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New study shows targeting arterial stiffening earlier in a person’s lifespan could provide cognitive benefits in older age and may help to delay the onset of dementia.
Socio-medical factors associated with neurodevelopmental disorders on the Kenyan coast.
Neurodevelopmental disorders (NDDs) are a group of conditions with their onset during the early developmental period and include conditions such as autism and intellectual disability. Occurrence of NDDs is thought to be determined by both genetic and environmental factors, but data on the role of environmental factors for NDD in Africa is limited. This study investigates environmental influences on NDDs in children from Kenya. This case-control study compared children with NDDs and typically developing children from two studies on the Kenyan coast. We included 172 study participants from the Kilifi Autism study and 151 from the NeuroDev study who had a diagnosis of at least one NDD and 112 and 73 with no NDD diagnosis from each study, respectively. Potential risk factors were identified using unadjusted univariable analysis and adjusted multivariable logistic regression. Univariable analysis in the Kilifi Autism study sample revealed hypoxic-ischaemic encephalopathy conferred the largest odds ratio (OR) 10.52 [95%CI: 4.04, 27.41] for NDDs, followed by medical complications during pregnancy (gestational hypertension & diabetes, eclampsia, maternal bleeding) (OR=3.17 [95%CI: 1.61, 6.23]). In the NeuroDev study sample, labour and birth complications (OR=7.30 [95%CI 2.17, 24.61]), neonatal jaundice (OR=5.49 [95%CI 1.61,18.72]) and infection during pregnancy (OR= 5.31 [95%CI 1.56, 18.11]) conferred the largest risk associated with NDDs. In the adjusted analysis, seizures before age 3 years in the Kilifi Autism study and labour and birth complications in the NeuroDev study conferred the largest increased risk. Higher parity, the child being older and delivery at home were associated with a reduced risk for NDDs. Recognition of important risk factors such as labour and birth complications could guide preventative interventions, developmental screening of at-risk children and monitoring progress of these children. Further studies examining the aetiology of NDDs in population-based samples, including investigating the interaction between genetic and environmental factors, are needed.
The relationship between lifetime trauma exposure and psychosis in a multi-country case-control study in Africa
Background: Exposure to traumatic events is a known risk factor for psychosis. Additionally, psychosis may be a risk factor for exposure to traumatic events. There are little data on the relationship between traumatic events and psychosis in sub-Saharan Africa, particularly in large, cross-country samples using the same instrument. Methods: In a case-control study, 21,606 adults were recruited with psychosis (cases) and 21,329 adults without any history of psychosis (controls) in Ethiopia, Kenya, South Africa, and Uganda from 2018 to 2023 (n = 42,935). Lifetime trauma exposure was assessed using the Life Events Checklist-5. Regression models included the: i) prevalence of any trauma exposure; ii) cumulative burden of trauma exposure; and iii) the odds of exposure to specific trauma types. Analyses were run by case-control status for the full sample and within each country; trauma types endorsed by cases and controls were further stratified by sex. Results: There was a modest increased odds of trauma among cases compared with controls. Cases had higher odds of reporting exposure to ≥1 trauma and ≥3 trauma types (adjusted odds ratio (AOR) = 1.23, 95 % CI: 1.18–1.28 and AOR = 1.19, 95 % CI: 1.15–1.23, respectively). The trauma types with the highest odds were sexual violence (AOR = 1.99, 95 % CI: 1.86–2.14), physical violence (AOR = 1.69, 95 % CI: 1.62–1.76), and network trauma (causing injury, harm, or death to someone else) (AOR = 1.52, 95 % CI: 1.38–1.67). Similar trends were seen within each country. Sexual violence and physical violence were most endorsed by female cases and male cases, respectively. Network trauma was most endorsed by male cases and particularly from South Africa. Conclusion: People in eastern and southern Africa report significant exposure to trauma with a slightly higher prevalence among individuals with psychosis. Special attention should be paid to potential trauma exposure including interpersonal violence when providing treatment for this population.
