Shared genetic aetiology of Alzheimer's disease and age-related macular degeneration by APOC1 and APOE genes.

Background: Alzheimer's disease (AD) and age-related macular degeneration (AMD) share similar pathological features, suggesting common genetic aetiologies between the two. Investigating gene associations between AD and AMD may provide useful insights into the underlying pathogenesis and inform integrated prevention and treatment for both diseases. Methods: A stratified quantile-quantile (QQ) plot was constructed to detect the pleiotropy among AD and AMD based on genome-wide association studies data from 17 008 patients with AD and 30 178 patients with AMD. A Bayesian conditional false discovery rate-based (cFDR) method was used to identify pleiotropic genes. UK Biobank was used to verify the pleiotropy analysis. Biological network and enrichment analysis were conducted to explain the biological reason for pleiotropy phenomena. A diagnostic test based on gene expression data was used to predict biomarkers for AD and AMD based on pleiotropic genes and their regulators. Results: Significant pleiotropy was found between AD and AMD (significant leftward shift on QQ plots). APOC1 and APOE were identified as pleiotropic genes for AD-AMD (cFDR <0.01). Network analysis revealed that APOC1 and APOE occupied borderline positions on the gene co-expression networks. Both APOC1 and APOE genes were enriched on the herpes simplex virus 1 infection pathway. Further, machine learning-based diagnostic tests identified that APOC1, APOE (areas under the curve (AUCs) >0.65) and their upstream regulators, especially ZNF131, ADNP2 and HINFP, could be potential biomarkers for both AD and AMD (AUCs >0.8). Conclusion: In this study, we confirmed the genetic pleiotropy between AD and AMD and identified APOC1 and APOE as pleiotropic genes. Further, the integration of multiomics data identified ZNF131, ADNP2 and HINFP as novel diagnostic biomarkers for AD and AMD.

The association between cataract surgery and mental health in older adults: a review.

BACKGROUND: Although cataract surgery has been proposed as a potentially modifiable protective factor for enhancing emotional well-being in cataract patients, studies examining the relationship between anxiety or depression and cataract surgery have yielded inconsistent findings. This review summarizes existing evidence to establish whether cataract surgery is associated with depression and anxiety in older adults. METHODS: A literature search was conducted across PubMed, Medline, Web of Science, and Embase databases. An initial screening by abstracts and titles was performed, followed by a review and assessment of the methodological quality of the relevant full papers, and final inclusion of 44 studies were deemed eligible for inclusion in this review. RESULTS: Among 44 included studies, 36 studies (81.8%) were observational studies concerning the association of cataract surgery or cataracts with anxiety or depression, four studies (9.1%) were interventional studies, and four studies (9.1%) were reviews. Cataract surgery notably enhances the mental health of individuals with impaired vision. However, the multifaceted nature of psychological well-being, influenced by various factors, suggests that cataract surgery may not address all aspects comprehensively. Additionally, preoperative anxiety and depression significantly impact cataract surgery outcomes. CONCLUSION: Vision impairment in older adults is closely associated with increased symptoms of depression and anxiety. While surgical intervention for cataracts improves these symptoms, it might be less effective for mental disorders with multifactorial causes. Notably, anxiety or depression poses challenges to successful preoperative and intraoperative cataract surgeries.

Epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adults.

Age-related cataract and hearing difficulties are major sensory disorders that often co-exist in the global-wide elderly and have a tangible influence on the quality of life. However, the epidemiologic association between cataract and hearing difficulties remains unexplored, while little is known about whether the two share their genetic etiology. We first investigated the clinical association between cataract and hearing difficulties using the UK Biobank covering 502,543 individuals. Both unmatched analysis (adjusted for confounders) and a matched analysis (one control matched for each patient with cataract according to confounding factors) were undertaken and confirmed that cataract was associated with hearing difficulties (OR, 2.12; 95% CI, 1.98-2.27; OR, 2.03; 95% CI, 1.86-2.23, respectively). Furthermore, we explored and quantified the shared genetic architecture of these two complex sensory disorders at the common variant level using the bivariate causal mixture model (MiXeR) and conditional/conjunctional false discovery rate method based on the largest available genome-wide association studies of cataract (N = 585,243) and hearing difficulties (N = 323,978). Despite detecting only a negligible genetic correlation, we observe polygenic overlap between cataract and hearing difficulties and identify 6 shared loci with mixed directions of effects. Follow-up analysis of the shared loci implicates candidate genes QKI, STK17A, TYR, NSF, and TCF4 likely contribute to the pathophysiology of cataracts and hearing difficulties. In conclusion, this study demonstrates the presence of epidemiologic association between cataract and hearing difficulties and provides new insights into the shared genetic architecture of these two disorders at the common variant level.

