Association of dietary and nutritional factors with cognitive decline, dementia, and depressive symptomatology in older individuals according to a neurogenesis-centred biological susceptibility to brain ageing.

Hippocampal neurogenesis (HN) occurs throughout the life course and is important for memory and mood. Declining with age, HN plays a pivotal role in cognitive decline (CD), dementia, and late-life depression, such that altered HN could represent a neurobiological susceptibility to these conditions. Pertinently, dietary patterns (e.g., Mediterranean diet) and/or individual nutrients (e.g., vitamin D, omega 3) can modify HN, but also modify risk for CD, dementia, and depression. Therefore, the interaction between diet/nutrition and HN may alter risk trajectories for these ageing-related brain conditions. Using a subsample (n = 371) of the Three-City cohort-where older adults provided information on diet and blood biobanking at baseline and were assessed for CD, dementia, and depressive symptomatology across 12 years-we tested for interactions between food consumption, nutrient intake, and nutritional biomarker concentrations and neurogenesis-centred susceptibility status (defined by baseline readouts of hippocampal progenitor cell integrity, cell death, and differentiation) on CD, Alzheimer's disease (AD), vascular and other dementias (VoD), and depressive symptomatology, using multivariable-adjusted logistic regression models. Increased plasma lycopene concentrations (OR [95% CI] = 1.07 [1.01, 1.14]), higher red meat (OR [95% CI] = 1.10 [1.03, 1.19]), and lower poultry consumption (OR [95% CI] = 0.93 [0.87, 0.99]) were associated with an increased risk for AD in individuals with a neurogenesis-centred susceptibility. Increased vitamin D consumption (OR [95% CI] = 1.05 [1.01, 1.11]) and plasma γ-tocopherol concentrations (OR [95% CI] = 1.08 [1.01, 1.18]) were associated with increased risk for VoD and depressive symptomatology, respectively, but only in susceptible individuals. This research highlights an important role for diet/nutrition in modifying dementia and depression risk in individuals with a neurogenesis-centred susceptibility.

LIFETIME AMBIENT ULTRAVIOLET RADIATION EXPOSURE AND INCIDENCE OF AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the link between lifelong exposure to ultraviolet radiation (UVR) and the development of age-related macular degeneration (AMD). METHODS: The Alienor study is a prospective population-based cohort involving 963 residents of Bordeaux, France, older than 73 years. A subset of 614 participants for advanced AMD and 422 participants for early AMD were included in the analysis. The participants' residential history combined with UVR estimates from the EuroSun satellite were used to estimate the amount of ambient UVR they have been exposed to over their lifetime. Age-related macular degeneration was classified from retinal fundus photographs and spectral domain optical coherence tomography at 2 to 3 years intervals over the 2006 to 2017 period. Associations between cumulative exposure to ultraviolet A, ultraviolet B, and total (total UV) and the incidence of early and advanced AMD were estimated using multivariate Cox models. RESULTS: Intermediate quartiles of total UV, ultraviolet A, and ultraviolet B exposures were associated with a higher risk for incident early AMD (Hazard Ratio [HR] =2.01 [95% confidence interval [CI] = 1.27-3.13], HR = 2.20 [95% CI = 1.38-3.50], HR = 1.79 [95% CI = 1.13-2.80], respectively) as compared with the lower quartile. However, this risk did not further increase in the highest quartiles of exposure. None of the three types of UVR exposure was significantly associated with incident advanced AMD. CONCLUSION: Despite an increased risk with intermediate compared with low UVR exposure, our study cannot confirm a dose-response relationship of UVR exposure with early AMD onset.

Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies.

INTRODUCTION: Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD). METHODS: We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8-11.5] years). RESULTS: General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes. DISCUSSION: These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia.

Association of retinal nerve layers thickness and brain imaging in healthy young subjects from the i-Share-Bordeaux study.

