Blood cancer journal

BACKGROUND: Gait impairments increase with advancing age and can lead to falls and loss of independence. Brain atrophy also occurs in older age and may contribute to gait decline. We aimed to investigate global and regional relationships of cerebral gray and white matter volumes with gait speed, and its determinants step length and cadence, in older people. METHODS: In a population-based study, participants aged >60 years without Parkinson's disease or brain infarcts underwent magnetic resonance imaging and gait measurements using a computerized walkway. Linear regression was used to study associations of total gray and white matter volumes with gait, adjusting for each other, age, sex, height and white matter hyperintensity volume. Other covariates considered in analyses included weight and vascular disease history. Voxel-based morphometry was used to study regional relationships of gray and white matter with gait. RESULTS: There were 305 participants, mean age 71.4 (6.9) years, 54% male, mean gait speed 1.16 (0.22) m/s. Smaller total gray matter volume was independently associated with poorer gait speed (p = 0.001) and step length (p<0.001), but not cadence. Smaller volumes of cortical and subcortical gray matter in bilateral regions important for motor control, vision, perception and memory were independently associated with slower gait speed and shorter steps. No global or regional associations were observed between white matter volume and gait independent of gray matter volume, white matter hyperintensity volume and other covariates. CONCLUSION: Smaller gray matter volume in bilaterally distributed brain networks serving motor control was associated with slower gait speed and step length, but not cadence

Medical, Sensorimotor and Cognitive Factors Associated With Gait Variability: A Longitudinal Population-Based Study

Background: Greater gait variability increases the risk of falls. However, little is known about changes in gait variability in older age. The aims of this study were to examine: (1) change in gait variability across time and (2) factors that predict overall mean gait variability and its change over time.Methods: Participants (n = 410; mean age 72 years) were assessed at baseline and during follow up visits at an average of 30 and 54 months. Step time, step length, step width and double support time (DST) were measured using a GAITRite walkway. Variability was calculated as the standard deviation of all steps for each individual. Covariates included demographic, medical, sensorimotor and cognitive factors. Mixed models were used to determine (1) change in gait variability over time (2) factors that predicted or modified any change.Results: Over 4.6 years the presence of cardiovascular disease at baseline increased the rate of change for step length variability (p = 0.04 for interaction), lower education increased the rate of change for DST variability (p = 0.04) and weaker quadriceps strength increased the rate of change for step width variability (p = 0.01). Greater postural sway predicted greater variability on average across the three phases (p &lt; 0.05). Arthritis, a higher body mass index (BMI), slower processing speed and lower quadriceps strength predicted greater mean step time variability (p &lt; 0.05). Arthritis and a higher BMI predicted greater mean step length variability, while slower processing speed and BMI predicted greater mean DST variability (p &lt; 0.05).Conclusion: Over a nearly 5-year period, variability in different gait measures do not show uniform changes over time. Furthermore, each variability measure appears to be modified and predicted by different factors. These results provide information on potential targets for future trials to maintain mobility and independence in older age

Identifying factors associated with sedentary time after stroke. Secondary analysis of pooled data from nine primary studies.

<p><b>Background</b>: High levels of sedentary time increases the risk of cardiovascular disease, including recurrent stroke.</p> <p><b>Objective</b>: This study aimed to identify factors associated with high sedentary time in community-dwelling people with stroke.</p> <p><b>Methods</b>: For this data pooling study, authors of published and ongoing trials that collected sedentary time data, using the activPAL monitor, in community-dwelling people with stroke were invited to contribute their raw data. The data was reprocessed, algorithms were created to identify sleep-wake time and determine the percentage of waking hours spent sedentary. We explored demographic and stroke-related factors associated with total sedentary time and time in uninterrupted sedentary bouts using unique, both univariable and multivariable, regression analyses.</p> <p><b>Results</b>: The 274 included participants were from Australia, Canada, and the United Kingdom, and spent, on average, 69% (SD 12.4) of their waking hours sedentary. Of the demographic and stroke-related factors, slower walking speeds were significantly and independently associated with a higher percentage of waking hours spent sedentary (p = 0.001) and uninterrupted sedentary bouts of <i>>30</i> and <i>>60 min</i> (p = 0.001 and p = 0.004, respectively). Regression models explained 11–19% of the variance in total sedentary time and time in prolonged sedentary bouts.</p> <p><b>Conclusion</b>: We found that variability in sedentary time of people with stroke was largely unaccounted for by demographic and stroke-related variables. Behavioral and environmental factors are likely to play an important role in sedentary behavior after stroke. Further work is required to develop and test effective interventions to address sedentary behavior after stroke.</p