Combination of serum markers with optical coherence tomography angiography for evaluating neuromyelitis optica spectrum disorders and multiple sclerosis.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS), autoimmune inflammatory diseases of the central nervous system, affect the optic nerve and brain. A lumbar puncture to obtain biomarkers is highly invasive. Serum biomarkers and optical coherence tomography angiography (OCTA) are more accessible and less expensive than magnetic resonance imaging and provide reliable, reproducible measures of neuroaxonal damage. This study investigated the association between serum neurofilament light chain (sNfL), serum glial fibrillary acidic protein (sGFAP), and OCTA metrics. Serum sNfL and sGFAP levels, OCTA values, and clinical characteristics were compared among 91 patients with NMOSD, 81 patients with MS, and 34 healthy controls (HCs) at baseline and 1-year follow-up. RESULTS: sNfL and sGFAP levels were higher while the sGFAP/sNfL quotients were significantly lower in NMOSD and MS patients than those in HCs. At baseline, the average thicknesses of the peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGC-IPL) were significantly smaller in NMOSD and MS patients than those in HCs (pRNFL: MS 92.0 [80.2; 101] µm, NMOSD 80.0 [59.0; 95.8] µm, vs HC 99.0 [92.0; 104] µm, p < 0.001; mGC-IPL: MS 74.5 [64.2; 81.0] µm, NMOSD 68.0 [56.0; 81.0] µm, vs HC 83.5 [78.0; 88.0] µm, p < 0.001). The vessel density (VD) and perfusion density (PD) were increased in MS patients without optic neuritis compared to HCs (VD: MS 16.7 [15.6; 17.9] HC 15.3 [13.4; 16.9], p = 0.008; PD: MS 0.41 [0.38; 0.43], HC 0.37 [0.32; 0.41], p = 0.017). In NMOSD patients without optic neuritis, sNfL was significantly associated with PD at baseline (r = 0.329, q = 0.041). The baseline and follow-up values of the sNfL level and average pRNFL and mGC-IPL thicknesses in MS patients showed significant differences. NMOSD patients showed significant differences between baseline and follow-up sNfL and sGFAP levels but not OCTA metrics. CONCLUSION: Changes in retinal microvasculature might occur earlier than those in retinal structure and may therefore serve as a promising diagnostic marker for early NMOSD. The combination of serum markers and OCTA metrics could be used to evaluate and differentiate between MS and NMOSD.

Evaluation of the Observational Associations and Shared Genetics Between Glaucoma With Depression and Anxiety.

Purpose: Glaucoma, a leading cause of blindness worldwide, is suspected to exhibit a notable association with psychological disturbances. This study aimed to investigate epidemiological associations and explore shared genetic architecture between glaucoma and mental traits, including depression and anxiety. Methods: Multivariable logistic regression and Cox proportional hazards regression models were employed to investigate longitudinal associations based on UK Biobank. A stepwise approach was used to explore the shared genetic architecture. First, linkage disequilibrium score regression inferred global genetic correlations. Second, MiXeR analysis quantified the number of shared causal variants. Third, specific shared loci were detected through conditional/conjunctional false discovery rate (condFDR/conjFDR) analysis and characterized for biological insights. Finally, two-sample Mendelian randomization (MR) was conducted to investigate bidirectional causal associations. Results: Glaucoma was significantly associated with elevated risks of hospitalized depression (hazard ratio [HR] = 1.54; 95% confidence interval [CI], 1.01-2.34) and anxiety (HR = 2.61; 95% CI, 1.70-4.01) compared to healthy controls. Despite the absence of global genetic correlations, MiXeR analysis revealed 300 variants shared between glaucoma and depression, and 500 variants shared between glaucoma and anxiety. Subsequent condFDR/conjFDR analysis discovered 906 single-nucleotide polymorphisms (SNPs) jointly associated with glaucoma and depression and two associated with glaucoma and anxiety. The MR analysis did not support robust causal associations but indicated the existence of pleiotropic genetic variants influencing both glaucoma and depression. Conclusions: Our study enhances the existing epidemiological evidence and underscores the polygenic overlap between glaucoma and mental traits. This observation suggests a correlation shaped by pleiotropic genetic variants rather than being indicative of direct causal relationships.

Metabolomic age and risk of 50 chronic diseases in community-dwelling adults: A prospective cohort study.