Given the anatomical and functional similarities between the retina and the brain, the retina could be a "window" for viewing brain structures. We investigated the association between retinal nerve fiber layers (peripapillary retinal nerve fiber layer, ppRNFL; macular ganglion cell-inner plexiform layer, GC-IPL; and macular ganglion cell complex, GCC), and brain magnetic resonance imaging (MRI) parameters in young health adults. We included 857 students (mean age: 23.3 years, 71.3% women) from the i-Share study. We used multivariate linear models to study the cross-sectional association of each retinal nerve layer thickness assessed by spectral-domain optical coherence tomography (SD-OCT) with structural (volumes and cortical thickness), and microstructural brain markers, assessed on MRI globally and regionally. Microstructural MRI parameters included diffusion tensor imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI). On global brain analysis, thicker ppRNFL, GC-IPL and GCC were all significantly associated with patterns of diffusion metrics consistent with higher WM microstructural integrity. In regional analyses, after multiple testing corrections, our results suggested significant associations of some retinal nerve layers with brain regional gray matter occipital volumes and with diffusion MRI parameters in a region involved in the visual pathway and in regions containing associative tracts. No associations were found with global volumes or with global or regional cortical thicknesses. Results of this study suggest that some retinal nerve layers may reflect brain structures. Further studies are needed to confirm these results in young subjects.

Association of Systemic Medication Use with Glaucoma and Intraocular Pressure: The European Eye Epidemiology Consortium.

PURPOSE: To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. DESIGN: Meta-analysis of 11 population-based cohort studies of the European Eye Epidemiology Consortium. PARTICIPANTS: The glaucoma analyses included 143 240 participants and the IOP analyses included 47 177 participants. METHODS: We examined associations of 4 categories of systemic medications-antihypertensive medications (ß-blockers, diuretics, calcium channel blockers [CCBs], α-agonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers), lipid-lowering medications, antidepressants, and antidiabetic medications-with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Results of multivariable regression analyses of each study were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in participants with diabetes only. MAIN OUTCOME MEASURES: Glaucoma prevalence and IOP. RESULTS: In the meta-analyses of our maximally adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.08 to 1.39). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR, 1.96; 95% CI, 1.23 to 3.12). No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with glaucoma. Use of systemic ß-blockers was associated with a lower IOP (ß coefficient, -0.33 mmHg; 95% CI, -0.57 to -0.08 mmHg). Monotherapy of both selective systemic ß-blockers (ß coefficient, -0.45 mmHg; 95% CI -0.74 to -0.16 mmHg) and nonselective systemic ß-blockers (ß coefficient, -0.54 mmHg; 95% CI, -0.94 to -0.15 mmHg) was associated with lower IOP. A suggestive association was found between use of high-ceiling diuretics and lower IOP (ß coefficient, -0.30 mmHg; 95% CI, -0.47 to -0.14 mmHg) but not when used as monotherapy. No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with IOP. CONCLUSIONS: We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic ß-blocker use. Both findings potentially are important, given that patients with glaucoma frequently use systemic antihypertensive medications. Determining causality of the CCB association should be a research priority. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Impaired hippocampal neurogenesis in vitro is modulated by dietary-related endogenous factors and associated with depression in a longitudinal ageing cohort study.

Environmental factors like diet have been linked to depression and/or relapse risk in later life. This could be partially driven by the food metabolome, which communicates with the brain via the circulatory system and interacts with hippocampal neurogenesis (HN), a form of brain plasticity implicated in depression aetiology. Despite the associations between HN, diet and depression, human data further substantiating this hypothesis are largely missing. Here, we used an in vitro model of HN to test the effects of serum samples from a longitudinal ageing cohort of 373 participants, with or without depressive symptomology. 1% participant serum was applied to human fetal hippocampal progenitor cells, and changes in HN markers were related to the occurrence of depressive symptoms across a 12-year period. Key nutritional, metabolomic and lipidomic biomarkers (extracted from participant plasma and serum) were subsequently tested for their ability to modulate HN. In our assay, we found that reduced cell death and increased neuronal differentiation were associated with later life depressive symptomatology. Additionally, we found impairments in neuronal cell morphology in cells treated with serum from participants experiencing recurrent depressive symptoms across the 12-year period. Interestingly, we found that increased neuronal differentiation was modulated by increased serum levels of metabolite butyrylcarnitine and decreased glycerophospholipid, PC35:1(16:0/19:1), levels - both of which are closely linked to diet - all in the context of depressive symptomology. These findings potentially suggest that diet and altered HN could subsequently shape the trajectory of late-life depressive symptomology.

Prescribed anti-glaucoma medication consumption and road traffic crash.

