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Tamuno Alfred,
Yoav Ben-Shlomo,
Rachel Cooper,
Rebecca Hardy,
Ian J Deary,
Jane Elliott,
Sarah E Harris,
Elina Hyppönen,
Mika Kivimaki,
Meena Kumari,
Jane Maddock,
Chris Power,
John M Starr,
Diana Kuh,
Ian N M Day
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ABSTRACT: Several investigations have observed positive associations between good nutritional status, as indicated by micronutrients, and cognitive measures; however, these associations may not be causal. Genetic polymorphisms that affect nutritional biomarkers may be useful for providing evidence for associations between micronutrients and cognitive measures. As part of the Healthy Ageing across the Life Course (HALCyon) program, men and women aged between 44 and 90 y from 6 UK cohorts were genotyped for polymorphisms associated with circulating concentrations of iron [rs4820268 transmembrane protease, serine 6 (TMPRSS6) and rs1800562 hemochromatosis (HFE)], vitamin B-12 [(rs492602 fucosyltransferase 2 (FUT2)], vitamin D ([rs2282679 group-specific component (GC)] and β-carotene ([rs6564851 beta-carotene 15,15'-monooxygenase 1 (BCMO1)]. Meta-analysis was used to pool within-study effects of the associations between these polymorphisms and the following measures of cognitive capability: word recall, phonemic fluency, semantic fluency, and search speed. Among the several statistical tests conducted, we found little evidence for associations. We found the minor allele of rs1800562 was associated with poorer word recall scores [pooled β on z-score for carriers vs. noncarriers: -0.05 (95% CI: -0.09, -0.004); P = 0.03, n = 14,105] and poorer word recall scores for the vitamin D-raising allele of rs2282679 [pooled β per T allele: -0.03 (95% CI: -0.05, -0.003); P = 0.03, n = 16,527]. However, there was no evidence for other associations. Our findings provide little evidence to support associations between these genotypes and cognitive capability in older adults. Further investigations are required to elucidate whether the previous positive associations from observational studies between circulating measures of these micronutrients and cognitive performance are due to confounding and reverse causality.
Journal of Nutrition 03/2013; · 3.92 Impact Factor
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Tamuno Alfred,
Yoav Ben-Shlomo,
Rachel Cooper,
Rebecca Hardy,
Cyrus Cooper,
Ian J Deary,
David Gunnell,
Sarah E Harris,
Meena Kumari,
Richard M Martin,
Avan Aihie Sayer,
John M Starr,
Diana Kuh,
Ian N M Day
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ABSTRACT: BACKGROUND: Good bone and joint health is essential for the physical tasks of daily living and poorer indicators of physical capability in older adults have been associated with increased mortality rates. Genetic variants of indicators of bone and joint health may be associated with measures of physical capability. METHODS: As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women aged between 52 and 90+ years from six UK cohorts were genotyped for a polymorphism associated with serum calcium (rs1801725, CASR), two polymorphisms associated with bone mineral density (BMD) (rs2941740, ESR1 and rs9594759, RANKL) and one associated with osteoarthritis risk rs3815148 (COG5). Meta-analysis was used to pool within-study effects of the associations between each of the polymorphisms and measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance. RESULTS: Few important associations were observed among the several tests. We found that carriers of the serum calcium-raising allele had poorer grip strength compared with non-carriers (pooled p=0.05, n=11,239) after adjusting for age and sex. Inconsistent results were observed for the two variants associated with BMD and we found no evidence for an association between rs3815148 (COG5) and any of the physical capability measures. CONCLUSION: Our findings suggest elevated serum calcium levels may lead to lower grip strength, though this requires further replication. Our results do not provide evidence for a substantial influence of these variants in ESR1, RANKL and COG5 on physical capability in older adults.
