Differentiating Alzheimer’s Disease and Vascular Dementia via Combined OCT and OCT‑Angiography Analysis

Differentiating Alzheimer’s Disease and Vascular Dementia via Combined OCT and OCT‑Angiography Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Differentiating Alzheimer’s Disease and Vascular Dementia via Combined OCT and OCT‑Angiography Analysis Semih Ceylan, Mert Egemen Çalışkan, Nazlı Çelik, Eray Atalay This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7206047/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Apr, 2026 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract The purpose of this cross-sectional study is to compare microvascular and structural retinal parameters between Alzheimer's disease (AD), vascular dementia (VD), and healthy controls (HCs). We recruited AD and VD patients aged 50–90 years and age-matched HCs who underwent ocular optical coherence tomography (OCT) and OCT angiography. Exclusion criteria included cataract, retinopathy, optic neuropathy, intraocular pressure ≥21 mmHg, and refractive error ≥±4D. The analysis included 118 participants: 29 with AD (14 female, mean age 70.0 ± 7.5), 30 with VD (11 female, mean age 69.9 ± 9.9) and 59 HC (28 females, mean age 69.7 ± 8.6 years). Parafoveal SCP VAD was slightly lower in AD than VD and HCs (p=0.034 overall ANOVA), while the difference between AD and HCs was more pronounced in the inferior zone (p=0.029). We found significantly thinner RNFL in VD than HCs in superior, inferior and temporal quadrants (superior; 121.8μm vs. 133μm, p=0.017, inferior; 126.6μm vs. 137.3μm, p=0.017, temporal; 67.5μm vs. 73.8μm, p=0.043). VD also had overall reduced macular thickness compared to AD, more pronounced in nasal perifoveal area (275.2μm vs. 285.5μm, p=0.039). Overall, VD was characterized by pronounced RNFL and macular thinning, whereas AD exhibited parafoveal vascular density reduction without overt structural thinning. Health sciences/Diseases Health sciences/Medical research Health sciences/Neurology Biological sciences/Neuroscience Alzheimer's Disease Vascular Dementia Optical Coherence Tomography Angiography Figures Figure 1 Figure 2 Introduction Dementia, defined as the irreversible decline of acquired cognitive abilities to a level that disrupts daily life, is a leading global health concern. According to the World Health Organization, dementia was the 7th leading cause of death in 2018 and is projected to affect 152 million people by 2050 (1). The economic impact of dementia is also significant, with the global cost estimated at $818 billion in 2015 (2). Alzheimer's disease (AD) is the most common type of dementia, accounting for an estimated 60-80% of cases (3). It is typically characterized by a gradual onset and slow progression of cognitive decline, primarily affecting short-term memory, in individuals over 65 years old. Studies in the United States have shown that more than 1 in 9 people aged 65 and older have AD. Vascular dementia (VD), on the other hand, is the second most common type of dementia after AD and is responsible for approximately 15-20% of cases in North America and Europe, and roughly about 30% in Asia and developing countries (4). Vascular dementia usually follows a different course than AD, which is marked by periodic exacerbations, followed by relatively stable periods and slow decline, often leading to the impairment of motor functions in relation to the brain area involved (5,6). Moreover, while memory is impaired relatively later in VD, it is more noticeable even in the early stages of AD (6). Another significant difference is that individuals with VD have an approximately 5 years shorter lifespan than individuals with AD (7). Unlike AD, preventing or slowing down the progression of VD seems possible only by identifying and treating the underlying cause of the underlying vascular event (6,8,9). Therefore, differentiating between these two etiologies of degenerative dementia is clinically crucial, however challenging. Ocular imaging has emerged as a practical means for diagnosing or distinguishing various neurological diseases such as Alzheimer’s Disease, Multiple Sclerosis, Parkinson’s Disease, etc. ((10–12)). Because retina and the brain share common embryological, anatomical, and physiological origins, OCT&OCTA-derived retinal biomarkers may help distinguish Alzheimer’s dementia from vascular dementia. This study therefore evaluates whether quantitative OCT and OCTA parameters can reliably differentiate Alzheimer’s dementia from vascular dementia. Results A total of 118 participants were enrolled: 29 with AD (14 female, mean age 70.0 ± 7.5), 30 with VD (11 female, mean age 69.9 ± 9.9) and 59 HC (28 females, mean age 69.7 ± 8.6 years). There was no statistically significant difference in mean age and gender distribution (p=0.99 and p=0.57, respectively). Among the angiographic parameters assessed, there were no statistically significant differences among the AD, VD and HC groups (Table 1). In contrast, RNFL and macular thickness analyses revealed significant differences. Eyes of patients with VD demonstrated significantly thinner RNFL than those of healthy controls in the superior (121.8 μm vs. 133 μm; p = 0.017), inferior (126.6 μm vs. 137.3 μm; p = 0.017) and temporal (67.5 μm vs. 73.8 μm; p = 0.043) quadrants (Table 2, Figure 1). In patients with AD, RNFL thickness in the superior and temporal quadrants was comparable to that of healthy controls; the temporal quadrant appeared thicker and the inferior quadrant thinner than controls, but these differences did not reach statistical significance. Although RNFL thickness was greater in the AD group than in the VD group, this difference was likewise not significant. Figure 2 depicts macular thickness in eyes of participants with AD, VD and HC. Foveal thickness was similar across all groups. Although mean thickness in the parafoveal and perifoveal quadrants was lower in patients with VD, only nasal perifoveal thickness differed significantly between the VD and AD cohorts (275.2 μm vs. 285.5 μm; p = 0.039) (Table 3). OCTAVA software analysis of the SCP microvasculature revealed that eyes of patients with AD exhibited reduced parafoveal VAD compared with those of patients with VD and HC; this reduction was most pronounced in the inferior parafoveal zone (30.5 % vs. 33.9 %; p = 0.029) (Table 4). Foveal VAD was lower in the AD group but higher in the VD group relative to healthy controls, although these differences did not reach statistical significance. Total vessel length and vessel length density did not differ significantly across the groups. Mean vessel length tended to be lower in the eyes of AD patients than in the eyes of both VD and HC, but these trends were not significant. Likewise, none of the FAZ–related parameters showed statistically significant differences. Discussion While Alzheimer’s disease and vascular dementia are fundamentally distinct entities with specific pathological pathways, there is a significant overlap in these two forms of dementia likely in part due to shared risk factors such as hypertension, diabetes mellitus, smoking, apolipoprotein E (ApoE) ε4 isoforms, hypercholesterolemia, homocysteinemia, and age (15). The primary driving factor of VD is alterations in vascular integrity leading to ischemic and hypoxic damage (16) On the other hand, AD is driven by direct neurotoxicity from the accumulation of amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles which leads to death of neurons (17). VD can develop due to large vessel infarcts but is also strongly associated with small vessel disease, which is considered the most common cause of dementia among cerebrovascular diseases (18). The clinical differentiation between AD and VD is challenging and requires sophisticated and expensive diagnostic equipment, such as functional MRI or PET, or invasive procedures such as lumbar puncture and/or postmortem analyses for cerebrospinal fluid analyses (15,19). In this regard, retinal biomarkers may serve as a non-invasive, repeatable and in vivo means to distinguish the two most common forms of dementia. Overall, structural OCT revealed that the eyes of the VD patients exhibited marked thinning of the retinal nerve fiber layer (RNFL) in all quadrants that is more prominent in the superior, inferior, and temporal quadrants when compared with HC. Alzheimer’s disease seems to affect RNFL thickness to a lesser degree, demonstrating comparable values with healthy controls. Macular thickness analysis revealed reduced values in eyes with VD patients compared to AD and HC groups. These findings indicate that VD may be more influential in structural deterioration, however AD may affect circulation more. These two findings imply primary structural involvement and relative preservation of macular involvement in cerebrovascular versus neurodegenerative pathology. Implying selective macular involvement in cerebrovascular versus neurodegenerative pathology. We found that RNFL thickness is more affected in VD while being relatively preserved in patients with AD. There are conflicting reports with regards to RNFL alterations in AD in and other subtypes of dementia. A systematic review and meta-analysis reported general reduction in RNFL thickness in all quadrants in AD (20) Using the identical imaging modality, namely spectral-domain OCT, other studies found contradicting results, showing either a much smaller change or no change in AD patients.