BACKGROUND: Glaucoma is one of the leading causes of visual impairment worldwide. Influence of visual defects associated with this condition, as well as potential side effects of anti-glaucoma medications on driving may be a relevant traffic safety concern. This study therefore aimed to investigate whether and/or to what extent prescribed anti-glaucoma medicine consumption is associated with increased likelihood of crash risk, and traffic crash responsibility among drivers involved in road traffic crashes. METHODS: Data from three French national databases were extracted and matched as part of the CESIR (a combination of studies on health and road safety) project. The sample included 201 497 drivers involved in an injurious road crash in France from July 1, 2005 to December 31, 2015, and an age- and sex-matched control group (113 357 drivers) that was randomly drawn from the general population. Exposure to anti-glaucoma medications were compared between responsible and non-responsible drivers involved in a crash and between drivers involved in a crash and people from the control group. RESULTS: The proportion of drivers with prescribed anti-glaucoma medicine markedly increased with age. One type (OR = 0.79, 95% CI: 0.72-0.86) and two or more types (OR = 0.82, 95% CI: 0.68-0.98) anti-glaucoma medicine prescriptions were less frequent in crash-involved drivers than in controls. One type (OR = 0.99, 95% CI: 0.88-1.12) and two or more types (OR = 1.04, 95% CI: 0.82-1.33) anti-glaucoma medicine prescriptions were not associated with crash responsibility. CONCLUSION: Our findings are reassuring as regard to existing guidelines for safe driving for individuals using anti-glaucoma medications. Our results also suggest that driving behavior adaptation is effective mitigating potential traffic crash risks for people diagnosed with glaucoma.

Association of long-term exposure to ambient air pollution with retinal neurodegeneration: the prospective Alienor study.

Chronic exposure to air pollution may have adverse effects on neurodegenerative diseases. Glaucoma, the second leading cause of blindness worldwide, is a neurodegenerative disease of the optic nerve, characterized by progressive thinning of the retinal nerve fiber layer (RNFL). We investigated the relationship of air pollution exposure with longitudinal changes of RNFL thickness in the Alienor study, a population-based cohort of residents of Bordeaux, France, aged 75 years or more. Peripapillary RNFL thickness was measured using optical coherence tomography imaging every 2 years from 2009 to 2020. Measurements were acquired and reviewed by specially trained technicians to control quality. Air pollution exposure (particulate matter ≤2.5 µm (PM2.5), black carbon (BC), nitrogen dioxide (NO2)) was estimated at the participants' geocoded residential address using land-use regression models. For each pollutant, the 10-year average of past exposure at first RNFL thickness measurement was estimated. Associations of air pollution exposure with RNFL thickness longitudinal changes were assessed using linear mixed models adjusted for potential confounders, allowing for intra-eye and intra-individual correlation (repeated measurements). The study included 683 participants with at least one RNFL thickness measurement (62% female, mean age 82 years). The average RNFL was 90 µm (SD:14.4) at baseline. Exposure to higher levels of PM2.5 and BC in the previous 10 years was significantly associated with a faster RNFL thinning during the 11-year follow-up (-0.28 µm/year (95% confidence interval (CI) [-0.44;-0.13]) and -0.26 µm/year (95% CI [-0.40;-0.12]) per interquartile range increment; p < 0.001 for both). The size of the effect was similar to one year of age in the fitted model (-0.36 µm/year). No statistically significant associations were found with NO2 in the main models. This study evidenced a strong association of chronic exposure to fine particulate matter with retinal neurodegeneration, at air pollution levels below the current recommended thresholds in Europe.

Real-World Outcomes of Ranibizumab Treatment in French Patients with Visual Impairment due to Macular Edema Secondary to Retinal Vein Occlusion: 24-Month Results from the BOREAL-RVO Study.

