The association of microvascular disease and endothelial dysfunction with vertebral trabecular bone mineral density : The MESA study.

Retinopathy and albuminuria are associated with hip fracture risk. We investigated whether these disorders and endothelial dysfunction (which underlies microvascular diseases) were associated with low trabecular bone density. No significant associations were found, suggesting that microvascular diseases are not related to fracture risk through low trabecular bone density. PURPOSE: Microvascular diseases of the eye, kidney, and brain are associated with endothelial dysfunction and increased hip fracture risk. To explore the basis for higher hip fracture risk, we comprehensively examined whether markers of microvascular disease and/or endothelial dysfunction are related to trabecular bone mineral density (BMD), a proximate risk factor for osteoporotic fractures. METHODS: Among 6814 participants in the Multi-Ethnic Study of Atherosclerosis study (MESA), we derived thoracic vertebral trabecular BMD from computed tomography of the chest and measured urine albumin to creatinine ratios (UACR), retinal arteriolar and venular widths, flow mediated dilation (FMD) of the brachial artery after 5 min of ischemia; and levels of five soluble endothelial adhesion markers (ICAM-1, VCAM-1, L-selectin, P-selectin, and E-selectin). Linear regression models were used to examine the association of trabecular BMD with markers of microvascular disease and with markers of endothelial dysfunction. RESULTS: We observed no significant associations of UACR, retinal arteriolar or venular widths, or FMD with BMD. We also observed no statistically significant association of spine trabecular BMD with levels of endothelial adhesion markers. Men and women had largely similar results. CONCLUSION: We conclude that there is little evidence to connect thoracic spine trabecular BMD to microvascular disorders or to endothelial dysfunction among multi-ethnic middle-aged and older adults. Other factors beyond trabecular BMD (e.g., bone quality or predisposition to falling) may be responsible for the associations of microvascular disease with osteoporotic fractures.

Association of fractal dimension and other retinal vascular network parameters with cognitive performance and neuroimaging biomarkers: The Multi-Ethnic Study of Atherosclerosis (MESA).

INTRODUCTION: Retinal vascular network changes may reflect the integrity of the cerebral microcirculation, and may be associated with cognitive impairment. METHODS: Associations of retinal vascular measures with cognitive function and MRI biomarkers were examined amongst Multi-Ethnic Study of Atherosclerosis (MESA) participants in North Carolina who had gradable retinal photographs at Exams 2 (2002 to 2004, n = 313) and 5 (2010 to 2012, n = 306), and detailed cognitive testing and MRI at Exam 6 (2016 to 2018). RESULTS: After adjustment for covariates and multiple comparisons, greater arteriolar fractal dimension (FD) at Exam 2 was associated with less isotropic free water of gray matter regions (ß = -0.0005, SE = 0.0024, p = 0.01) at Exam 6, while greater arteriolar FD at Exam 5 was associated with greater gray matter cortical volume (in mm3 , ß = 5458, SE = 20.17, p = 0.04) at Exam 6. CONCLUSION: Greater arteriolar FD, reflecting greater complexity of the branching pattern of the retinal arteries, is associated with MRI biomarkers indicative of less neuroinflammation and neurodegeneration.

Milk intake and hip fracture incidence in community-dwelling old Icelandic adults.

Milk and milk products have been known as important for bone health. Can ingestion of milk and milk products lower hip fracture risk for older adults? In this study, older Icelandic adults who were ingesting higher milk had a lower risk of hip fractures. INTRODUCTION: This study describes associations between milk intake and hip fracture risk in older Icelanders. The data indicate that no/low milk consumption is related to greater hip fracture risk. Hip fracture can have a severe effect on the life of older adults. Health authorities recommend milk intake for better bone health. However, previous studies addressing this association have been divergent. METHODS: This prospective study included 4614 subjects (mean age 76 years) recruited between 2002 and 2006 into the Age, Gene/Environment Susceptibility-Reykjavik (AGES-Reykjavik) study. Information on hip fractures occurring between recruitment and end of follow-up in 2012 was extracted from hospital records. RESULTS: A total of 14% of participants reported milk intake < 0.5 times/day (the lowest category) and 22% of the participants consumed at least milk two times/day (highest category). Milk consumption was positively related to the volumetric bone mineral density at baseline with a sex- and age-adjusted difference of 8.95 ± 2.5 mg/cm3 between the highest compared to lowest milk intake categories (P < 0.001). During the follow-up, 7.4% of participants had a hip fracture, and we observed a decreased risk of incident hip fractures in the highest compared to the lowest milk intake category with a hazard ratio of 0.69 (95% CI: 0.47-0.99) in adjusted model. Further analysis indicated a linear relationship between milk intake and fracture risk (P-value for linear trend < 0.001). CONCLUSION: Milk intake is associated with a lower risk of incident hip fracture in a linear way in Icelandic community-dwelling older adults.

