Prospective associations of plasma growth differentiation factor 15 with physical performance and cognitive functions in older adults

Background Growth differentiation factor 15 (GDF15) has been associated with several age-related disorders, but its associations with functional abilities in community-dwelling older adults are not well studied. Methods The study was a secondary analysis on 1096 community-dwelling older adults (aged 69 to 94 years) recruited from the Multidomain Alzheimer’s Preventive Trial. Plasma GDF15 was measured one year after participants’ enrolment. Annual data of physical performance (grip strength and short physical performance battery [SPPB]) and global cognitive functions (mini-mental state examination [MMSE] and a composite cognitive score) were measured for four years. Adjusted mixed-effects linear models were performed for cross-sectional and longitudinal association analyses. Results A higher GDF15 was cross-sectionally associated with a weaker grip strength (β = -1.1E-03, 95%CI [-2.0E-03, -1.5E-04]), a lower SPPB score (β = -3.1E-04, 95%CI [-5.4E-04, -9.0E-05]) and worse cognitive functions (β = -2.4E-04, 95%CI [-3.3E-04, -1.6E-04] for composite cognitive score; β = -4.0E-04, 95%CI [-6.4E-04, -1.6E-04] for MMSE). Participants with higher GDF15 demonstrated greater longitudinal declines in SPPB (β = -1.0E-04, 95%CI [-1.7E-04, -2.0E-05]) and composite cognitive score (β = -2.0E-05, 95%CI [-4.0E-05, -3.6E-06]). The optimal initial GDF15 cutoff values for identifying participants with minimal clinically significant decline after one year were 2189 pg/mL for SPPB (AUC: 0.580) and 2330 pg/mL for composite cognitive score (AUC: 0.587). Conclusions Plasma GDF15 is cross-sectionally and longitudinally associated with lower-limb physical performance and global cognitive function in older adults. Circulating GDF15 alone has limited capacity of discriminating older adults who will develop clinically significant functional declines.

Plasma angiopoietin-like protein 2 levels and mortality risk among younger-old Japanese people: a population-based case-cohort study

Aging is important medical and social problem. Excessive angiopoietin-like protein (ANGPTL)-2 signaling causes chronic tissue inflammation, promoting development and progression of aging-related diseases. Moreover, circulating ANGPTL2 levels reportedly predict risk of some aging-related diseases and subsequent death. However, there are as yet no reports of whether circulating ANGPTL2 levels predict vital prognosis in younger-old, community-dwelling populations. This study investigated associations between plasma ANGPTL2 levels and all-cause and specific-cause mortality in this population. The case-cohort study was abstracted from an on-going, age-specific prospective cohort study: the New Integrated Suburban Seniority Investigation Project. This project enrolled 3073 participants aged 64 years at the beginning of the investigation from 1996 through 2005. A sub-cohort of 714 randomly sampled participants plus 387 cases representing deceased participants followed through 2015 underwent survival analysis. Plasma ANGPTL2 concentrations were positively associated with >80% and 100% higher risk of all-cause mortality and cancer mortality, respectively, after adjustment for gender, smoking, alcohol consumption, walking time, sleep duration, caloric intake, medical status, disease history, BMI, and triglyceride, creatinine, uric acid, and high sensitivity C-reactive protein levels. More robust association between ANGPTL2 levels and all-cause and cancer mortality was seen in subjects with either frailties or with lifestyles of heavier drinking or current smoking. Elevated plasma ANGPTL2 levels are associated with high all-cause and cancer mortality in a community-dwelling sample of younger-old adults. These findings expand our knowledge of human aging and associated diseases.

