Reduced Glymphatic Function in Autism Revealed by the Diffusion Tensor Analysis Along the Perivascular Space Index

Reduced Glymphatic Function in Autism Revealed by the Diffusion Tensor Analysis Along the Perivascular Space Index | 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 Research Article Reduced Glymphatic Function in Autism Revealed by the Diffusion Tensor Analysis Along the Perivascular Space Index Laust Vind Knudsen, Manouchehr Seyedi Vafaee, Abigail Jane Sheldrick-Michel, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9047679/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background The glymphatic system supports brain homeostasis by clearing interstitial solutes via perivascular pathways. Alterations in glymphatic function have been linked to neurodevelopmental and neurodegenerative disorders, but its role in autism spectrum disorder (ASD) remains unclear. Methods We analyzed diffusion tensor imaging (DTI) magnetic resonance imaging data from five cohorts in the Autism Brain Imaging Data Exchange (ABIDE) project. Glymphatic function was estimated using the DTI analysis along the perivascular space (ALPS) index. ASD diagnoses were confirmed according to DSM-IV-TR or DSM-5 criteria, and neurotypical (NT) participants had no history of neurological, psychiatric, or developmental disorders. Results The final sample comprised 250 participants (128 ASD, mean age = 18.57 ± 13.81; 122 NT, mean age = 21.32 ± 14.37). Two-way analysis of variance (ANOVA) revealed a significant main effect of diagnosis, F(1, 246) = 10.44, p = 0.0014, with lower ALPS-indices in ASD. A diagnosis-by-age interaction was also observed, F(1, 246) = 4.71, p = 0.031. Post hoc tests demonstrated that autistic adults (≥ 18 years) had significantly lower ALPS-indices than NT adults (p = 0.0004), whereas no group differences were demonstrated between younger ASD and NT (< 18 years). In ASD adults, the ALPS-index correlated negatively with depressive symptoms (r = − 0.489, p = 0.013), but not with IQ or autistic traits. Conclusions These findings suggest that glymphatic dysfunction in ASD may follow a developmental trajectory, with alterations becoming most evident in adulthood, potentially contributing to an increased risk of developing neurodegenerative disorder in autistic individuals. Autism ASD Glymphatic system ALPS-index Diffusion tensor imaging MRI Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting more than 2.3% of 8-year-old children (Maenner et al. 2021 ). ASD is characterized by difficulties in social interaction and communication, along with restricted, repetitive behaviors and atypical sensory processing (American Psychiatric Association. 2013). In addition to these core features, sleep disturbances are highly prevalent in children with ASD, with reported rates ranging from 50% to 80%, compared to 9% to 50% in neurotypical (NT) children (Richdale and Schreck 2009 ; Burman et al. 2023 ). Furthermore, sleep-related problems often persist into adulthood, with some studies reporting that up to 86% of autistic adults experience at least one form of sleep disturbance (Lampinen et al. 2022 ). The most frequently reported sleep disturbances include difficulties initiating and maintaining sleep, as reported subjectively, and objectively measured patterns such as prolonged sleep onset latency, reduced total sleep duration, and decreased sleep efficiency (Lampinen et al. 2022 ; Burman et al. 2023 ). These sleep disturbances are associated with impairments in daytime functioning, increased behavioral challenges, and cognitive deficits, particularly in children with ASD (Carnett et al. 2021 ). Moreover, ASD is coupled with higher rates of depression and anxiety (Hudson et al. 2019 ), both of which have been linked to sleep disturbances in autistic individuals (Stewart et al. 2020 ; Puzino et al. 2021 ). Beyond its effects on cognitive abilities and mental health, sleep plays a critical role in clearing metabolic waste from the brain through the glymphatic system (Iliff et al. 2012 , 2013 ). The glymphatic system facilitates clearance of metabolic waste from the brain by directing cerebrospinal fluid (CSF) into the parenchyma along specialized perivascular spaces (PVSs) that surround cerebral blood vessels (Fig. 1 ). These spaces are bordered by astrocytic endfeet, which are densely enriched with aquaporin-4 (AQP4) water channels and form the structural barrier known as the glia limitans. Through this arrangement, CSF entering along arterial PVSs mixes with interstitial fluid (ISF), promoting solute exchange and supporting the removal of neurotoxic proteins and other metabolites. The mixture is then directed toward venous PVSs for clearance from the brain, making AQP4-mediated water transport at astrocytic endfeet a key driver of glymphatic function. Impaired glymphatic function has been associated with reduced cognitive performance (Kamagata et al. 2022 ), whereas an efficient glymphatic system may protect against age-related cognitive decline (Wang et al. 2023 ). This link between glymphatic activity and cognition is thought to be partially mediated by the accumulation of neurotoxic proteins, such as amyloid-β and tau neurofibrillary tangles, which are key neuropathological hallmarks of Alzheimer’s disease (AD) (Binette et al. 2022 ). Indeed, amyloid-β accumulation has been linked to impaired glymphatic function in both rodents (Iliff et al. 2013 ; Harrison et al. 2020 ) and humans (Park et al. 2023 ; Okazawa et al. 2024 ). Moreover, the role of the glymphatic system in clearance of amyloid-β and tau has been well established (Iliff et al. 2012 ). Consequently, reduced glymphatic function may play a role in age-related cognitive decline and neurodegeneration, potentially facilitating brain atrophy and the development of AD. Notably, although ASD is a neurodevelopmental disorder, it persists throughout life and has recently been linked with a 2.6-fold increased risk of developing AD (Vivanti et al. 2021 ). Supporting this, postmortem studies have reported significantly greater amyloid-β accumulation in autistic individuals compared to NT individuals (Wegiel et al. 2012 ). These findings suggest that impaired glymphatic function may contribute to the elevated risk of AD observed in ASD (Vivanti et al. 2021 ). Evidence suggests that glymphatic dysfunction in ASD may begin early in life. Studies report excessive CSF in the subarachnoid space surrounding the cortical surface, thought to reflect impaired CSF circulation, in autistic children as early as 6 months and up to 3 years of age (Shen et al. 2018 ; Garic et al. 2023 ). Enlarged PVS at 24 months have been linked to a 2.2-fold higher likelihood of ASD diagnosis and an increased risk of sleep problems by the age of 8 years (Garic et al. 2023 ). Such early alterations support the view that impaired glymphatic function may represent a core component of ASD neuropathology. Initially, human glymphatic function was assessed using invasive intrathecal injections of gadolinium, a technique referred to as glymphatic imaging. More recently, non-invasive methods such as diffusion tensor image (DTI) analysis along the perivascular space (ALPS-index) have been developed (Taoka et al. 2017 ). The ALPS-index utilizes diffusion imaging to quantify water diffusivity along perivascular spaces, thereby serving as an indirect proxy of glymphatic function. Glymphatic activity is believed to depend strongly on water movement within these spaces, particularly in regions adjacent to the lateral ventricles. Accordingly, the ALPS-index is derived from diffusivity in the radial direction (Fig. 1 ), which represents the most direct route for solute clearance from the ventricular bodies toward the brain surface or ventricular walls (Taoka et al. 2017 , 2024 ). Histological changes within the glymphatic pathway are expected to alter water diffusivity, especially along the right-left axis. Thus, the