difference in CVR following SAL infusion was due to an increase in YA (3.0 + 0.5 %/mmHg pre vs. 3.8 + 1.1 %/mmHg post, p = 0.047), whereas the difference in CVR following AA infusion was due to an increase in MA/O (3.3 + 1.7 %/mmHg pre vs. 4.1 + 1.9 %/mmHg post, p = 0.006). The difference in CVC was indicated to be due to both lower baseline CVC in MA/O (2.3 + 0.4 %/mmHg YA pre vs. 1.3 + 1.1 %/mmHg MA/O pre, p = 0.019) and an increase in CVC in MA/O following AA infusion (1.3 + 1.1 %/mmHg pre vs. 2.0 + 0.5 %/mmHg post, p = 0.047). CONCLUSION: Our main finding is that AA infusion restores CVR and CVC in MA/O, but not YA. This finding suggests that age-related increases in oxidative stress may impair cerebrovascular function. Supported by NIH Grant P20 GM113125. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The association between TyG and all-cause/non-cardiovascular mortality in general patients with type 2 diabetes mellitus is modified by age: results from the cohort study of NHANES 1999–2018

BackgroundThe prognostic value of triglyceride-glucose (TyG) index in general type 2 diabetes mellitus (T2DM) patients is still unclear. Therefore, we aimed to determine the associations between TyG and all-cause/cause-specific death in a T2DM cohort and explore whether such associations would be modified by age.MethodsA total of 3,376 patients with T2DM from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 were selected and divided into the younger group (< 65 yrs) and the older group (≥ 65 yrs). Baseline TyG was calculated and cause-specific mortality status [cardiovascular (CV), cancer, and non-CV] was determined by the NHANES Public-Use Linked Mortality Files through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were used to evaluate the association between TyG and all-cause/cause-specific mortality. Interaction between TyG and age to mortality was also evaluated. Sensitivity analyses were performed in patients without cardiovascular disease, chronic kidney disease, or insulin treatment.ResultsDuring a median follow-up of 107 months, 805 all-cause deaths occurred, of which 250 and 144 were attributed to CV and cancer deaths. There was a significant age interaction to the association between TyG and all-cause/non-CV mortality. After fully adjusting for potential confounding factors, higher TyG was associated with an increased risk of all-cause [TyG per unit increase Hazard Ratio (HR) 1.33, 95% Confidence Interval (CI) 1.06–1.66, p = 0.014] and non-CV mortality (TyG per unit increase HR 1.54, 95% CI 1.18–2.01, p = 0.002) only in the younger group, but not in the older group. There was no significant association between TyG and CV/cancer death in the total cohort and two age subgroups. Similar results were found in RCS and sensitivity analyses.ConclusionIn a national sample of patients with T2DM in the United States, we found that the association between TyG and all-cause/non-CV death was modified by age. Higher TyG was only associated with an increased risk of all-cause/non-CV only in T2DM patients younger than 65 years old, but not in older patients.

Family Transmission of Executive Functions: Mix of Traditional and Citizen Science Research Approach

The aim of this study was to examine the family transmission of executive functions deficits (working memory and inhibitory control) from parents to children, using a combination of traditional and citizen science research approaches. The final sample consisted of 110 families with two children (440 participants; 110 pairs of children, 110 fathers and 110 mothers). Children were preadolescent (6 to 10 years old; 24 pairs) or adolescent (11 to 15 years old; 86 pairs) siblings. The research results indicated that the inhibitory control of the mother is related to the inhibitory control of the younger child, and that the inhibitory control of the father is related to the inhibitory control of the older child in the family, regardless of developmental period. In the father-child relationship, it was revealed that there is a strong connection between parental and child working memory. On the other hand, there are significant interaction of mothers' working memory and age of children in the second-born child. Potential mechanisms of transmission were discussed, bearing in mind the specifics of mother's and father's involvement in raising children, as well as the potential direction of this research question towards the sphere of behavioral genetics and parenting styles.

