Epidemiological studies have shown that weaker grip strength in later life is associated with disability, morbidity, and mortality. Grip strength is a key component of the sarcopenia and frailty ...phenotypes and yet it is unclear how individual measurements should be interpreted. Our objective was to produce cross-sectional centile values for grip strength across the life course. A secondary objective was to examine the impact of different aspects of measurement protocol.
We combined 60,803 observations from 49,964 participants (26,687 female) of 12 general population studies in Great Britain. We produced centile curves for ages 4 to 90 and investigated the prevalence of weak grip, defined as strength at least 2.5 SDs below the gender-specific peak mean. We carried out a series of sensitivity analyses to assess the impact of dynamometer type and measurement position (seated or standing).
Our results suggested three overall periods: an increase to peak in early adult life, maintenance through to midlife, and decline from midlife onwards. Males were on average stronger than females from adolescence onwards: males' peak median grip was 51 kg between ages 29 and 39, compared to 31 kg in females between ages 26 and 42. Weak grip strength, defined as strength at least 2.5 SDs below the gender-specific peak mean, increased sharply with age, reaching a prevalence of 23% in males and 27% in females by age 80. Sensitivity analyses suggested our findings were robust to differences in dynamometer type and measurement position.
This is the first study to provide normative data for grip strength across the life course. These centile values have the potential to inform the clinical assessment of grip strength which is recognised as an important part of the identification of people with sarcopenia and frailty.
Intra-individual variability in reaction time (RT IIV) is considered to be an index of central nervous system functioning. Such variability is elevated in neurodegenerative diseases or following ...traumatic brain injury. It has also been suggested to increase with age in healthy ageing.
To investigate and quantify age differences in RT IIV in healthy ageing; to examine the effect of different tasks and procedures; to compare raw and mean-adjusted measures of RT IIV.
Four electronic databases: PsycINFO, Medline, Web of Science and EMBASE, and hand searching of reference lists of relevant studies.
English language journal articles, books or book chapters, containing quantitative empirical data on simple and/or choice RT IIV. Samples had to include younger (under 60 years) and older (60 years and above) human adults.
Studies were evaluated in terms of sample representativeness and data treatment. Relevant data were extracted, using a specially-designed form, from the published report or obtained directly from the study authors. Age-group differences in raw and RT-mean-adjusted measures of simple and choice RT IIV were quantified using random effects meta-analyses.
Older adults (60+ years) had greater RT IIV than younger (20-39) and middle-aged (40-59) adults. Age effects were larger in choice RT tasks than in simple RT tasks. For all measures of RT IIV, effect sizes were larger for the comparisons between older and younger adults than between older and middle-aged adults, indicating that the age-related increases in RT IIV are not limited to old age. Effect sizes were also larger for raw than for RT-mean-adjusted RT IIV measures.
RT IIV is greater among older adults. Some (but not all) of the age-related increases in RT IIV are accounted for by the increased RT means.
Objective To quantify the link between lower, subclinically symptomatic, levels of psychological distress and cause-specific mortality in a large scale, population based study. Design Individual ...participant meta-analysis of 10 large prospective cohort studies from the Health Survey for England. Baseline psychological distress measured by the 12 item General Health Questionnaire score, and mortality from death certification.Participants 68 222 people from general population samples of adults aged 35 years and over, free of cardiovascular disease and cancer, and living in private households in England at study baseline.Main outcome measures Death from all causes (n=8365), cardiovascular disease including cerebrovascular disease (n=3382), all cancers (n=2552), and deaths from external causes (n=386). Mean follow-up was 8.2 years (standard deviation 3.5).Results We found a dose-response association between psychological distress across the full range of severity and an increased risk of mortality (age and sex adjusted hazard ratio for General Health Questionnaire scores of 1-3 v score 0: 1.20, 95% confidence interval 1.13 to 1.27; scores 4-6: 1.43, 1.31 to 1.56; and scores 7-12: 1.94, 1.66 to 2.26; P<0.001 for trend). This association remained after adjustment for somatic comorbidity plus behavioural and socioeconomic factors. A similar association was found for cardiovascular disease deaths and deaths from external causes. Cancer death was only associated with psychological distress at higher levels.Conclusions Psychological distress is associated with increased risk of mortality from several major causes in a dose-response pattern. Risk of mortality was raised even at lower levels of distress.
