Introduction Biological age acceleration (BAA) is thought to be a major risk factor for age-related diseases, but its role in aortic valve stenosis (AVS) remains uncertain. We aimed to assess the associations between biological aging and the risk of AVS. Methods This study involved 4526 participants from the Real-world Data of Cardiometabolic Protection (RED-CARPET) study and 5114 participants from the Atherosclerosis Risk in Communities (ARIC) study. BAA was assessed using clinical biomarkers through the Klemera-Doubal method (KDM) and the PhenoAge algorithm. We employed multivariable logistic regression and restricted cubic spline (RCS) regression to examine the association between BAA and AVS risk. Additionally, Mendelian randomization (MR) analysis was conducted to assess causality. Results In the RED-CARPET cohort of 4526 participants (mean age 60.93 years, 33.5% female), 113 AVS events were recorded. In the ARIC cohort of 5114 participants (mean age 51.94 years, 56.4% female, 82.3% White), there were 266 AVS events. After fully adjusting for confounding variables, each standard deviation increase in BAA was significantly associated with elevated AVS risk (RED-CARPET: KDM-BA acceleration: OR 1.29, 95% CI 1.07−1.55; PhenoAge acceleration: OR 1.48, 95% CI 1.24−1.77; ARIC: KDM-BA acceleration: OR 1.42, 95% CI 1.24−1.63; PhenoAge acceleration: OR 1.30, 95% CI 1.11−1.51). The RCS regression model revealed significant linear relationships between BAA and the risk of AVS in both cohorts. MR analysis suggested a potential causal relationship between KDM-BA acceleration and AVS risk (OR 1.38, 95% CI 1.21–1.57). Conclusion BAA, as derived from clinical biomarkers, is independently associated with an increased risk of AVS. This finding suggests that BAA, as a composite indicator of systemic biological aging, may complement traditional risk factors in the early identification of high-risk populations for AVS, and offer the possibility of early intervention for prevention.
Objective To determine the effects of instability resistance training (IRT) on the cognitive function of older adults with probable mild cognitive impairment (MCI). Methods This was assessor-blinded, randomized controlled trial which included 162 adults aged ≥65 years, physically independent and who had indicative of MCI. Participants were randomly allocated to either 24-week of twice-weekly IRT (n=80) or active control group (n=82). IRT group underwent resistance exercises on unstable surfaces (i.e., Balance Pad, Bosu® ball), prescribed as seven exercises in 3 sets with target zone ranging between 10–15 repetitions. The active control group performed non-structured (no progression neither complexity), low intensity functional and stretching/relaxation exercises. Cognitive outcomes Executive Function (Stroop Color Task; Digit Symbol Substitution Test; Trail Making Test Part A and B; Digit Span Memory Test; Verbal fluency test) and Memory were assessed at baseline, after 12- and 24-week. Linear mixed modeling, adjusted for sex, age, and baseline levels of each outcome, were used to determine treatment effects. Results 162 participants with a mean age of 70.4±4.3 years and indicative of MCI (MoCA 20.1±4.2) were included. At 24-week, the IRT group demonstrated significant improvements in executive function performance (Verbal Fluency – Letter A: +1.2 letters; 95% CI 0.2–2.2; p=0.017; Digit Span Forward: +0.7 points; 95% CI 0.1–1.3; p=0.010) compared with active control group. No significant between-group differences were observed in the remaining cognitive outcomes. Conclusion Our findings revealed that 24-week IRT improved executive functioning domains among older adults with probable MCI. Trial Registration RBR-9bv3dc9.
Background & objective Consumption of diets insufficient in essential nutrients contributes to unhealthy aging. The objective of this study is to evaluate adequacy of key nutrients that reflect the food components of the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) dietary pattern, one deemed important for brain health. Setting/design Cross-sectional analyses of diets of participants in the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (US POINTER) trial Participants Adults, aged 60–79 years and at risk of cognitive impairment (sedentary, suboptimal diet, other risk factors) were enrolled in the US POINTER, a phase III two-year randomized controlled trial comparing the impact of two lifestyle interventions on brain health. Measurements Before randomization, participants completed a food frequency questionnaire (FFQ) assessing usual intake of foods and beverages, and vitamin and/or mineral supplements. Median daily nutrient intakes were expressed as a percentage of sex- and age-specific Estimated Average Requirement (EAR) or Adequate Intake (AI), and Tolerable Upper Limit (UL) criteria. Results Of the 2111 enrolled participants, 2041 completed the FFQs (69% women). Nearly half reported multivitamin multimineral supplement use (49%, men; 49%, women). Common individual supplements included vitamins D (36%), E (25%), C (23%), and B12 (19%) as well as calcium (16%). Based on food alone, the proportion of participants with inadequate intakes was high across several nutrients. Supplements improved nutrient adequacy for most (except for choline, fiber and potassium) but contributed to intakes for some that exceed the UL cutoffs (vitamins A (n=28), B9 (n=134), B3 (n=160) and zinc (n=196)). Conclusions Widespread nutrient inadequacy (especially those integral to the MIND dietary pattern) is evident among non-supplement users. Supplement use improves adequacy but raises concerns about excessive intakes that exceed ULs. Assessment of diet and supplement intake is essential to address nutrient inadequacies in at-risk older adults. Clinical Trial Registration Number : NCT03688126, submitted 9/26/2018.