OMEGA-3 FATTY ACIDS ARE ASSOCIATED WITH DECREASED PRESENCE AND SEVERITY OF DIABETIC RETINOPATHY: A Combined Analysis of MESA and GOLDR Cohorts.

PURPOSE: Inflammation is associated with diabetic retinopathy development and progression, and previous studies have demonstrated that omega-3 polyunsaturated fatty acids have anti-inflammatory properties. Therefore, the goal of this study was to determine if omega-3 polyunsaturated fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are associated with decreased risk and severity of retinopathy in individuals with type 2 diabetes. METHODS: In a combined population of 1,356 individuals with type 2 diabetes from the Multi-Ethnic Study of Atherosclerosis and Genetics of Latino Diabetic Retinopathy cohorts, odds ratios using logistic regression were determined to assess the association between polyunsaturated fatty acids and retinopathy. RESULTS: In 1,356 participants with type 2 diabetes, individuals in the fourth quartile of DHA were 17% less likely to have retinopathy compared with the first quartile ( P = 0.009, CI: 0.72-0.95). Secondary analysis revealed 38% lower severity of retinopathy in individuals in the fourth quartile compared with the first quartile of DHA ( P = 0.006; CI: 0.44-0.87) and EPA + DHA ( P = 0.004; CI: 0.44-0.85). No significant associations were observed between EPA and retinopathy. CONCLUSION: DHA is inversely associated with the presence and severity of diabetic retinopathy. Increased intake of dietary sources of DHA may provide some protection against retinopathy in individuals with type 2 diabetes and warrants more research as a preventative option.

Retinal Microvascular Caliber and Incident Depressive Symptoms: The Multi-Ethnic Study of Atherosclerosis.

Cerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. The retina allows for visualization of a microvascular bed that shares similarities with the cerebral microvasculature. We investigated the associations between baseline retinal arteriolar and venular calibers (central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively) and incident depressive symptoms in the Multi-Ethnic Study of Atherosclerosis (MESA). We used longitudinal data on 4,366 participants (mean age = 63.2 years; 48.5% women, 28.4% Black) without baseline depressive symptoms. Depressive symptoms, defined as Center for Epidemiologic Studies Depression Scale score ≥16 and/or use of antidepressant medication, were determined between 2002 and 2004 (baseline; MESA visit 2) and at 3 follow-up examinations conducted every 1.5-2 years thereafter. Fundus photography was performed at baseline. After a mean follow-up period of 6.1 years, 21.9% (n = 958) had incident depressive symptoms. After adjustment for sociodemographic, lifestyle, and cardiovascular factors, a 1-standard-deviation larger baseline CRVE was associated with a higher risk of depressive symptoms (hazard ratio = 1.10, 95% confidence interval: 1.02, 1.17), and a 1-standard-deviation larger baseline CRAE was not statistically significantly associated with incident depressive symptoms (hazard ratio = 1.04, 95% confidence interval: 0.97, 1.11). In this study, larger baseline CRVE, but not CRAE, was associated with a higher incidence of depressive symptoms.

Pre-diagnostic 25-hydroxyvitamin D levels and survival in cancer patients.