(21–23). In support of these observations, another study showed no relationship between RNFL thickness and cognitive decline (24). These contradictory results may be explained by the diverse pathophysiology of AD and significant overlap between VD and AD, the former of which may be more influential in the reduction of structural retinal parameters as observed in our study (15). In line with this conjecture, another systematic review reported consistently reduced RNFL in cerebrovascular disease, which is a major contributor to VD (25). Likewise, significant RNFL thinning was observed in cardiovascular diseases and stroke in large-scale population-based studies.(26) suggesting greater involvement of structural parameters with vascular impairment. Consistent with the pattern observed in RNFL analysis, a reduction in total macular thickness was observed in the eyes of patients with VD compared to those with AD and healthy controls. Notably, the degree of macular thinning in the VD group was greater than the differences in RNFL thickness between the same groups, indicating more pronounced structural compromise in the macula. However, eyes with AD patients showed slightly thicker macular thickness compared to that of healthy controls. Similar to RNFL, the significant reduction in retinal thickness in the VD group could be due to ischemic and hypoxic damage causing more deterioration and thinning. In terms of macular thickness in AD, two independent meta-analyses have shown a reduction in total macular thickness in eyes with AD patients that is more pronounced in the superior quadrant(20,27). The OCT modalities used in these studies were Fourier-domain and spectral-domain, which may account for the discrepancy with our findings, as we used swept-source OCT. Other factors potentially contributing to the conflicting results include differences in disease severity among study cohorts, age variations, and the aforementioned overlap with VD, which, based on our findings, may inflict greater impairment at the macular and RNFL level. Nevertheless, other studies have reported preserved macular thickness in AD patients, including amyloid-proven cases, and even an increase in foveal thickness and volume in one study.(28–31). . In their large-scale analysis, Sanchez et al. argue that the magnitude of macular thickness differences between controls and AD patients is minimal—occasionally less than 1 μm after adjustment—which falls within the intraindividual variability of the technique, suggesting that macular thickness may not serve as a reliable biomarker for distinguishing AD from controls. (32). More recently, Jáñez-García et al. suggested that there are interspersed thickened and thinned retinal regions in eyes of AD patients proposing the use of retinal roughness as an early biomarker of AD (33). While retinal thinning may reflect cellular degeneration and apoptosis, thickening in AD may result from balloon degeneration and cellular swelling associated with amyloid beta and tau-related degeneration in Müller and retinal ganglion cells (31,34). Angiographic parameters derived from OCTA did not differ significantly among the AD, VD, and HC groups. However, parafoveal vessel area density (VAD) computed by OCTAVA was reduced in AD relative to both VD and HC, most prominently in the inferior parafoveal zone, mirroring reports of retinal capillary attenuation in AD(35–37) . We also observed a non-significant trend toward reduced vessel length parameters in AD compared with VD and HC. On the other hand, FAZ morphology was preserved in both patient groups. Notably, VD patients exhibited angiographic metrics comparable to HC for both OCTA-derived and OCTAVA-generated parameters. One possible explanation for the similarity between VD and HC relates to how vessel density is computed: vessel density is defined as the percentage area occupied by the large vessels and microvasculature divided by total cross-section in a specific area (38). Because OCTA segmentation relies on predefined retinal layer boundaries, a reduction in total retinal thickness in VD eyes can decrease the cross-sectional tissue area used as the denominator, thereby artificially inflating vessel density values despite true perfusion loss. This study addresses a gap in literature by being, to our knowledge, the first to compare OCT and OCT-A parameters among vascular dementia (VD) patients, Alzheimer’s disease (AD) patients, and age-matched healthy controls. We employed a multimodal imaging protocol, integrating structural OCT with OCT angiography, which enabled simultaneous and detailed characterization of both retinal morphology and microvascular features. To mitigate confounding by demographic factors, we used individualized controls matched for age. While the sample size was small, obtaining high-quality OCT/OCT-A scans in cognitively impaired individuals who often demonstrate reduced cooperation and fixation stability is challenging. Finally, analysis of vascular parameters at the optic nerve head level was not available, as the relevant DRI OCT Triton Plus software update occurred after study initiation. In conclusion, these findings highlight divergent retinal structural and microvasculature profiles in AD and VD: VD is characterized by pronounced RNFL and macular thinning, whereas AD exhibits parafoveal vascular density reduction without overt structural thinning. The dissociation between structural and vascular alterations underscores the potential value of combining OCT and OCTA metrics to distinguish between neurodegenerative and vascular contributions to cognitive impairment. Future longitudinal studies with larger samples are warranted to validate these markers and to assess their utility in early diagnosis and monitoring of dementia subtypes. Methods This cross-sectional study prospectively recruited age-matched patients (50 – 90 years) with AD and VD and healthy controls from the neurology and ophthalmology outpatient clinics of Eskisehir Osmangazi University Hospital. The Alzheimer’s disease (AD) group included individuals diagnosed based on the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA). All AD participants were free from other neurological or psychiatric conditions. The vascular dementia (VD) group included participants diagnosed with vascular dementia according to the criteria established by the National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l’Enseignement en Neurosciences (NINDS-AIREN). Like the AD group, participants with comorbid neurological or psychiatric disorders were excluded. Each patient in the AD and VD groups was individually matched to a healthy control (HC) by age (±2 years). The control group consisted of individuals with a Clinical Dementia Rating (CDR) score of 0, no cognitive complaints, and no history of neurological or psychiatric disorders. Specifically, individuals with a history of ischemic or hemorrhagic cerebrovascular events, intellectual disability, epilepsy, Parkinson's disease, depression, any type of dementia, motor neuron disease, demyelinating diseases, mood disorders, or alcohol/substance abuse were excluded. Ophthalmological exclusion criteria were as follows: best-corrected visual acuity worse than 20/40; spherical equivalent refractive error exceeding ±4.0 D; axial length less than 22 mm or greater than 26 mm; OCT image quality index below 45 (13); advanced cataract or unstable fixation; intraocular pressure above 21 mmHg, any ocular pathology (age-related macular degeneration, diabetic retinopathy, epiretinal membrane, macular hole, retinal vascular occlusion, retinal dystrophy, glaucoma, optic neuropathy, or uveitis). Written informed consent was obtained from all participants and/or their legal guardians prior to inclusion in the study. This study adhered to the principles outlined in the Declaration of Helsinki and was approved by the Ethics Committee of the Faculty of Medicine at the Eskisehir Osmangazi University (decision number 28, dated May 24, 2022). All included participants underwent standardized neurological and ophthalmological examinations and additional structural and microvascular assessment using optical coherence tomography angiography (OCTA, DRI OCT Triton Plus device, Topcon, Tokyo, Japan). The imaging included 3D OCT imaging of the optic disc and macula and angiographic evaluation of the macula. In this study microvascular parameters, including vessel density (VD) at superficial (SCP) and deep capillary plexus (DCP), and structural parameters, including thicknesses of the retinal nerve fiber layer (RNFL) in four quadrants and macula in perifoveal and parafoveal zones in four quadrants, were assessed. VD analysis at the optic nerve head was unavailable at the time of the study, as this feature was added to the DRI OCT Triton Plus device only after our study began. To further analyze microvasculature changes, all OCT-A images (projection artifact-free) were exported and analyzed using an open-source software "Optical Coherence Tomography Angiography Vascular Analyzer (version 1.0) as per the developer guidelines (14). OCTAVA uses ImageJ, MATLAB, and angiogenesis analyzer software for preprocessing, feature identification, and image classification from the OCTA