Bone 10/2012; · 4.02 Impact Factor
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Tamuno Alfred,
Yoav Ben-Shlomo,
Rachel Cooper,
Rebecca Hardy,
Cyrus Cooper,
Ian J Deary,
Tom R Gaunt,
David Gunnell,
Sarah E Harris,
Meena Kumari,
Richard M Martin,
Avan Aihie Sayer,
John M Starr,
Diana Kuh,
Ian N M Day
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ABSTRACT: Low muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability.
As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women from seven UK cohorts aged between 52 and 90 years old were genotyped for six polymorphisms: rs35767 (IGF1), rs7127900 (IGF2), rs2854744 (IGFBP3), rs2943641 (IRS1), rs2665802 (GH1) and the exon-3 deletion of GHR. The polymorphisms have previously been robustly associated with age-related traits or are potentially functional. Meta-analysis was used to pool within-study genotypic effects of the associations between the polymorphisms and four measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.
Few important associations were observed among the several tests. We found evidence that rs2665802 in GH1 was associated with inability to balance for 5 s (pooled odds ratio per minor allele = 0.90, 95% CI: 0.82-0.98, p-value = 0.01, n = 10,748), after adjusting for age and sex. We found no evidence for other associations between the polymorphisms and physical capability traits.
Our findings do not provide evidence for a substantial influence of these common polymorphisms in the GH/IGF axis on objectively measured physical capability levels in older adults.
PLoS ONE 01/2012; 7(1):e29883. · 4.09 Impact Factor
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Tamuno Alfred,
Yoav Ben-Shlomo,
Rachel Cooper,
Rebecca Hardy,
Cyrus Cooper,
Ian J. Deary,
David Gunnell,
Sarah E. Harris,
Meena Kumari,
Richard M. Martin,
Colin N. Moran,
Yannis P. Pitsiladis,
Susan M. Ring,
Avan Aihie Sayer,
George Davey Smith,
John M. Starr,
Diana Kuh,
Ian N.M. Day
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ABSTRACT: The ACTN3 R577X (rs1815739) genotype has been associated with athletic status and muscle phenotypes, although not consistently. Our objective was to conduct a meta-analysis of the published literature on athletic status and investigate its associations with physical capability in several new population-based studies. Relevant data were extracted from studies in the literature, comparing genotype frequencies between controls and sprint/power and endurance athletes. For life course physical capability, data were used from two studies of adolescents and seven studies in the Healthy Ageing across the Life Course (HALCyon) collaborative research program, involving individuals aged between 53 and 90+ years. We found evidence from the published literature to support the hypothesis that in Europeans the RR genotype is more common among sprint/power athletes compared with their controls. There is currently no evidence that the X allele is advantageous to endurance athleticism. We found no association between R577X and grip strength (P = 0.09, n = 7,672 in males; P = 0.90, n = 7,839 in females), standing balance, timed get up and go, or chair rises in our studies of physical capability. The ACTN3 R577X genotype is associated with sprint/power athletic status in Europeans, but does not appear to be associated with objective measures of physical capability in the general population. Hum Mutat 32:1–11, 2011. © 2011 Wiley-Liss, Inc.
Human Mutation 07/2011; 32(9):1008 - 1018. · 5.69 Impact Factor
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Tamuno Alfred,
Yoav Ben-Shlomo,
Rachel Cooper,
Rebecca Hardy,
Cyrus Cooper,
Ian J Deary,
Jane Elliott,
David Gunnell,
Sarah E Harris,
Mika Kivimaki,
Meena Kumari,
Richard M Martin,
Chris Power,
Avan Aihie Sayer,
John M Starr,
Diana Kuh,
Ian N M Day
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[hide abstract]
ABSTRACT: Several age-related traits are associated with shorter telomeres, the structures that cap the end of linear chromosomes. A common polymorphism near the telomere maintenance gene TERT has been associated with several cancers, but relationships with other aging traits such as physical capability have not been reported. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women aged between 44 and 90 years from nine UK cohorts were genotyped for the single-nucleotide polymorphism (SNP) rs401681. We then investigated relationships between the SNP and 30 age-related phenotypes, including cognitive and physical capability, blood lipid levels and lung function, pooling within-study genotypic effects in meta-analyses. No significant associations were found between the SNP and any of the cognitive performance tests (e.g. pooled beta per T allele for word recall z-score = 0.02, 95% CI: -0.01 to 0.04, P-value = 0.12, n = 18,737), physical performance tests (e.g. pooled beta for grip strength = -0.02, 95% CI: -0.045 to 0.006, P-value = 0.14, n = 11,711), blood pressure, lung function or blood test measures. Similarly, no differences in observations were found when considering follow-up measures of cognitive or physical performance after adjusting for its measure at an earlier assessment. The lack of associations between SNP rs401681 and a wide range of age-related phenotypes investigated in this large multicohort study suggests that while this SNP may be associated with cancer, it is not an important contributor to other markers of aging.
