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

Background: The influence of overall air pollution on dementia risk and the potential effect modification by other risk factors remain to be clarified.

Methods: We included 459 844 UK residents who were free of dementia and had data on the exposure to particulate matter (PM)2.5, PM2.5-10, PM10, NO2, and NOx during baseline recruitment. The combined exposure to various PMs and NOx was estimated by using an air pollution score. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia were estimated by multivariable Cox models.

Results: During a median 11.7 years follow-up, 5 905 incident cases of all-cause dementia were identified. With the exception of PM2.5-10, all other air pollutants were separately associated with a higher risk of all-cause dementia (all p-trend < .001) with generally similar associations for dementia subtypes. An increasing air pollution score was associated with higher risks of all-cause as well as individual dementia outcomes, with adjusted HRs (95% CI) of 1.27 (1.18, 1.37) for all-cause dementia, 1.27 (1.14, 1.43) for Alzheimer's disease, and 1.35 (1.16, 1.57) for vascular dementia when comparing the highest with the lowest quartile of the score (all p-trend < .001). These associations of air pollution score with dementia and its subtypes were observed among never and former smokers but not among current smokers (all p-interaction 
< .030).

Conclusion: Air pollution was associated with a higher risk of dementia among nonsmokers but not current smokers. Additional studies are required to confirm our findings and to explore the potential mechanisms underlying the possible effect modification by smoking status.

Background: Severe hypoglycemia is associated with adverse clinical outcomes. We evaluated the risk of severe hypoglycemia in older adults initiating newer glucose-lowering medications overall and across strata of known indicators of high hypoglycemia risk.

Methods: We conducted a comparative-effectiveness cohort study of older adults aged >65 years with type 2 diabetes initiating sodium-glucose cotransporter 2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) or SGLT2i versus glucagon-like peptide-1 receptor agonists (GLP-1RA) using Medicare claims (3/2013-12/2018) and Medicare-linked-electronic health records. We identified severe hypoglycemia requiring emergency or inpatient visits using validated algorithms. After 1:1 propensity score matching, we estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years. Analyses were stratified by baseline insulin, sulfonylurea, cardiovascular disease (CVD), chronic kidney disease (CKD), and frailty.

Results: Over a median follow-up of 7 (interquartile range: 4-16) months, SGLT2i was associated with a reduced risk of hypoglycemia versus DPP-4i (HR 0.75 [0.68, 0.83]; RD -3.21 [-4.29, -2.12]), and versus GLP-1RA (HR 0.90 [0.82, 0.98]; RD -1.33 [-2.44, -0.23]). RD for SGLT2i versus DPP-4i was larger in patients using baseline insulin than in those not, although HRs were similar. In patients using baseline sulfonylurea, the risk of hypoglycemia was lower in SGLT2i versus DPP-4i (HR 0.57 [0.49, 0.65], RD -6.80 [-8.43, -5.16]), while the association was near-null in those without baseline sulfonylurea. Results stratified by baseline CVD, CKD and frailty were similar to the overall cohort findings. Findings for the GLP-1RA comparison were similar.

Conclusions: SGLT2i was associated with a lower hypoglycemia risk versus incretin-based medications, with larger associations in patients using baseline insulin or sulfonylurea.

Background: Unclean cooking fuels (ie, polluting fuels including kerosene/paraffin, and solid fuels) are a major contributor to diseases and mortality, specifically in low- and middle-income countries.

Methods: This review aimed to identify potential mechanisms, public health implications, and future directions of unclean cooking fuel use and health outcomes in older adults.

Results: There is an expanding body of literature to demonstrate associations between unclean cooking fuel use and multiple mental and physical health outcomes in older adults. Two key mechanisms likely driving such associations include inflammation and oxidative stress.

Conclusions: Considering that inflammation and oxidative stress have been implicated in multiple other health conditions (eg, arthritis and osteoporosis) in addition to those investigated to date on this topic it would be prudent to continue investigation of unclean cooking fuel use and with yet to be studied health outcomes. Moreover, future research is indeed now required to identify pathways to eliminating unclean cooking fuel globally to better the health of an aging global population and to support the implementation of Sustainable Development Goal 7.

