Objectively measured physical capability levels and mortality: systematic review and meta-analysis

Objective: To do a quantitative systematic review, including published and unpublished data, examining the associations between individual objective measures of physical capability (grip strength, walking speed, chair rising, and standing balance times) and mortality in community dwelling populations. Design: Systematic review and meta-analysis. Data sources: Relevant studies published by May 2009 identified through literature searches using Embase (from 1980) and Medline (from 1950) and manual searching of reference lists; unpublished results were obtained from study investigators. Study selection: Eligible observational studies were those done in community dwelling people of any age that examined the association of at least one of the specified measures of physical capability (grip strength, walking speed, chair rises, or standing balance) with mortality. Data synthesis: Effect estimates obtained were pooled by using random effects meta-analysis models with heterogeneity between studies investigated. Results: Although heterogeneity was detected, consistent evidence was found of associations between all four measures of physical capability and mortality; those people who performed less well in these tests were found to be at higher risk of all cause mortality. For example, the summary hazard ratio for mortality comparing the weakest with the strongest quarter of grip strength (14 studies, 53 476 participants) was 1.67 (95% confidence interval 1.45 to 1.93) after adjustment for age, sex, and body size (I2=84.0%, 95% confidence interval 74% to 90%; P from Q statistic <0.001). The summary hazard ratio for mortality comparing the slowest with the fastest quarter of walking speed (five studies, 14 692 participants) was 2.87 (2.22 to 3.72) (I2=25.2%, 0% to 70%; P=0.25) after similar adjustments. Whereas studies of the associations of walking speed, chair rising, and standing balance with mortality have only been done in older populations (average age over 70 years), the association of grip strength with mortality was also found in younger populations (five studies had an average age under 60 years). Conclusions: Objective measures of physical capability are predictors of all cause mortality in older community dwelling populations. Such measures may therefore provide useful tools for identifying older people at higher risk of death. With Contributions from Dr P.A. Bath, University of Sheffiel

Comparing associations of handgrip strength and chair stand performance with all-cause mortality—implications for defining probable sarcopenia: the Tromsø Study 2015–2020

Background Widely adopted criteria suggest using either low handgrip strength or poor chair stand performance to identify probable sarcopenia. However, there are limited direct comparisons of these measures in relation to important clinical endpoints. We aimed to compare associations between these two measures of probable sarcopenia and all-cause mortality. Methods Analyses included 7838 community-dwelling participants (55% women) aged 40–84 years from the seventh survey of the Tromsø Study (2015–2016), with handgrip strength assessed using a Jamar + Digital Dynamometer and a five-repetition chair stand test (5-CST) also undertaken. We generated sex-specific T-scores and categorised these as “not low”, “low”, and “very low” handgrip strength or 5-CST performance. Cox Proportional Hazard regression models were used to investigate associations between these two categorised performance scores and time to death (up to November 2020 ascertained from the Norwegian Cause of Death registry), adjusted for potential confounders including lifestyle factors and specific diseases. Results A total of 233 deaths occurred (median follow-up 4.7 years) with 1- and 5-year mortality rates at 3.1 (95% confidence interval [CI] 2.1, 4.6) and 6.3 (95% CI 5.5, 7.2) per 1000 person-years, respectively. There was poor agreement between the handgrip strength and 5-CST categories for men (Cohen’s kappa [κ] = 0.19) or women (κ = 0.20). Fully adjusted models including handgrip strength and 5-CST performance mutually adjusted for each other, showed higher mortality rates among participants with low (hazard ratio [HR] 1.22, 95% CI 0.87, 1.71) and very low (HR 1.68, 95% CI 1.02, 2.75) handgrip strength compared with the not low category. Similar associations, although stronger, were seen for low (HR 1.88, 95% CI 1.38, 2.56) and very low (HR 2.64, 95% CI 1.73, 4.03) 5-CST performance compared with the not low category. Conclusions We found poor agreement between T-score categories for handgrip strength and 5-CST performance and independent associations with mortality. Our findings suggest that these tests identify different people at risk when case-finding probable sarcopenia. As discussions on an international consensus for sarcopenia definitions proceed, testing both handgrip strength and chair stand performance should be recommended rather than viewing these as interchangeable assessments

The effect of stress on the expression of the amyloid precursor protein in rat brain

AbstractThe abnormal processing of the amyloid precursor protein (APP) is a pivotal event in the development of the unique pathology that defines Alzheimer's disease (AD). Stress, and the associated increase in corticosteroids, appear to accelerate brain ageing and may increase vulnerability to Alzheimer's disease via altered APP processing. In this study, rats were repeatedly exposed to an unavoidable stressor, an open elevated platform. Previous studies in this laboratory have shown that a single exposure produces a marked increase in plasma corticosterone levels but animals develop tolerance to this effect between 10 and 20 daily sessions. Twenty-four hours after stress, there was an increase in the ratio of the deglycosylated form of APP in the particulate fraction of the brain, which subsequently habituated after 20 days. The levels of soluble APP (APPs) tended to be lower in the stress groups compared to controls except for a significant increase in the hippocampus after 20 days of platform exposure. Since APPs is reported to have neurotrophic properties, this increased release may represent a neuroprotective response to repeated stress. It is possible that the ability to mount this response decreases with age thus increasing the vulnerability to stress-induced AD-related pathology

