Mélanie Le Goff

Elevated high-density lipoprotein cholesterol and age-related macular degeneration: the Alienor study.

Background Lipid metabolism and particularly high-density lipoprotein (HDL) may be involved in the pathogenic mechanism of age-related macular degeneration (AMD). However, conflicting results have been reported in the associations of AMD with plasma HDL and other lipids, which may be confounded by the recently reported associations of AMD with HDL-related genes. We explored the association of AMD with plasma lipid levels and lipid-lowering medication use, taking into account most of HDL-related genes associated with AMD. Methods The Alienor study is a population-based study on age-related eye diseases performed in 963 elderly residents of Bordeaux (France). AMD was graded from non mydriatic color retinal photographs in three exclusive stages: no AMD (nu200a=u200a430 subjects, 938 eyes); large soft distinct drusen and/or large soft indistinct drusen and/or reticular drusen and/or pigmentary abnormalities (early AMD, nu200a=u200a176, 247); late AMD (nu200a=u200a40, 61). Associations of AMD with plasma lipids (HDL, total cholesterol (TC), Low-density lipoprotein (LDL), and triglycerides (TG)) were estimated using Generalized Estimating Equation logistic regressions. Statistical analyses included 646 subjects with complete data. Results After multivariate adjustment for age, sex, educational level, smoking, BMI, lipid-lowering medication use, cardiovascular disease and diabetes, and for all relevant genetic polymorphisms (ApoE2, ApoE4, CFH Y402H, ARMS2 A69S, LIPC rs10468017, LIPC rs493258, LPL rs12678919, ABCA1 rs1883025 and CETP rs3764261), higher HDL was significantly associated with an increased risk of early (ORu200a=u200a2.45, 95%CI: 1.54–3.90; Pu200a=u200a0.0002) and any AMD (ORu200a=u200a2.29, 95%CI: 1.46–3.59; Pu200a=u200a0.0003). Association with late AMD was far from statistical significance (ORu200a=u200a1.58, 95%CI: 0.48–5.17; pu200a=u200a0.45). No associations were found for any stage of AMD with TC, LDL and TG levels, statin or fibrate drug use. Conclusions This study suggests that elderly patients with high HDL concentration may be at increased risk for AMD and, further, that HDL dysfunction might be implicated in AMD pathogenesis.

High Concentrations of Plasma n3 Fatty Acids Are Associated with Decreased Risk for Late Age-Related Macular Degeneration

High dietary intakes of n3 (ω3) polyunsaturated fatty acids (PUFA) and fish have been consistently associated with a decreased risk for age-related macular degeneration (AMD). We assessed the associations of late AMD with plasma n3 PUFA, a nutritional biomarker of n3 PUFA status. The Antioxydants Lipides Essentiels Nutrition et Maladies Occulaires (Alienor) Study is a prospective, population-based study on nutrition and age-related eye diseases performed in 963 residents of Bordeaux (France) aged ≥73 y. Participants had a first eye examination in 2006-2008 and were followed for 31 mo on average. Plasma fatty acids were measured by GC from fasting blood samples collected in 1999-2001. AMD was graded from non-mydriatic color retinal photographs at all examinations and spectral domain optical coherence tomography at follow-up. After adjustment for age, gender, smoking, education, physical activity, plasma HDL-cholesterol, plasma triglycerides, CFH Y402H, apoE4, and ARMS2 A69S polymorphisms, and follow-up time, high plasma total n3 PUFA was associated with a reduced risk for late AMD [OR = 0.62 for 1-SD increase (95% CI: 0.44-0.88); P = 0.008]. Associations were similar for plasma 18:3n3 [OR = 0.62 (95% CI: 0.43-0.88); P = 0.008] and n3 long-chain PUFA [OR = 0.65 (95% CI: 0.46-0.92); P = 0.01]. This study gives further support to the potential role of n3 PUFAs in the prevention of late AMD and highlights the necessity of randomized clinical trials to determine more accurately the value of n3 PUFAs as a means of reducing AMD incidence.