PURPOSE: Our main aim was to explore whether pre-diagnostic circulating levels of 25-hydroxyvitamin D (25(OH)D) among older individuals with cancer were associated with overall and cancer-specific survival after diagnosis. DESIGN: We used data from the Reykjavik-AGES Study on participants (n = 4,619) without cancer at entry, when blood samples were taken for 25(OH)D standardized measurements. The association with cancer risk, all-cause- and cancer-specific mortality was assessed among those later diagnosed with cancer, comparing four 25(OH)D categories, using 50-69.9 nmol/L as the reference category. RESULTS: Cancer was diagnosed in 919 participants on average 8.3 years after blood draw. No association was observed between the reference group and other 25(OH)D groups and total cancer incidence. Mean age at diagnosis was 80.9 (± 5.7) years. Of those diagnosed, 552 died during follow-up, 67% from cancer. Low pre-diagnostic levels of 25(OH)D < 30 nmol/L were significantly associated with increased total mortality (HR: 1.39, 95% CI 1.03, 1.88) and non-significantly with cancer-specific mortality (HR: 1.33, 95% CI 0.93, 1.90). Among patients surviving more than 2 years after diagnosis, higher pre-diagnostic 25(OH)D levels (≥ 70 nmol/L) were associated with lower risk of overall (HR: 0.68, 95% CI 0.46, 0.99) and cancer-specific mortality (HR: 0.47, 95% CI 0.26, 0.99). CONCLUSIONS: Among elderly cancer patients, low pre-diagnostic serum 25(OH)D levels (< 30 nmol/L) were associated with increased overall mortality.

Serum lipids in adults with late age-related macular degeneration: a case-control study.

BACKGROUND: Lipids are implicated in the pathogenesis of age-related macular degeneration (AMD). The relationship between systemic lipids and AMD has not been well characterized. The objective was to investigate the relationship between serum lipids and AMD in older adults using a lipidomic approach. METHODS: In a case-control study, 240 adults, aged ≥66 years, a third each having geographic atrophy, neovascular AMD, or no signs of AMD, were selected from a population-based sample of participants in the Age Gene/Environment Susceptibility-Reykjavik Study. The exposure was serum lipids and risk factors for AMD. The outcome was late AMD, assessed through fundus images taken through dilated pupils using a 45-degree digital camera and grading for neovascular AMD and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. RESULTS: Of 177 serum lipid species measured, there were no significant differences in serum lipids between controls and those with geographic atrophy or neovascular AMD, respectively. Adults with neovascular AMD had higher total serum lysophosphatidylcholine (LPC) (P = 0.004) and serum LPC 18:0 (P = 0.0002) compared to those with geographic atrophy. CONCLUSION: Late AMD was not characterized by alterations in systemic lipids compared with normal controls. These findings suggest that there may be differences in the LPC pathway between adults with neovascular AMD and geographic atrophy.

Hand and knee osteoarthritis are associated with reduced diameters in retinal vessels: the AGES-Reykjavik study.

To investigate the association between osteoarthritis (OA) and microvascular pathology, we examined the relationship between retinal microvascular caliber and osteoarthritis of the hand and knee in an elderly population. The AGES-Reykjavik is a population-based, multidisciplinary longitudinal cohort study of aging. Retinal vessel caliber, hand osteoarthritis and total knee joint replacements due to OA were examined in 4757 individuals (mean age 76 ± 5 years; 57% female). Incident knee joint replacements during 5-year follow-up (n = 2961, mean age 75 ± 5 years; 58% female) were also assessed. Logistic regression analysis, adjusting for age, sex, and body mass index, showed an association between narrow arteriolar caliber and hand OA, as well as knee replacement. After adjustment for other covariates, including statin therapy, this association was significant for both hand OA in men and women [OR 1.10(1.03-1.17), p < 0.01] (per unit standard deviation decrease in CRAE) and TKR prevalence [OR 1.15 (1.01-1.32), p = 0.04], especially for men [OR 1.22 (1.00-1.51) p = 0.04] and also for incident TKRs in men [OR 1.50 (1.07-2.10), p = 0.04]. Narrow venular caliber was associated with hand OA in women [OR 1.10 (1.01-1.21), p = 0.03]. Retinal arterial narrowing in hand and knee OA is present in males as well as females. Venular narrowing in hand OA in women was an unexpected finding and is in contrast with the venular widening usually observed in cardiovascular diseases.

Mortality in Older Persons with Retinopathy and Concomitant Health Conditions: The Age, Gene/Environment Susceptibility-Reykjavik Study.