"The traditional healer said, 'I had a genie that scared me in my eyes, and that is why I fall": An ethnographic study in Mahenge, Tanzania.
BACKGROUND: In many low-income countries, individuals with epilepsy often turn to traditional healers as their first source of treatment after the onset of seizures. However, their experiences with traditional healing practices remain poorly understood. This study examines the perceptions and experiences of people with epilepsy in relation to traditional healing in Mahenge, Tanzania. METHODS: A culturally specific ethnographic approach, centred on oral history, was employed to capture rich, contextually grounded narratives. A total of 45 oral history interviews were conducted with individuals living with epilepsy from 21 villages in Mahenge. Participants were purposively selected based on the following criteria: being at least 18 years of age, having a diagnosis of epilepsy, and the ability to recount their experiences in Swahili, the primary language spoken in the region. Data were manually analysed using thematic analysis. RESULTS: Traditional healers often attribute epilepsy to supernatural causes, such as curses or witchcraft, linking seizure onset to past events believed to have triggered the condition. Their treatment practices are frequently accompanied by strict behavioural restrictions, which can be challenging for individuals with epilepsy to follow and are sometimes cited as reasons for treatment failure. Moreover, some participants reported experiences of physical, emotional, and even sexual harassment during their encounters with traditional healers. CONCLUSION: There is a strong reliance on traditional healing practices for epilepsy, where cultural beliefs and rituals can hinder accurate diagnosis and effective care. Raising awareness about epilepsy, its medical management, and the rights of people with epilepsy, both among traditional healers and the broader community, is essential to improve care and protect the well-being of those affected.
Non-mental health inpatient and emergency care hospital costs associated with four mental disorders in Europe: a modelling study.
BackgroundThe prevalence of physical health conditions is higher among people with mental disorders than the general population, and these conditions have subsequent excess costs. Estimating the magnitude of these excess costs would support better integrated mental and physical health care. The aim of this study was to estimate the excess annual hospital costs of non-mental health related inpatient and emergency care utilisation for four mental disorders in 32 European countries.MethodsIn this modelling study, we obtained data on the working-age population (aged 20-64 years) of 32 European countries from the European Statistical Agency, the 2019 Global Burden of Disease, Injuries, and Risk Factors Study, epidemiological and cost evidence syntheses, and listed country-specific estimates. We estimated the non-mental health inpatient costs and emergency care hospital costs associated with the excess physical health burden of alcohol use disorders, bipolar disorder, depressive disorders, and schizophrenia in purchasing power standard Euros (PPS€) for 2019. Total physical comorbidity hospital costs were calculated by summing attributable non-mental health inpatient and emergency hospital costs across all physical health diagnoses by ICD-10 category for each mental disorder in all countries. Excess costs represent the proportion of total costs that were attributable to the excess physical health burden. People with lived experiences informed the original project plans.FindingsIn 2019, there were 312·5 million people of working age across 32 European countries. Total annual non-mental health inpatient and emergency care hospital costs were PPS€20·3 billion for alcohol use disorders, PPS€6·7 billion for bipolar disorder, PPS€26·5 billion for depressive disorders, and PPS€1·8 billion for schizophrenia, with considerable variation observed among countries. The proportion of excess costs were 59·4% (PPS€12·1 billion) for alcohol use disorder, 56·7% (PPS€3·8 billion) for bipolar disorder, 52·7% (PPS€14·0 billion) for depressive disorders, and 35·6% (PPS€0·7 billion) for schizophrenia.InterpretationThese first comprehensive European estimates indicate that non-mental health inpatient and emergency care hospital costs contributed substantially to the total costs associated with four mental disorders. The excess costs equated to 1·8% of the included countries' overall health-care expenditure and 0·16% of their gross domestic products. Estimates are conservative because they are limited to diagnosed mental disorders prevalent among working-age adults. A 1·0% reduction in the excess physical health burden of these mental disorders could lead to annual savings of more than PPS€190 million in non-mental health hospital costs in Europe.FundingEuropean College of Neuropsychopharmacology.
