Journals of Gerontology Series A-Biological Sciences and Medical Sciences最新文献

Background: The association between kidney function and dementia risk and the mechanisms underlying this relationship remain unclear.

Methods: Within the UK Biobank, 191 970 dementia-free participants aged ≥60 (mean age: 64.1 ± 2.9 years) were followed for 16 years to detect incident dementia. Serum creatinine and Cystatin C were measured at baseline to calculate estimated glomerular filtration rate (eGFR, mL/min/1.73 m2). Kidney function was categorized as normal (eGFR ≥ 90), mildly impaired (60 ≤ eGFR < 90), or moderately to severely impaired (eGFR < 60). Dementia was assessed based on self-reported medical history and medical records. During the follow-up, a subsample of 12 637 participants underwent brain MRI scans. Volumes of total brain, gray matter, white matter, hippocampus, and white matter hyperintensities were assessed.

Results: Over the follow-up, 5 327 (2.8%) participants developed dementia. Compared to normal kidney function, there was an increased risk of dementia with moderate to severely impaired kidney function (hazard ratio = 1.53, 95% confidence interval [CI]: 1.32-1.76) but not mildly impaired kidney function. In Laplace regression, dementia onset among people with moderate to severely impaired kidney function occurred 1.53 (95% CI: 0.98-2.08) years earlier than those with normal kidney function. Moderate to severely impaired kidney function was related to significantly lower gray matter volume (β = -0.11, 95% CI: -0.19 to -0.03), but not to other brain magnetic resonance imaging measures.

Conclusions: Impaired kidney function is associated with about 50% increased risk of dementia and anticipates dementia onset by more than 1.5 years. Brain neurodegeneration may underlie the kidney function-dementia association.

Background: We examined the relationship between baseline olfactory performance and incident significant depressive symptoms and longitudinal depression trajectories in well-functioning older adults. Inflammation and cognitive status were examined as potential mediators.

Methods: Older adults (n = 2 125, 71-82 years, 51% female, 37% Black) completed an odor identification task at Year 3 (our study baseline) of the Health, Aging, and Body Composition study. Cognitive assessments, depressive symptoms, and inflammatory markers were ascertained across multiple visits over 8 years. Discrete-time complementary log-log models, group-based trajectory models, and multivariable-adjusted multinomial logistic regression were employed to assess the relationship between baseline olfaction and incident depression and longitudinal depression trajectories. Mediation analysis assessed the influence of cognitive status on these relationships.

Results: Individuals with lower olfaction had an increased risk of developing significant depressive symptoms at follow-up (hazard ratio = 1.04, 95% confidence interval [CI]: 1.00, 1.08). Of the 3 patterns of longitudinal depression scores identified (stable low, stable moderate, and stable high), poorer olfaction was associated with a 6% higher risk of membership in the stable moderate (relative risk ratio [RRR] = 1.06, 95% CI: 1.02, 1.10)/stable high (RRR = 1.06, 95% CI: 1.00, 1.12) groups, compared to the stable low group. Poor cognitive status, but not inflammation, partially mediated the relationship between olfactory performance and incident depression symptom severity.

Conclusions: Suboptimal olfaction could serve as a prognostic indicator of vulnerability for the development of late-life depression. These findings underscore the need for a greater understanding of olfaction in late-life depression and the demographic, cognitive, and biological factors that influence these relationships over time.

Background: Some studies have linked late-life overweight to a reduced mortality risk compared to normal body mass index (BMI). However, the impact of late-life overweight and its combination with mid-life BMI status on healthy survival remains unclear. We aimed to investigate whether and to what extent mid- and/or late-life overweight are associated with chronic disease-free survival.

Methods: Within the Swedish Twin Registry, 11 597 chronic disease-free twins aged 60-79 years at baseline were followed up for 18 years. BMI (kg/m2) was recorded at baseline and 25-35 years before baseline (ie, midlife) and divided as underweight (<20), normal (≥20-25), overweight (≥25-30), and obese (≥30). Incident chronic diseases (cardiovascular diseases, type 2 diabetes, and cancer) and deaths were ascertained via registries. Chronic disease-free survival was defined as years lived until the occurrence of any chronic diseases or death. Data were analyzed using multistate survival analysis.