Linear and Non-linear associations between vitamin D and grip strength: a Mendelian Randomisation study in UK Biobank

BACKGROUND: Low vitamin D status is a widespread phenomenon. Similarly, muscle weakness, often indicated by low grip strength, is another public health concern; however, the vitamin D-grip strength relationship is equivocal. It is important to understand whether variation in vitamin D status causally influences muscle strength to elucidate whether supplementation may help prevent/treat muscle weakness. METHODS: UK Biobank participants, aged 37-73 years, with valid data on Vitamin D status (circulating 25-hydroxyvitamin D (25(OH)D) concentration) and maximum grip strength were included (N=368,890). We examined sex-specific cross-sectional associations between 25(OH)D and grip strength. Using Mendelian randomisation (MR), we estimated the strength of the 25(OH)D-grip strength associations using genetic instruments for 25(OH)D as our exposure. Crucially, because potential effects of vitamin D supplementation on strength could vary by underlying 25(OH)D status, we allowed for non-linear relationships between 25(OH)D and strength in all analyses. RESULTS: Mean(SD) of 25(OH)D was 50(21)nmol/L in males and females. In cross-sectional analyses there was evidence of non-linear associations between 25(OH)D and strength: e.g., compared to males with 50nmol/L circulating 25(OH)D, males with 75nmol/L had 0.36kg (0.31,0.40) stronger grip; males with 25nmol/L had 1.01kg (95% CI: 0.93,1.08) weaker grip. In MR analyses, linear and non-linear models fitted the data similarly well: e.g., 25nmol/L higher circulating 25(OH)D in males was associated with 0.25kg (-0.05,0.55) greater grip (regardless of initial 25(OH)D status). Results were similar, albeit weaker, for females. CONCLUSIONS: Using two different methods to triangulate evidence, our findings suggest moderate to small causal links between circulating 25(OH)D and grip strength

Milk intake across adulthood and muscle strength decline from mid- to late life: the MRC National Survey of Health and Development

Milk is a source of several nutrients which may be beneficial for skeletal muscle. Evidence that links lower milk intake with declines in muscle strength from midlife to old age is lacking. We used data from the MRC NSHD to test sex-specific associations between milk consumption from age 36 to 60-64 years, low grip strength (GS) or probable sarcopenia, and GS decline from age 53 to 69 years. We included 1340 men and 1383 women with at least one measure of both milk intake and GS. Milk intake was recorded in 5-day food diaries (ages 36, 43, 53 and 60-64), and grand mean of total, reduced-fat and full-fat milk each categorised in thirds (T1 (lowest) to T3 (highest), g/day). GS was assessed at ages 53, 60-64, and 69, and probable sarcopenia classified at age 69. We employed logistic regression to examine the odds of probable sarcopenia, and multilevel models to investigate decline in GS in relation to milk intake thirds. Compared with T1, only T2 (58.7-145.2g/day) of reduced-fat milk was associated with lower odds of sex-specific low GS at age 69 (OR (95% CI): 0.59 (0.37, 0.94), p=0.03). In multilevel models, only T3 of total milk (≥237.5g/day) was associated with stronger GS in midlife in men (β (95% CI) = 1.82 (0.18, 3.45)kg, p=0.03) compared with T1 (≤152.0g/day), but not with GS decline over time. A higher milk intake across adulthood may promote muscle strength in midlife in men. Its role in muscle health in late life needs further examination

Pond management enhances the local abundance and species richness of farmland bird communities

Agricultural intensification and the associated loss of non-cropped habitats have caused a major decline in UK farmland bird populations since the 1970s. As a consequence, there is an urgent need to implement effective conservation and habitat restoration measures in agricultural landscapes. Over the last 40–50 years, due to the cessation of traditional management practices, the majority of UK farmland ponds have become highly terrestrialised, resulting in major reductions in the diversity and abundance of aquatic plant and invertebrate assemblages. Recent research undertaken at farmland ponds in early summer, has shown restored open-canopy, macrophyte-dominated ponds support an increased abundance and diversity of farmland birds, compared to non-managed, overgrown ponds. Here, we expand on this previous research with a year-long field study to assess the implications of pond management for farmland birds by comparing bird diversity, abundance and activity at managed open-canopy ponds with those at unmanaged overgrown ponds. Driven strongly by pond management and connectivity to semi-natural landscape features such as hedgerows and woodland patches, bird abundance and species richness, as well as foraging and parental behaviour, were all significantly higher at managed open-canopy ponds. Further, a wider landscape analysis found that terrestrial land-use patterns in the vicinity of the ponds were not significant predictors of bird communities at the pond sites. In light of the numerous potential benefits to conservation-listed birds and other wildlife, we conclude that farmland pond management has been undervalued as a conservation measure to assist farmland birds. Consequently, we conclude that future agri-environment schemes, should more fully embrace farmland ponds