Impact of COVID-19 Pandemic Exacerbation of Depressive Symptoms for Social Frailty from the ORANGE Registry

Background: Recent longitudinal studies have reported proportion of frailty transition in older individuals during the COVID-19 pandemic. Our study aimed at clarifying the impact of social frailty in community-dwelling older adults during the COVID-19 pandemic and at identifying factors that can predict transition to social frailty. Methods: We performed this study from 2019 (before declaration of the state of emergency over the rising number of COVID-19 cases) to 2020 (after declaration of the emergency). We applied Makizako’s social frail index to our study subjects at the baseline and classified into robust, social prefrailty, and social frailty groups. Multiple logistic regression analysis was performed using robust, social prefrailty, or social frailty status as dependent variable. Results: Analysis by the Kruskal–Wallis test revealed significant differences in the score on the GDS-15 among the robust, social prefrailty, and social frailty groups (p < 0.05). Furthermore, multiple regression analysis identified a significant association between the social frailty status and the score on GDS-15 (odds ratio, 1.57; 95% confidence interval (95% CI), 1.15–2.13; p = 0.001). Conclusion: The increase in the rate of transition of elderly individuals to the social frailty group could have been related to the implementation of the stay-at-home order as part of the countermeasures for COVID-19. Furthermore, the increased prevalence of depressive symptoms associated with the stay-at-home order could also have influenced the increase in the prevalence of social frailty during the COVID-19 pandemic.

Association of zinc intake with risk of impaired physical function and frailty among older adults

Background Zinc could be a target nutrient in the prevention of physical impairment and frailty in older adults due to its anti-inflammatory/antioxidant properties. However, prospective studies evaluating this inquiry are scarce. Thus, we aimed to assess the association between zinc intake and impaired lower-extremity function (ILEF) and frailty among community-dwelling older adults. Methods We examined 2,963 adults aged ≥60 years from the Seniors-ENRICA cohort. At baseline (2008–2010) and subsequent follow-up (2012), zinc intake (mg/d) was estimated with a validated computerized face-to-face diet history and adjusted for total energy intake. From 2012 to 2017, the occurrence of ILEF was ascertained with the Short Physical Performance Battery, and of frailty according to the Fried phenotype criteria. Analyses were conducted using Cox proportional hazard models adjusted for relevant confounders, including lifestyle, comorbidity, and dietary factors. Results During follow-up, we identified 515 incident cases of ILEF and 241 of frailty. Compared to participants in the lowest tertile of zinc intake (3.99–8.36 mg/d), those in the highest tertile (9.51–21.2 mg/d) had a lower risk of ILEF [fully-adjusted hazard ratio (95% confidence interval): 0.75 (0.58–0.97); p for trend: 0.03] and of frailty [0.63 (0.44–0.92); p for trend: 0.02]. No differences in the association were seen by strata of socio-demographic and lifestyle factors. Conclusions Higher zinc intake was prospectively associated with a lower risk of ILEF and frailty among older adults, suggesting that adequate zinc intake, that can be achieved through a healthy diet, may help preserve physical function and reduce the progression to frailty.

Interactions between weight loss and plasma neurodegenerative markers for determining cognitive decline among community-dwelling older adults

This study aimed to investigate the interaction between weight loss (WL) and plasma amyloid-β42/40 (Aβ42/40), neurofilament light chain (NfL), progranulin, and their association with cognitive decline over time among older adults. This 5-year observational approach included 470 participants from the Multidomain Alzheimer Preventive Trial (MAPT), mean age 76.8y (SD=4.5), 59.4% women. WL was defined as ≥5% decrease over the first year. Biomarkers were measured at 12 months. Cognitive function was assessed yearly from 12 months onwards by Mini-Mental State Examination (MMSE); Clinical Dementia Rating sum of boxes (CDR-SB); a composite score based on Category Naming Test, Digit Symbol Substitution Test, ten MMSE orientation items (MMSEO) and Free and total recall of the Free and Cued Selective Reminding test; and these tests individually. Twenty-seven participants (5.7%) presented WL. In adjusted analyses, combined WL+lower Aβ42/40 (≤0.103, lowest quartile) was related with more pronounced 4-year cognitive decline according to CDR-SB (p&lt;0.0001) and MMSEO (p=0.021), compared to non-WL+higher Aβ42/40. WL+higher NfL (&gt;94.55pg/mL, highest quartile) or progranulin (&gt;38.4ng/mL, three higher quartiles) were related with higher cognitive decline according to CDR-SB, MMSE, MMSEO and composite score (all p&lt;0.03), compared to non-WL+lower NfL or higher progranulin. Regrouping progranulin quartiles (Q1-Q3 vs. Q4) revealed higher cognitive decline among the WL+lower progranulin group compared to non-WL+lower progranulin. In conclusion, 1-year WL was associated with subsequent higher 4-year cognitive decline among older adults presenting low Aβ42/40 or high NfL. Future studies combining plasma biomarker assessments and body weight surveillance may be useful for identifying people at risk of cognitive impairment.