Association of macular pigment density with plasma ω-3 fatty acids: the PIMAVOSA study

PURPOSEnTo assess the correlation between macular pigment optical density and plasma levels of lutein, zeaxanthin, and fatty acids, especially omega-3 polyunsaturated fatty acids (PUFAs).nnnMETHODSnThe PIMAVOSA study is an observational study of 107 healthy volunteers, aged 20 to 60 years and born in southwest France, without histories of ocular disease. Macular pigment optical density (MPOD) was measured using the two-wavelength autofluorescence method with a modified scanning laser ophthalmoscope. Plasma measurements (lutein, zeaxanthin, and fatty acids) were performed from fasting blood samples collected on the day of the eye examination.nnnRESULTSnMPOD within 6° correlated with plasma levels of lutein and zeaxanthin (r = 0.35, P < 0.001, and r = 0.30, P < 0.005, respectively). MPOD also significantly correlated with total plasma omega-3 PUFAs (r = 0.22, P < 0.05). Among the different omega-3 PUFAs, docosapentaenoic acid (DPA) had the highest correlation with MPOD (r = 0.31, P < 0.001), whereas correlation with eicosapentaenoic acid (EPA) was moderate (r = 0.21, P < 0.05) and did not reach statistical significance for docosahexaenoic acid (r = 0.14, P = 0.14).nnnCONCLUSIONSnIn the present study, macular pigment density was associated not only with plasma lutein and zeaxanthin but also with omega-3 long-chain PUFAs, particularly with EPA and DPA. Further studies will be needed to confirm these findings and to identify the underlying mechanisms.

Lifetime Exposure to Ambient Ultraviolet Radiation and the Risk for Cataract Extraction and Age-Related Macular Degeneration: The Alienor Study

PURPOSEnWhile exposure to ultraviolet radiation (UVR) is a recognized risk factor for cataract, its association is more controversial with age-related macular degeneration (AMD). We report the associations of lifetime exposure to ambient UVR with cataract extraction and AMD.nnnMETHODSnThe Alienor Study is a population-based study of 963 residents of Bordeaux (France), aged 73 years or more. Lifetime exposure to ambient UVR was estimated from residential history and Eurosun satellite-based estimations of ground UVR. It was divided in three groups (lower quartile, intermediate quartiles, upper quartile), using the intermediate quartiles as the reference. Early and late AMD was classified from retinal color photographs. Cataract extraction was defined as absence of the natural lens at slit-lamp.nnnRESULTSnAfter multivariate adjustment, subjects in the upper quartile of lifetime ambient UVR exposure were at increased risk for cataract extraction (odds ratio [OR] = 1.53; 95% confidence interval [CI], 1.04-2.26; P = 0.03) and for early AMD (OR = 1.59; 95% CI, 1.04-2.44; P = 0.03), by comparison with subjects in the intermediate quartiles. Subjects in the lower quartile of UVR exposure also were at increased risk for early AMD (OR = 1.69; 95% CI, 1.06-2.69; P = 0.03), by comparison with those with medium exposure. Associations of late AMD with UVR exposure was not statistically significant.nnnCONCLUSIONSnThis study further confirms the increased risk for cataract extraction in subjects exposed to high ambient UVR. Moreover, it suggests that risk for early AMD is increased in subjects exposed to high UVR, but also to low UVR, by comparison with medium exposures.

Association of HDL-related loci with age-related macular degeneration and plasma lutein and zeaxanthin: the Alienor study.

Background Several genes implicated in high-density lipoprotein (HDL) metabolism have been reported to be associated with age-related macular degeneration (AMD). Furthermore, HDL transport the two carotenoids, lutein and zeaxanthin, which are highly suspected to play a key-role in the protection against AMD. The objective is to confirm the associations of HDL-related loci with AMD and to assess their associations with plasma lutein and zeaxanthin concentrations. Methods Alienor study is a prospective population-based study on nutrition and age-related eye diseases performed in 963 elderly residents of Bordeaux, France. AMD was graded according to the international classification, from non-mydriatic colour retinal photographs. Plasma lutein and zeaxanthin were determined by normal-phase high-performance liquid chromatography. The following polymorphisms were studied: rs493258 and rs10468017 (LIPC), rs3764261 (CETP), rs12678919 (LPL) and rs1883025 (ABCA1). Results After multivariate adjustment, the TT genotype of the LIPC rs493258 variant was significantly associated with a reduced risk for early and late AMD (OR=0.64, 95%CI: 0.41-0.99; p=0.049 and OR=0.26, 95%CI: 0.08-0.85; p=0.03, respectively), and with higher plasma zeaxanthin concentrations (p=0.03), while plasma lipids were not significantly different according to this SNP. Besides, the LPL variant was associated with early AMD (OR=0.67, 95%CI: 0.45-1.00; p=0.05) and both with plasma lipids and plasma lutein (p=0.047). Associations of LIPC rs10468017, CETP and ABCA1 polymorphisms with AMD did not reach statistical significance. Conclusion These findings suggest that LIPC and LPL genes could both modify the risk for AMD and the metabolism of lutein and zeaxanthin.