Results From a Long-Term Observational Follow-Up Study of a Single Dose of Psilocybin for a Treatment-Resistant Episode of Major Depressive Disorder.
Background: The largest randomized study of psilocybin to date demonstrated the efficacy of COMP360 25 mg (Compass Pathways' investigational proprietary pharmaceutical-grade synthesized psilocybin formulation) in participants with treatment-resistant depression (COMP 001), compared with 10 mg and 1 mg doses. Here, we report findings from COMP 004, a 52-week observational follow-up of patients from COMP 001 and COMP 003, a small open-label study of the coadministration of 25 mg COMP360 with continuing antidepressant treatment. Methods: Adverse events (AEs) were collected over the full 52-week period. The primary efficacy endpoint was time to a prespecified depressive event over the 52 weeks following COMP360 administration in COMP 001 participants, presented as Kaplan-Meier estimates. A post hoc analysis included only participants that entered COMP 004. Data were collected from July 2020 to July 2022. Results: Sixty-six participants entered COMP 004 (COMP 001, n = 58 [25 mg group n = 22, 10 mg group n = 19, 1 mg group n = 17]; COMP 003, n = 8). Few AEs were reported post-entry into COMP 004, with 1 AE of mild suicidal ideation in the 1 mg group deemed possibly related to study drug. For all COMP 001 patients (n = 233), median time to depressive event was greater for the 25 mg group (92 days) compared to the 10 mg (83 days) and 1 mg (62 days) groups, with the majority of participants having had a depressive event by Week 12 (25 mg n = 37/75, 10 mg n = 38/79, 1 mg n = 44/75). The post hoc supplementary analysis of those who enrolled in COMP 004 from COMP 001 exhibited the difference between groups more strikingly (25 mg, 189 days; 10 mg, 43 days; 1 mg, 21 days); however, only 10 participants experienced a depressive event post-COMP 004 enrollment (25 mg n = 6, 10 mg n = 3, 1 mg n = 1) from COMP 001 and none from COMP 003. At COMP 004 entry, the 1 mg group had the highest number of participants on antidepressant medication (n = 10; 10 mg, n = 9; 25 mg, n = 6) and generally initiated treatment earlier. Conclusion: Over 52 weeks, a single administration of 25 mg psilocybin suggested longer maintenance of antidepressant effect than both 1 mg and 10 mg. Larger long-term studies are required to confirm these findings and provide clarity on the longer-term effects of psilocybin. Trial Registration: ClinicalTrials.gov identifier: NCT04519957.
A single dose of lamotrigine induces a positive memory bias in healthy volunteers.
BACKGROUND: Lamotrigine has been shown to be effective in the long-term treatment and relapse prevention of depression in bipolar disorder. However, the neuropsychological mechanisms underlying these effects are unclear. We investigated the effects of lamotrigine on a battery of emotional processing tasks in healthy volunteers, previously shown to be sensitive to antidepressant drug action in similar experimental designs. METHODS: Healthy volunteers (n = 36) were randomized in a double-blind design to receive a single dose of placebo or 300 mg lamotrigine. Mood and subjective effects were monitored throughout the study period, and emotional processing was assessed using the Oxford Emotional Test Battery (ETB) 3 hours post-administration. RESULTS: Participants receiving lamotrigine showed increased accurate recall of positive versus negative self-descriptors, compared to those in the placebo group. There were no other significant effects on emotional processing in the ETB, and lamotrigine did not affect ratings of mood or subjective experience. CONCLUSIONS: Lamotrigine did not induce widespread changes in emotional processing. However, there was increased positive bias in emotional memory, similar to the effects of antidepressants reported in previous studies. Further work is needed to assess whether similar effects are seen in the clinical treatment of patients with bipolar disorder and the extent to which this is associated with its clinical action in relapse prevention.