RACE AND SEX DIFFERENCES IN RELATIONS OF DIABETES BIOMARKERS WITH PHYSICAL FUNCTIONING BEFORE DIABETES ONSET

Abstract It remains unclear if declines in physical functioning linked to Type 2 diabetes (T2DM) occur even before T2DM onset. We examined the longitudinal associations of T2DM biomarkers with upper and lower extremity strength among adults without T2DM at baseline. Participants were 1,572 African American (AA) and White adults (M(SD) age at baseline = 47.3 (9.7) years, 55% female, 53% AA) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, assessed on up to 3 time points between 2004-2017. Participants provided blood samples for measurement of fasting glucose and glycosylated hemoglobin (HbA1c), and completed dominant and nondominant handgrip strength assessment, and a chair stands task to assess upper and lower extremity strength, respectively. Linear mixed effects regression models estimating relations of HbA1c on age-related change and adjusting for race, sex, literacy, and poverty status revealed significant four-way interactions of HbA1c, race, sex, and age (B = -.2.59, t(2853) = -2.0 p = 0.04), and to a lesser extent of fasting glucose, race, sex, and age (B = -.07, t(2863) = -1.84 p = 0.06) on change in the chair stands task, but not on handgrip strength (ps &amp;gt; 0.29). Among younger AA and White men, and younger White women, increasing HbA1c was related to worse lower extremity strength. However, among AA women, and older White women, increasing HBA1c was related to better lower extremity strength. Our findings suggest differential relations of worse glucose regulation on physical functioning amongst African American and White men and women.

DIFFERENCES IN WHITE MATTER MICROSTRUCTURE IN MIDDLE-TO-OLDER AGE ADULTS WITH CHRONIC KNEE PAIN

Abstract Abundant research suggests aberrant white matter microstructure in patients with chronic pain as well as in older adults independently, where pain can significantly impact daily function. However, most studies fail to consider pain and aging interactions, particularly in middle and older-age. We aimed to explore differences in white matter microstructure (i.e.,Fractional Anisotropy (FA)) by pain’s impact on daily function (i.e., high (n=60) versus low pain impact (n=111) in middle-(45-59 years old, n=129) versus older adults (60-XX years old, n=77) using diffusion tensor imaging. Participants (n=171) underwent laboratory visits to collect multi-modal pain and neuroimaging measures. We employed a linear mixed model approach to test main effects of pain impact and age groups as well as their interaction with Bonferroni-corrected multiple comparisons. Findings demonstrated a significant pain impact and age interaction on FA (p’s≤0.05) in the left caudal anterior cingulate, left caudal middle frontal, left and right rostral middle frontal and left and right insular regions. Specifically, middle-aged adults with high impact pain had significantly worse brain microstructure across these regions compared to the older adults reporting high impact pain (p’s≤0.05). These findings highlight the need to study pain across the lifespan. Given the higher prevalence of chronic pain in middle-age compared to older age, future studies are urgently needed to test whether interventions in middle-age could halt pain’s impact on brain and function.

Effect of BMI-Discordant Abdominal Tissue Thickness on Fracture Probability: A Registry-Based Study.

