Body size at birth and age-related macular degeneration in old age

Purpose To study associations between body size at birth and age-related macular degeneration (AMD) in old age. Methods The study sample consists of 1497 community-dwelling individuals (56.1% women) aged 67-89 years with birth data and retinal data collected twice in old age 5 years apart. Birth data (weight, length, birth order) were extracted from original birth records. Digital retinal photographs were graded to determine AMD status. Data on covariates were collected at the baseline physical examination in old age. Multivariable regression analyses were used to study the association between birth data and AMD adjusting for known confounding factors, including birth year cohort effects. Results The prevalence and 5-year incidence of any AMD were 33.1% and 17.0%, respectively. Men and women born in 1930-1936 were significantly leaner and slightly longer at birth compared to those in earlier birth cohorts. There were no consistent associations between weight, length or ponderal index (PI) at birth and AMD in old age even when stratified by birth cohort. Age-related macular degeneration (AMD) prevalence (39.8%) and 5-year incidence (28.6%) were highest in individuals who were in the highest quartile of PI at birth and who were obese in old age. Conclusion Body size at birth was not consistently associated with AMD in old age, suggesting that intrauterine growth might have little direct importance in the development of AMD in old age. It is possible that some yet unknown factors related to larger size at birth and obesity in old age may explain differences in the prevalence and incidence of AMD in the ageing population.Peer reviewe

Prevalence of age-related macular degeneration in old persons: Age, Gene/environment Susceptibility Reykjavik Study.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.PURPOSE: To describe the prevalence and signs of early and late age-related macular degeneration (AMD) in an old cohort. DESIGN: Population-based cohort study. PARTICIPANTS: We included 5272 persons aged ≥66 years, randomly sampled from the Reykjavik area. METHODS: Fundus images were taken through dilated pupils using a 45-degree digital camera and graded for drusen size, type, area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy (GA) using the modified Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOME MEASURES: Age-related macular degeneration in an elderly cohort. RESULTS: The mean age of participants was 76 years. The prevalence of early AMD was 12.4% (95% confidence interval [CI], 11.0-13.9) for those aged 66 to 74 years and 36% (95% CI, 30.9-41.1) for those aged ≥85 years. The prevalence of exudative AMD was 3.3% (95% CI, 2.8-3.8). The prevalence of pure GA was 2.4% (95% CI, 2.0-2.8). The highest prevalence of late AMD was among those aged ≥85 years: 11.4% (95% CI, 8.2-14.5) for exudative AMD and 7.6% (95% CI, 4.8-10.4) for pure GA. CONCLUSIONS: Persons aged ≥85 years have a 10-fold higher prevalence of late AMD than those aged 70 to 74 years. The high prevalence of late AMD in the oldest age group and expected increase of elderly people in the western world in coming years call for improved preventive measures and novel treatments.National Institutes of Health, National Institute on Ageing and the National Eye Institute Z01-EY00401 N01-AG-1-2100 IHA Icelandic Parliament University of Icelan