Results: Of all participants, 5 640 (48.6%) were overweight/obese at baseline. During the follow-up, 8 772 (75.6%) participants developed at least 1 chronic disease or died. Compared to normal BMI, late-life overweight and obesity were associated with 1.1 (95% CI, 0.3, 2.0) and 2.6 (1.6, 3.5) years shorter chronic disease-free survival. Compared to normal BMI through mid- to late life, consistent overweight/obesity and overweight/obesity only in mid-life led to 2.2 (1.0, 3.4) and 2.6 (0.7, 4.4) years shorter disease-free survival, respectively.

Conclusions: Late-life overweight and obesity may shorten disease-free survival. Further research is needed to determine whether preventing overweight/obesity from mid- to late life might favor longer and healthier survival.

Although several antidepressants have been identified as potential geroprotectors, the effect and mechanism of fluoxetine, a representative selective serotonin reuptake inhibitor, on longevity have not been fully elucidated. Here, we found that fluoxetine promoted longevity in Caenorhabditis elegans with a concomitant extension of a healthy life span as indicated by increasing mobility, reducing fertility and lipofuscin accumulation, and enhanced resistance to different abiotic stresses. Fluoxetine increased the level of reactive oxygen species (ROS), and antioxidant N-acetylcysteine abolished ROS elevation and the pro-longevity effect of fluoxetine. Additionally, fluoxetine extended life span through the daf-2-sod-3 pathway in daf-16-dependent and -independent manners, and fluoxetine-induced life-span extension was abolished in C. elegans sod-3, daf-2, and daf-16 mutants. In conclusion, these findings suggest that fluoxetine can promote health and longevity in C. elegans via the interaction of ROS and insulin signaling.

This is the first known comparative assessment of the associations of epigenetic age estimates with the prevalence of rheumatoid arthritis (RA). We used data available in Gene Expression Omnibus (GSE42861) from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study. Information regarding RA diagnosis and 450K DNA methylation (DNAm) of 18- to 70-year-old participants was available. Utilizing Horvath's online DNAm Age Calculator, we determined the DNAm estimate of Telomere length (DNAmTL), Hannum's epigenetic age, Horvath's 2013 and 2018 epigenetic ages, PhenoAge, GrimAge, and the respective age-acceleration measures. The association of RA prevalence with epigenetic age measures was assessed using linear regression, adjusting for sex and smoking status. The p values were corrected for multiple testing using a false discovery rate. We identified statistically significant associations of RA with Horvath 2013 age acceleration (estimate: -1.34; FDR p value: 1.0 × 10-2), Horvath 2018 age acceleration (estimate: -1.32; FDR p value: 4.0 × 10-5), extrinsic age acceleration (estimate: 1.34; FDR p value: 1.0 × 10-2), PhenoAge acceleration (estimate: 2.31; FDR p value: 1.1 × 10-5), GrimAge (estimate: 2.54; FDR p value: 1.0 × 10-2), and GrimAge acceleration (estimate: 3.15; FDR p-value: 1.7 × 10-17). Of note, the raw and age-adjusted GrimAge surrogate DNAm protein components were significantly higher in RA cases than controls. Interestingly, the first-generation measures were associated only with women. No sex-specific effects were identified for PhenoAge or GrimAge accelerations. In this cross-sectional assessment, the second-generation clocks show promise as markers of biological aging, with higher epigenetic age acceleration observed in RA cases compared with healthy controls.

The brainstem functions as a relay and integrative brain center and plays an essential role in motor function. Whether brainstem tissue deterioration, including demyelination, affects motor function has not been studied. Understanding the potential relationship between brainstem demyelination and motor function may be useful for the early diagnosis of neurodegenerative diseases and to understand age-related gait impairments that have no apparent cause. In this work, we investigated the associations between rapid or usual gait speeds, as integrative measures of motor function, and cerebral myelin content. In 118 individuals (age 22-94 years) free of neurodegenerative diseases or cognitive impairment, myelin content was assessed as the myelin water fraction, a direct magnetic resonance imaging measure of myelin content, and longitudinal and transverse relaxation rates (R1 and R2), which are sensitive magnetic resonance imaging measures of myelin content. Our results indicate that participants with lower usual or rapid gait speed exhibited lower values of myelin water fraction and R1 in the main brainstem regions, which were more evident and statistically significant in the midbrain. In contrast, we found no significant associations between gait speeds and R2, an expected result because various physiological factors confound R2. These original findings provide evidence that the level of brainstem myelination may affect gait performance among cognitively unimpaired adults who are free from any clinically detectable neurodegenerative diseases. Further studies are needed to understand the longitudinal changes in brainstem myelination with aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease.