device. It also allows for the calculation of various parameters including vessel area density (VAD), vessel length density (VLD), mean and median vessel diameter, total vessel length. It also computes foveal avascular zone area (FAZ), perimeter, circularity and acicularity indexes. For the purposes of this analysis, the average macular VD was calculated in the parafoveal region, defined as the annular area between 1 mm and 3 mm diameter circles centered on the fovea, with the central 1 mm diameter area considered the foveal region. To analyze these parameters, OCTA images of the macular and ONH regions were imported to the OCTAVA software package (version 1.0) for further analysis and processed as per the developer guidelines. All statistical analyses were performed using appropriate software packages. All statistical analyses were performed using R (version 4.4.3; R Foundation for Statistical Computing, Vienna, Austria). The normality of continuous variables was assessed using the Kolmogorov–Smirnov test. Variables with a normal distribution were compared using parametric tests (one-way ANOVA), while those with a non-normal distribution were analyzed with non-parametric tests (Kruskal–Wallis tests). Comparisons of categorical variables were performed using the chi-square test. P values were adjusted for multiple comparisons using the Bonferroni method. The left-eyes of the patients were included in the analyses; if left-eye data were ineligible or unavailable, right-eye scans were used instead. Declarations Written informed consent was obtained from all participants and/or their legal guardians prior to inclusion in the study. Acknowledgements: Funding/Support: This study was supported by Scientific and Technological Research Council of Türkiye (TUBITAK) under the Grant Number 1919B012222136 (2209-A) Conference presentation: This work has been presented at the ARVO 2025 Meeting as a poster presentation. Author contributions: Semih Ceylan: Conceptualization, Methodology, Data curation, Analysis, Writing the original draft. Mert Egemen Çalışkan: Conceptualization, Methodology, Data curation, Analysis, Writing the original draft. Nazlı Çelik: Methodology, Data curation, Analysis, Writing - review & editing. Eray Atalay: Conceptualization, Methodology, Supervision, Analysis, Resources, Writing - review & editing. Data availability statement: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Additional Information: Competing interest: The author(s) declare no competing interests. Declaration of generative AI and AI-assisted technologies in the writing process statement: During the preparation of this work the authors used ChatGPT 4o to improve language and readability in some sections of the manuscript. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. References Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet. 2020 Aug;396(10248):413–46. Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. Dementia prevention, intervention, and care. The Lancet. 2017 Dec;390(10113):2673–734. Alzheimer’s disease facts and figures. Alzheimers Dement. 2021 Mar;17(3):327–406. Wolters FJ, Ikram MA. 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Chu Z, Lin J, Gao C, Xin C, Zhang Q, Chen CL, et al. Quantitative assessment of the retinal microvasculature using optical coherence tomography angiography. J Biomed Opt. 2016 Jun 1;21(6):66008. Tables Table 1. Comparison of vessel density across Alzheimer’s disease, vascular dementia and healthy controls derived from DRI Triton Topcon OCT-A Alzheimer's Disease Vascular Dementia Healthy Controls p value SCP Central 18.4±4.7 18.2±4.1 17.1±3.8 0.476 Parafoveal 42.5±2.6 42.8±2.3 42.6±2.6 0.985 Superior parafoveal 42.6±3.6 43.5±2.9 43.1±3.1 0.901 Inferior parafoveal 41.4±3.7 41.9±3.5 42.3±3.5 0.596 Nasal parafoveal 41.5±3.7 42.5±3.8 42.2±2.6 0.679 Temporal parafoveal 44.3±2.3 43.2±2.4 42.9±3.2 0.087 DCP Central 10.8±4.2 10.4±4.1 9.8±4.9 0.346 Parafoveal 24.3±2.8 23.5±2.5 23.8±2.7 0.624 Superior parafoveal 25.0±3.3 24.3±3.4 24.2±3.7 0.41 Inferior parafoveal 23.5±4.1 22.7±3.7 23.6±3.6 0.795 Nasal parafoveal 25.3±4.6 24.5±3.8 25.1±4.3 0.891 Temporal parafoveal 23.5±3.2 22.6±3.3 22.4±3.3 0.337 SCP Superior capillary plexus, DCP Deep Capillary Plexus Table 2. Quadrant-wise retinal nerve fiber layer analysis across the groups Alzheimer's Disease Vascular Dementia Healthy Controls p value RNFL Superior Quadrant 132.8 (17.5) 121.8 (17.6) 133.0 (16.2) 0.016* Temporal Quadrant 72.2 (8.5) 67.5 (10.5) 73.8 (10.8) 0.049† Nasal Quadrant 87.6 (14.9) 80.6 (16.7) 83.4(13.9) 0.113 Inferior Quadrant 133.4 (17.5) 126.6 (18.9) 137.3 (16.6) 0.019‡ RNFL Retinal nerve fiber layer, *Statistically significant difference between Vascular Dementia and healthy controls (p=0.017, Bonferroni adjusted). †Statistically significant difference between Vascular dementia and healthy controls (p=0.043, Bonferroni adjusted). ‡Statistically significant difference between Vascular dementia and healthy controls (p=0.017, Bonferroni adjusted). Table 4. OCTAVA-generated OCT-A parameters at the superficial capillary plexus Alzheimer's Disease Vascular Dementia Healthy Controls p value Total VAD (%) 36.0 (2.7) 37.0 (2.7) 37.1 (2.7) 0.175 Foveal VAD (%) 14.0 (6.3) 16.9 (6.4) 15.6 (5.6) 0.240 Parafoveal VAD (%) 32.4 (4.8) 35.0 (4.2) 34.7(3.7) 0.034 * Superior parafoveal VAD (%) 29.6 (5.5) 32.0 (6.8) 31.9 (5.3) 0.324 Inferior parafoveal VAD (%) 30.5 (6.7) 33.3 (5.3) 33.9 (4.1) 0.027 ** Total VLD (%) 6.3 (0.7) 6.5 (0.7) 6.6 (0.7) 0.178 Parafoveal VLD (%) 6.2 (1.1) 6.7 (1.0) 6.6 (0.9) 0.064 Total VL (μm) 377.5 (41.5) 391.2 (40.1) 393.3 (41.7) 0.202 Parafoveal VL (μm) 64.6 (11.7) 70.0 (9.9) 70.0 (9.9) 0.056 Superior parafoveal VL (μm) 121.6 (37.5) 145.3 (49.4) 137.4 (43.3) 0.116 Inferior parafoveal VL (μm) 85.7 (29.7) 98.8 (27.6) 102.5 (31.5) 0.073 FAZ area 0.6 (0.2) 0.5 (0.2) 0.5 (0.2) 0.462 FAZ perimeter 3.5 (0.7) 3.3 (0.6) 3.3 (0.7) 0.617 FAZ circularity 0.6 (0.1) 0.6 (0.1) 0.6 (0.1) 0.105 FAZ acircularity index 1.3 (0.1) 1.3 (0.1) 1.3 (0.1) 0.109 VAD Vessel area density, VLD Vessel length density, VL Vessel length, FAZ Foveal avascular zone * No statistically significant differences in Bonferroni-adjusted pair-wise comparison. **Statistically significant difference between Alzheimer's disease and healthy controls (p=0.029, Bonferroni adjusted). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 06 Apr, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 16 Jan, 2026 Reviews received at journal 16 Jan, 2026 Reviews received at journal 07 Jan, 2026 Reviewers agreed at journal 21 Dec, 2025 Reviewers agreed at journal 16 Dec, 2025 Reviewers invited by journal 10 Aug, 2025 Editor assigned by journal 04 Aug, 2025 Editor invited by journal 29 Jul, 2025 Submission checks completed at journal 27 Jul, 2025 First submitted to journal 27 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7206047","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":492499535,"identity":"ecec4f59-af8b-481c-9267-b13ef7f1acb5","order_by":0,"name":"Semih Ceylan","email":"","orcid":"","institution":"Eskişehir City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Semih","middleName":"","lastName":"Ceylan","suffix":""},{"id":492499537,"identity":"b88be864-b2b6-4292-946f-f71ccafd0895","order_by":1,"name":"Mert Egemen Çalışkan","email":"","orcid":"","institution":"Eskişehir Osmangazi University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Mert","middleName":"Egemen","lastName":"Çalışkan","suffix":""},{"id":492499538,"identity":"5f6371b8-d1fe-49d9-bd3b-fd0253c7f798","order_by":2,"name":"Nazlı Çelik","email":"","orcid":"","institution":"Eskişehir Osmangazi University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Nazlı","middleName":"","lastName":"Çelik","suffix":""},{"id":492499539,"identity":"e10cc000-006b-4c19-9300-cf3b25aa5413","order_by":3,"name":"Eray Atalay","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIiWNgGAWjYLCCBwwMchAWG1HqmRkYEhgYjOFaeIjVkthAtBZ+9vMHPyTUHE7v519jwPCh7DCDvfQB/Foke5KZJRKOHc6dOeONAeOMc4cZePgS8GsxOJDMIJHAdjh3w40zBsy8bUAthFxmf/4x84+Ef4fTDUBa/hKjxUAimU0ise1wgsH5HgNmRmK0SNx4bGaR2JduOHMGW8HBnnPpPDxnCGjh7098fOPDN2t5fv7DGx/8KLOWY+8hoAUKmoH2JTAcYCAqJiGgDmjfAWIVj4JRMApGwUgDAAtdQTexlUQdAAAAAElFTkSuQmCC","orcid":"","institution":"Eskişehir Osmangazi University Faculty of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Eray","middleName":"","lastName":"Atalay","suffix":""}],"badges":[],"createdAt":"2025-07-24 13:23:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7206047/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7206047/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-026-47556-w","type":"published","date":"2026-04-06T15:59:22+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88029425,"identity":"4cc7b06c-a1a4-47f6-9231-4d626ad50b41","added_by":"auto","created_at":"2025-07-31 15:19:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1037113,"visible":true,"origin":"","legend":"\u003cp\u003eRetinal nerve fiber layer (RNFL) thickness profiles in Alzheimer's disease (AD), vascular dementia (VD) and healthy controls (HC). Error bars represent 95% confidence intervals. (ST1=Superotemporal 1, ST2=Superotemporal 2, SN1=Superonasal 1, SN2=Superonasal 2, IN1=Inferonasal 1, IN2=Inferonasal 2, IT1=Inferotemporal 1, IT2=Inferotemporal 2)\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7206047/v1/6d51011ad83849156435547a.png"},{"id":88031072,"identity":"6949881e-12f1-489b-a823-611775675940","added_by":"auto","created_at":"2025-07-31 15:35:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":9733673,"visible":true,"origin":"","legend":"\u003cp\u003eMacular thickness profiles in Alzheimer's disease, vascular dementia and healthy controls\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7206047/v1/96fdae5728cef172b1779365.png"},{"id":106809732,"identity":"a703b398-15c2-405f-a215-d2d3db8f93d4","added_by":"auto","created_at":"2026-04-13 16:12:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":13053470,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7206047/v1/fb56413b-a2a9-4fff-b6ac-ab3df5b9a686.