FRAX, which is used to assess fracture probability, considers body mass index (BMI), but BMI may not reflect individual variation in body composition and distribution. We examined the effect of BMI-discordant abdominal thickness on FRAX-derived fracture probability for major osteoporotic fracture (MOF) and hip fracture. We studied 73,105 individuals, mean age 64.2 years. During mean 8.7 years, 7048 (9.6%) individuals sustained incident MOF, including 2155 (3.0%) hip fractures. We defined abdominal thickness index (ATI) as the difference between abdominal thickness measured by dual-energy X-ray absorptiometry (DXA) and thickness predicted by BMI using sex-stratified regression. ATI was categorized from lower (<-2 cm, -2 to -1 cm) to higher (1-2 cm, >+2 cm) with referent around zero (-1 to +1 cm). Adjusted for FRAX probability, increasing ATI was associated with incident MOF and hip fracture (p < 0.001). For the highest ATI category, MOF risk was increased (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.12-1.35) independent of FRAX probability. Similar findings were noted for hip fracture probability (HR = 1.28, 95% CI 1.09-1.51). There was significant age-interaction with much larger effects before age 65 years (HR = 1.44, 95% CI 1.23-1.69 for MOF; 2.29, 95% CI 1.65-3.18 for hip fracture). In contrast, for the subset of individuals with diabetes, there was also increased risk for those in the lowest ATI category (HR = 1.73, 95% CI 1.12-2.65 for MOF; 2.81, 95% CI 1.59-4.97 for hip fracture). Calibration plots across ATI categories demonstrated deviation from the line of identity in women (calibration slope 2.26 for MOF, 2.83 for hip fracture). An effect of ATI was not found in men, but this was inconclusive as the sex-interaction terms did not show significant effect modification. In conclusion, these data support the need to investigate increased abdominal thickness beyond that predicted by BMI and sex as a FRAX-independent risk factor for fracture. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

58 Hippocampal Subregions Predict Executive Function Across the Adult Lifespan

Objective:Executive function is known to decline in later life, largely attributed to structural and functional changes in the prefrontal cortex. However, other regions of the brain are integral to executive functioning, including the hippocampus. The hippocampus plays a large role in memory but its intricate connections to limbic regions including the prefrontal cortex likely underlies associations between the hippocampus and executive functions. Due to the hippocampus’ complex structure, hippocampal subregions may be differentially associated with executive function, but this possibility remains largely unexplored. Therefore, we examined the association between volume of the hippocampus and its subregions with executive function to understand these relationships across the adult lifespan.Participants and Methods:The study included 32 healthy, community-dwelling participants (age range = 18-81, mean age = 51.06 ± 20.98, 91% white, 72% female) who received a 3-Tesla magnetic resonance imaging (MRI) scan and completed a cognitive battery. We calculated an executive composite based on Trail Making Test Part B and the interference score from the Stroop Color and Word Test. Freesurfer (version 5.3) as used to quantify total hippocampal volume and subfield volumes for CA1, CA2-3, CA4-dentate gyrus, subiculum, and presubiculum. We conducted mixed-effects regression analyses with total hippocampal and subfield volume, age group (young, middle-aged, and older), and their interaction predicting the executive function composite, controlling for total intracranial volume.Results:Larger hippocampal subregion volumes in CA1 (p = 0.03), the subiculum (p = 0.01), and the CA4-dentate gyrus (p = 0.04) predicted better executive function. Total hippocampal volume and the presubiculum were not significantly associated with the executive function composite. The age group interaction was not significant for any of the models. Follow-up analyses by hemisphere showed that the effects were right lateralized in CA1and CA4-dentate gyrus, and bilateral in the subiculum.Conclusions:These data support the literature demonstrating the involvement of the hippocampus in executive function and demonstrates variation across hippocampal subfields. The lack of significant age interactions suggests these relationships may not differ across the lifespan, although this finding would need to be replicated in larger samples. These findings support previous literature showing CA4-dentate gyrus’ association with neurogenesis may facilitate better executive function by increasing connection strength among CA1, CA2-3, and the frontal cortex. This study contributes to our understanding of how specific hippocampal subregions relate to executive function, which has both clinical and research implications.

Abstract P3116: Age-Related Cardiac Changes In S-Nitrosoglutathione Reductase Knockout Mice