Plasma Alzheimer's disease-related pathological biomarkers' role in Parkinson's disease (PD) remains unknown. We aimed to determine whether plasma Alzheimer's disease-related biomarkers can predict PD progression. A total of 184 PD patients and 86 healthy controls were included and followed up for 5 years. Plasma phosphorylated tau181 (p-tau181), Aβ40, and Aβ42 were measured at baseline and the 1- and 2-year follow-ups using the Quanterix-single-molecule array. Global cognitive function and motor symptoms were assessed using the Montreal Cognitive Assessment and Unified Parkinson's Disease Rating Scale part III. Genetic analyses were conducted to identify APOE and MAPT genotypes. Plasma p-tau181 levels were higher in PD than healthy controls. APOE-ε4 carriers had lower plasma Aβ42 levels and Aβ42/Aβ40 ratio. The linear mixed-effects models showed that Montreal Cognitive Assessment scores were associated with plasma p-tau181/Aβ42 ratio (β -1.719 [-3.398 to -0.040], p = .045). Higher baseline plasma p-tau181 correlated with faster cognitive decline and motor symptoms deterioration in total patients (β -0.170 [-0.322 to -0.018], p = .029; β 0.329 [0.032 to 0.626], p = .030) and APOE-ε4 carriers (β -0.318 [-0.602 to -0.034], p = .030; β 0.632 [0.017 to 1.246], p = .046), but not in the noncarriers. Higher baseline plasma Aβ40 correlated with faster cognitive decline in total patients (β -0.007 [-0.015 to -0.0001], p = .047) and faster motor symptoms deterioration in total patients (β 0.026 [0.010 to 0.041], p = .001) and APOE-ε4 carriers (β 0.044 [-0.026 to 0.049], p = .020), but not in the noncarriers. The plasma p-tau181/Aβ2 ratio monitors the cognitive status of PD. Higher baseline plasma p-tau181 and Aβ40 predict faster cognitive decline and motor symptoms deterioration in PD, especially in APOE-ε4 carriers.

Advancing age and many disease states are associated with declines in nicotinamide adenine dinucleotide (NAD+) levels. Preclinical studies suggest that boosting NAD+ abundance with precursor compounds, such as nicotinamide riboside or nicotinamide mononucleotide, has profound effects on physiological function in models of aging and disease. Translation of these compounds for oral supplementation in humans has been increasingly studied within the last 10 years; however, the clinical evidence that raising NAD+ concentrations can improve physiological function is unclear. The goal of this review was to synthesize the published literature on the effects of chronic oral supplementation with NAD+ precursors on healthy aging and age-related chronic diseases. We identified nicotinamide riboside, nicotinamide riboside co-administered with pterostilbene, and nicotinamide mononucleotide as the most common candidates in investigations of NAD+-boosting compounds for improving physiological function in humans. Studies have been performed in generally healthy midlife and older adults, adults with cardiometabolic disease risk factors such as overweight and obesity, and numerous patient populations. Supplementation with these compounds is safe, tolerable, and can increase the abundance of NAD+ and related metabolites in multiple tissues. Dosing regimens and study durations vary greatly across interventions, and small sample sizes limit data interpretation of physiological outcomes. Limitations are identified and future research directions are suggested to further our understanding of the potential efficacy of NAD+-boosting compounds for improving physiological function and extending human health span.

Background: Long-term exposure to PM2.5 is related to poor lung function and cognitive impairment, but less is known about the pathway involved in this association. We aimed to explore whether the effect of PM2.5 on cognitive function was mediated by lung function.

Methods: A total of 7 915 adults older than 45 years old were derived from the China Health and Retirement Longitudinal Study (CHARLS) collected in 2011 and 2015. PM2.5 exposure was estimated using a geographically weighted regression model. Lung function was measured by peak expiratory flow (PEF). Cognitive function was evaluated through a structured questionnaire with 4 dimensions: episodic memory, attention, orientation, and visuoconstruction. Under the counterfactual framework, causal mediation analysis was applied to examine direct and indirect associations.

Results: An interquartile range (IQR) increase in PM2.5 change was significantly related to an 8.480 (95% confidence interval [CI]: 3.116, 13.845) decrease in PEF change and a 0.301 (95% CI: 0.100, 0.575) decrease in global cognitive score change. The direct and indirect effects of PM2.5 exposure on global cognitive performance were -0.279 (95% CI: -0.551, -0.060) and -0.023 (95% CI: -0.041, -0.010), respectively. The proportion of the indirect effect was 7.48% (p = .010). The same significant association appeared in only 2 dimensions, episodic memory and attention, which were both mediated by PEF.

Conclusions: Lung function played a partially mediating role in the association between long-term PM2.5 exposure and cognition. More clean air actions should be undertaken to improve lung function and cognitive function in older adults.

