Physical activity and healthy ageing: A systematic review and meta-analysis of longitudinal cohort studies.

BACKGROUND: Older people constitute a significant proportion of the total population and their number is projected to increase by more than half by 2030. This increasing probability of late survival comes with considerable individual, economic and social impact. Physical activity (PA) can influence the ageing process but the specific relationship with healthy ageing (HA) is unclear. METHODS: We conducted a systematic review and meta-analysis of longitudinal studies examining the associations of PA with HA. Studies were identified from a systematic search across major electronic databases from inception as January 2017. Random-effect meta-analysis was performed to calculate a pooled effect size (ES) and 95% CIs. Studies were assessed for methodological quality. RESULTS: Overall, 23 studies were identified including 174,114 participants (30% men) with age ranges from 20 to 87 years old. There was considerable heterogeneity in the definition and measurement of HA and PA. Most of the identified studies reported a significant positive association of PA with HA, six reported a non-significant. Meta-analysis revealed that PA is positively associated with HA (ES: 1.39, 95% CI=1.23-1.57, n=17) even if adjusted for publication bias (ES: 1.27, 95% CI=1.11-1.45, n=20). CONCLUSIONS: There is consistent evidence from longitudinal observational studies that PA is positively associated with HA, regardless of definition and measurement. Future research should focus on the implementation of a single metric of HA, on the use of objective measures for PA assessment and on a full-range of confounding adjustment. In addition, our research indicated the limited research on ageing in low-and-middle income countries

Cohort Differences in Cognitive Aging in the Longitudinal Aging Study Amsterdam

OBJECTIVES: This study aims to examine cohort differences in cognitive performance and rates of change in episodic memory, processing speed, inductive reasoning, and general cognitive performance and to investigate whether these cohort effects may be accounted for by education attainment. METHOD: The first cohort (N = 705) was born between 1920 and 1930, whereas the second cohort (N = 646) was born between 1931 and 1941. Both birth cohorts were aged 65 to 75 years at baseline and were followed up 3 and 6 years later. Data were analyzed using linear mixed models. RESULTS: The later born cohort had better general cognitive performance, inductive reasoning, and processing speed at baseline, but cohort differences in inductive reasoning and general cognitive performance disappeared after adjusting for education. The later born cohort showed steeper decline in processing speed. Memory decline was steeper in the earlier born cohort but only from Time 1 to Time 3 when the same memory test was administered. Education did not account for cohort differences in cognitive decline. DISCUSSION: The later born cohort showed better initial performance in certain cognitive abilities, but no better preservation of cognitive abilities overtime compared with the earlier born cohort. These findings carry implications for healthy cognitive aging

A journey without maps—Understanding the costs of caring for dependent older people in Nigeria, China, Mexico and Peru

Purpose of the study: Populations in Latin America, Asia and sub-Saharan Africa are rapidly ageing. The extent to which traditional systems of family support and security can manage the care of increased numbers of older people with chronic health problems is unclear. Our aim was to explore the social and economic effects of caring for an older dependent person, including insight into pathways to economic vulnerability. Design & methods: We carried out a series of household case studies across urban and rural sites in Peru, Mexico, China and Nigeria (n = 24), as part of a cross-sectional study, nested within the 10/66 Dementia Research Group cohort. Case studies consisted of in-depth narrative style interviews (n = 60) with multiple family members, including the older dependent person. Results: Governments were largely uninvolved in the care and support of older dependent people, leaving families to negotiate a ‘journey without maps’. Women were de facto caregivers but the traditional role of female relative as caregiver was beginning to be contested. Household composition was flexible and responsive to changing needs of multiple generations but family finances were stretched. Implications: Governments are lagging behind sociodemographic and social change. There is an urgent need for policy frameworks to support and supplement inputs from families. These should include community-based and residential care services, disability benefits and carers allowances. Further enhancement of health insurance schemes and scale-up of social pensions are an important component of bolstering the security of dependent older people and supporting their continued social and economic participation

Post-mortem brain analyses of the Lothian Birth Cohort 1936:Extending lifetime cognitive and brain phenotyping to the level of the synapse