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Differentiating Alzheimer’s Disease and Vascular Dementia via Combined OCT and OCT‑Angiography Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDementia, defined as the irreversible decline of acquired cognitive abilities to a level that disrupts daily life, is a leading global health concern. According to the World Health Organization, dementia was the 7th leading cause of death in 2018 and is projected to affect 152 million people by 2050\u0026nbsp;(1). The economic impact of dementia is also significant, with the global cost estimated at $818 billion in 2015\u0026nbsp;(2).\u003c/p\u003e\n\u003cp\u003eAlzheimer\u0026apos;s disease (AD) is the most common type of dementia, accounting for an estimated 60-80% of cases\u0026nbsp;(3). It is typically characterized by a gradual onset and slow progression of cognitive decline, primarily affecting short-term memory, in individuals over 65 years old. Studies in the United States have shown that more than 1 in 9 people aged 65 and older have AD. Vascular dementia (VD), on the other hand, is the second most common type of dementia after AD and is responsible for approximately 15-20% of cases in North America and Europe, and roughly about 30% in Asia and developing countries\u0026nbsp;(4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eVascular dementia usually follows a different course than AD, which is marked by periodic exacerbations, followed by relatively stable periods and slow decline, often leading to the impairment of motor functions in relation to the brain area involved\u0026nbsp;(5,6). Moreover, while memory is impaired relatively later in VD, it is more noticeable even in the early stages of AD\u0026nbsp;(6). Another significant difference is that individuals with VD have an approximately 5 years shorter lifespan than individuals with AD\u0026nbsp;(7). Unlike AD, preventing or slowing down the progression of VD seems possible only by identifying and treating the underlying cause of the underlying vascular event\u0026nbsp;(6,8,9). Therefore, differentiating between these two etiologies of degenerative dementia is clinically crucial, however challenging.\u003c/p\u003e\n\u003cp\u003eOcular imaging has emerged as a practical means for diagnosing or distinguishing various neurological diseases such as Alzheimer\u0026rsquo;s Disease, Multiple Sclerosis, Parkinson\u0026rsquo;s Disease, etc. ((10\u0026ndash;12)). Because retina and the brain share common embryological, anatomical, and physiological origins, OCT\u0026amp;OCTA-derived retinal biomarkers may help distinguish Alzheimer\u0026rsquo;s dementia from vascular dementia. This study therefore evaluates whether quantitative OCT and OCTA parameters can reliably differentiate Alzheimer\u0026rsquo;s dementia from vascular dementia.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 118 participants were enrolled: 29 with AD (14 female, mean age 70.0 \u0026plusmn; 7.5), 30 with VD (11 female, mean age 69.9 \u0026plusmn; 9.9) and 59 HC (28 females, mean age 69.7 \u0026plusmn; 8.6 years). There was no statistically significant difference in mean age and gender distribution (p=0.99 and p=0.57, respectively). Among the angiographic parameters assessed, there were no statistically significant differences among the AD, VD and HC groups (Table 1).\u003c/p\u003e\n\u003cp\u003eIn contrast, RNFL and macular thickness analyses revealed significant differences. \u0026nbsp; Eyes of patients with VD demonstrated significantly thinner RNFL than those of healthy controls in the superior (121.8 \u0026mu;m vs. 133 \u0026mu;m; p = 0.017), inferior (126.6 \u0026mu;m vs. 137.3 \u0026mu;m; p = 0.017) and temporal (67.5 \u0026mu;m vs. 73.8 \u0026mu;m; p = 0.043) quadrants (Table 2, Figure 1). \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn patients with AD, RNFL thickness in the superior and temporal quadrants was comparable to that of healthy controls; the temporal quadrant appeared thicker and the inferior quadrant thinner than controls, but these differences did not reach statistical significance. \u0026nbsp;Although RNFL thickness was greater in the AD group than in the VD group, this difference was likewise not significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 2\u0026nbsp;\u003c/strong\u003edepicts macular thickness in eyes of participants with AD, VD and HC. Foveal thickness was similar across all groups. Although mean thickness in the parafoveal and perifoveal quadrants was lower in patients with VD, only nasal perifoveal thickness differed significantly between the VD and AD cohorts (275.2 \u0026mu;m vs. 285.5 \u0026mu;m; p = 0.039) (Table 3).\u003c/p\u003e\n\u003cp\u003eOCTAVA software analysis of the SCP microvasculature revealed that eyes of patients with AD exhibited reduced parafoveal VAD compared with those of patients with VD and HC; this reduction was most pronounced in the inferior parafoveal zone (30.5 % vs. 33.9 %; p = 0.029) (Table 4). Foveal VAD was lower in the AD group but higher in the VD group relative to healthy controls, although these differences did not reach statistical significance. Total vessel length and vessel length density did not differ significantly across the groups. Mean vessel length tended to be lower in the eyes of AD patients than in the eyes of both VD and HC, but these trends were not significant. Likewise, none of the FAZ\u0026ndash;related parameters showed statistically significant differences.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWhile Alzheimer\u0026rsquo;s disease and vascular dementia are fundamentally distinct entities with specific pathological pathways, there is a significant overlap in these two forms of dementia likely in part due to shared risk factors such as hypertension, diabetes mellitus, smoking, apolipoprotein E (ApoE) \u0026epsilon;4 isoforms, hypercholesterolemia, homocysteinemia, and age (15). The primary driving factor of VD is alterations in vascular integrity leading to ischemic and hypoxic damage (16) On the other hand, AD is driven by direct neurotoxicity from the accumulation of amyloid-\u0026beta; (A\u0026beta;) plaques and hyperphosphorylated tau tangles which leads to death of neurons (17).\u0026nbsp;VD can develop due to large vessel infarcts but is also strongly associated with small vessel disease, which is considered the most common cause of dementia among cerebrovascular diseases\u0026nbsp;(18). The clinical differentiation between AD and VD is challenging and requires sophisticated and expensive diagnostic equipment, such as functional MRI or PET, or invasive procedures such as lumbar puncture and/or postmortem analyses for cerebrospinal fluid analyses\u0026nbsp;(15,19). In this regard, retinal biomarkers may serve as a non-invasive, repeatable and \u003cem\u003ein vivo\u003c/em\u003e means to distinguish the two most common forms of dementia.\u003c/p\u003e\n\u003cp\u003eOverall, structural OCT revealed that the eyes of the VD patients exhibited marked thinning of the retinal nerve fiber layer (RNFL) in all quadrants that is more prominent in the superior, inferior, and temporal quadrants when compared with HC. Alzheimer\u0026rsquo;s disease seems to affect RNFL thickness to a lesser degree, demonstrating comparable values with healthy controls. Macular thickness analysis revealed reduced values in eyes with VD patients compared to AD and HC groups. These findings indicate that VD may be more influential in structural deterioration, however AD may affect circulation more. These two findings imply primary structural involvement and relative preservation of macular involvement in cerebrovascular versus neurodegenerative pathology. Implying selective macular involvement in cerebrovascular versus neurodegenerative pathology.\u003c/p\u003e\n\u003cp\u003eWe found that RNFL thickness is more affected in VD while being relatively preserved in patients with AD. There are conflicting reports with regards to RNFL alterations in AD in and other subtypes of dementia. A systematic review and meta-analysis reported general reduction in RNFL thickness in all quadrants in AD (20) Using the identical imaging modality, namely spectral-domain OCT, other studies found contradicting results, showing either a much smaller change or no change in AD patients.