Vitamin D Deficiency in Community-Dwelling Elderly Is Not Associated with Age-Related Macular Degeneration

BACKGROUNDnElderly persons are at elevated risk of vitamin D deficiency, which is involved in various health problems. However, its relation with age-related macular degeneration (AMD) is debated.nnnOBJECTIVESnWe investigated factors associated with plasma 25-hydroxyvitamin D [25(OH)D] deficiency and the associations between plasma 25(OH)D concentrations and AMD in elderly subjects.nnnMETHODSnAntioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes (ALIENOR) is a population-based study on eye diseases performed in elderly residents of Bordeaux, France. Plasma 25(OH)D concentrations were assessed from blood samples and categorized as <25 nmol/L (deficiency), 25-49 nmol/L (insufficiency), or ≥50 nmol/L (sufficiency). AMD was classified as: no AMD, early AMD, and late AMD. Associations between baseline characteristics and plasma 25(OH)D status were examined with multinomial logistic regression analysis. Associations between AMD and plasma 25(OH)D status were estimated using generalized estimating equation logistic regressions.nnnRESULTSnSix hundred ninety-seven subjects with complete data were included. The prevalence of plasma 25(OH)D deficiency and insufficiency were 27.3% and 55.9%, respectively. In multivariate analysis, 25(OH)D deficiency was significantly associated with older age (P = 0.0007), females (P = 0.0007), absence of physical activity (P = 0.01), absence of vitamin D supplementation (P < 0.0001), higher plasma total cholesterol (P = 0.007), use of fibrates (P < 0.0001), lower alcohol consumption (P = 0.02), and season of blood sampling (P < 0.0001). After adjustment for these covariates and dietary omega-3 polyunsaturated fatty acid intake, smoking, and body mass index, no significant associations were found between early AMD and 25(OH)D insufficiency or deficiency (OR: 0.71, P = 0.12; OR: 0.73, P = 0.23, respectively) or with late AMD (OR: 1.04, P = 0.93; OR: 0.74, P = 0.59, respectively).nnnCONCLUSIONnThese findings underline the very high prevalence of plasma 25(OH)D deficiency in this elderly population but do not support a specific role for vitamin D in AMD.

Diagnostic Performance of Peripapillary Retinal Nerve Fiber Layer Thickness for Detection of Glaucoma in an Elderly Population: The ALIENOR Study

PurposenTo assess diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) to discriminate glaucoma and control subjects in an elderly population.nnnMethodsnThe antioxidants, essential lipids, nutrition and ocular maladies study (ALIENOR: Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires) is a population-based study. From 2009 to 2010, a total of 624 subjects, aged 74 years or older underwent a complete eye examination, including optic disc color photography and SD-OCT examination of the macula and the optic nerve head. Glaucoma diagnosis was made using retinophotography of the optic nerve head and International Society for Epidemiologic and Geographical Ophthalmology criteria. Average and sectorial peripapillary retinal nerve fiber layer thicknesses (RNFLT) were compared between glaucoma and control subjects using area under the receiver operating characteristic curves (AUC), positive and negative likelihood ratios (LR+/LR-), and diagnostic odds ratios (DOR).nnnResultsnA total of 532 subjects had complete data, 492 were classified as controls and 40 were classified as glaucoma. Mean age was 82.1 ± 4.2 years and average RNFLT was significantly different between both groups (controls: 88.7 ± 12.2 μm, glaucoma: 65.4 ± 14.4 μm, P < 0.001). Highest AUC values were observed for average (0.895), temporal-inferior (0.874), and temporal-superior (0.868) RNFLT. Temporal-superior RNFLT had the highest DOR (25.31; LR+, 4.65; LR-, 0.18), followed by average RNFLT (DOR: 24.80; LR+, 6.36; LR-, 0.26). When using the normative database provided by the machine, DOR increased to 31.03 (LR+, 1.75; LR-, 0.06) if at least one parameter was considered abnormal (at P < 0.05).nnnConclusionsnParameters of SD-OCT RNFL may provide valuable information in a screening strategy to improve glaucoma detection in a general population of elderly people.