INTRODUCTION: Non-pathological, age-related cognitive decline varies markedly between individuals andplaces significant financial and emotional strain on people, their families and society as a whole.Understanding the differential age-related decline in brain function is critical not only for the development oftherapeutics to prolong cognitive health into old age, but also to gain insight into pathological ageing suchas Alzheimer’s disease. The Lothian Birth Cohort of 1936 (LBC1936) comprises a rare group of people forwhom there are childhood cognitive test scores and longitudinal cognitive data during older age, detailedstructural brain MRI, genome-wide genotyping, and a multitude of other biological, psycho-social, andepidemiological data. Synaptic integrity is a strong indicator of cognitive health in the human brain;however, until recently, it was prohibitively difficult to perform detailed analyses of synaptic and axonalstructure in human tissue sections. We have adapted a novel method of tissue preparation at autopsy toallow the study of human synapses from the LBC1936 cohort in unprecedented morphological andmolecular detail, using the high-resolution imaging techniques of array tomography and electronmicroscopy. This allows us to analyze the brain at sub-micron resolution to assess density, proteincomposition and health of synapses. Here we present data from the first donated LBC1936 brain andcompare our findings to Alzheimer’s diseased tissue to highlight the differences between healthy andpathological brain ageing. RESULTS: Our data indicates that compared to an Alzheimer’s disease patient, the cognitively normalLBC1936 participant had a remarkable degree of preservation of synaptic structures. However,morphological and molecular markers of degeneration in areas of the brain associated with cognition(prefrontal cortex, anterior cingulate cortex, and superior temporal gyrus) were observed. CONCLUSIONS: Our novel post-mortem protocol facilitates high-resolution neuropathological analysis of the well-characterized LBC1936 cohort, extending phenotyping beyond cognition and in vivo imaging to nowinclude neuropathological changes, at the level of single synapses. This approach offers an unprecedentedopportunity to study synaptic and axonal integrity during ageing and how it contributes to differences in agerelatedcognitive change. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-015-0232-0) contains supplementary material, which is available to authorized users

Socioeconomic predictors and consequences of depression among primary care attenders with non-communicable diseases in the Western Cape, South Africa:Cohort study within a randomised trial

Background: Socioeconomic predictors and consequences of depression and its treatment were investigated in 4393 adults with specified non-communicable diseases attending 38 public sector primary care clinics in the Eden and Overberg districts of the Western Cape, South Africa.   Methods: Participants were interviewed at baseline in 2011 and 14 months later, as part of a randomised controlled trial of a guideline-based intervention to improve diagnosis and management of chronic diseases. The 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) was used to assess depression symptoms, with higher scores representing more depressed mood. Results: Higher CESD-10 scores at baseline were independently associated with being less educated (p=0.004) and having lower income (p=0.003). CESD-10 scores at follow-up were higher in participants with less education (p=0.010) or receiving welfare grants (p=0.007) independent of their baseline scores. Participants with CESD-10 scores of 10 or more at baseline (56% of all participants) had 25% higher odds of being unemployed at follow-up (p=0.016), independently of baseline CESD-10 score and treatment status. Among participants with baseline CESD-10 scores of 10 or more, antidepressant medication at baseline was independently more likely in participants who had more education (p=0.002), higher income (p<0.001), or were unemployed (p=0.001). Antidepressant medication at follow up was independently more likely in participants with higher income (p=0.023), and in clinics with better access to pharmacists (p=0.053) and off-site drug delivery (p=0.013).  Conclusions: Socioeconomic disadvantage appears to be both a cause and consequence of depression, and may also be a barrier to treatment. There are opportunities for improving the prevention, diagnosis and treatment of depression in primary care in inequitable middle income countries like South Africa.  Trial registration: The trial is registered with Current Controlled Trials (ISRCTN20283604) and the Office for Human Research Protections Database (IRB00001938, FWA00001637)

Isatuximab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients with renal impairment: ICARIA-MM subgroup analysis