Abstract Cerebral small vessel disease (SVD) may cause cognitive dysfunction. We tested the association between the combined presence of magnetic resonance imaging (MRI) features of SVD and cognitive ...ability in older age. Cognitive testing and brain MRI were performed in 680 older participants. MRI presence of lacunes, white matter hyperintensities, microbleeds, and perivascular spaces were summed in a score of 0–4 representing all SVD features combined. We also applied latent variable modeling to test whether the 4 MRI features form a unitary SVD construct. The SVD score showed significant associations with general cognitive ability. Latent variable modeling indicated that the 4 MRI markers formed a unitary construct, which showed consistent associations with cognitive ability compared with the SVD score. Total MRI load of SVD is associated with lower general cognitive ability in older age. The total SVD score performed consistently with the more complex latent variable model, suggesting validity and potential utility in future research for determining total SVD load.
Alzheimer's disease (AD) is a public health priority for the 21st century. Risk reduction currently revolves around lifestyle changes with much research trying to elucidate the biological ...underpinnings. We show that self-report of parental history of Alzheimer's dementia for case ascertainment in a genome-wide association study of 314,278 participants from UK Biobank (27,696 maternal cases, 14,338 paternal cases) is a valid proxy for an AD genetic study. After meta-analysing with published consortium data (n = 74,046 with 25,580 cases across the discovery and replication analyses), three new AD-associated loci (P < 5 × 10
) are identified. These contain genes relevant for AD and neurodegeneration: ADAM10, BCKDK/KAT8 and ACE. Novel gene-based loci include drug targets such as VKORC1 (warfarin dose). We report evidence that the association of SNPs in the TOMM40 gene with AD is potentially mediated by both gene expression and DNA methylation in the prefrontal cortex. However, it is likely that multiple variants are affecting the trait and gene methylation/expression. Our discovered loci may help to elucidate the biological mechanisms underlying AD and, as they contain genes that are drug targets for other diseases and disorders, warrant further exploration for potential precision medicine applications.
Epigenetics has classically been recognized as crucial to neurodevelopment and neurodevelopmental disorders. More recently its role in ageing processes, including neurodegenerative disorders has ...emerged, although far more research is required in this area, particularly in humans. Epigenetic processes that regulate gene expression comprise strata of DNA modification (e.g. methylation), histone modification (e.g. histone acetylation), and mRNA translation (e.g. by microRNAs). These strata are progressively more fluid whereby changes in DNA methylation may persist for many years whilst expression of microRNAs fluctuates over short periods. There is considerable ‘cross‐talk’ between these epigenetic strata. Epigenetic mechanisms are open to parental imprinting and thus they are candidates for linking diseases, not just over the life course, but also intergenerationally. There is a genetic overlap between intellectual disability and cognitive ageing. Epigenetic pathways may strengthen the links between neurodevelopmental disorders and neurodegenerative diseases.
What this paper adds
DNA methylation has relevance to both neurological development and neurodegeneration.
Links between epigenetics, genotype and phenotype are emerging.
Resumen
Envejecimiento y epigenética: vinculación el neurodesarrollo y trastornos neurodegenerativos
La epigenética ha sido reconocida clásicamente como crucial para el neurodesarrollo y los trastornos del neurodesarrollo. Más recientemente, se ha propuesto, su papel en los procesos de envejecimiento, incluidos los trastornos neurodegenerativos, aunque se requiere mucha más investigación en esta área, particularmente en humanos. Los procesos epigenéticos que regulan la expresión génica comprenden estratos de modificación de ADN (por ejemplo, metilación), modificación de histonas (por ejemplo, acetilación de histonas) y traducción de ARNm (por ejemplo, por microARN). Estos estratos son cada vez más dinámicos, por lo que los cambios en la metilación del ADN pueden persistir durante muchos años, mientras que la expresión de los microARN fluctúa durante períodos cortos. Existe una considerable “conversación cruzada” entre estos estratos epigenéticos. Los mecanismos epigenéticos están abiertos a la impronta parental y, por lo tanto, son candidatos para vincular enfermedades, no solo en el transcurso de la vida, sino también intergeneracionalmente. Existe una superposición genética entre la discapacidad intelectual y el envejecimiento cognitivo. Las vías epigenéticas pueden fortalecer los vínculos entre los trastornos del neurodesarrollo y las enfermedades neurodegenerativas.