(21\u0026ndash;23). In support of these observations, another study showed no relationship between RNFL thickness and cognitive decline (24). These contradictory results may be explained by the diverse pathophysiology of AD and significant overlap between VD and AD, the former of which may be more influential in the reduction of structural retinal parameters as observed in our study (15). In line with this conjecture, another systematic review reported consistently reduced RNFL in cerebrovascular disease, which is a major contributor to VD (25). Likewise, significant RNFL thinning was observed in cardiovascular diseases and stroke in large-scale population-based studies.(26) suggesting greater involvement of structural parameters with vascular impairment.\u003c/p\u003e\n\u003cp\u003eConsistent with the pattern observed in RNFL analysis, a reduction in total macular thickness was observed in the eyes of patients with VD compared to those with AD and healthy controls. Notably, the degree of macular thinning in the VD group was greater than the differences in RNFL thickness between the same groups, indicating more pronounced structural compromise in the macula. However, eyes with AD patients showed slightly thicker macular thickness compared to that of healthy controls. Similar to RNFL, the significant reduction in retinal thickness in the VD group could be due to ischemic and hypoxic damage causing more deterioration and thinning. In terms of macular thickness in AD, two independent meta-analyses have shown a reduction in total macular thickness in eyes with AD patients that is more pronounced in the superior quadrant(20,27). The OCT modalities used in these studies were Fourier-domain and spectral-domain, which may account for the discrepancy with our findings, as we used swept-source OCT. Other factors potentially contributing to the conflicting results include differences in disease severity among study cohorts, age variations, and the aforementioned overlap with VD, which, based on our findings, may inflict greater impairment at the macular and RNFL level. Nevertheless, other studies have reported preserved macular thickness in AD patients, including amyloid-proven cases, and even an increase in foveal thickness and volume in one study.(28\u0026ndash;31). . In their large-scale analysis, Sanchez et al. argue that the magnitude of macular thickness differences between controls and AD patients is minimal\u0026mdash;occasionally less than 1 \u0026mu;m after adjustment\u0026mdash;which falls within the intraindividual variability of the technique, suggesting that macular thickness may not serve as a reliable biomarker for distinguishing AD from controls. (32). More recently, J\u0026aacute;\u0026ntilde;ez-Garc\u0026iacute;a et al. suggested that there are interspersed thickened and thinned retinal regions in eyes of AD patients proposing the use of retinal roughness as an early biomarker of AD (33). While retinal thinning may reflect cellular degeneration and apoptosis, thickening in AD may result from balloon degeneration and cellular swelling associated with amyloid beta and tau-related degeneration in M\u0026uuml;ller and retinal ganglion cells (31,34).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAngiographic parameters derived from OCTA did not differ significantly among the AD, VD, and HC groups. However, parafoveal vessel area density (VAD) computed by OCTAVA was reduced in AD relative to both VD and HC, most prominently in the inferior parafoveal zone, mirroring reports of retinal capillary attenuation in AD(35\u0026ndash;37) . We also observed a non-significant trend toward reduced vessel length parameters in AD compared with VD and HC. On the other hand, FAZ morphology was preserved in both patient groups. Notably, VD patients exhibited angiographic metrics comparable to HC for both OCTA-derived and OCTAVA-generated parameters. One possible explanation for the similarity between VD and HC relates to how vessel density is computed: vessel density is defined as the percentage area occupied by the large vessels and microvasculature divided by total cross-section in a specific area (38). Because OCTA segmentation relies on predefined retinal layer boundaries, a reduction in total retinal thickness in VD eyes can decrease the cross-sectional tissue area used as the denominator, thereby artificially inflating vessel density values despite true perfusion loss.\u003c/p\u003e\n\u003cp\u003eThis study addresses a gap in literature by being, to our knowledge, the first to compare OCT and OCT-A parameters among vascular dementia (VD) patients, Alzheimer\u0026rsquo;s disease (AD) patients, and age-matched healthy controls. We employed a multimodal imaging protocol, integrating structural OCT with OCT angiography, which enabled simultaneous and detailed characterization of both retinal morphology and microvascular features. To mitigate confounding by demographic factors, we used individualized controls matched for age. While the sample size was small, obtaining high-quality OCT/OCT-A scans in cognitively impaired individuals who often demonstrate reduced cooperation and fixation stability is challenging. Finally, analysis of vascular parameters at the optic nerve head level was not available, as the relevant DRI OCT Triton Plus software update occurred after study initiation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn conclusion, these findings highlight divergent retinal structural and microvasculature profiles in AD and VD: VD is characterized by pronounced RNFL and macular thinning, whereas AD exhibits parafoveal vascular density reduction without overt structural thinning. The dissociation between structural and vascular alterations underscores the potential value of combining OCT and OCTA metrics to distinguish between neurodegenerative and vascular contributions to cognitive impairment. Future longitudinal studies with larger samples are warranted to validate these markers and to assess their utility in early diagnosis and monitoring of dementia subtypes.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis cross-sectional study prospectively recruited age-matched patients (50 \u0026ndash; 90 years) with AD and VD and healthy controls from the neurology and ophthalmology outpatient clinics of Eskisehir Osmangazi University Hospital. The Alzheimer\u0026rsquo;s disease (AD) group included individuals diagnosed based on the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer\u0026rsquo;s Disease and Related Disorders Association (NINCDS-ADRDA). All AD participants were free from other neurological or psychiatric conditions. The vascular dementia (VD) group included participants diagnosed with vascular dementia according to the criteria established by the National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l\u0026rsquo;Enseignement en Neurosciences (NINDS-AIREN). Like the AD group, participants with comorbid neurological or psychiatric disorders were excluded. Each patient in the AD and VD groups was individually matched to a healthy control (HC) by age (\u0026plusmn;2 years). The control group consisted of individuals with a Clinical Dementia Rating (CDR) score of 0, no cognitive complaints, and no history of neurological or psychiatric disorders. Specifically, individuals with a history of ischemic or hemorrhagic cerebrovascular events, intellectual disability, epilepsy, Parkinson\u0026apos;s disease, depression, any type of dementia, motor neuron disease, demyelinating diseases, mood disorders, or alcohol/substance abuse were excluded.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOphthalmological exclusion criteria were as follows: best-corrected visual acuity worse than 20/40; spherical equivalent refractive error exceeding \u0026plusmn;4.0 D; axial length less than 22 mm or greater than 26 mm; OCT image quality index below 45 (13); advanced cataract or unstable fixation; intraocular pressure above 21 mmHg, any ocular pathology (age-related macular degeneration, diabetic retinopathy, epiretinal membrane, macular hole, retinal vascular occlusion, retinal dystrophy, glaucoma, optic neuropathy, or uveitis). \u0026nbsp; Written informed consent was obtained from all participants and/or their legal guardians prior to inclusion in the study. This study adhered to the principles outlined in the Declaration of Helsinki and was approved by the Ethics Committee of the Faculty of Medicine at the Eskisehir Osmangazi University (decision number 28, dated May 24, 2022).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll included participants underwent standardized neurological and ophthalmological examinations and additional structural and microvascular assessment using optical coherence tomography angiography (OCTA, DRI OCT Triton Plus device, Topcon, Tokyo, Japan). The imaging included 3D OCT imaging of the optic disc and macula and angiographic evaluation of the macula. In this study microvascular parameters, including vessel density (VD) at superficial (SCP) and deep capillary plexus (DCP), and structural parameters, including thicknesses of the retinal nerve fiber layer (RNFL) in four quadrants and macula in perifoveal and parafoveal zones in four quadrants, were assessed. VD analysis at the optic nerve head was unavailable at the time of the study, as this feature was added to the DRI OCT Triton Plus device only after our study began.