It is unclear how metabolomic age is associated with the risk of a wide range of chronic diseases. Our analysis included 110,692 participants (training: n = 27,673; testing: n = 27,673; validating: n = 55,346) aged 39-71 years at baseline (2006-2010) from the UK Biobank. Incident chronic diseases were identified using inpatient records, or death registers until January 2021. Predicted metabolomic age was trained and tested based on 168 metabolomics. Metabolomic age was linked to the risk of 50 diseases in the validation dataset. The median follow-up duration for individual diseases ranged from 11.2 years to 11.9 years. After controlling for false discovery rate, chronological age-adjusted age gap (CAAG) was significantly associated with the incidence of 25 out of 50 chronic diseases. After adjustment for full covariates, associations with 15 chronic diseases remained significant. Greater CAAG was associated with increased risk of eight cardiometabolic disorders (including cardiovascular diseases and diabetes), some cancers, alcohol use disorder, chronic obstructive pulmonary disease, chronic kidney disease, chronic liver disease and age-related macular degeneration. The association between CAAG and risk of peripheral vascular disease, other cardiac diseases, fracture, cataract and thyroid disorder was stronger among individuals with unhealthy diet than in those with healthy diet. The association between CAAG and risk of some conditions was stronger in younger individuals, those with metabolic disorders or low education. Metabolomic age plays an important role in the development of multiple chronic diseases. Healthy diet and high education may mitigate the risk for some chronic diseases due to metabolomic age acceleration.

Leading determinants of incident dementia among individuals with and without the apolipoprotein E ε4 genotype: a retrospective cohort study.

BACKGROUND: Little is known regarding the leading risk factors for dementia/Alzheimer's disease (AD) in individuals with and without APOE4. The identification of key risk factors for dementia/Alzheimer's disease (AD) in individuals with and without the APOE4 gene is of significant importance in global health. METHODS: Our analysis included 110,354 APOE4 carriers and 220,708 age- and sex-matched controls aged 40-73 years at baseline (between 2006-2010) from UK Biobank. Incident dementia was ascertained using hospital inpatient, or death records until January 2021. Individuals of non-European ancestry were excluded. Furthermore, individuals without medical record linkage were excluded from the analysis. Moderation analysis was tested for 134 individual factors. RESULTS: During a median follow-up of 11.9 years, 4,764 cases of incident all-cause dementia and 2065 incident AD cases were documented. Hazard ratios (95% CIs) for all-cause dementia and AD associated with APOE4 were 2.70(2.55-2.85) and 3.72(3.40-4.07), respectively. In APOE4 carriers, the leading risk factors for all-cause dementia included low self-rated overall health, low household income, high multimorbidity risk score, long-term illness, high neutrophil percentage, and high nitrogen dioxide air pollution. In non-APOE4 carriers, the leading risk factors included high multimorbidity risk score, low overall self-rated health, low household income, long-term illness, high microalbumin in urine, high neutrophil count, and low greenspace percentage. Population attributable risk for these individual risk factors combined was 65.1%, and 85.8% in APOE4 and non-APOE4 carriers, respectively. For 20 risk factors including multimorbidity risk score, unhealthy lifestyle habits, and particulate matter air pollutants, their associations with incident dementia were stronger in non-APOE4 carriers. For only 2 risk factors (mother's history of dementia, low C-reactive protein), their associations with incident all-cause dementia were stronger in APOE4 carriers. CONCLUSIONS: Our findings provide evidence for personalized preventative approaches to dementia/AD in APOE4 and non-APOE4 carriers. A mother's history of dementia and low levels of C-reactive protein were more important risk factors of dementia in APOE4 carriers whereas leading risk factors including unhealthy lifestyle habits, multimorbidity risk score, inflammation and immune-related markers were more predictive of dementia in non-APOE4 carriers.

Incidence of and risk factors for suspected and definitive glaucoma after bilateral congenital cataract surgery: a 5-year follow-up.