Effect of smoking on physical and cognitive capability in later life: a multicohort study using observational and genetic approaches

Objectives: The observed associations between smoking and functional measures at older ages are vulnerable to bias and confounding. Mendelian randomisation (MR) uses genotype as an instrumental variable to estimate unconfounded causal associations. We conducted a meta-analysis of the observational associations and implemented an MR approach using the smoking-related single nucleotide polymorphism rs16969968 to explore their causal nature. Setting: 9 British cohorts belonging to the HALCyon collaboration. Participants: Individual participant data on N=26 692 individuals of European ancestry (N from earliest phase analysed per study) of mean ages 50-79 years were available for inclusion in observational meta-analyses of the primary outcomes. Primary outcomes: Physical capability, cognitive capability and cognitive decline. The smoking exposures were cigarettes per day, current versus ex-smoker, current versus never smoker and ever versus never smoker. Results: In observational analyses current and ever smoking were generally associated with poorer physical and cognitive capability. For example, current smokers had a general fluid cognition score which was 0.17 z-score units (95% CI -0.221 to -0.124) lower than ex-smokers in cross-sectional analyses. Current smokers had a walk speed which was 0.25 z-score units lower than never smokers (95% CI -0.338 to -0.170). An MR instrumental variable approach for current versus ex-smoker and number of cigarettes smoked per day produced CIs which neither confirmed nor refuted the observational estimates. The number of genetic associations stratified by smoking status were consistent with type I error. Conclusions: Our observational analysis supports the hypothesis that smoking is detrimental to physical and cognitive capability. Further studies are needed for a suitably powered MR approach

Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages:an individual participant meta-analysis

The association between functioning of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages remains poorly understood. We carried out meta-analyses to test the hypothesis that dysregulation of the HPA axis, as indexed by patterns of diurnal cortisol release, is associated with worse physical performance. Data from six adult cohorts (ages 50–92 years) were included in a two stage meta-analysis of individual participant data. We analysed each study separately using linear and logistic regression models and then used meta-analytic methods to pool the results. Physical performance outcome measures were walking speed, balance time, chair rise time and grip strength. Exposure measures were morning (serum and salivary) and evening (salivary) cortisol. Total sample sizes in meta-analyses ranged from n = 2146 for associations between morning Cortisol Awakening Response and balance to n = 8448 for associations between morning cortisol and walking speed. A larger diurnal drop was associated with faster walking speed (standardised coefficient per SD increase 0.052, 95% confidence interval (CI) 0.029, 0.076, p < 0.001; age and gender adjusted) and a quicker chair rise time (standardised coefficient per SD increase −0.075, 95% CI −0.116, −0.034, p < 0.001; age and gender adjusted). There was little evidence of associations with balance or grip strength. Greater diurnal decline of the HPA axis is associated with better physical performance in later life. This may reflect a causal effect of the HPA axis on performance or that other ageing-related factors are associated with both reduced HPA reactivity and performance

Global variation in grip strength: a systematic review and meta-analysis of normative data.

Background: weak grip strength is a key component of sarcopenia and is associated with subsequent disability and mortality. We have recently established life course normative data for grip strength in Great Britain, but it is unclear whether the cut 209 Global variation in grip strength points we derived for weak grip strength are suitable for use in other settings. Our objective was to investigate differences in grip strength by world region using our data as a reference standard. Methods: we searched MEDLINE and EMBASE for reporting age- and gender-stratified normative data for grip strength. We extracted each item of normative data and converted it on to a Z-score scale relative to our British centiles. We performed meta-regression to pool the Z-scores and compare them by world region. Findings: our search returned 806 abstracts. Sixty papers met inclusion criteria and reported on 63 different samples. Seven UN regions were represented, although most samples (n = 44) were based in developed regions. We extracted 726 normative data items relating to 96,537 grip strength observations. Normative data from developed regions were broadly similar to our British centiles, with a pooled Z-score 0.12 SDs (95% CI: 0.07, 0.17) above the corresponding British centiles. By comparison, normative data from developing regions were clearly lower, with a pooled Z-score of −0.85 SDs (95% CI: −0.94, −0.76). Interpretation: our findings support the use of our British grip strength centiles and their associated cut points in consensus definitions for sarcopenia and frailty across developed regions, but highlight the need for different cut points in developing region