Aging cell 02/2011; 10(3):520-32. · 7.55 Impact Factor
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Emerging Infectious Diseases 10/2008; 14(9):1487-9. · 6.79 Impact Factor
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ABSTRACT: To investigate systemic and ocular risk factors for angle closure (AC) in older Singaporeans and to determine if these risk factors are different in men vs women and in Chinese vs non-Chinese persons.
A cross-sectional study of 2042 subjects with phakia 50 years or older recruited from a primary care clinic in Singapore. Subjects completed a detailed questionnaire and underwent refraction, biometry, and gonioscopy. Univariate and multivariate analyses were performed to determine risk factors for AC.
The prevalence of AC among this study population was 19.3% (n = 395); 89.4% (n = 1826) of the study population were Chinese. In univariate analysis, patients with AC were older, female, and of Chinese descent and had shorter axial length, lower body mass index, higher intraocular pressure, and shallower anterior chamber depth. In multivariate analysis, female sex (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.06-1.92; P =.02), Chinese race/ethnicity (OR, 3.58; 95% CI, 2.03-6.29; P < .001), axial length (OR per millimeter increase, 0.69; 95% CI, 0.58-0.81; P<.001), and central anterior chamber depth of less than 2.80 mm vs at least 3.00 mm (OR, 42.5; 95% CI, 27.4-66.2; P<.001) were independently associated with AC.
In this community-based study of older Singaporeans, statistically significant independent predictors of AC were female sex, shorter axial length, shallower central anterior chamber depth, and Chinese race/ethnicity. Sex and racial/ethnic differences in the risk of AC were not fully explained by sex and racial/ethnic variations in axial length or anterior chamber depth.
Archives of ophthalmology 06/2008; 126(5):686-91. · 3.86 Impact Factor
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Raghavan Lavanya,
Paul J Foster,
Lisandro M Sakata,
David S Friedman,
Kenji Kashiwagi,
Tien-Yin Wong,
Han T Aung, Tamuno Alfred,
Hong Gao,
Adrian G Ee,
Steve K Seah,
Tin Aung
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ABSTRACT: To assess the screening effectiveness of 3 new noncontact devices, the scanning peripheral anterior chamber depth analyzer (SPAC) (Takagi, Nagano, Japan), which measures peripheral anterior chamber depth (ACD); IOLMaster (Carl Zeiss Meditec, Jena, Germany), which measures central ACD; and Visante anterior segment optical coherence tomography (AS-OCT) (Visante, Carl Zeiss Meditec, Dublin, CA), which images the angles, and to compare these instruments with gonioscopy in identifying people with narrow angles (NAs).
Cross-sectional, observational, community-based study.
Phakic subjects aged >or=50 years without ophthalmic symptoms who were recruited from a community polyclinic in Singapore.
All subjects underwent examination with SPAC, IOLMaster, and AS-OCT in the dark by a single operator. Gonioscopy was performed by an ophthalmologist masked to the instruments' findings. The area under the curve (AUC) receiver operating characteristic (ROC) was generated to assess the performance of these tests in detecting people with a NA in either eye.