AIMS: To report the incidence and associated risk factors for developing suspected and definitive glaucoma after bilateral congenital cataract (CC) removal with a 5-year follow-up. METHODS: Secondary analysis of a prospective longitudinal cohort study. Bilateral CC patients who had undergone cataract surgery between January 2011 and December 2014 at Zhongshan Ophthalmic Centre were recruited. Suspected glaucoma was defined as persistent ocular hypertension requiring medical treatment. Definitive glaucoma was defined as accompanied by the progression of glaucomatous clinical features. According to postoperative lens status in 5 years follow-up: 130 eyes in the aphakia group; 219 in the primary intraocular lens (IOL) implantation group and 337 in the secondary IOL implantation group. The Kaplan-Meier survival and Cox regression analyses were used to explore the cumulative incidence and risk factors for suspected and definitive glaucoma. RESULTS: Three hundred fifty-one children (686 eyes) with bilateral CCs were enrolled in the study. The mean age at surgery was 1.82±2.08 years, and the mean follow-up duration was 6.26±0.97 years. Suspected and definitive glaucoma developed at a mean time of 2.84±1.75 years (range 0.02-7.33 years) postoperatively. The cumulative incidence of suspected and definitive glaucoma was 9.97% (35 of 351 patients), including 6.12% (42 eyes) for definitive glaucoma and 2.48% (17 eyes) for suspected glaucoma. Microcornea (HR 4.103, p<0.0001), CC family history (HR 3.285, p=0.001) and initial anterior vitrectomy (HR 2.365 p=0.036) were risk factors for suspected and definitive glaucoma. Gender, age at surgery, intraocular surgery frequency, length of follow-up and frequency of neodymium-doped yttrium aluminumaluminium garnet laser were non-statistically significant. Primary IOL implantation was a protective factor (HR 0.378, p=0.007). CONCLUSIONS: Identifying suspected and definitive glaucoma after bilateral CC surgery can lower the risk of secondary blindness in children. Patients with related risk factors need to pay more attention and thus reach early intervention and treatment during clinical practice. Primary IOL implantation may be a potential protective factor, need more clinical trials to be verified. TRIAL REGISTRATION NUMBER: NCT04342052.

Alterations of outer retinal reflectivity in diabetic patients without clinically detectable retinopathy.

PURPOSE: This study aimed to investigate alterations of outer retinal reflectivity on spectral-domain optical coherence tomography (OCT) in diabetic patients without clinically detectable retinopathy (NDR). METHODS: In this retrospective study, 64 NDR patients and 71 controls were included. Relative reflectivity (RR) of the ellipsoid zone (EZ), photoreceptor outer segment (OS) and inner segment (IS), and outer nuclear layer (ONL) at the foveola and at 500 µm, 1000 µm, and 2000 µm nasal (N), temporal (T), superior (S), and inferior (I) to the foveola was measured by cross-line OCT and ImageJ. Retinal vessel densities (VD) in fovea, parafovea, and perifovea areas were detected by OCT angiography (OCTA). RESULTS: EZ RR in most retinal locations was significantly lower in NDR eyes compared to controls (all P < 0.05), except the foveola. Compared with controls, NDR eyes also displayed lower RR at N2000, T2000, S1000, and I1000 of OS, at S500 and I500 of IS, and at I500 of ONL (all P < 0.05). Negative correlations could be observed between retinal RR and diabetes duration, HbA1c, and best-corrected visual acuity (BCVA) (r = - 0.303 to - 0.452). Compared to controls, EZ, OS, and IS RR of the NDR eyes showed lower correlation coefficients with whole image SCP and DCP VD of parafovea and perifovea regions. CONCLUSION: Outer retinal reflectivity, along with the coefficients between retinal reflectivity and VD, is reduced in NDR patients and is correlated with diabetes duration, HbA1c, and BCVA. The reduction of outer retinal reflectivity may be a potential biomarker of early retinal alterations in diabetic patients.

Healthy dietary patterns and the risk of individual chronic diseases in community-dwelling adults.

It is unclear regarding associations of dietary patterns with a wide range of chronic diseases and which dietary score is more predictive of major chronic diseases. Using the UK Biobank, we examine associations of four individual healthy dietary scores with the risk of 48 individual chronic diseases. Higher Alternate Mediterranean Diet score is associated with a lower risk of 32 (all 8 cardiometabolic disorders, 3 out of 10 types of cancers, 7 out of 10 psychological/neurological disorders, 5 out of 6 digestive disorders, and 9 out of 14 other chronic diseases). Alternate Healthy Eating Index-2010 and Healthful Plant-based Diet Index are inversely associated with the risk of 29 and 23 individual chronic diseases, respectively. A higher Anti-Empirical Dietary Inflammatory Index is associated with a lower risk of 14 individual chronic diseases and a higher incidence of two diseases. Our findings support dietary guidelines for the prevention of most chronic diseases.

Determinants of incident atherosclerotic cardiovascular disease events among individuals with type 2 diabetic microvascular complications in the UK: a prospective cohort study.