Age associated cardiac aging differs between males and females, yet these age-related sex-dimorphic pathways remain poorly explored. We have previously shown that inhibition of S-nitrosoglutathione reductase (GSNOR) was cardioprotective during ischemic injury in male but not female mice. We therefore, hypothesized that GSNOR activity might play a role in sex-related differences in cardiac aging, and GSNOR deletion (KO) might exacerbate age-related cardiac dysfunction in females but not males. WT and KO mice underwent longitudinal 2D-echocardiography at 4, 7, 10 and 14 months of age, and echocardiographic data were analyzed with mixed-effects analysis. We saw a significant decrease in GSNOR activity in old (18 months) WT mice relative to young (4 months) in both sexes but more pronounced in males (p&lt;0.0001) vs. females (p=0.02). Left ventricular (LV) internal diameter at end-diastole significantly increased with age in WT males (2.65 ± 0.02 to 3.60 ± 0.13) and females (2.61 ± 0.02 to 3.32 ± 0.04) with a significant effect of sex across age (p&lt;0.0001). LV Mass (indexed to group body weight at 18 months) increased with age in both males (82 ± 2 to 127 ± 3) and females (85 ± 3 to 113 ± 3) with a significant age and sex interaction (p&lt;0.0001). Similar trends were observed for other echocardiographic parameters. Contrary to our hypothesis, the age- and sex-related differences observed in WT were absent in KO mice. LV internal diameter at end-diastole and LV Mass did not significantly change in male or female KO mice from 4 to 14 months of age neither did the majority of echocardiographic parameters tested. No differences were observed between male and female KO mice. Taken together, our data show that GSNOR deletion attenuates aging-induced cardiac dysfunction and abrogates age-related sex differences in the mouse heart.

The LDL-C/ApoB ratio predicts cardiovascular and all-cause mortality in the general population

BackgroundGenerally, low-density lipoprotein (LDL) particle size can be inferred from the LDL cholesterol concentration to total apolipoprotein B concentration ratio (LDL-C/ApoB ratio, hereinafter called LAR), which is a good predictor of cardiovascular disease. However, the predictive ability of LAR for mortality risk in the general population is still unclear. This study aimed to explore the association between LAR and cardiovascular as well as all-cause mortality among American adults.MethodsThe present study was a secondary analysis of existing data from the National Health and Nutrition Examination Survey (NHANES). The final analysis included 12,440 participants from 2005 to 2014. Survival differences between groups were visualized using Kaplan‒Meier curves and the log-rank test. The association of LAR with cardiovascular and all-cause mortality was evaluated using multivariate Cox regression and restricted cubic spline analysis. Age, sex, coronary artery disease, diabetes, lipid-lowering medication use and hypertriglyceridemia were analyzed in subgroup analyses.ResultsThe median age in the study cohort was 46.0 years [interquartile range (IQR): 31.0–62.0], and 6,034 (48.5%) participants were male. During the follow-up period, there were 872 (7.0%) all-cause deaths and 150 (1.2%) cardiovascular deaths. Compared with individuals without cardiovascular events, those who experienced cardiovascular deaths had a lower LAR (1.13 vs. 1.25) (P < 0.001). The adjusted Cox regression model indicated that lower LAR was an independent risk factor for both cardiovascular [hazard ratio (HR) = 0.304, 95% confidence interval (CI): 0.114–0.812] and all-cause mortality (HR = 0.408, 95% CI: 0.270–0.617). Moreover, a significant age interaction was observed (P for interaction < 0.05), and there was a strong association between LAR and mortality among participants over 65 years of age. Further analysis showed an inverse association between LAR and both cardiovascular and all-cause mortality.ConclusionsLAR can independently predict cardiovascular and all-cause mortality in the general population.

Aberrant age-related alterations in spontaneous cortical activity in participants with cerebral palsy.