INTRODUCTION: Information about real-world ranibizumab use is needed to optimize treatment of macular edema secondary to retinal vein occlusion (RVO). The BOREAL-RVO study assessed treatment use, effectiveness, and safety of 24-month treatment with ranibizumab 0.5 mg in patients with visual impairment due to macular edema secondary to RVO in a real-world setting. METHODS: This was a multicenter, post-authorization, observational study in France, including patients starting ranibizumab for RVO. Primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) at month 6. Secondary endpoints were mean changes from baseline in BCVA at month 24 and central retinal thickness (CRT) at months 6 and 24, and treatment use in real-world setting. RESULTS: 226 branch RVO (BRVO) and 196 central RVO (CRVO) patients were enrolled; 71.7% and 70.9% completed the 24-month follow-up, respectively. In BRVO, mean (SD) baseline BCVA was 55.2 (18.7) letters, with gains of 14.3 (13.7), 14.1 (16.5), 13.0 (17.5), and 11.4 (20.1) letters at months 3, 6, 12, and 24, respectively. In CRVO, mean (SD) baseline BCVA was 40.4 (25.6) letters, with gains of 16.0 (21.2), 9.5 (25.4), 9.2 (27.7), and 8.3 (23.8) letters at months 3, 6, 12, and 24, respectively. At month 24, 52% of BRVO and 41% of CRVO patients had gains of 15 or more letters. In BRVO, mean (SD) CRT values at baseline and months 3, 6, 12, and 24 were 550 (175), 315 (104), 343 (122), 335 (137), and 340 (105) µm. In CRVO, mean (SD) CRT values at baseline and months 3, 6, 12, and 24 were 643 (217), 327 (152), 400 (203), 379 (175), and 348 (161) µm. On average, BRVO patients had 3.8 injections for 6.9 visits by month 6, and 7.2 injections for 19.7 visits by month 24. CRVO patients had 2.7 injections for 4.2 visits by month 6 and 7.1 injections for 21.1 visits by month 24. Factors predictive of better BCVA gain at month 6 were age under 60 at baseline, lower baseline BCVA and BCVA gain at month 3. There were no new safety findings. CONCLUSION: Major improvements in BCVA and CRT were observed at month 3 after the induction phase and then were sustained up to month 24, with a slight decrease, probably due to under-treatment. This study demonstrated ranibizumab to be a safe and effective treatment for BRVO and CRVO in the real-world setting, although more regular or proactive treatment could further improve outcomes.

The Phenotypic Course of Age-Related Macular Degeneration for ARMS2/HTRA1: The EYE-RISK Consortium.

PURPOSE: Age-related maculopathy susceptibility 2 (ARMS2) is considered the most enigmatic of the genes for age-related macular degeneration (AMD). We investigated the phenotypic course and spectrum of AMD for the risk haplotype at the ARMS2 and high-temperature requirement A serine peptidase 1 (HTRA1) locus in a large European consortium. DESIGN: Pooled analysis of 4 case-control and 6 cohort studies. PARTICIPANTS: Individuals (N = 17 204) aged 55 years or older participating in the European Eye Epidemiology consortium. METHODS: Age-related macular degeneration features and macular thickness were determined on multimodal images; data on genetics and phenotype were harmonized. Risks of AMD features for rs3750486 genotypes at the ARMS2/HTRA1 locus were determined by logistic regression and were compared with a genetic risk score (GRS) of 19 variants at the complement pathway. Lifetime risks were estimated with Kaplan-Meier analyses in population-based cohorts. MAIN OUTCOME MEASURES: Age-related macular degeneration features and stage. RESULTS: Of 2068 individuals with late AMD, 64.7% carried the ARMS2/HTRA1 risk allele. For homozygous carriers, the odds ratio (OR) of geographic atrophy was 8.6 (95% confidence interval [CI], 6.5-11.4), of choroidal neovascularization (CNV) was 11.2 (95% CI, 9.4-13.3), and of mixed late AMD was 12.2 (95% CI, 7.3-20.6). Cumulative lifetime risk of late AMD ranged from 4.4% for carriers of the nonrisk genotype to 9.4% and 26.8% for heterozygous and homozygous carriers. The latter received the diagnosis of late AMD 9.6 years (95% CI, 8.0-11.2) earlier than carriers of the nonrisk genotype. The risk haplotype was not associated with hard or soft drusen < 125 µm (OR, 1.2; 95% CI, 0.9-1.7), but risks increased significantly for soft drusen ≥ 125 µm (OR, 2.1; 95% CI, 1.5-3.0), up to an OR of 7.2 (95% CI, 3.8-13.8) for reticular pseudodrusen. Compared with persons with a high GRS for complement, homozygous carriers of ARMS2/HTRA1 showed a higher risk of CNV (OR, 4.1; 95% CI, 3.2-5.4); risks of other characteristics were not different. CONCLUSIONS: Carriers of the risk haplotype at ARMS2/HTRA1 have a particularly high risk of late AMD at a relatively early age. Data suggest that risk variants at ARMS2/HTRA1 act as a strong catalyst of progression once early signs are present. The phenotypic spectrum resembles that of complement genes, only with higher risks of CNV.

Children's Diet at 2 Years and Trajectories of Hyperactivity-Inattention Symptoms and Conduct Problems Between 3 and 8 Years: The EDEN Cohort.