OBJECTIVE: To evaluate the association of atherosclerotic cardiovascular disease (ASCVD) risk factors with incident ASCVD events among type 2 diabetes (T2D) individuals with microvascular complications. METHODS: We included T2D participants with only microvascular complications from the UK Biobank cohort at baseline (2006-2010). Multivariable-adjusted Cox proportional hazards models were used to study the association between ASCVD risk factors with adjudicated incident ASCVD in T2D participants with only microvascular complications. A restricted cubic spline approach was employed to evaluate potential nonlinear associations between ASCVD risk factors and ASCVD. RESULTS: We studied 4,129 T2D individuals with microvascular complications at baseline. Over a median follow-up of 11.7 years, a total of 1,180 cases of incident ASCVD were documented, of which 1,040 were CHD, 100 were stroke, and 40 were both CHD and stroke events. After multivariable-adjustment, high-density lipoprotein cholesterol (HDL-C) level was linearly associated with a decreased risk of incident ASCVD [hazard ratio (HR): 0.49, 95% Confidence interval (CI): 0.32-0.75, Plinear = 0.011] and each 10 nmol/L increase of lipoprotein(a) [Lp(a)] level (HR: 1.02, 95% CI: 1.00-1.04, Plinear = 0.012) was linearly associated with an increased risk of incident ASCVD in T2D participants with only microvascular complications. CONCLUSION: HDL-C levels and Lp(a) levels (per 10 nmol/L) showed an independent linear relation with ASCVD risk among T2D individuals with only microvascular complications at long-term follow-up.

Determinants of Incident Atherosclerotic Cardiovascular Disease Events and All-Cause Mortality in Patients With Age-Related Macular Degeneration: Prospective Cohort Study of UK Biobank.

PURPOSE: Major risk factors of atherosclerotic cardiovascular disease (ASCVD) and mortality have been well-established in the general population. Our study is aimed at assessing longitudinal relationships between ASCVD risk factors and incident ASCVD events or all-cause mortality in patients with age-related macular degeneration (AMD). METHODS: Multivariable-adjusted Cox proportional hazards models were used to study the association between cardiovascular risk factors with adjudicated incident ASCVD events and all-cause mortality outcomes followed until 2021. A restricted cubic spline approach was utilized to assess nonlinear associations between potential cardiovascular risk factors and ASCVD or mortality. RESULTS: We identified 3508 eligible patients [mean (SD) age = 61.45 (6.43) years; 37.76% males] with AMD at baseline. During a median follow-up year of 12, there were 110 cases of ASCVD events and 186 cases of all-cause mortality. After multivariable adjustment, each 10 U/L increase of serum gamma-glutamyl transferase level was linearly associated with incident ASCVD [hazard ratio (HR) = 1.03, 95% CI = 1.00-1.07, Pnonlinear = 0.85)] in AMD. A history of chronic kidney disease (HR = 1.94, 95% CI = 1.09-3.46) and lower vitamin D [HR = 0.98, 95% CI = 0.97-0.99, per nanomoles per liter (nmol/L)] were significantly associated with all-cause mortality in patients with AMD, with the association between vitamin D and all-cause mortality presenting a U shape (Pnonlinear = 0.02). In contrast, risk factors significantly associated with ASCVD and all-cause mortality in healthy controls differed from patients with AMD. CONCLUSIONS: Our findings demonstrate risk factors associated with ASCVD events and all-cause mortality among individuals with AMD differed from healthy controls and suggest the long-term management of risk factors in patients with AMD.

EBD: an eye biomarker database.

MOTIVATION: Many ophthalmic disease biomarkers have been identified through comprehensive multiomics profiling, and hold significant potential in advancing the diagnosis, prognosis, and management of diseases. Meanwhile, the eye itself serves as a natural biomarker for several systemic diseases including neurological, renal, and cardiovascular systems. We aimed to collect and standardize this eye biomarkers information and construct the eye biomarker database (EBD) to provide ophthalmologists with a platform to search, analyze, and download these eye biomarker data. RESULTS: In this study, we present the EBD , a world-first online compilation comprising 889 biomarkers for 26 ocular diseases and 939 eye biomarkers for 181 systemic diseases. The EBD also includes the information of 78 "nonbiomarkers"-the objects that have been proven cannot be biomarkers. Biological function and network analysis were conducted for these ocular disease biomarkers, and several hub pathways and common network topology characteristics were newly identified, which may promote future ocular disease biomarker discovery and characterizes the landscape of biomarkers for eye diseases at the pathway and network level. The EBD is expected to yield broader utility among developmental biologists and clinical scientists in and outside of the eye field by assisting in the identification of biomarkers linked to eye disorders and related systemic diseases. AVAILABILITY AND IMPLEMENTATION: EBD is available at http://www.eyeseeworld.com/ebd/index.html.

