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

Background: Associations of weight changes and intentionality of weight loss with longevity are not well described.

Methods: Using longitudinal data from the Women's Health Initiative (N = 54 437; 61-81 years), we examined associations of weight changes and intentionality of weight loss with survival to ages 90, 95, and 100. Weight was measured at baseline, year 3, and year 10, and participants were classified as having weight loss (≥5% decrease from baseline), weight gain (≥5% increase from baseline), or stable weight (<5% change from baseline). Participants reported intentionality of weight loss at year 3.

Results: A total of 30 647 (56.3%) women survived to ≥90 years. After adjustment for relevant covariates, 3-year weight loss of ≥5% vs stable weight was associated with lower odds of survival to ages 90 (OR, 0.67; 95% CI, 0.64-0.71), 95 (OR, 0.65; 95% CI, 0.60-0.71), and 100 (OR, 0.62; 95% CI, 0.49-0.78). Compared to intentional weight loss, unintentional weight loss was more strongly associated with lower odds of survival to age 90 (OR, 0.83; 95% CI, 0.74-0.94 and OR, 0.49; 95% CI, 0.44-0.55, respectively). Three-year weight gain of ≥5% vs stable weight was not associated with survival to age 90, 95, or 100. The pattern of results was similar among normal weight, overweight, and obese women in body mass index (BMI)-stratified analyses.

Conclusions: Weight loss of ≥5% vs stable weight was associated with lower odds of longevity, more strongly for unintentional weight loss than for intentional weight loss. Potential inaccuracy of self-reported intentionality of weight loss and residual confounding were limitations.

No acceptable biomarker can facilitate the early identification of cognitive impairment associated with cerebral small vessel disease (CSVD) in the older persons. The neutrophil extracellular traps (NETs) in the inflammation response of circulatory and central systems are essential in destroying the blood-brain barrier. The present study aims to explore the potential associations of plasma NETs with cognitive performance in CSVD. We recruited 146 CSVD patients and 66 healthy controls (HCs), and comprehensive neuropsychological assessments and multimodal magnetic resonance imaging were conducted. Three NETs markers, namely citrullination of histone H3, neutrophil elastase-DNA, and myeloperoxidase (MPO)-DNA, and 4 oxidative stress-related indexes in plasma samples, were measured. The plasma levels of 3 NETs markers were more significantly elevated in CSVD patients than in HCs. Significant correlations of the 3 NETs markers were observed with multiple cognitive domain scores. Furthermore, higher plasma malondialdehyde and NETs levels were significantly associated with the worse Montreal Cognitive Assessment scores among CSVD patients. Moreover, plasma MPO-DNA levels significantly mediated the effect of the amplitude of low-frequency fluctuation value within the bilateral caudate and the scores of global cognitive function, executive function, and information processing speed. Additionally, a panel of 3 NETs markers had the highest area under the curve value to distinguish the cognitively impaired CSVD patients from HCs and nonimpaired ones. Therefore, plasma NETs may be potential biomarkers for early diagnosis of CSVD-related cognitive impairment. Activated lipid peroxidation in circulation and impaired caudate function support potential associations of plasma NETs in cognitively impaired CSVD patients.

Background: Although previous studies have reported an association between multimorbidity and frailty, its direction and mechanism remain unclear. This study aimed to investigate the direction of this association, as well as the role of depression among older Europeans.

Methods: We used a cross-lagged panel design to evaluate the temporal relationship between multimorbidity and frailty and the role of depression. Multimorbidity status was assessed by the self-reporting of 14 chronic diseases. Frailty was assessed based on the frailty phenotype. The European-Depression Scale (EURO-D) was used to assess depression.

Results: There was a bidirectional relationship between frailty and multimorbidity. More severe multimorbidity predicted greater frailty (β = 0.159; p < .001) and vice versa (β = 0.107; p < .001). All paths from multimorbidity to frailty were stronger than the paths from frailty to multimorbidity (b1-a1: β = 0.051; p < .001). Likewise, early multimorbidity change was a significant predictive factor for late frailty change (β = 0.064; p < .001) and vice versa (β = 0.048; p < .001). Depression in Wave 5 (T5) mediated the association between frailty in Wave 4 (T4) and multimorbidity in Wave 6 (T6; indirect effect: β = 0.004; bootstrap 95% confidence interval: 0.003, 0.006).

Conclusions: A positive, bidirectional association was observed between multimorbidity and frailty. Depression may be a potential cause of an increased risk of multimorbidity later in life in frail older adults. Early monitoring of frailty and depression may slow the progression of multimorbidity, thereby interrupting the vicious cycle.

Background: Pneumonia is a leading cause of death worldwide. It is a particularly serious burden in older people, as they tend to have a weakened immune response. Identifying the role of oral self-care and pneumococcal vaccination in healthy, independent older people can aid pneumonia prevention among them. This study investigated the associations between oral self-care, pneumococcal vaccination, and pneumonia experience among independent older people.