\u003c/p\u003e\n\u003cp\u003eTo further analyze microvasculature changes, all OCT-A images (projection artifact-free) were exported and analyzed using an open-source software \u0026quot;Optical Coherence Tomography Angiography Vascular Analyzer (version 1.0) as per the developer guidelines (14). OCTAVA uses ImageJ, MATLAB, and angiogenesis analyzer software for preprocessing, feature identification, and image classification from the OCTA device. It also allows for the calculation of various parameters including vessel area density (VAD), vessel length density (VLD), mean and median vessel diameter, total vessel length. It also computes foveal avascular zone area (FAZ), perimeter, circularity and acicularity indexes. For the purposes of this analysis, the average macular VD was calculated in the parafoveal region, defined as the annular area between 1 mm and 3 mm diameter circles centered on the fovea, with the central 1 mm diameter area considered the foveal region. To analyze these parameters, OCTA images of the macular and ONH regions were imported to the OCTAVA software package (version 1.0) for further analysis and processed as per the developer guidelines.\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using appropriate software packages. All statistical analyses were performed using R (version 4.4.3; R Foundation for Statistical Computing, Vienna, Austria). The normality of continuous variables was assessed using the Kolmogorov\u0026ndash;Smirnov test. Variables with a normal distribution were compared using parametric tests (one-way ANOVA), while those with a non-normal distribution were analyzed with non-parametric tests (Kruskal\u0026ndash;Wallis tests). Comparisons of categorical variables were performed using the chi-square test. P values were adjusted for multiple comparisons using the Bonferroni method. The left-eyes of the patients were included in the analyses; if left-eye data were ineligible or unavailable, right-eye scans were used instead.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eWritten informed consent was obtained from all participants and/or their legal guardians prior to inclusion in the study.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;Funding/Support:\u003c/strong\u003e This study was supported by Scientific and Technological Research Council of T\u0026uuml;rkiye (TUBITAK) under the Grant Number 1919B012222136 (2209-A)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConference presentation:\u003c/strong\u003e This work has been presented at the ARVO 2025 Meeting as a poster presentation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003eSemih Ceylan: Conceptualization, Methodology, Data curation, Analysis, Writing the original draft. Mert Egemen \u0026Ccedil;alışkan: Conceptualization, Methodology, Data curation, Analysis, Writing the original draft. Nazlı \u0026Ccedil;elik: Methodology, Data curation, Analysis, Writing - review \u0026amp; editing. Eray Atalay: Conceptualization, Methodology, Supervision, Analysis, Resources, Writing - review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u003c/strong\u003e The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional Information:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest:\u003c/strong\u003e The author(s) declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of generative AI and AI-assisted technologies in the writing process statement:\u003c/strong\u003e During the preparation of this work the authors used ChatGPT 4o to improve language and readability in some sections of the manuscript. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLivingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet. 2020 Aug;396(10248):413\u0026ndash;46. \u003c/li\u003e\n\u003cli\u003eLivingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. Dementia prevention, intervention, and care. The Lancet. 2017 Dec;390(10113):2673\u0026ndash;734. \u003c/li\u003e\n\u003cli\u003eAlzheimer\u0026rsquo;s disease facts and figures. Alzheimers Dement. 2021 Mar;17(3):327\u0026ndash;406. \u003c/li\u003e\n\u003cli\u003eWolters FJ, Ikram MA. Epidemiology of Vascular Dementia: Nosology in a Time of Epiomics. Arterioscler Thromb Vasc Biol. 2019 Aug;39(8):1542\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eBallard C, Patel A, Oyebode F, Wilcock G. Cognitive Decline in Patients with Alzheimer\u0026rsquo;s Disease, Vascular Dementia and Senile Dementia of Lewy Body Type. Age Ageing. 1996;25(3):209\u0026ndash;13. \u003c/li\u003e\n\u003cli\u003eBowler JV, Eliasziw M, Steenhuis R, Munoz DG, Fry R, Merskey H, et al. Comparative Evolution of Alzheimer Disease, Vascular Dementia, and Mixed Dementia. Arch Neurol. 1997 Jun 1;54(6):697\u0026ndash;703. \u003c/li\u003e\n\u003cli\u003eH\u0026eacute;bert R, Brayne C. Epidemiology of Vascular Dementia. Neuroepidemiology. 1995;14(5):240\u0026ndash;57. \u003c/li\u003e\n\u003cli\u003eErkinjuntti T, Hachinski VC. Rethinking Vascular Dementia (Part 1 of 2). Cerebrovasc Dis. 1993;3(1):3\u0026ndash;14. \u003c/li\u003e\n\u003cli\u003eHachinski VC, Bowler JV, Loeb C. Vascular dementia. Neurology. 1993 Oct;43(10):2159. \u003c/li\u003e\n\u003cli\u003eRifai OM, McGrory S, Robbins CB, Grewal DS, Liu A, Fekrat S, et al. The application of optical coherence tomography angiography in Alzheimer\u0026rsquo;s disease: A systematic review. Alzheimers Dement Diagn Assess Dis Monit. 2021 Mar 3;13(1):e12149. \u003c/li\u003e\n\u003cli\u003eMohammadi S, Gouravani M, Salehi MA, Arevalo JF, Galetta SL, Harandi H, et al. Optical coherence tomography angiography measurements in multiple sclerosis: a systematic review and meta-analysis. J Neuroinflammation. 2023 Mar 27;20(1):85. \u003c/li\u003e\n\u003cli\u003eKatsimpris A, Papadopoulos I, Voulgari N, Kandarakis S, Petrou P, Karampitsakos T, et al. Optical coherence tomography angiography in Parkinson\u0026rsquo;s disease: a systematic review and meta-analysis. Eye Lond Engl. 2023 Oct;37(14):2847\u0026ndash;54. \u003c/li\u003e\n\u003cli\u003eHuang Y, Gangaputra S, Lee KE, Narkar AR, Klein R, Klein BEK, et al. Signal Quality Assessment of Retinal Optical Coherence Tomography Images. Invest Ophthalmol Vis Sci. 2012 Apr;53(4):2133\u0026ndash;41. \u003c/li\u003e\n\u003cli\u003eUntracht GR, Durkee MS, Zhao M, Kwok-Cheung Lam A, Sikorski BL, Sarunic MV, et al. Towards standardising retinal OCT angiography image analysis with open-source toolbox OCTAVA. Sci Rep. 2024 Mar 12;14:5979. \u003c/li\u003e\n\u003cli\u003eAttems J, Jellinger KA. The overlap between vascular disease and Alzheimer\u0026rsquo;s disease - lessons from pathology. BMC Med. 2014 Nov 11;12(1):206. \u003c/li\u003e\n\u003cli\u003eRom\u0026aacute;n GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, et al. Vascular dementia. Neurology. 1993 Feb;43(2):250\u0026ndash;250. \u003c/li\u003e\n\u003cli\u003eQuerfurth HW, LaFerla FM. Alzheimer\u0026rsquo;s Disease. N Engl J Med. 2010 Jan 28;362(4):329\u0026ndash;44. \u003c/li\u003e\n\u003cli\u003eKalaria RN. Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer\u0026rsquo;s disease. Acta Neuropathol (Berl). 2016 May;131(5):659\u0026ndash;85. \u003c/li\u003e\n\u003cli\u003eChalkias E, Chalkias IN, Bakirtzis C, Messinis L, Nasios G, Ioannidis P, et al. Differentiating Degenerative from Vascular Dementia with the Help of Optical Coherence Tomography Angiography Biomarkers. Healthcare. 2022 Mar 15;10(3):539. \u003c/li\u003e\n\u003cli\u003eChan VTT, Sun Z, Tang S, Chen LJ, Wong A, Tham CC, et al. Spectral-Domain OCT Measurements in Alzheimer\u0026rsquo;s Disease: A Systematic Review and Meta-analysis. Ophthalmology. 2019 Apr 1;126(4):497\u0026ndash;510. \u003c/li\u003e\n\u003cli\u003eden Haan J, Csinscik L, Parker T, Paterson RW, Slattery CF, Foulkes A, et al. Retinal thickness as potential biomarker in posterior cortical atrophy and typical Alzheimer\u0026rsquo;s disease. Alzheimers Res Ther. 2019 Jul 18;11(1):62. \u003c/li\u003e\n\u003cli\u003eMutlu U, Colijn JM, Ikram MA, Bonnemaijer PWM, Licher S, Wolters FJ, et al. Association of Retinal Neurodegeneration on Optical Coherence Tomography With Dementia: A Population-Based Study. JAMA Neurol. 2018 Oct 1;75(10):1256\u0026ndash;63. \u003c/li\u003e\n\u003cli\u003ePillai JA, Bermel R, Bonner-Jackson A, Rae-Grant A, Fernandez H, Bena J, et al. Retinal Nerve Fiber Layer Thinning in Alzheimer\u0026rsquo;s Disease: A Case-Control Study in Comparison to Normal Aging, Parkinson\u0026rsquo;s Disease, and Non-Alzheimer\u0026rsquo;s Dementia. Am J Alzheimers Dis Other Demen. 2016 Aug;31(5):430\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eUeda E, Hirabayashi N, Ohara T, Hata J, Honda T, Fujiwara K, et al. Association of Inner Retinal Thickness with Prevalent Dementia and Brain Atrophy in a General Older Population. Ophthalmol Sci. 2022 Apr 19;2(2):100157. \u003c/li\u003e\n\u003cli\u003eBiffi E, Turple Z, Chung J, Biffi A. Retinal biomarkers of Cerebral Small Vessel Disease: A systematic review. PloS One. 2022;17(4):e0266974. \u003c/li\u003e\n\u003cli\u003eMajithia S, Tham YC, Chong CCY, Yu M, Cheung CY, Bikbov MM, et al. Retinal Nerve Fiber Layer Thickness and Rim Area Profiles in Asians: Pooled Analysis from the Asian Eye Epidemiology Consortium. Ophthalmology. 2022 May;129(5):552\u0026ndash;61. \u003c/li\u003e\n\u003cli\u003eden Haan J, Verbraak FD, Visser PJ, Bouwman FH. Retinal thickness in Alzheimer\u0026rsquo;s disease: A systematic review and meta-analysis. Alzheimers Dement Amst Neth. 2017;6:162\u0026ndash;70. \u003c/li\u003e\n\u003cli\u003eden Haan J, van de Kreeke JA, Konijnenberg E, ten Kate M, den Braber A, Barkhof F, et al. Retinal thickness as a potential biomarker in patients with amyloid-proven early- and late-onset Alzheimer\u0026rsquo;s disease. Alzheimers Dement Diagn Assess Dis Monit. 