Hip fractures and bone mineral density in the elderly--importance of serum 25-hydroxyvitamin D.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.The significance of serum 25-hydroxyvitamin D [25(OH)D] concentrations for hip fracture risk of the elderly is still uncertain. Difficulties reaching both frail and healthy elderly people in randomized controlled trials or large cohort studies may in part explain discordant findings. We determined hazard ratios for hip fractures of elderly men and women related to serum 25(OH)D, including both the frail and the healthy segment of the elderly population.The significance of serum 25-hydroxyvitamin D [25(OH)D] concentrations for hip fracture risk of the elderly is still uncertain. Difficulties reaching both frail and healthy elderly people in randomized controlled trials or large cohort studies may in part explain discordant findings. We determined hazard ratios for hip fractures of elderly men and women related to serum 25(OH)D, including both the frail and the healthy segment of the elderly population.The AGES-Reykjavik Study is a prospective study of 5764 men and women, age 66-96 years, based on a representative sample of the population of Reykjavik, Iceland. Participation was 71.8%. Hazard ratios of incident hip fractures and baseline bone mineral density were determined according to serum concentrations of 25(OH)D at baseline.The AGES-Reykjavik Study is a prospective study of 5764 men and women, age 66-96 years, based on a representative sample of the population of Reykjavik, Iceland. Participation was 71.8%. Hazard ratios of incident hip fractures and baseline bone mineral density were determined according to serum concentrations of 25(OH)D at baseline.Mean follow-up was 5.4 years. Compared with referent values (50-75 nmol/L), hazard ratios for hip fractures were 2.24 (95% CI 1.63, 3.09) for serum 25(OH)D <30 nmol/L, adjusting for age, sex, body mass index, height, smoking, alcohol intake and season, and 2.08 (95% CI 1.51, 2.87), adjusting additionally for physical activity. No difference in risk was associated with 30-50 nmol/L or ≥75 nmol/L in either model compared with referent. Analyzing the sexes separately, hazard ratios were 2.61 (95% CI 1.47, 4.64) in men and 1.93 (95% CI 1.31, 2.84) in women. Values <30 nmol/L were associated with significantly lower bone mineral density of femoral neck compared with referent, z-scores -0.14 (95% CI -0.27, -0.00) in men and -0.11 (95% CI -0.22, -0.01) in women.Mean follow-up was 5.4 years. Compared with referent values (50-75 nmol/L), hazard ratios for hip fractures were 2.24 (95% CI 1.63, 3.09) for serum 25(OH)D <30 nmol/L, adjusting for age, sex, body mass index, height, smoking, alcohol intake and season, and 2.08 (95% CI 1.51, 2.87), adjusting additionally for physical activity. No difference in risk was associated with 30-50 nmol/L or ≥75 nmol/L in either model compared with referent. Analyzing the sexes separately, hazard ratios were 2.61 (95% CI 1.47, 4.64) in men and 1.93 (95% CI 1.31, 2.84) in women. Values <30 nmol/L were associated with significantly lower bone mineral density of femoral neck compared with referent, z-scores -0.14 (95% CI -0.27, -0.00) in men and -0.11 (95% CI -0.22, -0.01) in women.Our results lend support to the overarching importance of maintaining serum 25(OH)D above 30 nmol/L for bone health of elderly people while potential benefits of having much higher levels could not be detected.Our results lend support to the overarching importance of maintaining serum 25(OH)D above 30 nmol/L for bone health of elderly people while potential benefits of having much higher levels could not be detected.National Institutes of Health, USA N01-AG-12100 National Institute on Aging Intramural Research Program, the National Eye Institute USA Z01-EY000401 National Institutes of Health, Hjartavernd (The Icelandic Heart Association) Althingi (Icelandic Parliament

Retinal and cerebral microvascular signs and diabetes: the age, gene/environment susceptibility-Reykjavik study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: Diabetes increases the risk for microvascular disease. The retina and the brain both have intricate microvascular systems that are developmentally similar. We sought to examine whether microvascular lesions in the retina and in the brain are associated and whether this association differs among people with and without diabetes. RESEARCH DESIGN AND METHODS: The analysis included 4,218 participants of the Icelandic population-based Age, Gene/Environment Susceptibility-Reykjavik Study who were born in 1907-1935 and who were previously followed as a part of the Reykjavik Study. Retinal focal arteriolar narrowing, arteriovenous (AV) nicking, and microaneurysms/hemorrhages were evaluated on digital retinal images of both eyes. Cerebral microbleeds (CMBs) were evaluated from magnetic resonance images. Data were analyzed with logistic and multinomial logistic regression models controlling for demographics, major cardiovascular risk factors, cerebral infarcts, and white matter lesions. RESULTS: Evidence of brain microbleeds was found in 485 (11.5%) people, including 192 with multiple (>or=2) microbleeds. Subjects with signs of retinal microvascular lesions were at a significantly increased likelihood for having multiple CMBs. People with diabetes in combination with the presence of either retinal AV nicking (odds ratio [OR] 2.47 [95% CI 1.42-4.31]) or retinal microaneurysms/hemorrhages (2.28 [1.24-4.18]) were significantly more likely to have multiple CMBs. CONCLUSIONS: Retinal microvascular abnormalities and brain microbleeds may occur together in older adults. People with both diabetes and signs of retinal microvascular lesions (AV nicking and microaneurysms/hemorrhages) are more likely to have multiple microbleeds in the brain. Microvascular disease in diabetes extends to the brain

Impact of long-term measures of glucose and blood pressure on the retinal microvasculature

Retinopathy and retinal microvascular abnormalities are common in adult populations, yet few long-term predictors have been identified. We therefore examined the association between systolic blood pressure (SBP) and fasting plasma glucose, assessed over 18 years, with retinopathy and retinal vascular caliber in 2,066 Carotid MRI participants, an Atherosclerosis Risk in Communities ancillary study