Eyes were classified as having NAs by gonioscopy if the posterior pigmented trabecular meshwork could be seen for <or=2 quadrants of the angle circumference with or without peripheral anterior synechiae.
A total of 2052 subjects were examined and underwent all 3 tests. The prevalence of a NA in at least 1 eye diagnosed by gonioscopy was 20.4% (422 subjects). The AUC for the SPAC using a numeric grade <5 as a cutoff was 0.83 (95% confidence interval [CI], 0.82-0.85), with a sensitivity of 90.0% (95% CI, 86.8-92.7) and a specificity of 76.6% (95% CI, 74.4-78.6). The AUC for the IOLMaster at an ACD cutoff of <2.87 mm was 0.83 (95% CI, 0.81-0.85), with a sensitivity of 87.7% (95% CI, 84.2-90.7) and a specificity of 77.7% (95% CI, 75.6-79.7). The AUC for the AS-OCT was 0.76 (95% CI, 0.74-0.78), with a sensitivity of 88.4% (95% CI, 84.9-91.3) and a specificity of 62.9% (95% CI, 60.5-65.2).
The low specificity found with the SPAC, IOLMaster, and AS-OCT may limit the usefulness of these devices in screening for NAs.
Ophthalmology 05/2008; 115(10):1720-7, 1727.e1-2. · 5.45 Impact Factor
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Raghavan Lavanya,
Livia Teo,
David S Friedman,
Han T Aung,
Mani Baskaran,
Hong Gao, Tamuno Alfred,
Steve K Seah,
Kenji Kashiwagi,
Paul J Foster,
Tin Aung
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ABSTRACT: To compare anterior chamber depth measurements by three non-contact devices-the IOLMaster, scanning peripheral anterior chamber depth analyser (SPAC), and Visante anterior segment optical coherence tomography (AS-OCT) METHODS: Prospective, cross sectional study of 497 phakic subjects over 50 years of age attending a community clinic in Singapore. Anterior chamber depth of the right eye was measured using all three techniques by the same investigator. Depth measurements were made from the corneal epithelium to the anterior lens surface. The values obtained were compared using Bland-Altman analysis.
232 men and 265 women were examined (mean (SD) age, 63.4 (7.9) years). Mean anterior chamber depth was 3.08 (0.36) mm with IOLMaster, 3.10 (0.44) mm with SPAC, and 3.14 (0.34) mm with AS-OCT. A significant difference was present between the anterior chamber depth measurements recorded by the three devices (p<0.0001). Mean differences between the measurements were: AS-OCT v IOLMaster, 0.062 (0.007) mm (95% limits of agreement, -0.37 to 0.25 mm) (p<0.0001); AS-OCT v SPAC, 0.035 (0.011) mm (-0.44 to 0.51 mm) (p = 0.0001); SPAC v IOLMaster, 0.027 (0.012) mm (-0.57 to 0.50 mm) (p = 0.027).
AS-OCT gave systematically deeper anterior chamber measurements than SPAC and IOL-Master. However, as the differences found were small they are unlikely to be clinically important.
British Journal of Ophthalmology 08/2007; 91(8):1023-6. · 2.90 Impact Factor
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ABSTRACT: Transport noise is an increasingly prominent feature of the urban environment, making noise pollution an important environmental public health issue. This paper reports on the 2001-2003 RANCH project, the first cross-national epidemiologic study known to examine exposure-effect relations between aircraft and road traffic noise exposure and reading comprehension. Participants were 2,010 children aged 9-10 years from 89 schools around Amsterdam Schiphol, Madrid Barajas, and London Heathrow airports. Data from The Netherlands, Spain, and the United Kingdom were pooled and analyzed using multilevel modeling. Aircraft noise exposure at school was linearly associated with impaired reading comprehension; the association was maintained after adjustment for socioeconomic variables (beta = -0.008, p = 0.012), aircraft noise annoyance, and other cognitive abilities (episodic memory, working memory, and sustained attention). Aircraft noise exposure at home was highly correlated with aircraft noise exposure at school and demonstrated a similar linear association with impaired reading comprehension. Road traffic noise exposure at school was not associated with reading comprehension in either the absence or the presence of aircraft noise (beta = 0.003, p = 0.509; beta = 0.002, p = 0.540, respectively). Findings were consistent across the three countries, which varied with respect to a range of socioeconomic and environmental variables, thus offering robust evidence of a direct exposure-effect relation between aircraft noise and reading comprehension.