Identifying public healthcare priorities in virtual care for older adults : a participatory research study

There has been increasing adoption and implementation of virtual healthcare in recent years, especially with COVID-19 impacting the world. As a result, virtual care initiatives may not undergo stringent quality control processes to ensure that they are appropriate to their context and meet sector needs. The two objectives of this study were to identify virtual care initiatives for older adults currently in use in Victoria and virtual care challenges that could be prioritised for further investigation and scale-up and to understand why certain virtual care initiatives and challenges are prioritised over others for investigation and scale-up. Methods: This project used an Emerging Design approach. A survey of public health services in the state of Victoria in Australia was first carried out, followed by the co-production of research and healthcare priorities with key stakeholders in the areas of primary care, hospital care, consumer representation, research, and government. The survey was used to gather existing virtual care initiatives for older adults and any associated challenges. Co-production processes consisted of individual ratings of initiatives and group-based discussions to identify priority virtual care initiatives and challenges to be addressed for future scale-up. Stakeholders nominated their top three virtual initiatives following discussions. Results: Telehealth was nominated as the highest priority initiative type for scaling up, with virtual emergency department models of care nominated as the highest priority within this category. Remote monitoring was voted as a top priority for further investigations. The top virtual care challenge was data sharing across services and settings, and the user-friendliness of virtual care platforms was nominated as the top priority for further investigation. Conclusions: Stakeholders prioritised public health virtual care initiatives that are easy to adopt and address needs that are perceived to be more immediate (acute more so than chronic care). Virtual care initiatives that incorporate more technology and integrated elements are valued, but more information is needed to inform their potential scale-up. © 2023 by the authors

Frailty and cerebral small vessel disease:a cross-sectional analysis of the Tasmanian Study of Cognition and Gain (TASCOG)

Background: Frailty is a prevalent geriatric condition associated with poor health outcomes. The pathogenesis of frailty is incompletely understood. We aimed to evaluate the relationship between cerebral small vessel disease (SVD) and frailty. Methods: People aged between 60 and 85 years were randomly selected from the electoral roll into the Tasmanian Study of Cognition and Gait. Participants completed standardized questionnaires regarding medical history and underwent objective sensorimotor, gait, and cognitive testing. These data were used to calculate a frailty index score. Magnetic resonance imaging was performed on all participants to measure SVD. Automated quantification was used to measure white matter hyperintensities (WMH), with manual consensus for subcortical infarction (SI) and cerebral microbleeds (CMB). Multivariable linear regression was used to determine the association between SVD and frailty. Results: The mean age of the sample (n = 388) was 72.0 years (SD 7.0), 44% (172/388) were female and the median Frailty Index was 0.20 (interquartile range 0.12, 0.27). WMH, SI, and CMB in unadjusted models were positively associated with higher frailty scores (p < .05). In final models including all brain variables, higher burden of WMH (β = 2.16; 95% confidence interval [CI] 0.75, 3.57; p = .003), but not SI (β = 2.96; 95% CI −0.44, 6.35; p = .09) or CMB (β = −0.46; 95% CI −4.88, 3.96; p = .84), was independently associated with a higher frailty score. Conclusions: We provide cross-sectional evidence for a positive association between larger burden of WMH and frailty. Longitudinal design is required to determine the temporality of this relationship

The complex genetics of gait speed:Genome-wide meta-analysis approach

Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta-analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging

GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium

Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27 581 individuals of European descent over 65 years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5 × 10−8) and 39 suggestive (P-value< 5 × 10−5) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β = 0.47, SE = 0.08, P-value = 5.20 × 10−10). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein-β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength

Frailty is associated with cognitive decline independent of cerebral small vessel disease and brain atrophy