Background Frailty reflects declining physiological reserve and is a major barrier to healthy longevity. Methyl-donor nutrients, which serve as substrates and cofactors in one-carbon metabolism, are involved in several biological processes relevant to aging, including the regulation of oxidative stress. However, their association with frailty and the potential role of oxidative stress in this relationship remain unclear. Objective To examine the association between a composite Methyl-Donor Nutrient Quality Index (MNQI) and frailty and to evaluate whether oxidative stress may contribute to this association in middle-aged and older adults. Methods Cross-sectional data from NHANES 2005–2018 were analyzed among 13,528 adults aged ≥40 years. Frailty was assessed using a 53-item deficit accumulation frailty index categorized as robust, prefrail, or frail. The MNQI was calculated from seven methyl-donor and cofactor nutrients. The oxidative stress index (OSI) was derived from gamma-glutamyl transferase, uric acid, albumin, and bilirubin. Survey-weighted multinomial logistic regression examined MNQI and OSI associations with frailty, and exploratory mediation analyses evaluated the indirect effect through OSI. Results Higher MNQI was associated with 33% lower odds of frailty (OR=0.67; 95% CI: 0.52–0.88; P=0.004), with a significant dose–response relationship. Higher OSI was associated with 113% greater odds of frailty (OR=2.13; 95% CI: 1.92–2.36; P<0.001). Exploratory mediation analyses indicated a significant indirect effect through oxidative stress, accounting for approximately 29% of the MNQI–frailty association. Conclusions Higher dietary intake of methyl-donor nutrients was associated with lower odds of frailty and may support physiological processes relevant to healthy longevity, with oxidative stress potentially representing one pathway underlying this association. Longitudinal studies and randomized trials are needed to confirm these relationships and clarify the underlying mechanisms.
Objectives Plant-based diets are widely promoted for cardiometabolic and brain health, yet their associations with health may depend on the quality of the plant foods consumed. Whether healthy and unhealthy plant-based diet quality differ in their associations with brain structure across the whole brain remains unclear. Methods In a cross-sectional analysis of 23,460 participants with 24-h dietary recalls and brain MRI, we performed an imaging-wide association study of standardized healthy (hPDI) and unhealthy (uPDI) plant-based diet indices against 910 imaging-derived phenotypes (IDPs) spanning structural, diffusion, and functional MRI. Multivariable linear regression (adjusting for age, sex, ethnicity, household income, education, smoking, alcohol, physical activity, and total energy intake) yielded standardized beta coefficients; category-level and global false-discovery-rate (FDR) correction controlled multiple testing. The overall plant-based diet index (PDI), energy-adjusted Dietary Inflammatory Index (E-DII), DII, DASH, and AHEI served as comparison scores. Results uPDI showed widespread associations, with 187 white-matter diffusion and 110 structural-volume IDPs reaching category-FDR < 0.05, versus 1 and 19, respectively, for hPDI. Higher uPDI was associated with greater normalized grey-matter volume (beta=0.038, 95% CI 0.028 to 0.047) and higher fornix fractional anisotropy (beta=0.029, 95% CI 0.018 to 0.040). hPDI and uPDI were weakly correlated (Pearson r=0.230), and variance inflation factors were 1.16 and 1.13, respectively. In models including both indices, uPDI retained category-FDR-significant associations with 89 structural and 46 diffusion IDPs. The overall PDI and E-DII also showed widespread imaging associations; after mutual adjustment for overall PDI, uPDI retained associations with only 20 structural and 1 diffusion IDP. Conclusions Unhealthy plant-based diet quality was associated with broad structural and white-matter imaging signatures that were substantially more numerous than those observed for healthy plant-based diet quality and remained evident after mutual adjustment for hPDI. Higher uPDI was associated with greater normalized grey-matter volume and higher fornix fractional anisotropy, a direction that was contrary to expectations based on prior literature. The findings from the overall PDI further indicate that much of this uPDI signal overlapped with overall plant-versus-animal dietary composition, leaving only a limited independent signal after mutual adjustment; these associations therefore cannot be attributed specifically to the quality of plant foods and warrant longitudinal confirmation.