PURPOSE: To assess the impact of retinopathy on mortality in older persons with concomitant health conditions. DESIGN: Population-based prospective cohort study. PARTICIPANTS: A total of 4966 individuals aged 67 to 96 years (43.2% were male) from the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-RS). METHODS: Retinopathy was evaluated from digital fundus images (2002-2006) using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Mortality was assessed through September 2013 (cause of death assigned through 2009). Cox proportional hazards regression models, with age as the time scale, estimated the association between retinopathy and death while controlling for risk factors and the presence of concomitant health conditions. MAIN OUTCOME MEASURES: Mortality from all causes and cardiovascular disease (CVD). RESULTS: Among the 4966 participants, 503 (10.1%) had diabetes and 614 (12.4%) had retinopathy at baseline. A subset of these (136 [2.7%]) had both diabetes and retinopathy. After a median follow-up of 8.6 years, 1763 persons died, 276 (45.0%) with retinopathy and 1487 (34.2%) without retinopathy, of whom 76 and 162 persons, respectively, also had diabetes. There were 366 deaths from CVD through 2009, 72 (11.7%) in persons with retinopathy and 294 (6.8%) in those without retinopathy. In multivariable analyses, retinopathy was significantly associated with all-cause mortality (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.10-1.43; P < 0.01) and CVD-related mortality (HR, 1.57; 95% CI, 1.20-2.06; P < 0.01). Findings were more striking in men: all-cause HR, 1.33 (95% CI, 1.11-1.60) and CVD HR, 1.81 (95% CI, 1.25-2.63). Risk of mortality was further increased among those with retinopathy concomitant with microalbuminuria (all-cause HR, 1.70; 95% CI, 1.03-2.23, and CVD HR, 2.04; 95% CI, 1.27-3.28) and those with retinopathy, microalbuminuria, and diabetes (all-cause HR, 2.01; 95% CI, 1.22-3.31, and CVD HR, 5.24; 95% CI, 1.91-14.42). History of clinical stroke increased the risk of CVD-related mortality among persons with retinopathy (HR, 3.30; 95% CI, 2.05-5.32), particularly those with retinopathy and diabetes (HR, 5.38; 95% CI, 1.80-16.06). CONCLUSIONS: Even minimal retinopathy was a significant predictor of increased mortality in older persons, particularly men, irrespective of diabetes status. Persons with retinopathy may warrant closer clinical management of general health.

Incidence of Age-Related Macular Degeneration in a Multi-Ethnic United States Population: The Multi-Ethnic Study of Atherosclerosis.

PURPOSE: To describe the incidence of age-related macular degeneration (AMD) and associated risk factors in 4 racial/ethnic groups (white, black, Hispanic, and Chinese) residing in the United States. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 3811 participants, aged 46 to 86 years, from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, with retinal data collected twice, on average, 8 years apart. METHODS: Fundus images, taken using a digital camera through dark-adapted pupils using a standard protocol and the same equipment at both study visits, were graded centrally for early and late AMD on the basis of drusen size, type and area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Demographic, clinical, and laboratory measures were included in multivariable regression models to determine their impact on the variation in AMD incidence among racial/ethnic groups. MAIN OUTCOME MEASURES: Incident early and late AMD. RESULTS: The overall 8-year age- and sex-standardized incidence of early and late AMD were 4.1% and 2.3%, respectively, with incidence of early and late AMD highest in whites (5.3% and 4.1%, respectively), intermediate in Chinese (4.5% and 2.2%, respectively) and Hispanics (3.3% and 0.8%, respectively), and lowest in blacks (1.6% and 0.4%, respectively). By adjusting for age and sex, blacks had a 70% lower risk of developing early AMD than whites, and this decreased only slightly to a 67% lower risk after multivariable adjustment. By adjusting for age, sex, and race/ethnicity, hyperopia was associated with early AMD (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.20), as was astigmatism (OR, 1.47; 95% CI, 1.00-2.16), but not myopia (P = 0.29). Age, race/ethnicity, current smoking, hyperopia, and AMD-susceptibility genotypes Complement Factor H (CFH) RS1061170 and Age Related Maculopathy Susceptibility 2 (ARMS2) RS3793917 were independently associated with incident early AMD in multivariable models for the combined sample. However, the only statistically significant factor consistently associated with incident early AMD across the 4 racial/ethnic groups was increasing age. Risk factors for late AMD were not assessed because of its low incidence, particularly across racial/ethnic groups. CONCLUSIONS: Variation in the incidence of early AMD exists among racial/ethnic groups in the United States and is not explained by the clinical, genetic, and environmental factors included in this study.