Methods: This cross-sectional study used data from the 2016 Japan Gerontological Evaluation Study. We used machine learning to examine the association between oral self-care and the experience of pneumonia over the previous year, stratified by pneumococcal vaccination. The covariates were sex, age, years of education, equivalent annual income, medical history of stroke, oral health status (choking, dryness, number of teeth), and smoking status. The analysis included 17 217 independent older people aged 65 and over.

Results: The prevalence of pneumonia experienced among those who brushed their teeth once or less per day was 4.5% and 5.3% for those with and those without pneumococcal vaccinations, respectively. In the unvaccinated group, the odds ratio of pneumonia experience for those who brushed their teeth once or less a day was 1.57 (95% confidence interval: 1.15-2.14) compared to those who brushed their teeth 3 or more times a day. By contrast, there was no significant association between the frequency of toothbrushing and the experience of pneumonia among people who received pneumococcal vaccination.

Conclusions: Oral care influenced the experience of pneumonia among independent older people who did not receive pneumococcal vaccination.

Background: Myostatin, a cytokine produced by skeletal muscle, may influence Alzheimer's disease (AD) pathogenesis, but sparse evidence exists in humans. We assessed the association between circulating levels of myostatin at Year 1 and plasma levels of β-amyloid 42/40 at Year 2, a marker of AD pathology, in a biracial cohort of older adults.

Methods: We studied 403 community-dwelling older adults enrolled in the Health, Aging and Body Composition Study from Memphis, Tennessee, and Pittsburgh, PA. Mean age was 73.8 ± 3 years; 54% were female; and 52% were Black. Serum myostatin levels were measured at Year 1, plasma β-amyloid 42/40 levels in Year 2 (higher ratio indicating lower amyloid load). Multivariable linear regression analyses tested the association of serum myostatin with plasma levels of β-amyloid 42/40 adjusted for computed-tomography-derived thigh muscle cross-sectional area, demographics, APOe4 allele, and risk factors for dementia. We tested for 2-way.interactions between myostatin and race or sex; results were stratified by race and sex.

Results: In multivariable models, myostatin was positively associated with plasma levels of β-amyloid 42/40 (standardized regression coefficient: 0.145, p = .004). Results were significant for white men and women (0.279, p = .009, and 0.221, p = .035, respectively) but not for Black men or women; interactions by race and gender were not statistically significant.

Conclusions: Higher serum myostatin was associated with lower amyloid burden, independently of APOe4 alleles, muscle area and other established risk factors for dementia. The role of myostatin in AD pathogenesis and the influence of race should be further investigated.

Background: The aging process is accompanied by decline in kidney functioning. It remains unknown to what extent age-related decline in kidney functioning can be attributed to health indicators, and whether rate of decline differs across sociodemographic groups.

Methods: Using data from the Health and Retirement Study from 2006/2008 through 2014/2016, we estimated kidney functioning trajectories, determined by cystatin C, among adults aged over 51 over 8 years. We evaluated the role of age, health conditions/behaviors, and genetics in the decline and also examined sociodemographic differentials.

Results: Kidney function declined with age and accelerated at older ages, even after adjusting for health conditions/behaviors and genetic differences (eg, 0.019 mg/L annual increase in cystatin C among 70-79 compared to 0.007 mg/L among 52-59 at baseline). Decline occurred faster among those with uncontrolled diabetes (0.008, p = .009), heart conditions (0.007, p < .000), and obesity (0.005, p = .033).Hispanic participants (0.007, p = .039) declined faster than non-Hispanic White persons due to diabetes, heart conditions, and obesity; non-Hispanic Black participants had worse baseline kidney functioning (0.099, p < .000), but only one fourth of this Black-White difference was explained by investigated risk factors. People with higher education experienced slower decline (-0.009, p = .004).

Conclusions: Age was a significant predictor of decline in kidney functioning, and its association was not fully explained by health conditions/behaviors, or genetics. Better management of diabetes, heart conditions, and obesity is effective in slowing this decline. Baseline differences in kidney functioning (eg, between non-Hispanic White and Black persons; those with and without hypertension) suggest disparities occur early in the life course and require early interventions.

Background: Identification of novel risk factors for dementia in older adults could facilitate development of methods to identify patients most at risk and improve their cognitive outcomes. We aimed to determine whether lower appendicular lean mass (ALM), assessed by dual-energy x-ray absorptiometry (DXA), and lower grip strength are associated with a greater likelihood of incident dementia among older adults in the Health Aging and Body Composition Study (Health ABC).

Methods: Health ABC data from 1997 to 2008 were analyzed (n = 2 704). Baseline ALM to body mass index (BMI) ratio (ALMBMI) was assessed by DXA. Baseline grip strength was assessed by hand-held dynamometry. Incident dementia diagnosis was defined as either (i) dementia-related hospitalization plus a Modified Mini-Mental State Examination (3MS) score of ≤ 90; or (ii) record of prescription for anti-dementia medication; or (iii) decline of at least 1.5 SDs on the 3MS score compared to baseline. Cox proportional hazard models estimated associations of ALMBMI and grip strength with incident dementia over follow-up with and without adjusting for covariates, stratified by sex.

