The Heritability of Kidney Function Using an Older Australian Twin Population

Introduction: Twin studies are unique population models which estimate observed rather than inferred genetic components of complex traits. Nonmonogenic chronic kidney disease (CKD) is a complex disease process with strong genetic and environmental influences, amenable to twin studies. We aimed to assess the heritability of CKD using twin analysis and modeling within Older Australian Twin Study (OATS) data. Methods: OATS had 109 dizygotic (DZ) and 126 monozygotic (MZ) twin pairs with paired serum creatinine levels. Heritability of kidney function as estimated glomerular filtration rate (eGFR CKD Epidemiology Collaboration [CKD-EPI]) was modeled using the ACE model to estimate additive heritability (A), common (C), and unique (E) environmental factors. Intratwin pair analysis using mixed effects logistic regression allowed analysis of variation in eGFR from established CKD risk factors. Results: The median age was 69.71 (interquartile range 78.4–83.0) years, with 65% female, and a mean CKD-EPI of 82.8 ml/min (SD 6.7). The unadjusted ACE model determined kidney function to be 33% genetically determined (A), 18% shared genetic-environmental (C), and 49% because of unique environment (E). This remained unchanged when adjusted for age, hypertension, and sex. Hypertension was associated with eGFR; however, intertwin variance in hypertension did not explain variance in eGFR. Two or more hypertension medications were associated with decreased eGFR (P = 0.009). Conclusion: This study estimates observed heritability at 33%, notably higher than inferred heritability in genome-wide association study (GWAS) (7.1%–18%). Epigenetics and other genomic phenomena may explain this heritability gap. Difference in antihypertension medications explains part of unique environmental exposures, though discordance in hypertension and diabetes does not

Does cognitive impairment influence outcomes from cataract surgery? Results from a 1-year follow-up cohort study

BACKGROUND/AIMS: To assess the impact of impaired cognition on visual outcomes 1 year following cataract surgery in a cohort of older people.METHODS: Participants aged 75 years or more with bilateral cataract and scheduled for cataract surgery were recruited consecutively. Cognition was assessed using the revised Addenbrooke\u27s cognitive examination (ACE-R). Participants were divided into two groups: normal (ACE-R ≥88) and impaired cognition (ACE-R <88). Visual quality of life (VQOL) and logarithm of minimum angle of resolution visual acuity (VA) were assessed at baseline and 1 year following cataract surgery.RESULTS: Of 112 participants, 48 (43%) had normal cognition and 64 (57%) had impaired cognition. One year following cataract surgery participants in both groups had significant improvements in VQOL and VA. Visual outcomes at 1 year were significantly better in participants with normal cognition than in those with impaired cognition (95% CIs for difference 0.4-7.0 and 0.02-0.1, for VQOL and VA, respectively). Regression analyses correcting for potential confounders showed a relationship between baseline cognition and VA at 1 year (R2=0.30, p=0.001) and a possible relationship between baseline cognition and VQOL at 1 year (R2=0.41, p=0.01, this became insignificant after removal of outliers).CONCLUSIONS: Patients with impaired cognition benefit from cataract surgery, but not to the same extent as patients with normal cognitio

Trajectories of objectively measured physical activity in free-living older men.

BACKGROUND: The steep decline in physical activity (PA) among the oldest old is not well understood; there is little information about the patterns of change in PA and sedentary behaviour (SB) in older people. Longitudinal data on objectively measured PA data can give insights about how PA and SB change with age. METHODS: Men age 70-90 yr, from a United Kingdom population-based cohort wore a GT3X accelerometer over the hip annually on up to three occasions (56%, 50%, and 51% response rates) spanning 2 yr. Multilevel models were used to estimate change in activity. Men were grouped according to achieving ≥150 min·wk of MVPA in bouts of ≥10 min (current guidelines) at two or three time points. RESULTS: A total of 1419 ambulatory men had ≥600 min wear time on ≥3 d at ≥2 time points. At baseline, men took 4806 steps per day and spent 72.5% of their day in SB, 23.1% in light PA, and 4.1% in moderate-to-vigorous PA (MVPA). Mean change per year was -341 steps, +1.1% SB, -0.7% light PA, and -0.4% MVPA each day (all P 30 min increased from 5.1 by 0.1 per year (P = 0.02). CONCLUSIONS: Among older adults, the steep decline in total PA occurred because of reductions in MVPA, while light PA is relatively spared and sedentary time and long sedentary bouts increase

Cognitive benefits of social dancing and walking in old age: the Dancing Mind randomized controlled trial

Background: A physically active lifestyle has the potential to prevent cognitive decline and dementia, yet the optimal type of physical activity/exercise remains unclear. Dance is of special interest as it complex sensorimotor rhythmic activity with additional cognitive, social, and affective dimensions. Objectives: To determine whether dance benefits executive function more than walking, an activity that is simple and functional. Methods: Two-arm randomized controlled trial among community-dwelling older adults. The intervention group received 1 h of ballroom dancing twice weekly over 8 months (~69 sessions) in local community dance studios. The control group received a combination of a home walking program with a pedometer and optional biweekly group-based walking in local community park to facilitate socialization. Main outcomes: Executive function tests: processing speed and task shift by the Trail Making Tests, response inhibition by the Stroop Color-Word Test, working memory by the Digit Span Backwards test, immediate and delayed verbal recall by the Rey Auditory Verbal Learning Test, and visuospatial recall by the Brief Visuospatial Memory Test (BVST). Results: One hundred and fifteen adults (mean 69.5 years, SD 6.4) completed baseline and delayed baseline (3 weeks apart) before being randomized to either dance (n = 60) or walking (n = 55). Of those randomized, 79 (68%) completed the follow-up measurements (32 weeks from baseline). In the dance group only, “non-completers” had significantly lower baseline scores on all executive function tests than those who completed the full program. Intention-to-treat analyses showed no group effect. In a random effects model including participants who completed all measurements, adjusted for baseline score and covariates (age, education, estimated verbal intelligence, and community), a between-group effect in favor of dance was noted only for BVST total learning (Cohen’s D Effect size 0.29, p = 0.07) and delayed recall (Cohen’s D Effect size = 0.34, p = 0.06). Conclusion: The superior potential of dance over walking on executive functions of cognitively healthy and active older adults was not supported. Dance improved one of the cognitive domains (spatial memory) important for learning dance. Controlled trials targeting inactive older adults and of a higher dose may produce stronger effects, particularly for novice dancers. Trial registration: Australian and New Zealand Clinical Trials Register (ACTRN12613000782730)