BACKGROUND: Although the role of diet is increasingly acknowledged in psychiatry, data are still scarce regarding its early impact on the most significant behavioral disorders of childhood (i.e., hyperactivity-inattention and conduct problems). OBJECTIVES: The objective of this study was to explore the relation between children's dietary patterns at 2 years and developmental trajectories of hyperactivity-inattention and conduct problems between 3 and 8 years. METHODS: We recruited 1432 mother-child dyads from the French EDEN (etude sur les déterminants pré- et postnatals du développement et de la santé de l'enfant) mother-child cohort to conduct the analyses. Three dietary patterns, labeled guidelines, processed and fast foods, and baby foods, were identified using an FFQ in children aged 2 years in a previous study. The Strengths and Difficulties Questionnaire was used to assess hyperactivity-inattention and conduct problems at 3, 5, and 8 years of age and build related trajectories from 3 to 8 years. The relation between children's dietary patterns at 2 years and the worst developmental trajectories of hyperactivity-inattention and conduct problems were determined with multivariable logistic regressions adjusted for potential socioeconomic, maternal, and child confounders. RESULTS: The score on the guidelines dietary pattern was negatively associated with the risk of hyperactivity-inattention problems (OR: 0.75; 95% CI: 0.60-0.94), contrary to adherence to the baby foods dietary pattern (OR: 1.41; 95% CI: 1.16-1.71). CONCLUSIONS: Distinct patterns of children's diet at 2 years were predictive of developmental trajectories of hyperactivity-inattention problems between 3 and 8 years. These results highlight the relevance of conducting further studies to clarify the mechanisms involved.

Skin autofluorescence of Advanced Glycation End-products and mortality in older adults: The roles of chronic kidney disease and diabetes.

BACKGROUND AND AIM: Advanced glycation end products are involved in age-related multisystem decline. They accumulate in body tissues with age, diabetes and chronic kidney disease (CKD), and can be measured non-invasively by the skin autofluorescence (SAF). We studied the relation between SAF and later mortality in old adults. METHODS AND RESULTS: The SAF was measured using an AGE-Reader in 451 individuals from the general population aged over 75 years, and all-cause mortality was assessed during an average follow-up of 6.4 years. The association between SAF and mortality was analyzed using a multivariate Cox survival model, adjusted for age and gender. Analyses were further adjusted for diabetes and stratified on the presence of CKD due to its interaction with SAF for the risk of mortality. Participants were 82 years old on average (SD 4.1). Their mean SAF was 2.8 AU (SD 0.6). One hundred and forty-four individuals (31.9%) died during the follow-up. Adjusted for age and gender, SAF was associated with an increased risk of all-cause mortality (HR 1.44, 95%CI: 1.14-1.82 for a one-AU increase of SAF). The association was no longer significant after adjustment for diabetes. However, after stratification for the presence of CKD, higher SAF was associated with an increased risk of all-cause mortality in the participants with CKD at baseline (HR 1.68, 95%CI: 1.11-2.55), whereas there was no association among participants without CKD (HR 0.95, 95%CI: 0.63-1.44). CONCLUSION: Skin autofluorescence is associated with increased all-cause mortality in older adults already suffering from CKD.

Vision Impairment and Adverse Health Conditions in Congolese Older People: A Population-Based Study.

INTRODUCTION: In sub-Saharan Africa, many older people experience vision impairment (VI) and its adverse health outcomes. In this study, we examined separately the association between VI and each adverse health conditions (cognitive disorders, vision-related quality of life [VRQoL], and daily functioning interference [DFI]) among Congolese older people. We also explored whether VI had a significant effect on VRQoL components in our population. METHOD: We performed cross-sectional analyses on data from 660 Congolese people aged ≥65 years who participated in the 2013 survey of the EPIDEMCA population-based cohort study. VI was defined as having a near visual acuity <20/40 (assessed at 30 cm using a Parinaud chart). Cognitive disorders were assessed using neuropsychological tests and neurological examinations. VRQoL was assessed using a reduced version of the National Eye Institute Visual Function Questionnaire (VFQ-22) and DFI using 11 items of participation restrictions and activity limitations. Regarding our main objective, each association was explored separately using multivariable logistic and linear regression models. Additionally, the effects of VI on each VRQoL components were explored using univariable linear regression models. RESULTS: VI was not associated with cognitive disorders after adjustment for residence area (adjusted odds ratio = 1.7; 95% confidence interval [CI]: 0.6; 4.7), but it was associated with a low VRQoL score (adjusted ß = -12.4; 95% CI: -17.5; -7.3) even after controlling for several covariates. An interaction between VI and age (p = 0.007) was identified, and VI was associated with DFI only among people aged >73 years (adjusted ß = 0.5; 95% CI: 0.2; 0.8). Our exploratory analysis showed that all components of VRQoL decreased with a decrease in visual acuity (corrected p ≤ 0.05). CONCLUSION: VI was associated with poor VRQoL and high DFI. Residence area seems to play a confounding role in the association between VI and cognitive disorders. Our findings suggest that targeting interventions on vision could reduce DFI among older people and improve their well-being.