Cerebral Palsy (CP) is the most common neurodevelopmental motor disability, resulting in life-long sensory, perception and motor impairments. Moreover, these impairments appear to drastically worsen as the population with CP transitions from adolescents to adulthood, although the underlying neurophysiological mechanisms remain poorly understood. We began to address this knowledge gap by utilizing magnetoencephalographic (MEG) brain imaging to study how the amplitude of spontaneous cortical activity (i.e., resting state) is altered during this transition period in a cohort of 38 individuals with spastic diplegic CP (Age range = 9.80-47.50 years, 20 females) and 67 neurotypical controls (NT) (Age range = 9.08-49.40 years, Females = 27). MEG data from a five-minute eyes closed resting-state paradigm were source imaged, and the power within the delta (2-4 Hz), theta (5-7 Hz), alpha (8-12 Hz), beta (15-29 Hz), and gamma (30-59 Hz) frequency bands were computed. For both groups, the delta and theta spontaneous power decreased in the bilateral temporoparietal and superior parietal regions with age, while alpha, beta, and gamma band spontaneous power increased in temporoparietal, frontoparietal and premotor regions with age. We also found a significant group x age interaction, such that participants with CP demonstrated significantly less age-related increases in the spontaneous beta activity in the bilateral sensorimotor cortices compared to NT controls. Overall, these results demonstrate that the spontaneous neural activity in individuals with CP has an altered trajectory when transitioning from adolescents to adulthood. We suggest that these differences in spontaneous cortical activity may play a critical role in the aberrant motor actions seen in this patient group, and may provide a neurophysiological marker for assessing the effectiveness of current treatment strategies that are directed at improving the mobility and sensorimotor impairments seen in individuals with CP.

Allostatic load and incident heart failure in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study

BackgroundAllostatic load (AL) is the physiologic “wear and tear” on the body from stress. Yet, despite stress being implicated in the development heart failure (HF), it is unknown whether AL is associated with incident HF events.MethodsWe examined 16,765 participants without HF at baseline from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The main exposure was AL score quartile. AL was determined according to 11 physiologic parameters, whereby each parameter was assigned points (0–3) based on quartiles within the sample, and points were summed to create a total AL score ranging from 0–33. The outcome was incident HF event. We examined the association between AL quartile (Q1-Q4) and incident HF events using Cox proportional hazards models, adjusted for demographics, socioeconomic factors, and lifestyle.ResultsThe mean age was 64 ± 9.6 years, 61.5% were women, and 38.7% were Black participants. Over a median follow up of 11.4 years, we observed 750 incident HF events (635 HF hospitalizations and 115 HF deaths). Compared to the lowest AL quartile (Q1), the fully adjusted hazards of an incident HF event increased in a graded fashion: Q2 HR 1.49 95% CI 1.12–1.98; Q3 HR 2.47 95% CI 1.89–3.23; Q4 HR 4.28 95% CI 3.28–5.59. The HRs for incident HF event in the fully adjusted model that also adjusted for CAD were attenuated, but remained significant and increased in a similar, graded fashion by AL quartile. There was a significant age interaction (p-for-interaction < 0.001), whereby the associations were observed across each age stratum, but the HRs were highest among those aged < 65 years.ConclusionAL was associated with incident HF events, suggesting that AL could be an important risk factor and potential target for future interventions to prevent HF.

Alcohol cue reactivity in the brain: Age-related differences in the role of social processes in addiction in male drinkers.

Social attunement (SA)-the tendency to harmonize behavior with the social environment-has been proposed to drive the escalation of alcohol use in adolescence, while reducing use in adulthood. Little is known about how heightened social sensitivity in adolescence may interact with neural alcohol cue reactivity-a marker of alcohol use disorder-and its relationship to alcohol use severity over time. The aims of this study were to test whether (1) adolescents and adults differ in social alcohol cue reactivity in the nucleus accumbens, anterior cingulate cortex, and right medial prefrontal cortex (mPFC), and (2) age moderates the relationship between social alcohol cue reactivity and social attunement, measures of drinking at baseline, and changes in drinking over time. A sample of male adolescents (16-18 years) and adults (29-35 years) completed an fMRI social alcohol cue-exposure task at baseline and an online follow-up two to three years later. No main effects of age or drinking measures were observed in social alcohol cue reactivity. However, age significantly moderated associations of social alcohol cue reactivity in the mPFC and additional regions from exploratory whole-brain analyses with SA, with a positive association in adolescents and negative association in adults. Significant age interactions emerged only for SA in predicting drinking over time. Adolescents with higher SA scores escalated drinking, while adults with higher SA scores reduced drinking. These findings warrant further research on SA as a risk and protective factor and suggest that social processes influence cue reactivity differentially in male adolescents and adults.