Where and when matter in visual recognition.
Our perceptual system processes only a selected subset of an incoming stream of stimuli due to sensory biases and limitations in spatial and temporal attention and working memory capacity. In this study, we investigated perceptual access to sensory information that was temporally predictable or unpredictable and spread across the visual field. In a visual recognition task, participants were presented with an array of different number of alphabetical stimuli that were followed by a probe with a delay. They had to indicate whether the probe was included in the stimulus-set or not. To test the impact of temporal attention, coloured cues that were displayed before the visual stimuli indicated the presentation onset of the stimulus-set. We found that temporal predictability of stimulus onset yields higher performance. In addition, recognition performance was biased across the visual field with higher performance for stimuli that were presented on the upper and right visual quadrants. Our findings demonstrate that recognition accuracy is enhanced by temporal cues and has an inherently asymmetric shape across the visual field.
Current and prospective roles of magnetic resonance imaging in mild traumatic brain injury
There is unmet clinical need for biomarkers to predict recovery or the development of long-term sequelae of mild traumatic brain injury, a highly prevalent condition causing a constellation of disabling symptoms. A substantial proportion of patients live with long-lasting sequelae affecting their quality of life and ability to work. At present, symptoms can be assessed through clinical tests; however, there are no imaging or laboratory tests fully reflective of pathophysiology routinely used by clinicians to characterize post-concussive symptoms. Magnetic resonance imaging has potential to link subtle pathophysiological alterations to clinical outcomes. Here, we review the state of the art of MRI research in adults with mild traumatic brain injury and provide recommendations to facilitate transition into clinical practice. Studies utilizing MRI can inform on pathophysiology of mild traumatic brain injury. They suggest presence of early cytotoxic and vasogenic oedema. They also show that mild traumatic brain injury results in cellular injury and microbleeds affecting the integrity of myelin and white matter tracts, all processes that appear to induce delayed vascular reactions and functional changes. Crucially, correlates between MRI parameters and post-concussive symptoms are emerging. Clinical sequences such as T1-weighted MRI, susceptibility-weighted MRI or fluid attenuation inversion recovery could be easily implementable in clinical practice, but are not sufficient, in isolation for prognostication. Diffusion sequences have shown promises and, although in need of analysis standardization, are a research priority. Lastly, arterial spin labelling is emerging as a high-utility research as it could become useful to assess delayed neurovascular response and possible long-term symptoms.
Critical components of ‘Early Intervention in Psychosis’: national retrospective cohort study
Background Psychotic disorders are severe mental health conditions frequently associated with long-term disability, reduced quality of life and premature mortality. Early Intervention in Psychosis (EIP) services aim to provide timely, comprehensive packages of care for people with psychotic disorders. However, it is not clear which components of EIP services contribute most to the improved outcomes they achieve. Aims We aimed to identify associations between specific components of EIP care and clinically significant outcomes for individuals treated for early psychosis in England. Method This national retrospective cohort study of 14 874 EIP individuals examined associations between 12 components of EIP care and outcomes over a 3-year follow-up period, by linking data from the National Clinical Audit of Psychosis (NCAP) to routine health outcome data held by NHS England. The primary outcome was time to relapse, defined as psychiatric inpatient admission or referral to a crisis resolution (home treatment) team. Secondary outcomes included duration of admissions, detention under the Mental Health Act, emergency department and general hospital attendances and mortality. We conducted multilevel regression analyses incorporating demographic and service-level covariates. Results Smaller care coordinator case-loads and the use of clozapine for eligible people were associated with reduced relapse risk. Physical health interventions were associated with reductions in mortality risk. Other components, such as cognitive–behavioural therapy for psychosis (CBTp), showed associations with improvements in secondary outcomes. Conclusions Smaller case-loads should be prioritised and protected in EIP service design and delivery. Initiatives to improve the uptake of clozapine should be integrated into EIP care. Other components, such as CBTp and physical health interventions, may have specific benefits for those eligible. These findings highlight impactful components of care and should guide resource allocation to optimise EIP service delivery.
