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1.  Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies 
Human mutation  2011;32(12):1407-1416.
Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status, has been reported. We present a pooled analysis (n=21,160) demonstrating associations between late AMD and APOε4 (OR=0.72 per haplotype; CI: 0.65–0.74; P=4.41×10−11) and APOε2 (OR=1.83 for homozygote carriers; CI: 1.04–3.23; P=0.04), following adjustment for age-group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR=1.54; CI: 1.38–1.72; P=2.8×10−15) and atrophic (OR=1.38; CI: 1.18–1.61; P=3.37×10−5) AMD but not early AMD (OR=0.94; CI: 0.86–1.03; P=0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyondε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.
doi:10.1002/humu.21577
PMCID: PMC3217135  PMID: 21882290
age-related macular degeneration; AMD; apolipoprotein E; APOE; case-control association study
2.  Prevalence and Risk Factors for Vitamin C Deficiency in North and South India: A Two Centre Population Based Study in People Aged 60 Years and Over 
PLoS ONE  2011;6(12):e28588.
Background
Studies from the UK and North America have reported vitamin C deficiency in around 1 in 5 men and 1 in 9 women in low income groups. There are few data on vitamin C deficiency in resource poor countries.
Objectives
To investigate the prevalence of vitamin C deficiency in India.
Design
We carried out a population-based cross-sectional survey in two areas of north and south India. Randomly sampled clusters were enumerated to identify people aged 60 and over. Participants (75% response rate) were interviewed for tobacco, alcohol, cooking fuel use, 24 hour diet recall and underwent anthropometry and blood collection. Vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid. We categorised vitamin C status as deficient (<11 µmol/L), sub-optimal (11–28 µmol/L) and adequate (>28 µmol/L). We investigated factors associated with vitamin C deficiency using multivariable Poisson regression.
Results
The age, sex and season standardized prevalence of vitamin C deficiency was 73.9% (95% confidence Interval, CI 70.4,77.5) in 2668 people in north India and 45.7% (95% CI 42.5,48.9) in 2970 from south India. Only 10.8% in the north and 25.9% in the south met the criteria for adequate levels. Vitamin C deficiency varied by season, and was more prevalent in men, with increasing age, users of tobacco and biomass fuels, in those with anthropometric indicators of poor nutrition and with lower intakes of dietary vitamin C.
Conclusions
In poor communities, such as in our study, consideration needs to be given to measures to improve the consumption of vitamin C rich foods and to discourage the use of tobacco.
doi:10.1371/journal.pone.0028588
PMCID: PMC3232233  PMID: 22163038
3.  Inverse Association of Vitamin C with Cataract in Older People in India 
Ophthalmology  2011;118(10):1958-1965.e2.
Objective
To examine the association between vitamin C and cataract in the Indian setting.
Design
Population-based cross-sectional analytic study.
Participants
A total of 5638 people aged ≥60 years.
Methods
Enumeration of randomly sampled villages in 2 areas of north and south India to identify people aged ≥60 years. Participants were interviewed for socioeconomic and lifestyle factors (tobacco, alcohol, household cooking fuel, work, and diet); attended a clinical examination, including lens photography; and provided a blood sample for antioxidant analysis. Plasma vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid, and other antioxidants were measured by reverse-phase high-pressure liquid chromatography.
Main Outcome Measures
Cataract and type of cataract were graded from digital lens images using the Lens Opacity Classification System III (LOCS III), and cataract was classified from the grade in the worse eye of ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any cataract was defined as any unoperated or operated cataract.
Results
Of 7518 enumerated people, 5638 (75%) provided data on vitamin C, antioxidants, and potential confounders. Vitamin C was inversely associated with cataract (adjusted odds ratio [OR] for highest to lowest quartile = 0.61; 95% confidence interval (CI), 0.51–0.74; P=1.1×10−6). Inclusion of other antioxidants in the model (lutein, zeaxanthin, retinol, β-carotene, and α-tocopherol) made only a small attenuation to the result (OR 0.68; 95% CI, 0.57–0.82; P < 0.0001). Similar results were seen with vitamin C by type of cataract: nuclear cataract (adjusted OR 0.66; CI, 0.54–0.80; P < 0.0001), cortical cataract (adjusted OR 0.70; CI, 0.54–0.90; P < 0.002), and PSC (adjusted OR 0.58; CI, 0.45–0.74; P < 0.00003). Lutein, zeaxanthin, and retinol were significantly inversely associated with cataract, but the associations were weaker and not consistently observed by type of cataract. Inverse associations were also observed for dietary vitamin C and cataract.