Sex differences in age-related differences in joint motion during gait in community-dwelling middle-age and older individuals

BackgroundWalking is the most important mode of human locomotion; however, the ability to walk often decreases with age. Age-related differences in lower-limb kinematics during gait may differ depending on sex. However, the question of the compounded effects of age and sex on gait kinematics remains unsolved. Research questionThe present study aimed to clarify the interaction between age and sex in differences in gait kinematics of community-dwelling middle-age and older individuals. MethodsThis study included 836 community-dwelling middle-age and older adults (61.8 % female). Joint motion during comfortable gait was measured using magnetic and inertial measurement units. Hip, knee, and ankle joint angles were calculated in the sagittal plane. Participants were divided into four groups according to age: 50–59, 60–69, 70–79, and 80–89 years. The interaction of sex and age on spatiotemporal gait parameters and the peak value of joint angles was analyzed using two-way analysis of variance (ANOVA) and Tukey’s post hoc test. ResultsGait speed (F = 43.92, P < 0.001), step length (F = 73.00, P < 0.001), hip extension (F = 12.89, P = 0.002), knee flexion (F = 39.99, P < 0.001), and ankle plantar flexion (F = 27.43, P < 0.001) significantly decreased with age. Significant differences according to sex were observed in all parameters except gait speed. Significant age and sex interaction effects were observed for knee flexion (F = 4.97, P = 0.002) and ankle dorsiflexion (F = 4.04, P = 0.007). SignificanceA significant interaction effect of age and sex was observed for peak angle of knee flexion and ankle dorsiflexion during gait. In particular, the knee flexion angle among females during gait began to decrease from 60 years of age, and the decreasing trend was faster and more prominent than that among males.

Development and validation of the Chinese osteoporosis screening algorithm (COSA) in identification of people with high risk of osteoporosis

ObjectivesTo enhance the public awareness and facilitate diagnosis of osteoporosis, we aim to develop a new Chinese Osteoporosis Screening Algorithm (COSA) to identify people at high risk of osteoporosis. MethodsA total of 4747 postmenopausal women and men aged ≥ 50 from the Hong Kong Osteoporosis Study were randomly split into a development (N = 2373) and an internal validation cohort (N = 2374). An external validation cohort comprising 1876 community-dwelling subjects was used to evaluate the positive predictive value (PPV). ResultsAmong 11 predictors included, age, sex, weight, and history of fracture were significantly associated with osteoporosis after correction for multiple testing. Age- and sex-stratified models were developed due to the presence of significant sex and age interactions. The area under the curve of the COSA in the internal validation cohort was 0.761 (95% CI, 0.711–0.811), 0.822 (95% CI, 0.792–0.851), and 0.946 (95% CI, 0.908–0.984) for women aged < 65, women aged ≥ 65, and men, respectively. The COSA demonstrated improved reclassification performance when compared to Osteoporosis Self-Assessment Tool for Asians. In the external validation cohort, the PPV of COSA was 40.6%, 59.4%, and 19.4% for women aged < 65, women aged ≥ 65, and men, respectively. In addition, COSA > 0 was associated with an increased 10-year risk of hip fracture in women ≥ 65 (OR, 4.65; 95% CI, 2.24–9.65) and men (OR, 11.51; 95% CI, 4.16–31.81). ConclusionsWe have developed and validated a new osteoporosis screening algorithm, COSA, specific for Hong Kong Chinese.

Age- and sex-related differences in cortical morphology and their relationships with cognitive performance in healthy middle-aged and older adults.