Integrating oculomics with genomics reveals imaging biomarkers for preventive and personalized prediction of arterial aneurysms.

Objective: Arterial aneurysms are life-threatening but usually asymptomatic before requiring hospitalization. Oculomics of retinal vascular features (RVFs) extracted from retinal fundus images can reflect systemic vascular properties and therefore were hypothesized to provide valuable information on detecting the risk of aneurysms. By integrating oculomics with genomics, this study aimed to (i) identify predictive RVFs as imaging biomarkers for aneurysms and (ii) evaluate the value of these RVFs in supporting early detection of aneurysms in the context of predictive, preventive and personalized medicine (PPPM). Methods: This study involved 51,597 UK Biobank participants who had retinal images available to extract oculomics of RVFs. Phenome-wide association analyses (PheWASs) were conducted to identify RVFs associated with the genetic risks of the main types of aneurysms, including abdominal aortic aneurysm (AAA), thoracic aneurysm (TAA), intracranial aneurysm (ICA) and Marfan syndrome (MFS). An aneurysm-RVF model was then developed to predict future aneurysms. The performance of the model was assessed in both derivation and validation cohorts and was compared with other models employing clinical risk factors. An RVF risk score was derived from our aneurysm-RVF model to identify patients with an increased risk of aneurysms. Results: PheWAS identified a total of 32 RVFs that were significantly associated with the genetic risks of aneurysms. Of these, the number of vessels in the optic disc ('ntreeA') was associated with both AAA (ß = -0.36, P = 6.75e-10) and ICA (ß = -0.11, P = 5.51e-06). In addition, the mean angles between each artery branch ('curveangle_mean_a') were commonly associated with 4 MFS genes (FBN1: ß = -0.10, P = 1.63e-12; COL16A1: ß = -0.07, P = 3.14e-09; LOC105373592: ß = -0.06, P = 1.89e-05; C8orf81/LOC441376: ß = 0.07, P = 1.02e-05). The developed aneurysm-RVF model showed good discrimination ability in predicting the risks of aneurysms. In the derivation cohort, the C-index of the aneurysm-RVF model was 0.809 [95% CI: 0.780-0.838], which was similar to the clinical risk model (0.806 [0.778-0.834]) but higher than the baseline model (0.739 [0.733-0.746]). Similar performance was observed in the validation cohort, with a C-index of 0.798 (0.727-0.869) for the aneurysm-RVF model, 0.795 (0.718-0.871) for the clinical risk model and 0.719 (0.620-0.816) for the baseline model. An aneurysm risk score was derived from the aneurysm-RVF model for each study participant. The individuals in the upper tertile of the aneurysm risk score had a significantly higher risk of aneurysm compared to those in the lower tertile (hazard ratio = 17.8 [6.5-48.8], P = 1.02e-05). Conclusion: We identified a significant association between certain RVFs and the risk of aneurysms and revealed the impressive capability of using RVFs to predict the future risk of aneurysms by a PPPM approach. Our finds have great potential to support not only the predictive diagnosis of aneurysms but also a preventive and more personalized screening plan which may benefit both patients and the healthcare system. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00315-7.

Physicochemical Characterizations, Digestibility, and Lipolysis Inhibitory Effects of Highland Barley Resistant Starches Prepared by Physical and Enzymatic Methods.

This study aimed to investigate the differences in the physicochemical and structural characteristics, digestibility, and lipolysis inhibitory potential in vitro of highland barley resistant starches (HBRSs) prepared by autoclaving (HBSA), microwave-assisted autoclaving (HBSM), isoamylase (HBSI) and pullulanase (HBSP) debranching modifications. Results revealed that the resistant starch content of native starch was significantly elevated after modifications. HBSA and HBSM showed distinctly higher swelling power and water-binding capacities along with lower amylose amounts and solubilities than those of HBSI and HBSP (p < 0.05). Fourier transform infrared spectroscopy and X-ray diffraction exhibited that HBSP displayed the highest degree of the ordered crystalline region and crystallinity with a mixture of CB- and V-type polymorphs. Meanwhile, HBSA and HBSM were characterized by their high degree of the amorphous region with a mixture of B- and V-type polymorphs. Physical and enzymatic modifications resulted in different functionalities of HBRSs, among which HBSP showed the lowest digestibility and HBSM exhibited the highest inhibitory activity on lipolysis due to their structure and structure-based morphology and particle size. This study provided significant insights into the development of native starch from highland barley as an alternative functional food.

The associations and mediators between visual disabilities and anxiety disorders in middle-aged and older adults: A population-based study.

Visual disabilities significantly impact an individual's mental health. Little is known about the prospective relationship between visual disabilities and anxiety disorders and the underlying effects of modifiable risk factors. Our analysis was based on 117,252 participants from the U.K. Biobank, with baseline data collected between 2006 and 2010. Habitual visual acuity was measured by a standardized logarithmic chart, and ocular disorders reported using questionnaires were collected at baseline. Incident hospitalized anxiety recorded using longitudinal linkage with hospital inpatient data, lifetime anxiety disorder, and current anxiety symptoms assessed by a comprehensive online mental health questionnaire were identified over a 10-year follow-up. After adjustments for confounding factors, one-line worse visual acuity (0.1 logarithm of the minimum angle of resolution [logMAR]) was associated with an increased risk of incident hospitalized anxiety (HR = 1.05, 95% CI = 1.01-1.08), lifetime anxiety disorder (OR = 1.07, 95% CI [1.01-1.12]), and current anxiety scores (ß = 0.028, 95% CI [0.002-0.054]). Besides poorer visual acuity, the longitudinal analysis also supported that each ocular disorder (including cataracts, glaucoma, macular degeneration, and diabetes-related eye disease) was significantly associated with at least two anxiety outcomes. Mediation analyses highlighted that subsequent onsets of eye diseases, especially cataracts, and lower socioeconomic status (SES) partly mediated the association between poorer visual acuity and anxiety disorders. This study demonstrates an overall association between visual disabilities and anxiety disorders in middle-aged and older adults. In particular, early interventions involving treatments for visual disabilities and effective psychological counseling services sensitive to socioeconomic status may help prevent anxiety in those living with poor vision. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Leading mediators of sex differences in the incidence of dementia in community-dwelling adults in the UK Biobank: a retrospective cohort study.

BACKGROUND: Little is known regarding whether sex assigned at birth modifies the association between several predictive factors for dementia and the risk of dementia itself. METHODS: Our retrospective cohort study included 214,670 men and 214,670 women matched by age at baseline from the UK Biobank. Baseline data were collected between 2006 and 2010, and incident dementia was ascertained using hospital inpatient or death records until January 2021. Mediation analysis was tested for 133 individual factors. RESULTS: Over 5,117,381 person-years of follow-up, 5928 cases of incident all-cause dementia (452 cases of young-onset dementia, 5476 cases of late-onset dementia) were documented. Hazard ratios (95% CI) for all-cause, young-onset, and late-onset dementias associated with the male sex (female as reference) were 1.23 (1.17-1.29), 1.42 (1.18-1.71), and 1.21 (1.15-1.28), respectively. Out of 133 individual factors, the strongest mediators for the association between sex and incident dementia were multimorbidity risk score (percentage explained (95% CI): 62.1% (45.2-76.6%)), apolipoprotein A in the blood (25.5% (15.2-39.4%)), creatinine in urine (24.9% (16.1-36.5%)), low-density lipoprotein cholesterol in the blood (23.2% (16.2-32.1%)), and blood lymphocyte percentage (21.1% (14.5-29.5%)). Health-related conditions (percentage (95% CI) explained: 74.4% (51.3-88.9%)) and biomarkers (83.0% (37.5-97.5%)), but not lifestyle factors combined (30.1% (20.7-41.6%)), fully mediated sex differences in incident dementia. Health-related conditions combined were a stronger mediator for late-onset (75.4% (48.6-90.8%)) than for young-onset dementia (52.3% (25.8-77.6%)), whilst lifestyle factors combined were a stronger mediator for young-onset (42.3% (19.4-69.0%)) than for late-onset dementia (26.7% (17.1-39.2%)). CONCLUSIONS: Our analysis matched by age has demonstrated that men had a higher risk of all-cause, young-onset, and late-onset dementias than women. This association was fully mediated by health-related conditions or blood/urinary biomarkers and largely mediated by lifestyle factors. Our findings are important for understanding potential mechanisms of sex in dementia risk.

Association of hyperopia with incident clinically significant depression: epidemiological and genetic evidence in the middle-aged and older population.

AIMS: To investigate the association between hyperopia and clinically significant depression (CSD) in middle-aged and older individuals. The effect of genetic determinants of hyperopia on incident CSD was also explored. METHODS: We included participants who had available data on mean spherical equivalent (MSE) and were free of depression at baseline from the UK Biobank. For the phenotypic association, hyperopia was defined as MSE of+2.00 dioptres (D) or greater, and was divided into mild, moderate and high groups. Diagnosis of CSD across follow-up was determined based on electronic hospital inpatients records. For the genetic association analysis, the association between hyperopia Polygenic Risk Score and incident CSD was assessed. Mendelian randomisation was assessed for causality association. RESULTS: Over a median follow-up of 11.11 years (IQR: 10.92-11.38), hyperopia was significantly associated with incident CSD independent of genetic risk (HR 1.29, 95% CI 1.05 to 1.59) compared with emmetropia participants, especially in those hyperopic patients without optical correction (HR 1.38, 95% CI 1.07 to 1.76). In addition, participants in the high degree of hyperopia were more likely to have incident CSD than participants in the mild degree of hyperopia (P for trend=0.009). Genetic analyses did not show any significant associations between hyperopia and incident CSD (p≥0.1). CONCLUSIONS: Hyperopia was significantly associated with an increased risk of incident CSD. This was independent of genetic predisposition to hyperopia, emphasising the importance of regular vision screening and correction of hyperopia to reduce the risk of CSD regardless of genetic risk.

Development and validation of a deep learning system to classify aetiology and predict anatomical outcomes of macular hole.

AIMS: To develop a deep learning (DL) model for automatic classification of macular hole (MH) aetiology (idiopathic or secondary), and a multimodal deep fusion network (MDFN) model for reliable prediction of MH status (closed or open) at 1 month after vitrectomy and internal limiting membrane peeling (VILMP). METHODS: In this multicentre retrospective cohort study, a total of 330 MH eyes with 1082 optical coherence tomography (OCT) images and 3300 clinical data enrolled from four ophthalmic centres were used to train, validate and externally test the DL and MDFN models. 266 eyes from three centres were randomly split by eye-level into a training set (80%) and a validation set (20%). In the external testing dataset, 64 eyes were included from the remaining centre. All eyes underwent macular OCT scanning at baseline and 1 month after VILMP. The area under the receiver operated characteristic curve (AUC), accuracy, specificity and sensitivity were used to evaluate the performance of the models. RESULTS: In the external testing set, the AUC, accuracy, specificity and sensitivity of the MH aetiology classification model were 0.965, 0.950, 0.870 and 0.938, respectively; the AUC, accuracy, specificity and sensitivity of the postoperative MH status prediction model were 0.904, 0.825, 0.977 and 0.766, respectively; the AUC, accuracy, specificity and sensitivity of the postoperative idiopathic MH status prediction model were 0.947, 0.875, 0.815 and 0.979, respectively. CONCLUSION: Our DL-based models can accurately classify the MH aetiology and predict the MH status after VILMP. These models would help ophthalmologists in diagnosis and surgical planning of MH.

Daily Patterns of Accelerometer-Measured Movement Behaviors in Glaucoma Patients: Insights From UK Biobank Participants.

PURPOSE: The purpose of this study is to compare daily patterns of accelerometer-measured movement behaviors between glaucoma patients and those without glaucoma. METHODS: From 2013 to 2015, 106,053 UK Biobank participants took part in a 7-day accelerometer test. Based on established algorithms, continuous accelerometer data were classified into 4 movement behaviors: moderate to vigorous physical activity (MVPA), light physical activity, sedentary behaviors, and sleep. Glaucoma and other covariates were defined according to baseline assessments and inpatient diagnosis records. Negative binomial regression models were used to compare daily patterns of movement behaviors between glaucoma patients and those without glaucoma. RESULTS: Accelerometer data from 1262 glaucoma patients and 81,551 participants without glaucoma were included. Compared with participants without glaucoma, glaucoma patients spent 4.7% less time on MVPA in multivariable models [mean=28.3 vs 31.4 min/d; incidence-rate ratio (IRR) 0.953, 95% confidence interval (CI): 0.910-0.998; P=0.044], which was mainly attributed to the decreased MVPA time during 18:00-23:59 (IRR=0.863, Bonferroni-corrected 95% CI: 0.768-0.970; P=0.002). Subgroup analyses indicated that compared with those with normal body mass index, the decreased MVPA time was more pronounced in participants with overweight and obesity (IRR=0.912, Bonferroni-corrected 95% CI: 0.851-0.978; P for interaction=0.007). No significant association was found between glaucoma and time spent on other movement behaviors including light physical activity, sedentary behaviors, and sleep. CONCLUSIONS: Daily patterns of movement behaviors were significantly changed in glaucoma patients. Compared with those without glaucoma, glaucoma patients spent less time on MVPA, especially in the evening.