Background: Although studies have demonstrated associations between sleep quality (SQ) and grip strength (GS) in older adults, the direction and underlying mechanisms of this relationship are yet to be better delineated. We aimed to longitudinally investigate the bidirectional association between SQ and GS and the mediating role of depression in this association.

Methods: Based on 2 nationally representative samples with people aged ≥50 years from the China Health and Retirement Longitudinal Study (CHARLS; 4 200 participants) and English Longitudinal Study of Ageing (ELSA; 5 922 participants), cross-lagged panel models were employed to examine the potential bidirectional relationships between objectively measured GS and self-reported SQ.

Results: We observed a GS-SQ bidirectional association dominated by GS. After adjusting for potential confounders, a higher GS at T1 predicted better SQ at T2 (ELSA: β = 0.075; CHARLS: β = 0.104, p < .001) and vice versa (ELSA: β = 0.034; CHARLS: β = 0.030, p < .01). Moreover, depression partially mediated the impact of GS on subsequent SQ (ELSA, indirect effect: 0.0057, 95% confidence interval [CI]: 0.0035-0.0084; CHARLS, indirect effect: 0.0086, 95% CI: 0.0051, 0.0131), but not vice versa.

Conclusions: The results regarding data from both cohorts consistently supported a bidirectional association between GS and SQ and the mediating role of depression in the dominant pathway of this bidirectional relationship. Older adults with a low GS should be made aware of a potentially vicious cycle related to depression that can affect their sleep. Regular screening for depression may help to break this cycle.

The standard evolutionary theory of aging predicts a negative relationship (trade-off) between fecundity and longevity. However, in principle, the fecundity-longevity relationship can become positive in populations in which individuals have unequal resources. Positive fecundity-longevity relationships also occur in queens of eusocial insects such as ants and bees. Developmental diet is likely to be central to determining trade-offs as it affects key fitness traits, but its exact role remains uncertain. For example, in Drosophila melanogaster, changes in adult diet can affect fecundity, longevity, and gene expression throughout life, but it is unknown how changes in developmental (larval) diet affect fecundity-longevity relationships and gene expression in adults. Using D. melanogaster, we tested the hypothesis that varying developmental diets alters the directionality of fecundity-longevity relationships in adults, and characterized associated gene expression changes. We reared larvae on low (20%), medium (100%), and high (120%) yeast diets, and transferred adult females to a common diet. We measured fecundity and longevity of individual adult females and profiled gene expression changes with age. Adult females raised on different larval diets exhibited fecundity-longevity relationships that varied from significantly positive to significantly negative, despite minimal differences in mean lifetime fertility or longevity. Treatments also differed in age-related gene expression, including for aging-related genes. Hence, the sign of fecundity-longevity relationships in adult insects can be altered and even reversed by changes in larval diet quality. By extension, larval diet differences may represent a key mechanistic factor underpinning positive fecundity-longevity relationships observed in species such as eusocial insects.

Background: Co-occurring insomnia and daytime sleepiness has an undetermined clinical significance in older adults. We aimed to investigate the relationship between various combinations of insomnia and daytime sleepiness with mortality risk in community-dwelling older adults. The moderation effect of sex was also assessed.

Methods: We conducted this follow-up study including community-dwelling adults aged ≥65 in Yilan City, Taiwan. Daytime sleepiness was defined as scoring ≥11 on the Epworth Sleepiness Scale. Insomnia was defined as scores ≥5 on the Athens Insomnia Scale-5. Four phenotypes were defined based on the presence of insomnia or daytime sleepiness. The 9-year mortality risks for various phenotypic combinations were estimated using Cox regression analysis. Sex-specific risks were examined using an interaction term.

Results: In total, 2 702 older adults participated in the study, and 59.1% were women. The total 9-year mortality rate was 27.5%. After adjusting for all covariates, compared with those without insomnia or daytime sleepiness, the phenotype of co-occurring insomnia with daytime sleepiness predicted higher mortality risk (hazard ratio [HR]: 1.76, confidence interval [CI]: 1.20-2.58). In contrast, insomnia and daytime sleepiness alone did not correlate with higher mortality. The interaction between sex with co-occurring insomnia and daytime sleepiness was significant (p = .01). When stratifying by sex, the association between co-occurring insomnia and daytime sleepiness with higher mortality risk was male-specific (HR: 3.07, CI: 1.87-5.04).

Conclusions: Concurrence of insomnia and daytime sleepiness indicates a toxic phenotypic combination in older adults, particularly in men. Precise public health and preventive medicine can be implemented through geriatric sleep medicine.

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.