2019 Jun 18;11:463\u0026ndash;71. \u003c/li\u003e\n\u003cli\u003eKnoll B, Simonett J, Volpe NJ, Farsiu S, Ward M, Rademaker A, et al. Retinal nerve fiber layer thickness in amnestic mild cognitive impairment: Case-control study and meta-analysis. Alzheimers Dement Amst Neth. 2016;4:85\u0026ndash;93. \u003c/li\u003e\n\u003cli\u003eLad EM, Mukherjee D, Stinnett SS, Cousins SW, Potter GG, Burke JR, et al. Evaluation of inner retinal layers as biomarkers in mild cognitive impairment to moderate Alzheimer\u0026rsquo;s disease. PloS One. 2018;13(2):e0192646. \u003c/li\u003e\n\u003cli\u003ePoroy C, Y\u0026uuml;cel A\u0026Acirc;. Optical Coherence Tomography: Is Really a New Biomarker for Alzheimer\u0026rsquo;s Disease? Ann Indian Acad Neurol. 2018;21(2):119\u0026ndash;25. \u003c/li\u003e\n\u003cli\u003eS\u0026aacute;nchez D, Castilla-Marti M, Marqui\u0026eacute; M, Valero S, Moreno-Grau S, Rodr\u0026iacute;guez-G\u0026oacute;mez O, et al. Evaluation of macular thickness and volume tested by optical coherence tomography as biomarkers for Alzheimer\u0026rsquo;s disease in a memory clinic. Sci Rep. 2020 Jan 31;10(1):1580. \u003c/li\u003e\n\u003cli\u003eJ\u0026aacute;\u0026ntilde;ez-Garc\u0026iacute;a L, Bachtoula O, Salobrar-Garc\u0026iacute;a E, de Hoz R, Ramirez AI, Gil P, et al. Roughness of retinal layers in Alzheimer\u0026rsquo;s disease. Sci Rep. 2021 Jun 3;11(1):11804. \u003c/li\u003e\n\u003cli\u003eFujino Y, Delucia MW, Davies P, Dickson DW. Ballooned neurones in the limbic lobe are associated with Alzheimer type pathology and lack diagnostic specificity. Neuropathol Appl Neurobiol. 2004 Dec;30(6):676\u0026ndash;82. \u003c/li\u003e\n\u003cli\u003evan de Kreeke JA, Nguyen HT, Konijnenberg E, Tomassen J, den Braber A, Ten Kate M, et al. Optical coherence tomography angiography in preclinical Alzheimer\u0026rsquo;s disease. Br J Ophthalmol. 2020 Feb;104(2):157\u0026ndash;61. \u003c/li\u003e\n\u003cli\u003eZabel P, Kaluzny JJ, Wilkosc-Debczynska M, Gebska-Toloczko M, Suwala K, Zabel K, et al. Comparison of Retinal Microvasculature in Patients With Alzheimer\u0026rsquo;s Disease and Primary Open-Angle Glaucoma by Optical Coherence Tomography Angiography. Invest Ophthalmol Vis Sci. 2019 Aug 13;60(10):3447\u0026ndash;55. \u003c/li\u003e\n\u003cli\u003eZhang YS, Zhou N, Knoll BM, Samra S, Ward MR, Weintraub S, et al. Parafoveal vessel loss and correlation between peripapillary vessel density and cognitive performance in amnestic mild cognitive impairment and early Alzheimer\u0026rsquo;s Disease on optical coherence tomography angiography. PLOS ONE. 2019 Apr 2;14(4):e0214685. \u003c/li\u003e\n\u003cli\u003eChu Z, Lin J, Gao C, Xin C, Zhang Q, Chen CL, et al. Quantitative assessment of the retinal microvasculature using optical coherence tomography angiography. J Biomed Opt. 2016 Jun 1;21(6):66008. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"756\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1. Comparison of vessel density across Alzheimer\u0026rsquo;s disease, vascular dementia and healthy controls derived from DRI Triton Topcon OCT-A\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eAlzheimer\u0026apos;s Disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVascular Dementia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eHealthy Controls\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eSCP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eCentral\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e18.4\u0026plusmn;4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e18.2\u0026plusmn;4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e17.1\u0026plusmn;3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.476\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eParafoveal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42.5\u0026plusmn;2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42.8\u0026plusmn;2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42.6\u0026plusmn;2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.985\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSuperior parafoveal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42.6\u0026plusmn;3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e43.5\u0026plusmn;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e43.1\u0026plusmn;3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.901\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eInferior parafoveal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e41.4\u0026plusmn;3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e41.9\u0026plusmn;3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42.3\u0026plusmn;3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.596\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eNasal parafoveal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e41.5\u0026plusmn;3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42.5\u0026plusmn;3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42.2\u0026plusmn;2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.679\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTemporal parafoveal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e44.3\u0026plusmn;2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e43.2\u0026plusmn;2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42.9\u0026plusmn;3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eDCP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eCentral\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10.8\u0026plusmn;4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10.4\u0026plusmn;4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9.8\u0026plusmn;4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.346\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eParafoveal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e24.3\u0026plusmn;2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e23.5\u0026plusmn;2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e23.8\u0026plusmn;2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.624\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSuperior parafoveal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25.0\u0026plusmn;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e24.3\u0026plusmn;3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e24.2\u0026plusmn;3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eInferior parafoveal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e23.5\u0026plusmn;4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22.7\u0026plusmn;3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e23.6\u0026plusmn;3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.795\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eNasal parafoveal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25.3\u0026plusmn;4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e24.5\u0026plusmn;3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25.1\u0026plusmn;4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.891\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTemporal parafoveal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e23.5\u0026plusmn;3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22.6\u0026plusmn;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22.4\u0026plusmn;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.337\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" rowspan=\"2\"\u003e\n \u003cp\u003eSCP Superior capillary plexus, DCP Deep Capillary Plexus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"33\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd height=\"16\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"756\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2. \u0026nbsp;Quadrant-wise retinal nerve fiber layer analysis across the groups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eAlzheimer\u0026apos;s Disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVascular Dementia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eHealthy Controls\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eRNFL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSuperior Quadrant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e132.8 (17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e121.8 (17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e133.0 (16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.016*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTemporal Quadrant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e72.2 (8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e67.5 (10.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e73.8 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.049\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eNasal Quadrant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e87.6 (14.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e80.6 (16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e83.4(13.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.113\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eInferior Quadrant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e133.4 (17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e126.6 (18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e137.3 (16.