Associations between Serum Betaine, Methyl-Metabolizing Genetic Polymorphisms and Risk of Incident Type 2 Diabetes: A Prospective Cohort Study in Community-Dwelling Chinese Adults

Previous studies have explored associations between betaine and diabetes, but few have considered the effects of genes on them. We aimed to examine associations between serum betaine, methyl-metabolizing genetic polymorphisms and the risk of type 2 diabetes in Chinese adults. This prospective study comprised 1565 subjects aged 40–75 without type 2 diabetes at baseline. Serum betaine was measured by high-performance liquid chromatography tandem mass spectrometry. Genotyping of methyl-metabolizing genes was detected by Illumina ASA-750K arrays. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median of 8.9 years of follow-up, 213 participants developed type 2 diabetes. Compared with participants in the lowest quartile of serum betaine, those in the highest quartile had lower risk of type 2 diabetes, adjusted HRs (95%CIs) was 0.46 (0.31, 0.69). For methylenetetrahydrofolate reductase (MTHFR) G1793A (rs2274976) and MTHFR A1298C (rs1801131), participants carrying 1793GA + AA and 1298AC + CC had lower risk of type 2 diabetes. Interactions of serum betaine and genotype of MTHFR G1793A and MTHFR A1298C could be found influencing type 2 diabetes risk. Our findings indicate that higher serum betaine, mutations of MTHFR G1793A and A1298C, as well as the joint effects of them, are associated with lower risk of type 2 diabetes.

A Review on Aging, Sarcopenia, Falls, and Resistance Training in Community-Dwelling Older Adults

As aging continues to grow in our society, sarcopenia and associated fall risk is considered a public health problem since falling is the third cause of chronic disability. Falls are negatively related to functionality and independence and positively associated with morbidity and mortality. The cost of treatment of secondary injuries related to falls is high. For example, one in ten fall incidents leads to bone fractures and several other comorbidities. As demonstrated by several experimental studies, adopting a more active lifestyle is critical for reducing the number of fall episodes and their consequences. Therefore, it is essential to debate the proven physical exercise methods to reduce falls and fall-related effects. Since muscle mass, muscle strength, bone density, and cartilage function may play significant roles in daily activities, resistance training may positively and significantly affect the elderly. This narrative review aimed to examine current evidence on existing resistance training using resistance machines and bodyweight or low-cost equipment for the elderly and how they are related to falls and fall-related consequences. We provide theoretical links between aging, sarcopenia, and falls linking to resistance training and offer practical suggestions to exercise professionals seeking to promote regular physical exercise to promote quality of life in this population. Exercise programs focusing on strength may significantly influence muscle mass and muscle strength, minimizing functional decline and risk of falling. Resistance training programs should be customized to each elderly according to age, sex, and other fundamental and individual aspects. This narrative review provides evidence to support recommendations for practical resistance training in the elderly related to intensity and volume. A properly designed resistance training program with adequate instructions and technique is safe for the elderly. It should include an individualized approach based on existing equipment (i.e., body weight, resistance machines). Existing literature shows that exercise performance towards 2–3 sets of 1–2 exercises per major muscle group, performing 5–8 repetitions or achieving intensities of 50–80% of 1RM, 2–3 times per week should be recommended, followed by training principles such as periodization and progression. Bearing this in mind, health and exercise professionals should combine efforts focusing on efficient strategies to reduce falls among the elderly and promote higher experiences of well-being at advanced stages in life.