Envelhecimento e epigenética: ligando transtornos neurodesenvolvimentais e neurodegenerativas
A epigenética tem sido classicamente reconhecida como crucial para o neurodesenvolvimento e transtornos neurodesenvolvimentais. Mais recentemente, seu papel nos processos de envelhecimento, incluindo doenças neurodegenerativas emergiu, embora muito mais pesquisas sejam necessárias nesta área, particularmente em humanos. Processos epigenéticos que regulam a expressão gênica incluem estratos de modificação de DNA (ex: metilação), modificação de histonas (ex: acetilação de histonas), e translação de mRNA (ex: por micro RNAs). Estes estratos são progressivamente mais fluidos, portanto mudanças na metilação do DNA podem persistir por muitos anoss, enquanto a expressão de micro RNAs flutua por curtos períodos. Há considerável troca entre estes estratos epigenéticos. Mecanismos epigenéticos são abertos ao impressão genómica (imprinting parental), e portanto, candidados a se relacionar com doenças, não apenas no curso da vida, mas também entre gerações. Há sobreposição genética entre deficiência intelectual e envelhecimento cognitivo. Vias epigenéticas podem fortalecer as relações entre transtornos neurodesenvolvimentais e doenças neurodegenerativas.
What this paper adds
DNA methylation has relevance to both neurological development and neurodegeneration.
Links between epigenetics, genotype and phenotype are emerging.
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Neurological disorders are one of the most important public health concerns in developed countries. Established brain imaging techniques such as magnetic resonance imaging (MRI) and x-ray ...computerised tomography (CT) have been essential in the identification and diagnosis of a wide range of disorders, although usually are insufficient in sensitivity for detecting subtle pathological alterations to the brain prior to the onset of clinical symptoms-at a time when prognosis for treatment is more favourable. The mechanical properties of biological tissue provide information related to the strength and integrity of the cellular microstructure. In recent years, mechanical properties of the brain have been visualised and measured non-invasively with magnetic resonance elastography (MRE), a particularly sensitive medical imaging technique that may increase the potential for early diagnosis. This review begins with an introduction to the various methods used for the acquisition and analysis of MRE data. A systematic literature search is then conducted to identify studies that have specifically utilised MRE to investigate the human brain. Through the conversion of MRE-derived measurements to shear stiffness (kPa) and, where possible, the loss tangent (rad), a summary of results for global brain tissue and grey and white matter across studies is provided for healthy participants, as potential baseline values to be used in future clinical investigations. In addition, the extent to which MRE has revealed significant alterations to the brain in patients with neurological disorders is assessed and discussed in terms of known pathophysiology. The review concludes by predicting the trends for future MRE research and applications in neuroscience.
This cohort profile describes the origins, tracing, recruitment, testing and follow-up of the University of Edinburgh-based Lothian Birth Cohorts of 1921 (LBC1921; N = 550) and 1936 (LBC1936; N = ...1091). The participants undertook a general intelligence test at age 11 years and were recruited for these cohorts at mean ages of 79 (LBC1921) and 70 (LBC1936). The LBC1921 have been examined at mean ages of 79, 83, 87 and 90 years. The LBC1936 have been examined at mean ages of 70 and 73 years, and are being seen at 76 years. Both samples have an emphasis on the ageing of cognitive functions as outcomes. As they have childhood intelligence test scores, the cohorts' data have been used to search for determinants of lifetime cognitive changes, and also cognitive change within old age. The cohorts' outcomes also include a range of physical and psycho-social aspects of well-being in old age. Both cohorts have a wide range of variables: genome-wide genotyping, demographics, psycho-social and lifestyle factors, cognitive functions, medical history and examination, and biomarkers (from blood and urine). The LBC1936 participants also have a detailed structural magnetic resonance imaging (MRI) brain scan. A range of scientific findings is described, to illustrate the possible uses of the cohorts.
Abstract Purpose To determine associations between multiple vascular risk factors (VRF) at ∼73 years and progression of white matter hyperintensities (WMH) from ∼73 to ∼76 years. Methods We ...calculated correlations and generalised estimating equation (GEE) models of a comprehensive range of VRF at 73 years and change in WMH volume from 73 to 76 years. Results Higher systolic (rho=0.126, P =0.009) and diastolic (rho=0.120, P =0.013) blood pressure at 73 years were significant predictors for greater WMH volume at 76 years in a simple correlation model. However, neither measured blood pressure nor self-reported hypertension at 73 years were significant predictors of WMH volume change in a fully adjusted model which accounted for initial WMH volume at 73 years. Lower HDL cholesterol (Beta=-0.15 %ICV, -1.80 ml; P <0.05) and current smoking (Beta=0.43 %ICV, 5.49 ml; P <0.05) were the only significant VRF predictors of WMH volume change from 73 to 76 years. Conclusions A focus on smoking cessation and lipid lowering, not just anti-hypertensives, may lead to a reduction in WMH growth in the eighth decade of life.
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