The serum metabolome mediates the concert of diet, exercise, and neurogenesis, determining the risk for cognitive decline and dementia.

INTRODUCTION: Diet and exercise influence the risk of cognitive decline (CD) and dementia through the food metabolome and exercise-triggered endogenous factors, which use the blood as a vehicle to communicate with the brain. These factors might act in concert with hippocampal neurogenesis (HN) to shape CD and dementia. METHODS: Using an in vitro neurogenesis assay, we examined the effects of serum samples from a longitudinal cohort (n = 418) on proxy HN readouts and their association with future CD and dementia across a 12-year period. RESULTS: Altered apoptosis and reduced hippocampal progenitor cell integrity were associated with exercise and diet and predicted subsequent CD and dementia. The effects of exercise and diet on CD specifically were mediated by apoptosis. DISCUSSION: Diet and exercise might influence neurogenesis long before the onset of CD and dementia. Alterations in HN could signify the start of the pathological process and potentially represent biomarkers for CD and dementia.

Predicting Progression to Advanced Age-Related Macular Degeneration from Clinical, Genetic, and Lifestyle Factors Using Machine Learning.

PURPOSE: Current prediction models for advanced age-related macular degeneration (AMD) are based on a restrictive set of risk factors. The objective of this study was to develop a comprehensive prediction model applying a machine learning algorithm allowing selection of the most predictive risk factors automatically. DESIGN: Two population-based cohort studies. PARTICIPANTS: The Rotterdam Study I (RS-I; training set) included 3838 participants 55 years of age or older, with a median follow-up period of 10.8 years, and 108 incident cases of advanced AMD. The Antioxydants, Lipids Essentiels, Nutrition et Maladies Oculaires (ALIENOR) study (test set) included 362 participants 73 years of age or older, with a median follow-up period of 6.5 years, and 33 incident cases of advanced AMD. METHODS: The prediction model used the bootstrap least absolute shrinkage and selection operator (LASSO) method for survival analysis to select the best predictors of incident advanced AMD in the training set. Predictive performance of the model was assessed using the area under the receiver operating characteristic curve (AUC). MAIN OUTCOME MEASURES: Incident advanced AMD (atrophic, neovascular, or both), based on standardized interpretation of retinal photographs. RESULTS: The prediction model retained (1) age, (2) a combination of phenotypic predictors (based on the presence of intermediate drusen, hyperpigmentation in one or both eyes, and Age-Related Eye Disease Study simplified score), (3) a summary genetic risk score based on 49 single nucleotide polymorphisms, (4) smoking, (5) diet quality, (6) education, and (7) pulse pressure. The cross-validated AUC estimation in RS-I was 0.92 (95% confidence interval [CI], 0.88-0.97) at 5 years, 0.92 (95% CI, 0.90-0.95) at 10 years, and 0.91 (95% CI, 0.88-0.94) at 15 years. In ALIENOR, the AUC reached 0.92 at 5 years (95% CI, 0.87-0.98). In terms of calibration, the model tended to underestimate the cumulative incidence of advanced AMD for the high-risk groups, especially in ALIENOR. CONCLUSIONS: This prediction model reached high discrimination abilities, paving the way toward making precision medicine for AMD patients a reality in the near future.

Genetic Risk, Lifestyle, and Age-Related Macular Degeneration in Europe: The EYE-RISK Consortium.