The impacts of age and sex on brain structures related to cognitive function may be important for understanding the role of aging in Alzheimer disease for both sexes. We intended to investigate the age and sex differences of cortical morphology in middle-aged and older adults and their relationships with the decline of cognitive function. In this cross-sectional study, we examined the cortical morphology in 204 healthy middle-aged and older adult participants aged 45 to 89 years using structural magnetic resonance imaging (sMRI) data from the Dallas Lifespan Brain Study data set. Brain cortical thickness, surface complexity, and gyrification index were analyzed through a completely automated surface-based morphometric analysis using the CAT12 toolbox. Furthermore, we explored the correlation between cortical morphology differences and test scores for processing speed and working memory. There were no significant interactions of age and sex with cortical thickness, fractal dimension, or gyrification index. Rather, we found that both males and females showed age-related decreases in cortical thickness, fractal dimension, and gyrification index. There were significant sex differences in the fractal dimension in middle-aged participants and the gyrification index in older adult participants. In addition, there were significant positive correlations between the cortical thickness of the right superior frontal gyrus and Wechsler Adult Intelligence Scale (WAIS)-III Letter-Number Sequencing test scores in males (r=0.394; P<0.001; 95% CI for r values 0.216-0.577) and females (r=0.344; P<0.001; 95% CI for r values 0.197-0.491), respectively. Furthermore, a significant relationship between the gyrification index of the right supramarginal gyrus (SupraMG) and WAIS-III Digit Symbol test scores was observed in older adult participants (r=0.375; P<0.001; 95% CI for r values 0.203-0.522). The results suggest that, compared with males, females have more extensive differences in cortical morphology. The gyrification index of the right SupraMG can be used as an imaging marker of sexual cognitive differences between males and females in older adults. This study helps to further understand sex differences in the aging of the brain and cognition.

Significant age by childhood trauma interactions on grey matter volumes: A whole brain VBM analysis.

Childhood trauma is deleterious to long term brain development. The changes are variable, and depend on gender, age and the nature of the trauma. In this exploratory analysis, we investigated the effects of exposure to emotional trauma on grey matter (GM) volumes in adolescent females. We explored GM volumes in non-clinical females aged 12-17 years who had been exposed to either higher (HET; N=75) or minimal (MET; N=127) emotional trauma. High-resolution T1-weighted structural images were analysed with an optimised FSL-VBM protocol. The General Linear Model was run on HET versus MET with continuous age as an interaction. Mean GM volumes were extracted from significant corrected age interaction statistical maps and scrutinised with SPSS®. We observed greater HET*age than MET*age interactions (corrected p-value=0.0002), in 4 separate bilateral cortical regions associated with mood disorders. Scrutiny of these regions showed significant GM volume enlargements in the early adolescent HET group (p=0.017) and reductions in the late adolescent HET group (p < 0.0001). Notably, there were no differences in middle adolescence (p > 0.05). Causality cannot be inferred from this cross-sectional study and the onset of trauma cannot be determined using retrospective measures. Whilst GM volumes diminish from early adolescence onwards, our results show that HET impacts this brain development, perhaps first via unstable adaptative mechanisms, followed by maladaptive processes in late adolescence. This suggests that compromises of emotional and cognitive self-regulation in mood disorders may underpin the structural abnormalities observed across multiple brain regions in these teenage girls.

Scale-free and oscillatory spectral measures of sleep stages in humans.

Power spectra of sleep electroencephalograms (EEG) comprise two main components: a decaying power-law corresponding to the aperiodic neural background activity, and spectral peaks present due to neural oscillations. “Traditional” band-based spectral methods ignore this fundamental structure of the EEG spectra and thus are susceptible to misrepresenting the underlying phenomena. A fitting method that attempts to separate and parameterize the aperiodic and periodic spectral components called “fitting oscillations and one over f” (FOOOF) was applied to a set of annotated whole-night sleep EEG recordings of 251 subjects from a wide age range (4–69 years). Most of the extracted parameters exhibited sleep stage sensitivity; significant main effects and interactions of sleep stage, age, sex, and brain region were found. The spectral slope (describing the steepness of the aperiodic component) showed especially large and consistent variability between sleep stages (and low variability between subjects), making it a candidate indicator of sleep states. The limitations and arisen problems of the FOOOF method are also discussed, possible solutions for some of them are suggested.