The randomized, phase 3 ICARIA-MM study investigated isatuximab (Isa) with pomalidomide and dexamethasone (Pd) versus Pd in patients with relapsed/refractory multiple myeloma and ≥2 prior lines. This prespecified subgroup analysis examined efficacy in patients with renal impairment (RI; estimated glomerular filtration rate <60 mL/min/1.73 m²). Isa 10 mg/kg was given intravenously once weekly in cycle 1, and every 2 weeks in subsequent 28-day cycles. Patients received standard doses of Pd. Median progression-free survival (PFS) for patients with RI was 9.5 months with Isa-Pd (n = 55) and 3.7 months with Pd (n = 49; hazard ratio [HR] 0.50; 95% confidence interval [CI], 0.30–0.85). Without RI, median PFS was 12.7 months with Isa-Pd (n = 87) and 7.9 months with Pd (n = 96; HR 0.58; 95% CI, 0.38–0.88). The overall response rate (ORR) with and without RI was higher with Isa-Pd (56 and 68%) than Pd (25 and 43%). Complete renal response rates were 71.9% (23/32) with Isa-Pd and 38.1% (8/21) with Pd; these lasted ≥60 days in 31.3% (10/32) and 19.0% (4/21) of patients, respectively. Isa pharmacokinetics were comparable between the subgroups, suggesting no need for dose adjustment in patients with RI. In summary, the addition of Isa to Pd improved PFS, ORR and renal response rates

Predictors of mortality among elderly people living in a south Indian urban community; a 10/66 Dementia Research Group prospective population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Eighty percent of deaths occur in low and middle income countries (LMIC), where chronic diseases are the leading cause. Most of these deaths are of older people, but there is little information on the extent, pattern and predictors of their mortality. We studied these among people aged 65 years and over living in urban catchment areas in Chennai, south India.</p> <p>Methods</p> <p>In a prospective population cohort study, 1005 participants were followed-up after three years. Baseline assessment included sociodemographic and socioeconomic characteristics, health behaviours, physical, mental and cognitive disorders, disability and subjective global health.</p> <p>Results</p> <p>At follow-up, 257 (25.6%) were not traced. Baseline characteristics were similar to the 748 whose vital status was ascertained; 154 (20.6%) had died. The mortality rate was 92.5/1000 per annum for men and 51.0/1000 per annum for women. Adjusting for age and sex, mortality was associated with older age, male sex, having no friends, physical inactivity, smaller arm circumference, dementia, depression, poor self-rated health and disability. A parsimonious model included, in order of aetiologic force, male sex, smaller arm circumference, age, disability, and dementia. The total population attributable risk fraction was 0.90.</p> <p>Conclusion</p> <p>A balanced approach to prevention of chronic disease deaths requires some attention to proximal risk factors in older people. Smoking and obesity seem much less relevant than in younger people. Undernutrition is preventable. While dementia makes the largest contribution to disability and dependency, comorbidity is the rule, and more attention should be given to the chronic care needs of those affected, and their carers.</p

Liver-Targeting of Interferon-Alpha with Tissue-Specific Domain Antibodies

PMCID: PMC3581439This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Lack of correlation of stem cell markers in breast cancer stem cells

BACKGROUND: Various markers are used to identify the unique sub-population of breast cancer cells with stem cell properties. Whether these markers are expressed in all breast cancers, identify the same population of cells, or equate to therapeutic response is controversial. METHODS: We investigated the expression of multiple cancer stem cell markers in human breast cancer samples and cell lines in vitro and in vivo, comparing across and within samples and relating expression with growth and therapeutic response to doxorubicin, docetaxol and radiotherapy. RESULTS: CD24, CD44, ALDH and SOX2 expression, the ability to form mammospheres and side-population cells are variably present in human cancers and cell lines. Each marker identifies a unique rather than common population of cancer cells. In vivo, cells expressing these markers are not specifically localized to the presumptive stem cell niche at the tumour/stroma interface. Repeated therapy does not consistently enrich cells expressing these markers, although ER-negative cells accumulate. CONCLUSIONS: Commonly employed methods identify different cancer cell sub-populations with no consistent therapeutic implications, rather than a single population of cells. The relationships of breast cancer stem cells to clinical parameters will require identification of specific markers or panels for the individual cancer

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo