APOE alleles are associated with sex-specific structural differences in brain regions affected in Alzheimer's disease and related dementia.

Alzheimer's disease is marked by intracellular tau aggregates in the medial temporal lobe (MTL) and extracellular amyloid aggregates in the default network (DN). Here, we examined codependent structural variations between the MTL's most vulnerable structure, the hippocampus (HC), and the DN at subregion resolution in individuals with Alzheimer's disease and related dementia (ADRD). By leveraging the power of the approximately 40,000 participants of the UK Biobank cohort, we assessed impacts from the protective APOE ɛ2 and the deleterious APOE ɛ4 Alzheimer's disease alleles on these structural relationships. We demonstrate ɛ2 and ɛ4 genotype effects on the inter-individual expression of HC-DN co-variation structural patterns at the population level. Across these HC-DN signatures, recurrent deviations in the CA1, CA2/3, molecular layer, fornix's fimbria, and their cortical partners related to ADRD risk. Analyses of the rich phenotypic profiles in the UK Biobank cohort further revealed male-specific HC-DN associations with air pollution and female-specific associations with cardiovascular traits. We also showed that APOE ɛ2/2 interacts preferentially with HC-DN co-variation patterns in estimating social lifestyle in males and physical activity in females. Our structural, genetic, and phenotypic analyses in this large epidemiological cohort reinvigorate the often-neglected interplay between APOE ɛ2 dosage and sex and link APOE alleles to inter-individual brain structural differences indicative of ADRD familial risk.

POSTOPERATIVE PHOTORECEPTOR INTEGRITY AND ANATOMICAL OUTCOMES BASED ON PRESENTING MORPHOLOGIC STAGE OF RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To evaluate outer retinal recovery on postoperative optical coherence tomography (OCT) based on presenting morphologic stage of rhegmatogenous retinal detachment (RRD). METHODS: Retrospective cohort of consecutive primary fovea-involving RRDs, referred from January 2012 to September 2022. Baseline OCTs were assessed for morphologic stage of RRD. Postoperative OCT scans were graded at 3, 6, and 12 months for external limiting membrane, ellipsoid zone and interdigitation zone discontinuity, epiretinal membrane formation and severity, and residual subfoveal fluid. RESULTS: Three hundred and fifty-one patients were included. Increasing baseline morphologic stage of RRD was significantly associated with external limiting membrane, ellipsoid zone, and interdigitation zone discontinuity at all time points postoperatively ( P < 0.001) and was shown to be an independent predictor of foveal photoreceptor integrity after adjusting for height of detachment, time to surgery, and duration of fovea involvement ( P < 0.001). Earlier stages were associated with residual subfoveal fluid ( P < 0.001). There was no association between the stages of RRD and epiretinal membrane severity. However, late stages presented with earlier development of epiretinal membrane ( P = 0.012). CONCLUSION: Increasing morphologic stage of RRD is associated with delayed recovery of outer retinal bands in the first year and faster development of epiretinal membrane after RRD repair. The results of this study suggest that the stages may serve as a prognostic biomarker for postoperative photoreceptor recovery.

ADAPTIVE OPTICS IMAGING IN DIABETIC RETINOPATHY: A Prospective Cohort Study.

PURPOSE: To investigate the correlation between diabetic retinopathy (DR) severity and microscopic retinal and vascular alterations using adaptive optics imaging. METHODS: In this single-center, prospective cohort study, adult participants with healthy eyes or DR underwent adaptive optics imaging. Participants were classified into control/mild nonproliferative DR, moderate/severe nonproliferative DR, and proliferative DR. Adaptive optics imaging using the RTX1 camera was obtained from 48 participants (87 eyes) for photoreceptor data and from 36 participants (62 eyes) for vascular data. RESULTS: Photoreceptor parameters significantly differed between DR groups at 2° and 4° of retinal eccentricity. Wall-to-lumen ratio varied significantly at 2° eccentricity, while other vascular parameters remained nonsignificant. Cone density and dispersion were the strongest predictors for DR severity ( P < 0.001) in multivariable generalized estimating equation modeling, while other vascular parameters remained nonsignificant between DR severity groups. All photoreceptor parameters showed significant correlations with visual acuity overall and across most DR severity groups. CONCLUSION: To date, this is one of the largest studies evaluating the use of adaptive optics imaging in DR. Adaptive optics imaging was demonstrated to differentiate between various levels of disease severity in DR. These results support the potential role in diagnostic and therapeutic microstructural evaluation in research and clinical practice.

Home alone: A population neuroscience investigation of brain morphology substrates.

As a social species, ready exchange with peers is a pivotal asset - our "social capital". Yet, single-person households have come to pervade metropolitan cities worldwide, with unknown consequences in the long run. Here, we systematically explore the morphological manifestations associated with singular living in ∼40,000 UK Biobank participants. The uncovered population-level signature spotlights the highly associative default mode network, in addition to findings such as in the amygdala central, cortical and corticoamygdaloid nuclei groups, as well as the hippocampal fimbria and dentate gyrus. Both positive effects, equating to greater gray matter volume associated with living alone, and negative effects, which can be interpreted as greater gray matter associations with not living alone, were found across the cortex and subcortical structures Sex-stratified analyses revealed male-specific neural substrates, including somatomotor, saliency and visual systems, while female-specific neural substrates centered on the dorsomedial prefrontal cortex. In line with our demographic profiling results, the discovered neural pattern of living alone is potentially linked to alcohol and tobacco consumption, anxiety, sleep quality as well as daily TV watching. The persistent trend for solitary living will require new answers from public-health decision makers. SIGNIFICANCE STATEMENT: Living alone has profound consequences for mental and physical health. Despite this, there has been a rapid increase in single-person households worldwide, with the long-term consequences yet unknown. In the largest study of its kind, we investigate how the objective lack of everyday social interaction, through living alone, manifests in the brain. Our population neuroscience approach uncovered a gray matter signature that converged on the 'default network', alongside targeted subcortical, sex and demographic profiling analyses. The human urge for social relationships is highlighted by the evolving COVID-19 pandemic. Better understanding of how social isolation relates to the brain will influence health and social policy decision-making of pandemic planning, as well as social interventions in light of global shifts in houseful structures.

Loneliness is linked to specific subregional alterations in hippocampus-default network covariation.

Social interaction complexity makes humans unique. But in times of social deprivation, this strength risks exposure of important vulnerabilities. Human social neuroscience studies have placed a premium on the default network (DN). In contrast, hippocampus (HC) subfields have been intensely studied in rodents and monkeys. To bridge these two literatures, we here quantified how DN subregions systematically covary with specific HC subfields in the context of subjective social isolation (i.e., loneliness). By codecomposition using structural brain scans of ∼40,000 UK Biobank participants, loneliness was specially linked to midline subregions in the uncovered DN patterns. These association cortex patterns coincided with concomitant HC patterns implicating especially CA1 and molecular layer. These patterns also showed a strong affiliation with the fornix white matter tract and the nucleus accumbens. In addition, separable signatures of structural HC-DN covariation had distinct associations with the genetic predisposition for loneliness at the population level.NEW & NOTEWORTHY The hippocampus and default network have been implicated in rich social interaction. Yet, these allocortical and neocortical neural systems have been interrogated in mostly separate literatures. Here, we conjointly investigate the hippocampus and default network at a subregion level, by capitalizing structural brain scans from ∼40,000 participants. We thus reveal unique insights on the nature of the "lonely brain" by estimating the regimes of covariation between the hippocampus and default network at population scale.

Quality of Life after Pars Plana Vitrectomy, Scleral Buckle, or Pneumatic Retinopexy for Rhegmatogenous Retinal Detachment: A Meta-Analysis.

PURPOSE: Comparisons of the surgical and anatomic results of rhegmatogenous retinal detachment surgery have been investigated previously. A systematic evaluation of the available evidence comparing quality of life outcomes of either pars plana vitrectomy, scleral buckling, or pneumatic retinopexy has not been evaluated to date. This article analyzes whether pars plana vitrectomy, scleral buckling, or pneumatic retinopexy for the treatment of rhegmatogenous retinal detachment results in differing quality of life outcomes. METHODS: In February of 2022, a comprehensive search of MEDLINE, EMBASE, CINHAL, and Cochrane Library was conducted for studies on patients treated surgically for rhegmatogenous retinal detachment and included follow-up measurements of quality of life outcomes. Meta-analysis was completed using STATA v. 14.0. The main outcomes of interest were the mean vision-related quality of life score (VRQOL) and SD of VRQOL of each type of surgical procedure. RESULTS: In this systematic review of 13 distinct trials including follow-up of patient quality of life after rhegmatogenous retinal detachment surgery (n = 1063), a better correlation was found between higher quality of life outcomes with scleral buckling than with pars plana vitrectomy (SMD = 0.62, CI: [0.31, 0.93]). There was also no signficant difference in quality of life outcomes between pneumatic retinopexy and pars plana vitrectomy (SMD = 0.08, CI: [-0.07, 0.22]). CONCLUSIONS: Scleral buckling results in better quality of life outcomes for patients when compared to pars plana vitrectomy. Pneumatic retinopexy did not show a difference in quality of life outcomes compared to pars plana vitrectomy.

The Need for Health Policy Training for Surgeons.

BACKGROUND: Improvements in surgery at a systems level can be mediated by effective health policy. METHODS: We reviewed three contemporary challenges in surgical care to understand the potential role of health policy. RESULTS: The pandemic-related backlog, and international economic and logistical challenges to surgical care may be improved through policy change and advocacy by surgeons. CONCLUSIONS: A surgeon-policy expert training pathway and professional role will ensure surgeons contribute meaningfully to health policy development.

Impact of Baseline Morphologic Stage of Rhegmatogenous Retinal Detachment on Postoperative Visual Acuity.

PURPOSE: To evaluate the association of baseline morphologic stage of rhegmatogenous retinal detachment (RRD) using OCT with postoperative anatomic and visual acuity (VA) outcomes. DESIGN: Retrospective cohort study. SUBJECTS: Consecutive primary fovea-involving RRDs referred from January 2012 to September 2022. METHODS: Patients with primary RRD and no prior macular pathology with gradable baseline OCT were assessed. Best-corrected VA (BCVA) was assessed at presentation and at 3, 6, and 12 months postoperatively. OCT scans were graded for parafoveal morphologic stage of RRD and foveal photoreceptor integrity. MAIN OUTCOME MEASURES: Association of morphologic stage of RRD with 12-month BCVA. RESULTS: Three hundred fifty-one patients were included. Sixty-eight percent (238/351) were male, the mean (standard deviation) age was 61.2 (± 12.8) years, and 59% (206/351) were phakic. Thirteen percent (47/351) presented in stages 1 and 2, 15% (54/351) in stage 3a, 36% (126/351) in stage 3b, 24% (83/351) in stage 4, and 12% (41/351) in stage 5. Increasing stage was associated with worse foveal photoreceptor integrity, reduced baseline BCVA and longer duration of central vision loss (P < 0.001). Mean (standard deviation) 12-month BCVA by stage was 0.77 (± 0.64) for stages 1 and 2, 1.00 (± 0.53) for stage 3a, 1.36 (± 0.55) for stage 3b, 1.33 (± 0.66) for stage 4 and 1.55 (± 0.47) for stage 5. Increasing stage was associated with reduced postoperative BCVA (P < 0.001) at all time points after adjusting for covariates. A subgroup analysis of acute detachments with retinal pigment epithelium-photoreceptor dysregulation demonstrated no difference in postoperative BCVA between stages 1, 2, and 3a. However, 12-month BCVA was significantly better in stages 1, 2, and 3a vs. stage 3b (P = 0.002) and stage 3a vs. 3b (P = 0.008). CONCLUSIONS: This study validates the clinical relevance of a recently proposed OCT-based staging system for outer retinal morphologic changes over time in RRD. Postoperative BCVA was significantly reduced in patients with worse presenting stage at all time points. In acute RRDs, 12-month BCVA was significantly better in stages 1, 2, and 3a vs. stage 3b, which suggests early stages may have better retinal recovery compared with stage 3b or worse. Stage 3b may represent a critical point where substantial structural changes occur, leading to worse outcomes in acute RRDs. Patients presenting with fovea-involving RRDs in stages 1, 2, or 3a may benefit from more urgent intervention. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Relationship Between Disease and Treatment Factors in Diabetes With Vision Difficulty: A Cross-Sectional, Population-Based Analysis.

BACKGROUND AND OBJECTIVE: Relationships between disease and treatment factors of diabetes and vision difficulty remain largely unknown. This study investigated the relationship between disease and treatment factors in diabetes and participants' self-reported vision difficulty. PATIENTS AND METHODS: This was a cross-sectional, population-based analysis. Data from the National Health Interview Survey was used and analyzed through univariable and multivariable logistic regression. RESULTS: From the 29,464 included participants, logistic regression showed increased odds of self-reported vision difficulty among participants with diabetes (odds ratio [OR] = 2.14, P < 0.001), prediabetes (OR = 1.95, P < 0.001), or gestational diabetes (OR = 1.54, P < 0.001) compared to participants without diabetes. Those who reported having diabetes for more than a year had higher odds of vision difficulty (OR = 1.97, P = 0.02), as did those who were taking insulin (OR = 1.62, P < 0.001), those who had taken less insulin to save money within the past year (OR = 1.87, P = 0.01), and those who reported experiencing diabetes-related stress (OR = 2.14, P < 0.001). CONCLUSIONS: Duration of diabetes, diabetes-related stress, and taking less insulin than recommended to save money were associated with vision difficulty. [Ophthalmic Surg Lasers Imaging Retina 2024;55:142-153.].

Pneumatic Retinopexy for Rhegmatogenous Retinal Detachment in Elderly Patients.

PURPOSE: To assess clinical outcomes in elderly patients aged ≥ 75 years who underwent pneumatic retinopexy (PnR) for primary rhegmatogenous retinal detachment (RRD). DESIGN: Retrospective cohort study. SUBJECTS: Patients aged ≥ 75 years with primary RRD undergoing PnR. METHODS: This study evaluates clinical outcomes among eligible patients who presented from October 1, 2010, to December 31, 2022, with a minimum of 3 months' follow-up. There were no limitations with respect to the number, size, or location of retinal breaks. Exclusion criteria included significant proliferative vitreoretinopathy or previous retinal detachment repair in the index eye, inability to maintain the postoperative posturing requirements or inability to carry out adequate examination of the peripheral retina because of media opacity. Lens status did not impact the decision to offer PnR. MAIN OUTCOME MEASURES: Pneumatic retinopexy primary anatomic reattachment rate and postoperative best corrected visual acuity (BCVA) at 3 months. RESULTS: Eighty patients with a mean age of 80.6 ± 4.6 years were included in this study; 35% (28/80) were phakic and 34% (27/80) presented with a fovea-on RRD. The mean number of breaks in the detached retina was 1.52 ± 1.13, and the mean number of quadrants of detached retina was 2.35 ± 0.93. The primary anatomic reattachment rate at 3 months after PnR was 78.8% (63/80), whereas the remaining 21.2% (17/80) failed PnR and underwent an operating room procedure. There was a statistically significant improvement in logarithm of the minimum angle of resolution (logMAR) BCVA from baseline to 3 months (1.29 ± 0.94 and 0.69 ± 0.67, respectively, P < 0.001). A subgroup analysis that only included patients aged > 80 years was also performed, with a total of 39 patients with a mean age of 84.4 ± 3.5 years. The primary anatomic reattachment rate with PnR in this subgroup was 74.4% (29/39), with a statistically significant improvement in BCVA from baseline to 3 months (1.4 ± 1.05 and 0.77 ± 0.70, respectively; P = 0.004). CONCLUSIONS: Elderly patients treated with PnR for primary RRD had relatively comparable primary anatomic reattachment rates with other surgical techniques such as pars plana vitrectomy and scleral buckle. Pneumatic retinopexy is an effective, minimally invasive office-based procedure that may be desirable for some elderly patients. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Outer Retinal Hyperreflective Dots: A Potential Imaging Biomarker in Rhegmatogenous Retinal Detachment.

PURPOSE: To investigate hyperreflective dots (HRDs) on baseline OCT in rhegmatogenous retinal detachment (RRD). DESIGN: Retrospective cohort study. SUBJECTS: Consecutive primary fovea-off RRDs presenting between January 2012 and September 2022. METHODS: Visual acuity (VA) was obtained at baseline, 3, 6, and 12 months. Baseline foveal OCT scans were graded for the presence of HRDs in the outer retina, morphologic stage of RRD in the parafovea, and foveal photoreceptor integrity (intact, patchy or complete loss of the bacillary layer). Epiretinal membrane (ERM) and cystoid macular edema (CME) were graded after surgery. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients in each morphologic stage with HRDs present on OCT and their association with postoperative VA. Secondary outcomes included association with the height of foveal detachment, duration of central vision loss, RRD extent, and development of ERM/CME. RESULTS: A total of 351 patients were included. The presence of HRDs by morphologic stage of RRD was 0% in stage 1, 4.5% (2/42) in stage 2, 13% (7/54) in stage 3a, 16% (20/126) in stage 3b, 48% (40/83) in stage 4, and 85% (35/41) in stage 5. Hyperreflective dots were associated with increasing stage of RRD (P < 0.001), reduced integrity of foveal photoreceptors (P < 0.001), and reduced postoperative VA at 3, 6, and 12 months (P < 0.001), after excluding visually significant cataracts and adjusting for covariates. There was also a significant association between HRDs and height of foveal detachment, duration of central vision loss, and RRD extent (P < 0.001). Hyperreflective dots were neither associated with postoperative ERM formation nor with its severity (P = 0.27). Nevertheless, they were associated with the occurrence of CME at 3 and 6 months after surgery (P = 0.01; P = 0.006). CONCLUSIONS: Hyperreflective dots have been hypothesized to consist of intraretinal inflammatory cells. We found that HRDs were significantly associated with the morphologic stage, extent, duration, and height of the RRD before surgery and with reduced VA and CME after surgery. Our results suggest that HRDs are associated with photoreceptor degeneration, as longstanding and extensive RRDs are more likely to present with HRDs. The association of HRDs with CME provides insight into the possible importance of inflammatory processes in RRD before and after surgery. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Association Between Sociodemographic Factors and Vision Difficulty in the National Health Interview Survey: A Population-Based Analysis.

PURPOSE: To investigate the relationship between social determinants of health with self-reported vision difficulty. DESIGN: Cross-sectional, population-based analysis. METHODS: The National Health Interview Survey (NHIS) is an annual survey based on the U.S. population ≥18 years of age. It provides self-reported data on demographic characteristics, socioeconomic factors, health status, and health care access. The 2021 NHIS database was used in this study. Adult participants of the NHIS who responded to the vision difficulty question "Do you have difficulty seeing, even when wearing glasses or contact lenses?" were included in this analysis. The outcome of interest was self-reported vision difficulty by participants. Analysis was done through univariable and multivariable logistic regression. RESULTS: Overall, there were 29,464 participants included in the analysis. Univariable logistic regression showed an increased odds of self-reported vision difficulty among female (odds ratio [OR] 1.28 [95% confidence interval {CI} 1.20-1.38]; P < .001), gay, lesbian, or bisexual participants (OR 1.24 [95% CI 1.04-1.49]; P = .02), those who possessed public compared with private insurance (OR 1.83 [95% CI 1.69-1.99]; P < .001), those with less than a high school education (OR 1.88 [95% CI 1.67-2.13]; P < .001), and those with an income below the poverty threshold (OR 2.22 [95% CI 1.96-2.51]; P < .001). Multivariable analysis revealed an increased risk of vision difficulty reported amongst non-Hispanic Black participants (OR 1.65 [95% CI 1.21-2.25]; P = .002). CONCLUSIONS: A multitude of sociodemographic factors are associated with self-reported vision difficulty in the U.S. POPULATION: Our findings emphasize the importance of considering factors of social determinants of health in clinical practice and policymaking for patients with vision loss.

Magnetic resonance imaging datasets with anatomical fiducials for quality control and registration.

Tools available for reproducible, quantitative assessment of brain correspondence have been limited. We previously validated the anatomical fiducial (AFID) placement protocol for point-based assessment of image registration with millimetric (mm) accuracy. In this data descriptor, we release curated AFID placements for some of the most commonly used structural magnetic resonance imaging datasets and templates. The release of our accurate placements allows for rapid quality control of image registration, teaching neuroanatomy, and clinical applications such as disease diagnosis and surgical targeting. We release placements on individual subjects from four datasets (N = 132 subjects for a total of 15,232 fiducials) and 14 brain templates (4,288 fiducials), totalling more than 300 human rater hours of annotation. We also validate human rater accuracy of released placements to be within 1 - 2 mm (using more than 45,000 Euclidean distances), consistent with prior studies. Our data is compliant with the Brain Imaging Data Structure allowing for facile incorporation into neuroimaging analysis pipelines.

Lacking social support is associated with structural divergences in hippocampus-default network co-variation patterns.

Elaborate social interaction is a pivotal asset of the human species. The complexity of people's social lives may constitute the dominating factor in the vibrancy of many individuals' environment. The neural substrates linked to social cognition thus appear especially susceptible when people endure periods of social isolation: here, we zoom in on the systematic inter-relationships between two such neural substrates, the allocortical hippocampus (HC) and the neocortical default network (DN). Previous human social neuroscience studies have focused on the DN, while HC subfields have been studied in most detail in rodents and monkeys. To bring into contact these two separate research streams, we directly quantified how DN subregions are coherently co-expressed with specific HC subfields in the context of social isolation. A two-pronged decomposition of structural brain scans from ∼40 000 UK Biobank participants linked lack of social support to mostly lateral subregions in the DN patterns. This lateral DN association co-occurred with HC patterns that implicated especially subiculum, presubiculum, CA2, CA3 and dentate gyrus. Overall, the subregion divergences within spatially overlapping signatures of HC-DN co-variation followed a clear segregation into the left and right brain hemispheres. Separable regimes of structural HC-DN co-variation also showed distinct associations with the genetic predisposition for lacking social support at the population level.