ALPS-index offers a highly reproducible (Liu et al. 2024 ) non-invasive alternative to gadolinium-based glymphatic imaging (Taoka et al. 2024 ), with the two methodologies demonstrating strong correlation (Zhang et al. 2021 ). Despite the well-established association between ASD and sleep disturbances (Lampinen et al. 2022 ; Burman et al. 2023 ), the increased risk of AD (Vivanti et al. 2021 ), and evidence of glymphatic abnormalities in autistic infants and young children (Shen et al. 2018 ; Garic et al. 2023 ), only a few studies to date have examined the ALPS-index in autistic individuals. All reported significantly lower ALPS-index values in autistic children aged 2–7 years compared to NT children (Li et al. 2022 ; Wang et al. 2025 ; Tian et al. 2025 ), suggesting reduced glymphatic function in this population. Because previous investigations were limited to young children and modest sample sizes, the present study aimed to: 1) test whether ALPS-index is reduced in autistic compared to NT individuals, 2) examine whether this reduction is present in autistic adults, and 3) evaluate whether prior reports of reduced ALPS-index in autistic children could be replicated in a larger sample. Methods Given the limited number of studies applying the ALPS-index in autistic individuals, and that the existing studies focused exclusively on young children (< 7 years), we did not restrict participant age. Instead, participants were stratified into two groups: youth (< 18 years) and adults (≥ 18 years), enabling evaluation of ALPS-index across age ranges not previously examined. Participants Data for the present study were obtained from the publicly available Autism Brain Imaging Data Exchange (ABIDE) repository (Di Martino et al. 2014 ). Sites were included if their datasets contained diffusion MRI scans for both autistic and neurotypical participants. This resulted in the inclusion of five cohorts: Barrow Neurological Institute (n = 58), Institute Pasteur and Robert Debré Hospital (n = 56), NYU Langone Medical Center – Sample 1 (n = 78), Trinity Centre for Health Sciences (n = 42), and San Diego State University (n = 58). Participants in the ASD group had a prior clinical diagnosis of ASD, which was confirmed at each site using gold-standard diagnostic instruments, including the Autism Diagnostic Observation Schedule (ADOS) and/or the Autism Diagnostic Interview–Revised (ADI-R), in accordance with DSM-IV-TR or DSM-5 criteria (American Psychiatric Association. 2013). NT participants had no history of neurological, psychiatric, or developmental disorders. Exclusion criteria included: 1) missing T1-weighted or diffusion-weighted images, 2) full-scale IQ < 70 when available, and 3) poor imaging quality, determined through visual inspection and site-specific quality control procedures. After applying these criteria, the final sample comprised 250 participants: 128 with ASD and 122 NT (Fig. 2 ). All MRI data were acquired on 3 Tesla scanners. Detailed information on scanner models, sequence parameters, and site-specific acquisition protocols is available on the ABIDE project website ( https://fcon_1000.projects.nitrc.org/indi/abide/ ). Diffusion Tensor Imaging Preprocessing The 4D DTI datasets were converted from DICOM to NIfTI format using dcm2niix (Li et al. 2010 ). Image preprocessing included artifact correction via the Marchenko-Pastur principal component analysis (MP-PCA) denoising algorithm and Gibbs ringing removal, implemented with the Mrtrix3 (Tournier et al. 2019 ) commands dwidenoise and mrdegibbs, respectively. Susceptibility-induced distortion, eddy current, and motion corrections were performed using the FMRIB Software Library (FSL) version 6.0.1 commands topup and eddy (Andersson et al. 2003 ). Fractional anisotropy (FA) maps and diffusivity maps along the x-, y-, and z-axes were generated with the FSL command dtifit (Jenkinson et al. 2012 ). Each subject’s FA map was co-registered to the JHU-ICBM-FA template