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.019\u0026Dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e\n \u003cp\u003eRNFL Retinal nerve fiber layer, *Statistically significant difference between Vascular Dementia and healthy controls (p=0.017, Bonferroni adjusted). \u0026dagger;Statistically significant difference between Vascular dementia and healthy controls (p=0.043, Bonferroni adjusted). \u0026Dagger;Statistically significant difference between Vascular dementia and healthy controls (p=0.017, Bonferroni adjusted).\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1753950692.png\"\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"756\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 4. OCTAVA-generated OCT-A parameters at the superficial capillary plexus\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlzheimer\u0026apos;s Disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVascular Dementia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHealthy Controls\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal VAD (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e36.0 (2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e37.0 (2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e37.1 (2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFoveal VAD (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14.0 (6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16.9 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15.6 (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.240\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eParafoveal VAD (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e32.4 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e35.0 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e34.7(3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.034\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSuperior parafoveal VAD (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e29.6 (5.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e32.0 (6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e31.9 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.324\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInferior parafoveal VAD (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e30.5 (6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e33.3 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e33.9 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.027\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal VLD (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.3 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.5 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.6 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eParafoveal VLD (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.2 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.7 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.6 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal VL (\u0026mu;m)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e377.5 (41.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e391.2 (40.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e393.3 (41.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eParafoveal VL (\u0026mu;m)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e64.6 (11.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e70.0 (9.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e70.0 (9.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSuperior parafoveal VL (\u0026mu;m)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e121.6 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e145.3 (49.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e137.4 (43.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInferior parafoveal VL (\u0026mu;m)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e85.7 (29.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e98.8 (27.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e102.5 (31.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFAZ area\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.6 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.5 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.5 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.462\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFAZ perimeter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.5 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.3 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.3 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.617\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFAZ circularity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.6 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.6 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.6 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFAZ acircularity index\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.3 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.3 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.3 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"20\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" rowspan=\"2\"\u003e\n \u003cp\u003eVAD Vessel area density, VLD Vessel length density, VL Vessel length, FAZ Foveal avascular zone * No statistically significant differences in Bonferroni-adjusted pair-wise comparison. **Statistically significant difference between Alzheimer\u0026apos;s disease and healthy controls (p=0.029, Bonferroni adjusted).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"33\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd height=\"33\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Alzheimer's Disease, Vascular Dementia, Optical Coherence Tomography Angiography","lastPublishedDoi":"10.21203/rs.3.rs-7206047/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7206047/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"The purpose of this cross-sectional study is to compare microvascular and structural retinal parameters between Alzheimer's disease (AD), vascular dementia (VD), and healthy controls (HCs). We recruited AD and VD patients aged 50–90 years and age-matched HCs who underwent ocular optical coherence tomography (OCT) and OCT angiography. Exclusion criteria included cataract, retinopathy, optic neuropathy, intraocular pressure ≥21 mmHg, and refractive error ≥±4D. The analysis included 118 participants: 29 with AD (14 female, mean age 70.0 ± 7.5), 30 with VD (11 female, mean age 69.9 ± 9.9) and 59 HC (28 females, mean age 69.7 ± 8.6 years). Parafoveal SCP VAD was slightly lower in AD than VD and HCs (p=0.034 overall ANOVA), while the difference between AD and HCs was more pronounced in the inferior zone (p=0.029). We found significantly thinner RNFL in VD than HCs in superior, inferior and temporal quadrants (superior; 121.8μm vs. 133μm, p=0.017, inferior; 126.6μm vs. 137.3μm, p=0.017, temporal; 67.5μm vs. 73.8μm, p=0.043). VD also had overall reduced macular thickness compared to AD, more pronounced in nasal perifoveal area (275.2μm vs. 285.5μm, p=0.039). Overall, VD was characterized by pronounced RNFL and macular thinning, whereas AD exhibited parafoveal vascular density reduction without overt structural thinning.","manuscriptTitle":"Differentiating Alzheimer’s Disease and Vascular Dementia via Combined OCT and OCT‑Angiography Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-31 15:19:48","doi":"10.21203/rs.3.rs-7206047/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-16T17:43:12+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-16T06:39:24+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-07T09:43:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"157044911110130624177600582322162054481","date":"2025-12-21T12:51:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"141406859897455694826814073469687196339","date":"2025-12-16T09:58:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-11T00:32:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-05T02:20:41+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-29T09:44:23+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-28T01:24:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-07-27T18:24:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"50902a1b-2f2d-4954-a258-5b2e174ea27d","owner":[],"postedDate":"July 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":52292600,"name":"Health sciences/Diseases"},{"id":52292601,"name":"Health sciences/Medical research"},{"id":52292602,"name":"Health sciences/Neurology"},{"id":52292603,"name":"Biological sciences/Neuroscience"}],"tags":[],"updatedAt":"2026-04-13T16:09:28+00:00","versionOfRecord":{"articleIdentity":"rs-7206047","link":"https://doi.org/10.1038/s41598-026-47556-w","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-04-06 15:59:22","publishedOnDateReadable":"April 6th, 2026"},"versionCreatedAt":"2025-07-31 15:19:48","video":"","vorDoi":"10.1038/s41598-026-47556-w","vorDoiUrl":"https://doi.org/10.1038/s41598-026-47556-w","workflowStages":[]},"version":"v1","identity":"rs-7206047","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7206047","identity":"rs-7206047","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}