Sleep apnea and retinal signs in cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis.

PURPOSE: The aim of the study was to examine the relationship between sleep apnea, retinal vascular caliber and retinopathy, and their impact on cardiovascular disease (CVD) risk. METHODS: A multi-ethnic cohort of 5,803 participants was examined based on standardized grading of retinal vascular caliber and retinopathy from digital fundus photographs, self-reported physician-diagnosed sleep apnea (PDSA), and incident cardiovascular events. RESULTS: In women, PDSA was associated with narrower arterioles (regression coefficient [ß] -5.76; 95 % confidence Interval [CI] -8.51, -3.02) after adjusting for cardio-metabolic risk factors. The incident rate ratio (IRR) of CVD was also associated with narrower arterioles (IRR for highest versus lowest tertile 1.91; 95 % CI 1.08, 3.38). In men, PDSA was not associated with arteriolar caliber. However, incident CVD was associated with narrower arterioles (IRR 1.67; 95 % CI 1.10, 2.52), wider venules (IRR 1.71; 95 % CI 1.13, 2.59) and PDSA (IRR 2.03, 95 % CI 1.17, 3.51). The IRR of CVD in men with PDSA increased minimally to 2.06 (95 % CI 1.18, 3.56) after adjustment for retinal arteriolar and venular caliber. Combining women and men, the IRR of CVD was 3.41 (95 % CI 1.79, 6.50) in those with both PDSA and narrower retinal arterioles. CONCLUSIONS: Sleep apnea was associated with narrower retinal arterioles in women but not in men. However, sleep apnea was also associated with incident CVD in men. These suggest potential gender differences in susceptibility to microvascular disease in association with sleep apnea.

Retinal microvascular calibre and risk of diabetes mellitus: a systematic review and participant-level meta-analysis.

AIMS/HYPOTHESIS: The calibre of the retinal vessels has been linked to diabetes mellitus but studies have not shown consistent results. We conducted a participant-level meta-analysis to evaluate the association between retinal arteriolar and venular calibre and diabetes. METHODS: We performed a systematic review on MEDLINE and EMBASE for articles published up to December 2014. We identified five population-based prospective cohort studies that provided individual-level data on 18,771 diabetes-free participants. We used discrete time proportional hazards models to estimate pooled HRs of diabetes associated with 1 SD (20 µm) change in retinal vascular calibre. RESULTS: We identified 2,581 incident cases of diabetes over a median follow-up period of 10 years (interquartile interval of 3.4-15.8 years). After adjustment for demographic, lifestyle and clinical factors, retinal venular calibre was significantly associated with incident diabetes (pooled HR 1.09 [95% CI 1.02, 1.15] per SD increase in venular calibre). This association persisted in analyses excluding individuals with <5 years of follow-up (1.07 [1.0, 1.12]) or those with impaired fasting glucose at baseline (1.10 [1.03, 1.17]); in subgroup analyses, the association was stronger in men than in women but was consistent across subgroups of race/ethnicity, smoking status, hypertension and BMI categories. Retinal arteriolar calibre was not associated with diabetes (0.95 [0.86, 1.06] per SD decrease in arteriolar calibre). CONCLUSIONS/INTERPRETATION: Wider retinal venules but not narrower retinal arterioles were associated with a modestly increased risk for diabetes. Knowledge of pathological mechanisms underlying wider retinal venule may provide further insights concerning microvascular alterations in diabetes.

Meta-analysis of genome-wide association studies in five cohorts reveals common variants in RBFOX1, a regulator of tissue-specific splicing, associated with refractive error.