Differential associations between retinal signs and CMBs by location

Objective To test the hypothesis that age-related macular degeneration (AMD) and retinal microvascular signs are differentially associated with lobar and deep cerebral microbleeds (CMBs). Methods CMBs in lobar regions indicate cerebral amyloid angiopathy (CAA). β-Amyloid deposits are implicated in both CAA and AMD. Deep CMBs are associated with hypertension, a major risk factor for retinal microvascular damage. This population-based cohort study included 2,502 participants in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study who undertook binocular digital retinal photographs at baseline (2002–2006) to assess retinal microvascular signs and AMD and brain MRI scan at both baseline and follow-up (2007–2011) to assess CMBs. We assessed retinal microvascular lesion burden by counting the 3 retinal microvascular signs (focal arteriolar narrowing, arteriovenous nicking, and retinopathy) concurrently present in the participant. We used multiple logistic models to examine the association of baseline retinal pathology to incident CMBs detected at follow-up. Results During an average 5.2 years of follow-up, 461 people (18.3%) developed new CMBs, including 293 in exclusively lobar regions and 168 in deep regions. Pure geographic atrophy was significantly associated with strictly lobar CMBs (multivariable-adjusted odds ratio 2.59, 95% confidence interval [CI] 1.01–6.65) but not with deep CMBs. Concurrently having ≥2 retinal microvascular signs was associated with a 3-fold (95% CI 1.73–5.20) increased likelihood for deep CMBs but not exclusively lobar CMBs. Conclusions Retinal microvascular signs and pure geographic atrophy may be associated with deep and exclusively lobar CMBs, respectively, in older people. These results have implications for further research to define the role of small vessel disease in cognitive impairment.The AGES-Reykjavik Study was funded by the NIH (contract N01-AG-12100); the Intramural Research Program of the National Institute on Aging and the National Eye Institute (ZIAEY000401), NIH; and the Icelandic Heart Association and the Icelandic Parliament. None of the funding organizations or sponsors were involved in study design; in the collection, analysis, or interpretation of data; in writing of the report; or in the decision to submit the manuscript for publication.Peer Reviewe

Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist

Effect of genetically low 25-hydroxyvitamin D on mortality risk: Mendelian randomization analysis in 3 large European cohorts

Source at https://doi.org/10.3390/nu11010074.The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes CYP2R1 (rs12794714, rs10741657) and DHCR7/NADSYN1 (rs12785878, rs11234027), were combined in two allelic scores. Cox proportional hazards regression models were used with the ratio estimator and the delta method for calculating the hazards ratio (HR) and standard error of genetically determined 25(OH)D effect on all-cause mortality. We included 10,501 participants (50.1% females, 67.1±10.1 years) of whom 4003 died during a median follow-up of 10.4 years. The observed adjusted HR for all-cause mortality per decrease in 25(OH)D by 20 nmol/L was 1.20 (95% CI: 1.15–1.25). The HR per 20 nmol/L decrease in genetically determined 25(OH)D was 1.32 (95% CI: 0.80–2.24) and 1.35 (95% CI of 0.81 to 2.37) based on the two scores. In conclusion, the results of this MR study in a combined sample from three European cohort studies provide further support for a causal relationship between vitamin D deficiency and increased all-cause mortality. However, as the current study, even with ~10,000 participants, was underpowered for the study of the effect of the allele score on mortality, larger studies on genetics and mortality are needed to improve the precision

Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium

Source at http://doi.org/10.1371/journal.pone.0170791Background:Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standardization of laboratory methods for 25-hydroxyvitamin D (25[OH]D) concentrations and used aggregate data instead of individual participant data (IPD). We therefore performed an IPD meta-analysis on the association between standardized serum 25(OH)D and mortality.Methods:In a European consortium of eight prospective studies, including seven general population cohorts, we used the Vitamin D Standardization Program (VDSP) protocols to standardize 25(OH)D data. Meta-analyses using a one step procedure on IPD were performed to study associations of 25(OH)D with all-cause mortality as the primary outcome, and with cardiovascular and cancer mortality as secondary outcomes. This meta-analysis is registered at ClinicalTrials.gov, number NCT02438488.Findings:We analysed 26916 study participants (median age 61.6 years, 58% females) with a median 25(OH)D concentration of 53.8 nmol/L. During a median follow-up time of 10.5 years, 6802 persons died. Compared to participants with 25(OH)D concentrations of 75 to 99.99 nmol/L, the adjusted hazard ratios (with 95% confidence interval) for mortality in the 25(OH)D groups with 40 to 49.99, 30 to 39.99, and Interpretation:In the first IPD meta-analysis using standardized measurements of 25(OH)D we observed an association between low 25(OH)D and increased risk of all-cause mortality. It is of public health interest to evaluate whether treatment of vitamin D deficiency prevents premature deaths