American Journal of Epidemiology 02/2006; 163(1):27-37. · 5.22 Impact Factor
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ABSTRACT: Chronic aircraft noise exposure in children is associated with impairment of reading and long-term memory. Most studies have not differentiated between day or nighttime noise exposure. It has been hypothesized that sleep disturbance might mediate the association of aircraft noise exposure and cognitive impairment in children. This study involves secondary analysis of data from the Munich Study and the UK Road Traffic and Aircraft Noise Exposure and Children's Cognition and Health (RANCH) Study sample to test this. In the Munich study, 330 children were assessed on cognitive measures in three measurement waves a year apart, before and after the switchover of airports. Self-reports of sleep quality were analyzed across airports, aircraft noise exposure and measurement wave to test whether changes in nighttime noise exposure had any effect on reported sleep quality, and whether this showed the same pattern as for changes in cognitive performance. For the UK sample of the RANCH study, night noise contour information was linked to the children's home and related to sleep disturbance and cognitive performance. In the Munich study, analysis of sleep quality questions showed no consistent interactions between airport, noise, and measurement wave, suggesting that poor sleep quality does not mediate the association between noise exposure and cognition. Daytime and nighttime aircraft noise exposure was highly correlated in the RANCH study. Although night noise exposure was significantly associated with impaired reading and recognition memory, once home night noise exposure was centered on daytime school noise exposure, night noise had no additional effect to daytime noise exposure. These analyses took advantage of secondary data available from two studies of aircraft noise and cognition. They were not initially designed to examine sleep disturbance and cognition, and thus, there are methodological limitations which make it less than ideal in giving definitive answers to these questions. In conclusion, results from both studies suggest that night aircraft noise exposure does not appear to add any cognitive performance decrement to the cognitive decrement induced by daytime aircraft noise alone. We suggest that the school should be the main focus of attention for protection of children against the effects of aircraft noise on school performance.
Noise and Health 12(49):255-62. · 1.25 Impact Factor
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[show abstract]
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ABSTRACT: Transport noise is an increasingly prominent feature of the urban environment, making noise pollution an important environmental public health issue. This paper reports on the 2001–2003 RANCH project, the first cross-national epidemiologic study known to examine exposure-effect relations between aircraft and road traffic noise exposure and reading comprehension. Participants were 2,010 children aged 9–10 years from 89 schools around Amsterdam Schiphol, Madrid Barajas, and London Heathrow airports. Data from the Netherlands, Spain, and the United Kingdom were pooled and analyzed using multilevel modeling. Aircraft noise exposure at school was linearly associated with impaired reading comprehension; the association was maintained after adjustment for socioeconomic variables (ß = –0.008, p = 0.012), aircraft noise annoyance, and other cognitive abilities (episodic memory, working memory, and sustained attention). Aircraft noise exposure at home was highly correlated with aircraft noise exposure at school and demonstrated a similar linear association with impaired reading comprehension. Road traffic noise exposure at school was not associated with reading comprehension in either the absence or the presence of aircraft noise (ß = 0.003, p = 0.509; ß = 0.002, p = 0.540, respectively). Findings were consistent across the three countries, which varied with respect to a range of socioeconomic and environmental variables, thus offering robust evidence of a direct exposure-effect relation between aircraft noise and reading comprehension. Environmental Health (SOEH), School of Health and Environment Research (CHER), Centre for Occupational and Environmental Hygiene, School of Peer-Reviewed