Visual refractive errors (REs) are complex genetic traits with a largely unknown etiology. To date, genome-wide association studies (GWASs) of moderate size have identified several novel risk markers for RE, measured here as mean spherical equivalent (MSE). We performed a GWAS using a total of 7280 samples from five cohorts: the Age-Related Eye Disease Study (AREDS); the KORA study ('Cooperative Health Research in the Region of Augsburg'); the Framingham Eye Study (FES); the Ogliastra Genetic Park-Talana (OGP-Talana) Study and the Multiethnic Study of Atherosclerosis (MESA). Genotyping was performed on Illumina and Affymetrix platforms with additional markers imputed to the HapMap II reference panel. We identified a new genome-wide significant locus on chromosome 16 (rs10500355, P = 3.9 × 10(-9)) in a combined discovery and replication set (26 953 samples). This single nucleotide polymorphism (SNP) is located within the RBFOX1 gene which is a neuron-specific splicing factor regulating a wide range of alternative splicing events implicated in neuronal development and maturation, including transcription factors, other splicing factors and synaptic proteins.

Age-related macular degeneration and mortality in community-dwelling elders: the age, gene/environment susceptibility Reykjavik study.

OBJECTIVE: To investigate the association between age-related macular degeneration (AMD) and mortality in older persons. DESIGN: Population-based prospective cohort study. PARTICIPANTS: Participants 67 to 96 years of age (43.1% male) enrolled between 2002 and 2006 in the Age, Gene/Environment Susceptibility-Reykjavik Study. METHODS: Retinal photographs of the macula were acquired digitally and evaluated for the presence of AMD lesions using the Wisconsin Age-Related Maculopathy grading scheme. Mortality was assessed prospectively through 2013 with cause of death available through 2009. The association between AMD and death, resulting from any cause and specifically cardiovascular disease (CVD), was examined using Cox proportional hazards regression with age as the time scale, adjusted for significant risk factors and comorbid conditions. To address a violation in the proportional hazards assumption, analyses were stratified into 2 groups based on the mean age at death (83 years). MAIN OUTCOME MEASURES: Mortality resulting from all causes and CVD. RESULTS: Among 4910 participants, after a median follow-up of 8.6 years, 1742 died (35.5%), of whom 614 (35.2%) had signs of AMD at baseline. Cardiovascular disease was the cause of death for 357 people who died before the end of 2009, of whom 144 (40%) had AMD (101 with early disease and 43 with late disease). After considering covariates, including comorbid conditions, having early AMD at any age or having late AMD in individuals younger than 83 years (n = 4179) were not associated with all-cause or CVD mortality. In individuals 83 years of age and older (n = 731), late AMD was associated significantly with increased risk of all-cause mortality (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.20-2.57) and CVD-related mortality (HR, 2.37; 95% CI, 1.41-3.98). In addition to having AMD, older individuals who died were more likely to be male and to have low body mass index, impaired cognition, and microalbuminuria. CONCLUSIONS: Competing risk factors and concomitant conditions are important in determining mortality risk resulting from AMD. Individuals with early AMD are not more likely to die than peers of comparable age. Late AMD becomes a predictor of mortality by the mid-octogenarian years.

Higher Plasma Phospholipid n-3 PUFAs, but Lower n-6 PUFAs, Are Associated with Lower Pulse Wave Velocity among Older Adults.

BACKGROUND: Higher intake of polyunsaturated fatty acids (PUFAs) and higher circulating PUFAs are associated with lower cardiovascular disease (CVD) risk. The positive influence of PUFAs might be via lowering arterial stiffness, resulting in a better CVD risk profile; however, studies investigating circulating PUFAs in relation to arterial stiffness in a general population are limited. OBJECTIVE: We investigated the associations of plasma phospholipid n-3 (ω-3) and n-6 PUFAs and fish oil intake with arterial stiffness. METHODS: We used data from a subgroup of the Age, Gene/Environment Susceptibility-Reykjavik (AGES-Reykjavik) Study (n = 501, 75.0 ± 4.96 y, 46% men), a population-based study of community-dwelling older adults. Plasma phospholipid PUFAs were measured by GC at baseline, and fish oil intake was assessed at 3 time points: early life (ages 14-19 y), midlife (ages 40-50 y), and late life (ages 66-96 y, AGES-Reykjavik baseline) with the use of a validated food-frequency questionnaire. Arterial stiffness was determined as carotid-femoral pulse wave velocity (cf-PWV) with the use of an electrocardiogram after a mean follow-up of 5.2 ± 0.3 y. Regression coefficients (95% CIs), adjusted for demographics, follow-up time, risk factors, cholesterol, triglycerides, and serum vitamin D, were calculated by linear regression per SD increment in PUFAs. RESULTS: Plasma total n-3 PUFAs, eicosapentaenoic acid, and docosahexaenoic acid were associated with lower cf-PWV [ß (95% CI): -0.036 (-0.064, -0.008); -0.031 (-0.059, -0.003); -0.036 (-0.064, -0.009), respectively]. In contrast, plasma total n-6 PUFAs and linoleic acid were associated with higher cf-PWV [0.035 (0.009, 0.061) and 0.034 (0.008, 0.059)]. Regular fish oil consumption at early-, mid-, and late-life was not associated with cf-PWV. CONCLUSIONS: Our results show a positive association between plasma n-6 PUFAs and arterial stiffness, and suggest that higher concentrations of plasma long-chain n-3 PUFAs are associated with less arterial stiffness and therein may be one of the mechanisms underlying the association between plasma n-3 PUFAs and lower CVD risk.