PURPOSE: Age-related macular degeneration (AMD) is a common multifactorial disease in the elderly with a prominent genetic basis. Many risk variants have been identified, but the interpretation remains challenging. We investigated the genetic distribution of AMD-associated risk variants in a large European consortium, calculated attributable and pathway-specific genetic risks, and assessed the influence of lifestyle on genetic outcomes. DESIGN: Pooled analysis of cross-sectional data from the European Eye Epidemiology Consortium. PARTICIPANTS: Seventeen thousand one hundred seventy-four individuals 45 years of age or older participating in 6 population-based cohort studies, 2 clinic-based studies, and 1 case-control study. METHODS: Age-related macular degeneration was diagnosed and graded based on fundus photographs. Data on genetics, lifestyle, and diet were harmonized. Minor allele frequencies and population-attributable fraction (PAF) were calculated. A total genetic risk score (GRS) and pathway-specific risk scores (complement, lipid, extra-cellular matrix, other) were constructed based on the dosage of SNPs and conditional ß values; a lifestyle score was constructed based on smoking and diet. MAIN OUTCOME MEASURES: Intermediate and late AMD. RESULTS: The risk variants with the largest difference between late AMD patients and control participants and the highest PAFs were located in ARMS2 (rs3750846) and CHF (rs570618 and rs10922109). Combining all genetic variants, the total genetic risk score ranged from -3.50 to 4.63 and increased with AMD severity. Of the late AMD patients, 1581 of 1777 (89%) showed a positive total GRS. The complement pathway and ARMS2 were by far the most prominent genetic pathways contributing to late AMD (positive GRS, 90% of patients with late disease), but risk in 3 pathways was most frequent (35% of patients with late disease). Lifestyle was a strong determinant of the outcome in each genetic risk category; unfavorable lifestyle increased the risk of late AMD at least 2-fold. CONCLUSIONS: Genetic risk variants contribute to late AMD in most patients. However, lifestyle factors have a strong influence on the outcome of genetic risk and should be a strong focus in patient management. Genetic risks in ARMS2 and the complement pathway are present in most late AMD patients but are mostly combined with risks in other pathways.

Prenatal Diet and Children's Trajectories of Anxiety and Depression Symptoms from 3 to 8 Years: The EDEN Mother-Child Cohort.

BACKGROUND: Maternal diet quality during pregnancy has been linked to offspring's physical and mental health outcomes across the lifespan. However, few studies have examined its association with subsequent offspring's anxiety and depression issues. OBJECTIVES: The objective of the study was to examine the relationship between maternal prenatal dietary patterns and offspring's anxiety and depression symptoms from 3 to 8 years. METHODS: We used data from 1242 children enrolled in the French EDEN (Etude des déterminants pré- et postnatals précoces du développement et de la santé de l'enfant) birth cohort. Maternal third trimester dietary patterns-namely, "Healthy" (i.e., high intake in fruit, vegetables, fish, and whole-grain cereals) and "Western" (i.e., high intake in processed and snacking foods) patterns-were evaluated using a validated qualitative FFQ. Children's anxiety and depression symptoms (i.e., fears, worries, misery, nervousness, and somatic symptoms) were assessed by mothers using the Strengths and Difficulties Questionnaire at ages 3, 5, and 8 years, from which trajectories were derived using group-based trajectory modeling. We used logistic regressions to analyze the associations between maternal dietary patterns and children's anxiety and depression symptom trajectories. RESULTS: We identified 2 trajectories of anxiety and depression symptoms from 3 to 8 years of age: low to moderate (n = 1058; reference group) and moderately high (n = 184). Maternal low adherence to the Healthy dietary pattern in the third trimester was significantly associated with moderately high children's anxiety and depression symptom trajectories from 3 to 8 years (OR, 1.87; 95% CI, 1.40-2.51), in crude and adjusted analyses. The maternal Western dietary pattern was not significantly associated with anxiety and depression symptom trajectories. CONCLUSIONS: High maternal prenatal adherence to a Healthy dietary pattern was negatively related to anxiety and depression symptoms in children. As maternal diet is a key lifestyle factor, further research should investigate its association with subsequent offspring anxiety and depression symptoms in aiming to later inform prevention strategies focusing on pregnancy.

Self-Reported Vision Impairment and Frailty among Older People with Low Cognitive Performance in Central Africa: EPIDEMCA Population-Based Study.