Conclusions
We found a strong association with vitamin C and cataract in a vitamin C–depleted population.
Financial Disclosure(s)
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
doi:10.1016/j.ophtha.2011.03.016
PMCID: PMC3185206  PMID: 21705085
4.  CKD and Hospitalization in the Elderly: A Community-Based Cohort Study in the United Kingdom 
Background
We previously have shown that chronic kidney disease (CKD) is associated with cardiovascular and all-cause mortality in community-dwelling people 75 years and older. The present study addresses the hypothesis that CKD is associated with a higher rate of hospital admission at an older age.
Study Design
Cohort study.
Setting & Participants
15,336 participants from 53 UK general practices underwent comprehensive health assessment between 1994 and 1999.
Predictor
Data for estimated glomerular filtration rate (eGFR, derived from creatinine levels using the CKD Epidemiology Collaboration [CKD-EPI] study equation) and dipstick proteinuria were available for 12,371 participants.
Outcomes
Hospital admissions collected from hospital discharge letters for 2 years after assessment.
Measurements
Age, sex, cardiovascular risk factors, possible biochemical and health consequences of kidney disease (hemoglobin, phosphate, and albumin levels; physical and mental health problems).
Results
2,310 (17%) participants had 1 hospital admission, and 981 (7%) had 2 or more. After adjusting for age, sex, and cardiovascular risk factors, HRs were 1.66 (95% CI, 1.21-2.27), 1.17 (95% CI, 0.95-1.43), 1.08 (95% CI, 0.90-1.30), and 1.11 (95% CI, 0.91-1.35) for eGFRs <30, 30-44, 45-59, and ≥75 mL/min/1.73 m2, respectively, compared with eGFRs of 60-74 mL/min/1.73 m2 for hospitalizations during <6 months of follow-up. HRs were weaker for follow-up of 6-18 months. Dipstick-positive proteinuria was associated with an increased HR throughout follow-up (HR, 1.29 [95% CI, 1.11-1.49], adjusting for cardiovascular risk factors). Dipstick-positive proteinuria and eGFR <30 mL/min/1.73 m2 were independently associated with 2 or more hospital admissions during the 2-year follow-up. Adjustment for other health factors and laboratory measurements attenuated the effect of eGFR, but not the effect of proteinuria.
Limitations
Follow-up limited to 2 years, selection bias due to nonparticipation in study, missing data for potential covariates, and single noncalibrated measurements from multiple laboratories.
Conclusions
The study indicates that community-dwelling older people who have dipstick-positive proteinuria and/or eGFR <30 mL/min/1.73 m2 are at increased risk of hospitalization.
doi:10.1053/j.ajkd.2010.09.026
PMCID: PMC3392651  PMID: 21146270
Chronic kidney disease; cohort study; dipstick proteinuria testing; general population; hospitalization; older people
5.  A randomised controlled trial investigating the effect of vitamin B12 supplementation on neurological function in healthy older people: the Older People and Enhanced Neurological function (OPEN) study protocol [ISRCTN54195799] 
Nutrition Journal  2011;10:22.
Background
Vitamin B12 deficiency is common in older people and the prevalence increases with age. Vitamin B12 deficiency may present as macrocytic anaemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older people. The diagnosis and indications for treatment are clear for individuals with low plasma levels of vitamin B12 in the setting of megaloblastic anaemia and neuropathy, but the relevance of treatment of vitamin B12 deficiency in the absence of such clinical signs is uncertain.