Sex-specific predictors of hearing-aid use in older persons: The age, gene/environment susceptibility - Reykjavik study.

OBJECTIVE: We estimate the prevalence of hearing-aid use in Iceland and identify sex-specific factors associated with use. DESIGN: Population-based cohort study. STUDY SAMPLE: A total of 5172 age, gene/environment susceptibility - Reykjavik study (AGES-RS) participants, aged 67 to 96 years (mean age 76.5 years), who completed air-conduction and pure-tone audiometry. RESULTS: Hearing-aid use was reported by 23.0% of men and 15.9% of women in the cohort, although among participants with at least moderate hearing loss in the better ear (pure-tone average [PTA] of thresholds at 0.5, 1, 2, and 4 kHz ≥ 35 dB hearing level [HL]) it was 49.9% and did not differ by sex. Self-reported hearing loss was the strongest predictor of hearing-aid use in men [OR: 2.68 (95% CI: 1.77, 4.08)] and women [OR: 3.07 (95% CI: 1.94, 4.86)], followed by hearing loss severity based on audiometry. Having diabetes or osteoarthritis were significant positive predictors of use in men, whereas greater physical activity and unimpaired cognitive status were important in women. CONCLUSIONS: Hearing-aid use was comparable in Icelandic men and women with moderate or greater hearing loss. Self-recognition of hearing loss was the factor most predictive of hearing-aid use; other influential factors differed for men and women.

Spousal loss and cognitive function in later life: a 25-year follow-up in the AGES-Reykjavik study.

The aim of this study was to investigate the associations between loss of a life partner and the development of dementia and decline in cognitive function in later life. We used an Icelandic cohort of 4,370 participants in the Age, Gene/Environment Susceptibility-Reykjavik Study who were living as married in 1978 (born in 1907-1935) and were either still married (unexposed cohort) or widowed (exposed cohort) at follow-up (in 2002-2006). We ascertained history of marital status and spouse's death by record linkage to the Registry of the Total Population, Statistics Iceland. The outcome measures were as follows: 1) dementia and mild cognitive impairment; and 2) memory, speed of processing, and executive function. During the observation period, 3,007 individuals remained married and 1,363 lost a spouse through death. We did not find any significant associations between loss of a spouse and our outcome variables, except that widowed women had poorer executive function (mean = -0.08) during the first 2 years after their husbands' deaths compared with still-married women (mean = 0.09). Our findings do not support the notion that the risk of dementia is increased following the loss of a spouse, yet women demonstrate a seemingly temporary decline in executive function following the death of a partner.

Five-year incidence, progression, and risk factors for age-related macular degeneration: the age, gene/environment susceptibility study.