Regional Integration of Equity Markets in Sub-Saharan Africa

Equity markets in developing and emerging economies have grown in number and importance as a result of financial market globalisation. However, their role in economic growth and development is enhanced if nascent markets are integrated with well-established ones. Market integration, measured by the transmission of returns volatility, is identified across a sample of SSA countries, using a unique dataset. Evidence for potential integration between financial markets in Sub-Saharan Africa (SSA) is found. Spillovers are found across markets, some unidirectional and others bi-directional. However, continued illiquidity and incomplete institutions indicate that an integrated financial community remains premature, and considerable regulatory reform and harmonisation will be necessary for this to succeed

A Neural Circuit Arbitrates between Persistence and Withdrawal in Hungry Drosophila

In pursuit of food, hungry animals mobilize significant energy resources and overcome exhaustion and fear. How need and motivation control the decision to continue or change behavior is not understood. Using a single fly treadmill, we show that hungry flies persistently track a food odor and increase their effort over repeated trials in the absence of reward suggesting that need dominates negative experience. We further show that odor tracking is regulated by two mushroom body output neurons (MBONs) connecting the MB to the lateral horn. These MBONs, together with dopaminergic neurons and Dop1R2 signaling, control behavioral persistence. Conversely, an octopaminergic neuron, VPM4, which directly innervates one of the MBONs, acts as a brake on odor tracking by connecting feeding and olfaction. Together, our data suggest a function for the MB in internal state-dependent expression of behavior that can be suppressed by external inputs conveying a competing behavioral drive

Objectively measured physical activity and cardiac biomarkers: A cross sectional population based study in older men.

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) and high sensitivity Troponin T (hsTnT) are markers of cardiac injury used in diagnosis of heart failure and myocardial infarction respectively, and associated with increased risk of cardiovascular disease. Since physical activity is protective against cardiovascular disease and heart failure, we investigated whether higher levels of physical activity, and less sedentary behaviour were associated with lower NT-proBNP and hsTnT. METHODS AND RESULTS: Cross sectional study of 1130 men, age 70-91years, from the British Regional Heart Study, measured in 2010-2012. Fasting blood samples were analysed for NT-proBNP and hsTnT. Physical activity and sedentary behaviour were measured using ActiGraph GT3X accelerometers. Relationships between activity and NT-proBNP or hsTnT were non-linear; biomarker levels were lower with higher total activity, steps, moderate/vigorous activity and light activity only at low to moderate levels of activity. For example, for each additional 10min of moderate/vigorous activity, NT-proBNP was lower by 35.7% (95% CI -47.9, -23.6) and hsTnT by 8.4% (95% CI -11.1, -5.6), in men who undertook <25 or 50min of moderate/vigorous activity per day respectively. Biomarker levels increased linearly with increasing sedentary behaviour, but not independently of moderate/vigorous activity. CONCLUSION: Associations between biomarkers and moderate/vigorous activity (and between hsTnT and light activity) were independent of sedentary behaviour, suggesting activity is driving the relationships. In these older men with concomitantly low levels of physical activity, activity may be more important in protecting against cardiac health deterioration in less active individuals, although reverse causality might be operating

Objectively measured physical activity, sedentary behaviour and all-cause mortality in older men: does volume of activity matter more than pattern of accumulation?

OBJECTIVES: To understand how device-measured sedentary behaviour and physical activity are related to all-cause mortality in older men, an age group with high levels of inactivity and sedentary behaviour. METHODS: Prospective population-based cohort study of men recruited from 24 UK General Practices in 1978-1980. In 2010-2012, 3137 surviving men were invited to a follow-up, 1655 (aged 71-92 years) agreed. Nurses measured height and weight, men completed health and demographic questionnaires and wore an ActiGraph GT3x accelerometer. All-cause mortality was collected through National Health Service central registers up to 1 June 2016. RESULTS: After median 5.0 years' follow-up, 194 deaths occurred in 1181 men without pre-existing cardiovascular disease. For each additional 30 min in sedentary behaviour, or light physical activity (LIPA), or 10 min in moderate to vigorous physical activity (MVPA), HRs for mortality were 1.17 (95% CI 1.10 to 1.25), 0.83 (95% CI 0.77 to 0.90) and 0.90 (95% CI 0.84 to 0.96), respectively. Adjustments for confounders did not meaningfully change estimates. Only LIPA remained significant on mutual adjustment for all intensities. The HR for accumulating 150 min MVPA/week in sporadic minutes (achieved by 66% of men) was 0.59 (95% CI 0.43 to 0.81) and 0.58 (95% CI 0.33 to 1.00) for accumulating 150 min MVPA/week in bouts lasting ≥10 min (achieved by 16% of men). Sedentary breaks were not associated with mortality. CONCLUSIONS: In older men, all activities (of light intensity upwards) were beneficial and accumulation of activity in bouts ≥10 min did not appear important beyond total volume of activity. Findings can inform physical activity guidelines for older adults