Results: Among older men, each standard deviation decrement in ALMBMI (adjusted hazard ratio [aHR]: 1.33; 95% confidence interval [CI]: 1.07, 1.65) or grip strength (aHR 1.22; 95% CI: 1.06, 1.41) was associated with increased likelihood of incident dementia.

Conclusions: Lower ALMBMI and grip strength may be important risk factors for the development of dementia among older men. How these factors may belong to a causal pathway of dementia must be elucidated in future work.

Background: Based on studies from animal models, growth differentiation factor-11 (GDF-11) may have rejuvenating effects in humans. GDF-11 has high sequence homology with GDF-8 (also known as myostatin); follistatin and follistatin-like protein-3 (FSTL-3) are inhibitory proteins of both GDF-8 and GDF-11.

Methods: Using highly specific liquid chromatography with tandem mass spectrometry assays for GDF-11 and GDF-8 and immunoassays for follistatin and FSTL-3, we quantified the association of these factors with muscle size, strength, and physical performance in 2 prospective cohort studies of community-dwelling older adults (Health, Aging, and Body Composition study [Health ABC] and Cardiovascular Health Study [CHS]).

Results: GDF-8 levels were positively associated with thigh muscle cross-sectional area and density in Health ABC (data not available in CHS). GDF-8 levels were positively associated with lean mass (a surrogate of muscle mass) in Health ABC but not CHS, and grip strength in CHS but not Health ABC. FSTL-3 (and perhaps follistatin) was negatively associated with lean mass and had variable associations with other variables. In contrast, GDF-11 was not significantly associated with strength or performance.

Conclusions: GDF-8 and its binding proteins, follistatin and FSTL-3, may constitute a counterregulatory system (chalones) to restrain age-related loss of muscle mass and strength.

Background: Although frailty was associated with cardiometabolic diseases (CMDs, including coronary heart disease, stroke, and diabetes here), there was no systematic analyses estimating its role in incidence, progression, and prognosis of cardiometabolic multimorbidity (CMM).

Methods: We included 351 205 participants without CMDs at baseline in UK Biobank. Occurrences of first CMD, CMM, and death were recorded. We used multistate models to assess transition-specific role of baseline frailty measured by frailty phenotype and frailty index in CMM progression trajectory from no disease to single CMD, CMM, and death. Association between changes in frailty and outcomes was investigated among 17 264 participants.

Results: Among 351 205 participants (44.0% male, mean age 56.55 years), 8 190 (2.3%) had frail phenotype, and 13 615 (3.9%) were moderate/severe frail according to the frailty index. During median follow-up of 13.11 years, 41 558 participants experienced ≥1 CMD, 4 952 had CMM, and 20 670 died. In multistate models, frail phenotype-related hazard ratios were 1.94 and 2.69 for transitions from no CMD to single disease and death, 1.63 and 1.67 for transitions from single CMD to CMM and death, and 1.57 for transitions from CMM to death (all p < .001). Consistent results were observed for frailty index. Improvement of frailty reduced the risk of CMD progression and death.

Conclusions: Frailty is an independent risk factor for all transitions of CMM progression trajectory. Frailty-targeted management is a potential strategy for primary and secondary prevention of CMM beyond chronological age.

Background: Studies using heterochronic parabiosis discovered that circulating factors mediate brain aging in animal models.

Methods: We assessed growth differentiation factors (GDF)-11 and GDF-8 using mass spectrometry and inhibitors follistatin and follistatin-like protein-3 (FSTL-3) with ELISA in the Cardiovascular Health Study (CHS; N = 1 506) and the Health, Aging and Body Composition (Health ABC) Study (N = 1 237). CLL-11 and beta-2 microglobulin (β2M) were measured with ELISA in a subset of 400 individuals in Health ABC. Associations were assessed with cognitive function, brain magnetic resonance imaging (MRI) findings (CHS only), and incident dementia using correlations, linear regression, and Cox proportional hazards models.

Results: In CHS, levels of GDF-11, GDF-8, and follistatin were not correlated cross-sectionally with the 3MSE or DSST, brain MRI findings of white matter hyperintensity, atrophy, or small infarcts, nor were they associated with incident dementia. FSTL-3 was modestly correlated with poorer cognitive function, greater white matter hyperintensities, and atrophy on MRI, as well as with incident dementia with an adjusted hazard ratio (HR) of 1.72 (95% CI = 1.13, 2.61) per doubling of FSTL-3. FSTL-3 was not associated with cognition or dementia in Health ABC, but GDF-8 was associated with both. The adjusted HR for incident dementia was 1.50 (95% CI = 1.07, 2.10) per doubling of GDF-8.

Conclusions: Total GDF-11 level was not related to cognition or dementia in older adults. Associations of GDF-8 with cognitive outcomes in Health ABC were not expected, but consistent with animal models. Associations of FSTL-3 with cognition, brain abnormalities, and incident dementia in CHS implicate TGFβ superfamily inhibition in the pathogenesis of dementia.