Cannabis Withdrawal and Psychiatric Intensive Care.
IMPORTANCE: Cannabis use is common in people with severe mental illness and its adverse effects on outcomes are well established. However, adverse outcomes may also result from cannabis withdrawal syndrome (CWS). CWS includes symptoms such as agitation, irritability, and aggression, and typically peaks after 3 to 5 days of abstinence. OBJECTIVE: To assess whether cannabis use prior to admission is associated with an increase in the risk of transfer to a psychiatric intensive care unit (PICU) during the cannabis withdrawal risk period. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used clinical data from a secondary mental health care database and took place at 4 psychiatric hospitals in London, United Kingdom, between January 2008 and December 2023. Patients included adults admitted to general psychiatric wards and PICUs. Data were analyzed from June 2023 to February 2025. EXPOSURE: Cannabis use was determined from clinical records, using natural language processing and manual review. MAIN OUTCOMES AND MEASURES: The primary outcome was transfer from a general ward to PICU during the cannabis withdrawal risk period (3 to 5 days after presentation to the hospital). Secondary outcomes included admission to PICU at any time point. Outcomes were analyzed according to cannabis use status with multivariable models, which adjusted for age, gender, ethnicity, diagnosis, tobacco use, stimulant use, comorbid alcohol or substance use disorder, and admission year. RESULTS: There were 52 088 hospital admissions identified, of which 4691 involved admission to a PICU (9.0%). Cannabis users were more likely to be admitted to a PICU than nonusers (adjusted odds ratio [aOR], 1.44; 95% CI, 1.33-1.55; P
Integrating the environmental and genetic architectures of aging and mortality.
Both environmental exposures and genetics are known to play important roles in shaping human aging. Here we aimed to quantify the relative contributions of environment (referred to as the exposome) and genetics to aging and premature mortality. To systematically identify environmental exposures associated with aging in the UK Biobank, we first conducted an exposome-wide analysis of all-cause mortality (n = 492,567) and then assessed the associations of these exposures with a proteomic age clock (n = 45,441), identifying 25 independent exposures associated with mortality and proteomic aging. These exposures were also associated with incident age-related multimorbidity, aging biomarkers and major disease risk factors. Compared with information on age and sex, polygenic risk scores for 22 major diseases explained less than 2 percentage points of additional mortality variation, whereas the exposome explained an additional 17 percentage points. Polygenic risk explained a greater proportion of variation (10.3-26.2%) compared with the exposome for incidence of dementias and breast, prostate and colorectal cancers, whereas the exposome explained a greater proportion of variation (5.5-49.4%) compared with polygenic risk for incidence of diseases of the lung, heart and liver. Our findings provide a comprehensive map of the contributions of environment and genetics to mortality and incidence of common age-related diseases, suggesting that the exposome shapes distinct patterns of disease and mortality risk, irrespective of polygenic disease risk.
Adversarial testing of global neuronal workspace and integrated information theories of consciousness.
Different theories explain how subjective experience arises from brain activity1,2. These theories have independently accrued evidence, but have not been directly compared3. Here we present an open science adversarial collaboration directly juxtaposing integrated information theory (IIT)4,5 and global neuronal workspace theory (GNWT)6-10 via a theory-neutral consortium11-13. The theory proponents and the consortium developed and preregistered the experimental design, divergent predictions, expected outcomes and interpretation thereof12. Human participants (n = 256) viewed suprathreshold stimuli for variable durations while neural activity was measured with functional magnetic resonance imaging, magnetoencephalography and intracranial electroencephalography. We found information about conscious content in visual, ventrotemporal and inferior frontal cortex, with sustained responses in occipital and lateral temporal cortex reflecting stimulus duration, and content-specific synchronization between frontal and early visual areas. These results align with some predictions of IIT and GNWT, while substantially challenging key tenets of both theories. For IIT, a lack of sustained synchronization within the posterior cortex contradicts the claim that network connectivity specifies consciousness. GNWT is challenged by the general lack of ignition at stimulus offset and limited representation of certain conscious dimensions in the prefrontal cortex. These challenges extend to other theories of consciousness that share some of the predictions tested here14-17. Beyond challenging the theories, we present an alternative approach to advance cognitive neuroscience through principled, theory-driven, collaborative research and highlight the need for a quantitative framework for systematic theory testing and building.