Background: Multimorbidity, defined as the presence of 2 or more chronic health conditions, is increasingly common among older adults. The combination of lifestyle characteristics such as diet quality, smoking status, alcohol intake, physical activity (PA), sleep duration, and body fat as assessed by body mass index (BMI) or waist circumference, and risk of multimorbidity are not well understood.

Objectives: We investigated the association between the healthy lifestyle index (HLI), generated by combining indicators of diet quality, smoking, alcohol, PA, sleep amount, and BMI, and risk of multimorbidity, a composite outcome that included cardiovascular disease (CVD), diabetes, cancer, and fracture.

Methods: We studied 62 037 postmenopausal women aged 50-79 years at enrollment in the Women's Health Initiative, with no reported history of CVD, diabetes, cancer, or fracture at baseline. Lifestyle characteristics measured at baseline were categorized and a score (0-4) was assigned to each category. The combined HLI (0-24) was grouped into quintiles, with higher quintiles indicating a healthier lifestyle. Multivariable adjusted estimates of hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of developing multimorbidity were obtained using Cox proportional hazard models.

Results: Over an average follow-up period of 16.3 years, 5 656 women developed multimorbidity. There was an inverse association between the HLI levels and risk of multimorbidity (compared to the HLI_1st quintile: HR_2nd quintile = 0.81 95% CI 0.74-0.83, HR_3rd quintile = 0.77 95% CI 0.71-0.83, HR_4th quintile = 0.70 95% CI 0.64-0.76, and HR_5th quintile = 0.60 95% CI 0.54-0.66; p trend < .001). Similar associations were observed after stratification by age or BMI categories.

Conclusions: Among postmenopausal women, higher levels of the HLI were associated with a reduced risk of developing multimorbidity.

Background: Outdoor air pollution has been reported to be associated with frailty (including slow gait speed) in older adults. However, to date, no literature exists on the association between indoor air pollution (eg, unclean cooking fuel use) and gait speed. Therefore, we aimed to examine the cross-sectional association between unclean cooking fuel use and gait speed in a sample of older adults from 6 low- and middle-income countries (China, Ghana, India, Mexico, Russia, and South Africa).

Methods: Cross-sectional, nationally representative data from the World Health Organization Study on global AGEing and adult health were analyzed. Unclean cooking fuel use referred to the use of kerosene/paraffin, coal/charcoal, wood, agriculture/crop, animal dung, and shrubs/grass based on self-report. Slow gait speed referred to the slowest quintile based on height, age, and sex-stratified values. Multivariable logistic regression and meta-analysis were done to assess associations.

Results: Data on 14 585 individuals aged ≥65 years were analyzed (mean [standard deviation] age 72.6 [11.4] years; 45.0% males). Unclean cooking fuel use (vs clean cooking fuel use) was significantly associated with higher odds for slow gait speed (odds ratio = 1.45; 95% confidence interval: 1.14-1.85) based on a meta-analysis using country-wise estimates. The level of between-country heterogeneity was very low (I2 = 0%).

Conclusions: Unclean cooking fuel use was associated with slower gait speed among older adults. Future studies of longitudinal design are warranted to provide insight into the underlying mechanisms and possible causality.

Background: Several hip fracture clinical prediction models have been developed. We conducted this study to (i) map outcomes used in clinical prediction models for hip fracture, (ii) identify the domains and instruments of predictors, and (iii) assess the risk of bias.

Methods: We performed systematic searches of studies published from June 2002 to June 2023 in the PubMed, Cochrane Library, CINAHL, CiNii, and Ichushi databases. After the relevant articles were identified, we performed the data extraction and bias risk assessment. We used the Prediction Study Risk Of Bias Assessment Tool (PROBAST) to assess each study's risk of bias. Outcome mapping was performed for the core outcome set of hip fractures. Qualitative synthesis and the PROBAST evaluation were performed on other-than-mortality core outcomes, which are difficult to target in rehabilitation.

Results: We screened 3 206 studies for eligibility; 45 studies were included in the outcome mapping, and 10 studies were included in the qualitative synthesis. Outcomes included mortality (n = 35), mobility (n = 8), and activities of daily living (n = 2). No clinical prediction models had pain or health-related quality of life as an outcome. Predictors were reported in 8 domains and 38 measures. The PROBAST evaluation showed a high risk of bias in all 10 studies that were eligible for a qualitative synthesis.

Conclusions: The clinical prediction models had only mortality, mobility, and activities of daily living as outcomes. The development of clinical prediction models with pain and health-related quality of life as outcomes is necessary. Clinical prediction models overcoming the risk of bias identified in this study are also needed.