BACKGROUND: To examine the effect of frailty on cognitive decline independent of cerebral small vessel disease (cSVD) and brain atrophy, and whether associations between neuropathology and cognition differed depending on frailty status. METHODS: The Tasmanian Study of Cognition and Gait was a population-based longitudinal cohort study with data collected at 3 phases from 2005 to 2012. Participants aged 60-85 were randomly selected from the electoral roll. Various data were used to operationalize a 36-item frailty index (FI) at baseline. Brain MRI was undertaken to obtain baseline measures of neuropathology. A neuropsychological battery was used to assess cognition at each time point. Generalized linear mixed models were used to examine the effect of frailty and MRI measures on cognition over time. The associations between MRI measures and cognition were explored after stratifying the sample by baseline frailty status. All analyses were adjusted for age, sex, and education. RESULTS: A total of 385 participants were included at baseline. The mean age was 72.5 years (standard deviation [SD] 7.0), 44% were female (n = 171). In fully adjusted linear mixed models, frailty (FI × time β -0.001, 95% confidence interval [CI] -0.003, -0.001, p = .03) was associated with decline in global cognition, independent of brain atrophy, and cSVD. The association between cSVD and global cognition was significant only in those with low levels of frailty (p = .03). CONCLUSION: These findings suggest that frailty is an important factor in early cognitive dysfunction, and measuring frailty may prove useful to help identify future risk of cognitive decline

Motoric Cognitive Risk Syndrome: Multicountry Prevalence and Dementia Risk

OBJECTIVES: Our objective is to report prevalence of motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints, in multiple countries, and its association with dementia risk. METHODS: Pooled MCR prevalence analysis of individual data from 26,802 adults without dementia and disability aged 60 years and older from 22 cohorts from 17 countries. We also examined risk of incident cognitive impairment (Mini-Mental State Examination decline ≥4 points) and dementia associated with MCR in 4,812 individuals without dementia with baseline Mini-Mental State Examination scores ≥25 from 4 prospective cohort studies using Cox models adjusted for potential confounders. RESULTS: At baseline, 2,808 of the 26,802 participants met MCR criteria. Pooled MCR prevalence was 9.7% (95% confidence interval [CI] 8.2%-11.2%). MCR prevalence was higher with older age but there were no sex differences. MCR predicted risk of developing incident cognitive impairment in the pooled sample (adjusted hazard ratio [aHR] 2.0, 95% CI 1.7-2.4); aHRs were 1.5 to 2.7 in the individual cohorts. MCR also predicted dementia in the pooled sample (aHR 1.9, 95% CI 1.5-2.3). The results persisted even after excluding participants with possible cognitive impairment, accounting for early dementia, and diagnostic overlap with other predementia syndromes. CONCLUSION: MCR is common in older adults, and is a strong and early risk factor for cognitive decline. This clinical approach can be easily applied to identify high-risk seniors in a wide variety of settings

Sex differences in total cholesterol of Vietnamese adults

Background The mid-life emergence of higher levels of total cholesterol (TC) for women than for men has been observed in different Western and Asian populations. The aim of this study was to investigate whether there is evidence of this in Vietnam and, if so, whether it can be explained by ageing, by body size and fatness, or by socio-demographic characteristics and behavioural factors.Methods Participants (n = 14706, 50.9% females) aged 25-64 years were selected by multi-stage stratified cluster sampling from eight provinces each representing one of the eight geographical regions of Vietnam. Measurements were made using the World Health Organization STEPS protocols. Linear regression was used to assess the independent contributions of potential explanatory factors to mean levels of TC. Data were analysed using complex survey methods.Results Men and women had similar mean levels of body mass index (BMI), and men had modestly higher mean levels of waist circumference (WC), in each 5-year age category. The mean TC of women increased more or less continuously across the age range but with a step-up at age 50 years to reach higher concentrations on average than those of their male counterparts. The estimated step-up was not eliminated by adjustment for anthropometric indices including BMI or WC, or by adjustment for socio-demographic characteristics or behavioural factors. The estimated step-up was least for women with the greatest weight.Conclusion There is a marked step-up in TC at age 50 years for Vietnamese women that cannot be explained by their age, or by their body fatness or its distribution, or by their socio-demographic characteristics or behavioural factors, and which results in greater mean levels of TC for middle-aged women than for their male counterparts in Vietnam.</p