INTRODUCTION: Very little is known about the impact of vision impairment (VI) on physical health in late-life in sub-Saharan Africa populations, whereas many older people experience it. We investigated the association between self-reported VI and frailty in Central African older people with low cognitive performance. METHODS: It was cross-sectional analysis of data from the Epidemiology of Dementia in Central Africa (EPIDEMCA) population-based study. After screening for cognitive impairment, older people with low cognitive performance were selected. Frailty was assessed using the Study of Osteoporotic Fracture index. Participants who met one of the 3 parameters assessed (unintentional weight loss, inability to do 5 chair stands, and low energy level) were considered as pre-frail, and those who met 2 or more parameters were considered as frail. VI was self-reported. Associations were investigated using multinomial logistic regression models. RESULTS: Out of 2,002 older people enrolled in EPIDEMCA, 775 (38.7%) had low cognitive performance on the screening test. Of them, 514 participants (sex ratio: 0.25) had available data on VI and frailty and were included in the analyses. In total, 360 (70%) self-reported VI. Prevalence of frailty was estimated at 64.9% [95% confidence interval: 60.9%-69.1%] and 23.7% [95% CI: 20.1%-27.4%] for pre-frailty. After full adjustment, self-reported VI was associated with frailty (adjusted odds ratio = 2.2; 95% CI: 1.1-4.3) but not with pre-frailty (adjusted odds ratio = 1.8; 95% CI: 0.9-3.7). CONCLUSION: In Central African older people with low cognitive performance, those who self-reported VI were more likely to experience frailty. Our findings suggest that greater attention should be devoted to VI among this vulnerable population in order to identify early frailty onset and provide adequate care management.

INCIDENCE, PROGRESSION, AND RISK FACTORS OF EPIRETINAL MEMBRANES IN THE ELDERLY.

PURPOSE: To determine the incidence, progression rate, and risk factors for epiretinal membranes (ERMs) in a population of French elderly subjects. METHODS: Seven hundred and thirty-five eyes of 413 participants of the population-based ALIENOR study were included between 2009 and 2010. Participants were re-evaluated every 2 years between 2011 and 2017 (i.e., three follow-up visits). The mean duration of follow-up was 5.09 years (SD, 1.8; range, 0.99-7.85). Epiretinal membranes were graded from spectral-domain optical coherence tomography images according to a standardized classification. RESULTS: The incidence rate of ERMs was 9.42 per 100 eye-years (95% confidence interval, 7.36-12.05), corresponding to a 5-year cumulative incidence of 37.6%. In the final multivariable model, ERM incidence was significantly associated with vitreomacular or vitreopapillary adhesion at baseline (hazard ratio, 2.15; P = 0.02), choroidal thinning (hazard ratio, 1.04 per 10 µm decrease; P = 0.02), ERM in the contralateral eye (P = 0.02), and smoking after 85 years (hazard ratio, 6.01; P = 0.003). The 5-year cumulative progression rate was 6.9%. CONCLUSION: Incidence of ERMs was higher in our population than that previously reported, most probably because of the use of spectral-domain optical coherence tomography images. Incident ERMs were found to be associated with vitreous adhesion at baseline, choroidal thinning, ERM in the contralateral eye, and smoking after 85 years.

EPIDEMIOLOGY OF VITREOMACULAR INTERFACE ABNORMALITIES USING MACULAR SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY IN AN ELDERLY POPULATION (THE MONTRACHET STUDY).

PURPOSE: The aim of this study was to investigate the prevalence of vitreomacular interface abnormalities (VMIAs) and to identify associated factors in an elderly population in Europe. METHODS: The MONTRACHET (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases) Study is a population-based study, conducted in subjects older than 75 years. Vitreomacular adhesions, vitreomacular tractions, macular holes, epiretinal membranes, and macular cysts were assessed on spectral-domain optical coherence tomography examinations. The prevalence of VMIAs was estimated. We studied the association of demographic and clinical factors with VMIAs. RESULTS: The mean age of the participants was 82.3 (SD, 3.8) years, and 37.3% were men. The prevalence rates of VMIAs were vitreomacular adhesions (17.7%), vitreomacular tractions (1.4%), lamellar macular holes (1.0%), full-thickness macular holes (0.2%), macular pseudoholes (0.4%), epiretinal membranes (38.9%), and macular cysts (5.8%). In multivariate analysis, vitreomacular adhesions were positively associated with male sex (P < 0.001) and negatively associated with older age (P < 0.001) and cataract extraction (P < 0.001). Epiretinal membranes were positively associated with older age (P < 0.001) and cataract extraction (P < 0.001). CONCLUSION: The prevalence of VMIAs based on spectral-domain optical coherence tomography analysis was high in subjects older than 75 years.