in FSL, and the resulting transformation matrix was applied to all diffusivity maps using the FSL command flirt. ALPS-index The ALPS-index was used to assess glymphatic function following the methods described by Taoka et al. ( 2017 ). This approach quantifies water diffusivity along the PVS at the level of the lateral ventricle bodies, where perivascular flow is oriented predominantly along the right-left axis, corresponding to the x-axis in the diffusion image (Fig. 1 ). Diffusivity coefficients were extracted from two major fiber systems traversing this region: projection fibers adjacent to the ventricular wall (craniocaudal, z-axis) and association fibers located more laterally (anteroposterior, y-axis). The x-axis diffusivity in projection (Dx_proj​) and association (Dx_assoc​) fiber ROIs was normalized by the y-axis diffusivity in projection fibers (Dy_proj​) and z-axis diffusivity in association fibers (Dz_assoc​). We utilized an automatic pipeline to reduce subjectivity in placement of the regions of interest (ROIs) as described by Zhang et al. ( 2021 ). ROIs (5 mm diameter) were defined using an atlas-based approach (ICBM-DTI-81 template) (Hua et al. 2008 ) and restricted to regions perpendicular to the lateral ventricles. Voxels with FA ≤ 0.2 were excluded to avoid cerebrospinal fluid contamination. The ALPS-index was determined according to previously described methods (Taoka et al. 2017 ). Specifically, it was calculated as: ALPS-index = \(\frac{\text{m}\text{e}\text{a}\text{n}(\text{D}\text{x}.\text{p}\text{r}\text{o}\text{j}+\text{D}\text{x}.\text{a}\text{s}\text{s}\text{o}\text{c})}{\text{m}\text{e}\text{a}\text{n}(\text{D}\text{y}.\text{p}\text{r}\text{o}\text{j}+\text{D}\text{z}.\text{a}\text{s}\text{s}\text{o}\text{c})}\) The computation was performed separately for the left and right hemispheres. The resulting values were then averaged to obtain a single bilateral ALPS-index, which was subsequently used for statistical analyses. Statistical analysis All analyses were performed in R (version 2025.05.1 + 513). Continuous variables were summarized as means and standard deviations, and group differences in demographic and clinical characteristics between ASD and NT participants were assessed using independent-samples t -tests. Categorical variables were compared using χ² tests. The primary analysis examined whether the ALPS-index differed by diagnosis (ASD vs. NT), by age group (younger participants < 18 years vs. adults ≥ 18 years), and by their interaction, using a two-way analysis of variance (ANOVA). Partial eta squared (ηp²) with 95% confidence intervals (CI) was calculated as an effect size measure for the ANOVA. When significant main effects or interactions were detected, we performed post hoc pairwise comparisons using estimated marginal means ( emmeans ), applying Bonferroni adjustments to control for multiple comparisons within each family of tests. Cohen’s d was reported for effect size of post hoc tests. Due to the high reproducibility of the ALPS-index, even between scanner vendors (Liu et al. 2024 ) we did not correct for scanner albeit the use of data acquired from different scanners. However, a cohort-wise comparison is available in Supporting Information Table S1 and Fig. S1 . Associations between ALPS-index and continuous clinical or cognitive measures were examined using Pearson correlation coefficients ( r ), computed in the whole sample, and stratified by diagnosis and age group. Correlations were performed for Full-scale Intelligence Quotient (FIQ), ADOS total scores, and Beck Depression Inventory (BDI) scores (BDI was assessed only in the Barrow Neurological Institute cohort). Two-tailed p - values < 0.05 were considered statistically significant. Effect sizes for correlations were interpreted according to conventional benchmarks (small: | r | ≥ 0.10, medium: | r | ≥ 0.30, large: | r | ≥ 0.50). Results The final sample comprised 250 participants, including 128 autistic and 