OBJECTIVE: To investigate the incidence and progression of age-related macular degeneration (AMD) and associated risk factors. DESIGN: Population-based, prospective, cohort study. PARTICIPANTS: We included 2868 participants from the Age Gene/Environment Susceptibility-Reykjavik Study with retinal data at baseline and 5-year follow-up. METHODS: Digital macular photographs were graded for presence of AMD. Participants completed a questionnaire and extensive clinical battery. Biomarkers were assessed. Risk factors for AMD were analyzed using multivariate regression analysis with odds ratios (ORs) and 95% CIs. MAIN OUTCOME MEASURES: We assessed AMD, defined as early or late. RESULTS: Among 2196 participants free of AMD at baseline, 14.9% developed incident AMD. In multivariate models, incident AMD was significantly associated with age (OR per year, 1.14; 95% CI, 1.11-1.17), current smoking (OR, 2.07; 95% CI, 1.38-3.11), former smoking (OR, 1.36; 95% CI, 1.04-1.79), plasma high-density lipoprotein (HDL) cholesterol level (OR, 1.62 per mmol/L; 95% CI, 1.19-2.22), and body mass index (BMI; OR, 1.04 per kg/m(2); 95% CI, 1.01-1.07). Among 563 participants with early AMD at baseline, 22.7% progressed to late AMD (11.0% pure geographic atrophy [GA] and 11.7% exudative AMD). On multivariate analyses, age was significantly associated with progression to GA (OR 1.14; 95% CI, 1.07-1.21) and exudative AMD (OR, 1.08; 95% CI, 1.01-1.14). Adjusting for age, female sex was associated with exudative AMD (OR, 2.10; 95% CI, 1.10-3.98) and plasma HDL cholesterol with GA (OR, 2.03 per mmol/L; 95% CI, 1.02-4.05). CONCLUSIONS: By age 85, 57.4% of participants had signs of AMD. Age, smoking, plasma HDL cholesterol, BMI, and female sex are associated with AMD. Elevated HDL cholesterol is associated with GA development.

Impairments in hearing and vision impact on mortality in older people: the AGES-Reykjavik Study.

OBJECTIVE: to examine the relationships between impairments in hearing and vision and mortality from all-causes and cardiovascular disease (CVD) among older people. DESIGN: population-based cohort study. PARTICIPANTS: the study population included 4,926 Icelandic individuals, aged ≥67 years, 43.4% male, who completed vision and hearing examinations between 2002 and 2006 in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-RS) and were followed prospectively for mortality through 2009. METHODS: participants were classified as having 'moderate or greater' degree of impairment for vision only (VI), hearing only (HI), and both vision and hearing (dual sensory impairment, DSI). Cox proportional hazard regression, with age as the time scale, was used to calculate hazard ratios (HR) associated with impairment and mortality due to all-causes and specifically CVD after a median follow-up of 5.3 years. RESULTS: the prevalence of HI, VI and DSI were 25.4, 9.2 and 7.0%, respectively. After adjusting for age, significantly (P < 0.01) increased mortality from all causes, and CVD was observed for HI and DSI, especially among men. After further adjustment for established mortality risk factors, people with HI remained at higher risk for CVD mortality [HR: 1.70 (1.27-2.27)], whereas people with DSI remained at higher risk of all-cause mortality [HR: 1.43 (1.11-1.85)] and CVD mortality [HR: 1.78 (1.18-2.69)]. Mortality rates were significantly higher in men with HI and DSI and were elevated, although not significantly, among women with HI. CONCLUSIONS: older men with HI or DSI had a greater risk of dying from any cause and particularly cardiovascular causes within a median 5-year follow-up. Women with hearing impairment had a non-significantly elevated risk. Vision impairment alone was not associated with increased mortality.

Is renal function associated with early age-related macular degeneration?

PURPOSE: Age-related macular degeneration (AMD) and chronic kidney disease both involve immune dysregulation and may share underlying pathophysiologic changes to systemic homeostasis. Hence, we aim to evaluate associations between impaired kidney function and early AMD, in a search for urinary biomarkers for AMD. METHODS: A population-based, cross-sectional analysis of persons aged 45 to 84 years was conducted with renal function measured using serum creatinine and cystatin C levels and the estimated glomerular filtration rate (eGFR) calculated. Age-related macular degeneration status was ascertained from retinal photographs. RESULTS: Of 5874 participants, 221 had early AMD. High serum cystatin C and low eGFR (≤60 ml/min/1.73 m) were not associated with early AMD in our multivariate analyses. Among normotensive persons, however, highest versus other deciles of cystatin C were associated with an increased prevalence of early AMD (odds ratio, 1.80; 95% confidence interval, 1.00 to 3.23). CONCLUSIONS: Results could not confirm an association between kidney function and early AMD. The borderline association between cystatin C and early AMD in normotensive persons require further verification.