Associations of Biomechanical Properties of the Cornea With Environmental and Metabolic Factors in an Elderly Population: The ALIENOR Study

PURPOSEnThe purpose of this study was to assess the associations of biomechanical properties of the cornea with metabolic and environmental factors in an elderly population.nnnMETHODSnThe ALIENOR (Antioxydants, Lipides Essentiels, Nutrition, and Maladies OculaiRes) study is a population-based study. In 2009-2010, 624 subjects, aged 74 years or more, underwent an eye examination, including intraocular pressure (IOP), central corneal thickness (CCT), and biomechanical properties of the cornea measurements using the Ocular Response Analyzer. Socio-demographic, lifestyle, and medical history data were collected using standardized questionnaires. Mean lifetime ambient ultraviolet (UV) exposure was estimated using residential history and statistics of UV radiation at each location using the Eurosun UV database.nnnRESULTSnMean age was 82.2 ± 4.3 years. Mean corneal hysteresis (CH), corneal resistance factor (CRF), and CCT were 9.4 ± 1.9, 9.8 ± 1.9 mm Hg, and 551.6 ± 36.8 μm, respectively. In the multivariate analysis, CH and CRF values were significantly lower in subjects older than 80 years (-0.56; 95% confidence interval [CI]: -0.89; -0.24); P < 0.001 and -0.48; 95% CI: -0.75;-0.20; P < 0.001, respectively), in subjects having higher ambient UV exposure (-0.50; 95% CI: -0.88; -0.12; P < 0.01; and -0.46; 95% CI: -0.78; -0.13); P < 0.05, respectively), and in subjects with high plasma LDL cholesterol (CH: -0.46; 95% CI: -0.86; -0.03; P < 0.05; and CRF: -0.37; 95% CI: -0.72; -0.008; P < 0.05). Central corneal thickness was significantly higher in former smokers than in never smokers (+11.01; 95% CI: 0.48; 21.55; P < 0.05) and was not significantly associated with age, ambient UV exposure, diabetes, or LDL cholesterol.nnnCONCLUSIONSnBiomechanical properties of the cornea are modified by metabolic and lifetime environmental factors, especially UV exposure. The manner these factors may influence onset and progression of ocular diseases or IOP measurements need further investigation.

The Decreasing Prevalence of Nonrefractive Visual Impairment in Older Europeans A Meta-analysis of Published and Unpublished Data

TOPICnTo estimate the prevalence of nonrefractive visual impairment and blindness in European persons 55 years of age and older.nnnCLINICAL RELEVANCEnFew visual impairment and blindness prevalence estimates are available for the European population. In addition, many of the data collected in European population-based studies currently are unpublished and have not been included in previous estimates.nnnMETHODSnFourteen European population-based studies participating in the European Eye Epidemiology Consortium (nxa0= 70u2009723) were included. Each study provided nonrefractive visual impairment and blindness prevalence estimates stratified by age (10-year strata) and gender. Nonrefractive visual impairment and blindness were defined as best-corrected visual acuity worse than 20/60 and 20/400 in the better eye, respectively. Using random effects meta-analysis, prevalence rates were estimated according to age, gender, geographical area, and period (1991-2006 and 2007-2012). Because no data were available for Central and Eastern Europe, population projections for numbers of affected people were estimated using Eurostat population estimates for European high-income countries in 2000 andxa02010.nnnRESULTSnThe age-standardized prevalence of nonrefractive visual impairment in people 55 years of age or older decreased from 2.22% (95% confidence interval [CI], 1.34-3.10) from 1991 through 2006 to 0.92% (95% CI, 0.42-1.42) from 2007 through 2012. It strongly increased with age in both periods (up to 15.69% and 4.39% in participants 85 years of age or older from 1991 through 2006 and from 2007 through 2012, respectively). Age-standardized prevalence of visual impairment tended to be higher in women than men from 1991 through 2006 (2.67% vs. 1.88%), but not from 2007 through 2012 (0.87% vs. 0.88%). No differences were observed between northern, western, and southern regions of Europe. The projected numbers of affected older inhabitants in European high-income countries decreased from 2.5 million affected individuals in 2000 to 1.2 million in 2010. Of those, 584u2009000 were blind in 2000, in comparison with 170u2009000 who were blind inxa02010.nnnCONCLUSIONSnDespite the increase in the European older population, our study indicated that the number of visually impaired people has decreased in European high-income countries in the last 20 years. This may be the result of major improvements in eye care and prevention, the decreasing prevalence of eye diseases, or both.

Identification of prodromal Alzheimer's with serial neuropsychological tests

memory complaints, and the APOE e4 carriage was best in predicting incident probable Alzheimer dementia (R 1⁄4 0.42). An area under the ROC curve of 0.91 was reached. The model achieved a positive predictive value of 23.3% and a negative predictive value of 98.7% and is able to predict Alzheimer dementia with a sensitivity of 82.8% and specificity of 82.4%. Conclusions: AD can be predicted by neuropsychological instruments measuring episodic memory and motor speed. 98.7% of subjects at age 75 years could be predicted as remaining nondemented at age 80 years. Whether the age associated cognitive slowing expressed as a decline in motor speed is a predictor of AD needs further inverstigation.