Classification of asthma based on nonlinear analysis of breathing pattern
Normal human breathing exhibits complex variability in both respiratory rhythm and volume. Analyzing such nonlinear fluctuations may provide clinically relevant information in patients with complex illnesses such as asthma. We compared the cycle-by-cycle fluctuations of inter-breath interval (IBI) and lung volume (LV) among healthy volunteers and patients with various types of asthma. Continuous respiratory datasets were collected from forty agematched men including 10 healthy volunteers, 10 patients with controlled atopic asthma, 10 patients with uncontrolled atopic asthma, and 10 patients with uncontrolled non-atopic asthma during 60 min spontaneous breathing. Complexity of breathing pattern was quantified by calculating detrended fluctuation analysis, largest Lyapunov exponents, sample entropy, and cross-sample entropy. The IBI as well as LV fluctuations showed decreased long-range correlation, increased regularity and reduced sensitivity to initial conditions in patients with asthma, particularly in uncontrolled state. Our results also showed a strong synchronization between the IBI and LV in patients with uncontrolled asthma. Receiver operating characteristic (ROC) curve analysis showed that nonlinear analysis of breathing pattern has a diagnostic value in asthma and can be used in differentiating uncontrolled from controlled and non-atopic from atopic asthma.We suggest that complexity analysis of breathing dynamics may represent a novel physiologic marker to facilitate diagnosis and management of patients with asthma. However, future studies are needed to increase the validity of the study and to improve these novel methods for better patient management.
FLUX: A pipeline for MEG analysis.
Magnetoencephalography (MEG) allows for quantifying modulations of human neuronal activity on a millisecond time scale while also making it possible to estimate the location of the underlying neuronal sources. The technique relies heavily on signal processing and source modelling. To this end, there are several open-source toolboxes developed by the community. While these toolboxes are powerful as they provide a wealth of options for analyses, the many options also pose a challenge for reproducible research as well as for researchers new to the field. The FLUX pipeline aims to make the analyses steps and setting explicit for standard analysis done in cognitive neuroscience. It focuses on quantifying and source localization of oscillatory brain activity, but it can also be used for event-related fields and multivariate pattern analysis. The pipeline is derived from the Cogitate consortium addressing a set of concrete cognitive neuroscience questions. Specifically, the pipeline including documented code is defined for MNE Python (a Python toolbox) and FieldTrip (a Matlab toolbox), and a data set on visuospatial attention is used to illustrate the steps. The scripts are provided as notebooks implemented in Jupyter Notebook and MATLAB Live Editor providing explanations, justifications and graphical outputs for the essential steps. Furthermore, we also provide suggestions for text and parameter settings to be used in registrations and publications to improve replicability and facilitate pre-registrations. The FLUX can be used for education either in self-studies or guided workshops. We expect that the FLUX pipeline will strengthen the field of MEG by providing some standardization on the basic analysis steps and by aligning approaches across toolboxes. Furthermore, we also aim to support new researchers entering the field by providing education and training. The FLUX pipeline is not meant to be static; it will evolve with the development of the toolboxes and with new insights. Furthermore, with the anticipated increase in MEG systems based on the Optically Pumped Magnetometers, the pipeline will also evolve to embrace these developments.