Methods
The aim of the present study is to assess whether dietary supplementation with crystalline vitamin B12 will improve electrophysiological indices of neurological function in older people who have biochemical evidence of vitamin B12 insufficiency in the absence of anaemia. To test this hypothesis we designed a randomized double-blind placebo-controlled trial involving 200 older people aged 75 years or greater who were randomly allocated to receive either a daily oral tablet containing 1 mg vitamin B12 or a matching placebo tablet. The primary outcome assessed at 12 months is change in electrophysiological indices of peripheral and central neurosensory responses required for mobility and sensory function. We here report the detailed study protocol.
Conclusions
In view of the high prevalence of vitamin B12 deficiency in later life, the present trial could have considerable significance for public health.
doi:10.1186/1475-2891-10-22
PMCID: PMC3062585  PMID: 21396086
6.  Higher Levels and Intensity of Physical Activity Are Associated with Reduced Mortality among Community Dwelling Older People 
Journal of Aging Research  2011;2011:651931.
Introduction. There is limited evidence on physical activity and mortality in older people. Methods. People aged 75–84 years (n = 1449) participating in a randomized trial of health screening in UK general practice were interviewed about their physical activity (PA) and were assessed for a wide range of health and social problems. Mortality data were collected over 7 years of followup. Results. Full information on PA and potential confounders was available in 946 people. Those in the highest third of duration of PA had a lower mortality, confounder-adjusted Hazard Ratio (HR) = 0.74, and 95% Confidence Interval (CI) 0.56–0.97, compared to the lowest third. Similar benefits were seen when categorized by intensity of PA, with those in the highest group having a lower mortality, confounder-adjusted HR = 0.61, and 95% CI 0.47–0.79, compared to the lowest category. Conclusions. Our results suggest the importance of providing older people with opportunities for physical activity.
doi:10.4061/2011/651931
PMCID: PMC3062144  PMID: 21437004
7.  Prevalence of Cataract in an Older Population in India 
Ophthalmology  2011;118(2-19):272-278.e2.
Purpose
To describe the prevalence of cataract in older people in 2 areas of north and south India.
Design
Population-based, cross-sectional study.
Participants
Randomly sampled villages were enumerated to identify people aged ≥60 years. Of 7518 enumerated people, 78% participated in a hospital-based ophthalmic examination.
Methods
The examination included visual acuity measurement, dilatation, and anterior and posterior segment examination. Digital images of the lens were taken and graded by type and severity of opacity using the Lens Opacity Classification System III (LOCS III).
Main Outcome Measures
Age- and gender-standardized prevalence of cataract and 95% confidence intervals (CIs). We defined type of cataract based on the LOCS III grade in the worse eye of: ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any unoperated cataract was based on these criteria or ungradable dense opacities. Any cataract was defined as any unoperated or operated cataract.
Results
The prevalence of unoperated cataract in people aged ≥60 was 58% in north India (95% CI, 56–60) and 53% (95% CI, 51–55) in south India (P = 0.01). Nuclear cataract was the most common type: 48% (95% CI, 46–50) in north India and 38% (95% CI, 37–40) in south India (P<0.0001); corresponding figures for PSC were 21% (95% CI, 20–23) and 17% (95% CI, 16–19; P = 0.003), respectively, and for cortical cataract 7.6% (95% CI, 7–9) and 10.2% (95% CI, 9–11; P<0.004). Bilateral aphakia/pseudophakia was slightly higher in the south (15.5%) than in the north (13.2%; P<0.03). The prevalence of any cataracts was similar in north (73.8%) and south India (71.8%). The prevalence of unoperated cataract increased with age and was higher in women than men (odds ratio [OR], 1.8). Aphakia/pseudophakia was also more common in women, either unilateral (OR, 1.2; P<0.02) or bilateral (OR, 1.3; P<0.002).
Conclusions
We found high rates of unoperated cataract in older people in north and south India. Posterior subcapsular cataract was more common than in western studies. Women had higher rates of cataract, which was not explained by differential access to surgery.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
doi:10.1016/j.ophtha.2010.05.020
PMCID: PMC3146699  PMID: 20801514

Results 1-7 (7)