Modulation of alpha oscillations by attention is predicted by hemispheric asymmetry of subcortical regions.
Evidence suggests that subcortical structures play a role in high-level cognitive functions such as the allocation of spatial attention. While there is abundant evidence in humans for posterior alpha band oscillations being modulated by spatial attention, little is known about how subcortical regions contribute to these oscillatory modulations, particularly under varying conditions of cognitive challenge. In this study, we combined MEG and structural MRI data to investigate the role of subcortical structures in controlling the allocation of attentional resources by employing a cued spatial attention paradigm with varying levels of perceptual load. We asked whether hemispheric lateralization of volumetric measures of the thalamus and basal ganglia predicted the hemispheric modulation of alpha-band power. Lateral asymmetry of the globus pallidus, caudate nucleus, and thalamus predicted attention-related modulations of posterior alpha oscillations. When the perceptual load was applied to the target and the distractor was salient caudate nucleus asymmetry predicted alpha-band modulations. Globus pallidus was predictive of alpha-band modulations when either the target had a high load, or the distractor was salient, but not both. Finally, the asymmetry of the thalamus predicted alpha band modulation when neither component of the task was perceptually demanding. In addition to delivering new insight into the subcortical circuity controlling alpha oscillations with spatial attention, our finding might also have clinical applications. We provide a framework that could be followed for detecting how structural changes in subcortical regions that are associated with neurological disorders can be reflected in the modulation of oscillatory brain activity.
Retinal morphological differences in atypical Parkinsonism: A cross-sectional analysis of the AlzEye cohort
Objective: Atypical Parkinsonian syndrome (APS) describes a heterogeneous group of disorders mimicking the clinical presentation of Parkinson disease (PD) but with disparate natural history and pathophysiology. While retinal markers of PD are increasingly described, APS has been afforded less attention possibly owing to its lower prevalence. Here, we investigate retinal morphological differences in individuals with APS in a large real world cohort. Methods: We conducted a cross-sectional analysis of the AlzEye study, a retrospective cohort where ophthalmic data of individuals attending Moorfields Eye Hospital between January 2008 and March 31st 2018 (inclusive) has been linked with systemic disease data through national hospital admissions. Retinal features were extracted from macula-centered color fundus photography (CFP) and optical coherence tomography (OCT) and compared between individuals with APS and those unaffected. Individuals with idiopathic PD were excluded. Retinal neural and vascular features were measured using automated segmentation and analyzed with multivariable-adjusted regression models. Results: Among a cohort of 91,170 patients, there were 51 patients with APS and 91,119 controls. Individuals with APS were older and more likely to have hypertension and diabetes mellitus. After adjusting for age, sex, hypertension and diabetes melitus, individuals with APS had a thinner ganglion cell-inner plexiform layer (-3.95 microns, 95% CI: −7.53, −0.37, p = 0.031) but no difference in other retinoneural or retinovascular indices. Optic nerve cup-to-disc ratio was similar between groups. Conclusion: Our cross-sectional analysis of the AlzEye cohort reveals distinct retinal morphological characteristics in APS compared to healthy controls. The study notably identifies a thinner ganglion cell-inner plexiform layer in APS patients, without accompanying changes in the inner nuclear layer or significant alterations in retinovascular indices and optic nerve cup-disc ratio. These changes are distinct from those observed in PD, where thinning of the inner nuclear layer (INL) is a characteristic feature. Significance: These findings demonstrate a retinal phenotype in APS, markedly different from both healthy controls and idiopathic Parkinson's disease, highlighting the potential of retinal imaging in differentiating neurodegenerative disorders. By establishing a distinct retinal phenotype for APS, our findings underscore the potential of retinal imaging as a valuable, non-invasive diagnostic tool. This advancement is particularly significant for enhancing diagnostic accuracy, facilitating early detection, and offering a window into the underlying disease mechanisms in APS, thereby aiding in the development of targeted therapeutic interventions and personalized patient care strategies.