122 NT individuals (Fig. 3 ). No significant differences were observed between the ASD and NT groups in terms of age or gender distribution, either in the overall sample or when stratified by age (< 18 vs. ≥18 years). However, the ASD group exhibited significantly higher proportions of comorbidity and medicine use, as well as lower FIQ scores and higher BDI scores compared to the NT group (Table 1). Table 1. Demographic and Clinical Characteristics of The ASD and NT Group. Variable Group ASD NT Analysis N Mean SD N Mean SD t df p Age (years) Whole sample 128 18.57 13.81 122 21.32 14.37 1.538 246 0.125 <18 years 86 11.25 3.49 65 11.88 3.19 1.394 143.5 0.166 ≥18 years 42 33.83 14.51 57 32.08 14.61 0.594 88.8 0.554 N N % N N % X 2 df p Female Whole sample 128 16 12.50 122 19 15.57 0.489 1 0.484 0.001 0.001 <18 years 86 17 19.76 65 1 1.54 10.232 1 0.001 ≥18 years 42 8 19.05 57 1 1.75 6.936 1 0.008 N Mean SD N Mean SD t df p FIQ Whole sample 123 104.8 15.70 99 111.6 14.45 3.353 216.1 0.001 <18 years 82 103.7 16.55 62 110.6 16.07 2.526 133 0.013 ≥18 years 41 107.1 13.73 37 113.32 11.21 2.202 75.2 0.031 ADOS Whole sample 12.17 4.53 <18 years 12.38 4.79 ≥18 years 11.32 3.73 BDI Whole sample 25 11.22 10.09 29 5.12 6.50 2.595 39.8 0.013 <18 years ≥18 years 25 11.22 10.09 29 5.12 6.50 2.595 39.8 0.013 Continuous variables are reported as mean ± standard deviation (SD), and group differences were assessed with independent-samples t-tests, applying Welch’s correction when appropriate. Categorical variables (gender) are presented as counts and percentages, and group differences were assessed using Chi-squared tests (χ²). Autism Diagnostic Observation Schedule (ADOS); Degrees of freedom (df); Full-scale Intelligence Quotient (FIQ); Beck Depression Inventory (BDI). ALPS-index We first examined the effects of diagnosis (ASD vs. NT) and age group (< 18 vs. ≥18 years) on the ALPS-index using a two-way ANOVA (Table 2 ). The analysis revealed a significant main effect of diagnosis, F (1, 246) = 10.44, p = 0.0014, η²ₚ = 0.041, indicating overall lower ALPS-indices in the ASD group compared to NT. A significant diagnosis × age group interaction was also observed, F (1, 246) = 4.71, p = 0.031, η²ₚ = 0.019, suggesting that the effect of diagnosis differed by age group. This indicates that the diagnostic effect (ASD vs NT) varied across age groups (< 18 vs. ≥18 years), suggesting an age-dependent difference in ALPS-index. Post hoc pairwise comparisons showed no significant ALPS-index difference between ASD and NT participants in the young (< 18-year) group ( p = 0.342, Cohen’s d = − 0.16, N = 151), whereas the adult (≥ 18-year) ASD group demonstrated significantly lower ALPS-indices compared with age-matched NT participants ( p = 0.0004, Cohen’s d = − 0.72, N = 99) (Fig. 4 ). In contrast, no significant main effect of age group was detected in the ANOVA, F (1, 246) = 1.98, p = 0.123, η²ₚ = 0.010. Overall, these results indicate that the reduction in ALPS-index is primarily driven by autistic adults. Table 2. ALPS-index Two-way ANOVA and Post-hoc Comparisons The upper portion displays the two-way ANOVA results, including F-statistics, p-values, and Partial eta squared (ηp²) for the effects of diagnosis (ASD vs NT), age group (<18 vs ≥18 years), and their interaction (Diagnosis × Age Group). The lower panel provides ALPS-index group means ± standard deviation (SD) with 95% confidence intervals (CI), ASD-NT group differences (Δ) , post-hoc p-values, and Cohen’s d effect sizes, where negative values indicate lower ALPS-index in ASD than NT. Correlation between ALPS-index and clinical measures Given that FIQ differed significantly between ASD and NT groups (Table 1), we examined the relationship between the ALPS-index and FIQ. In the whole sample, no significant correlation was observed (r = − 0.060, p = 0.372). Stratified analyses revealed no significant correlations in either the ASD (r = − 0.101, p = 0.267) or NT group (r = − 0.037, p = 0.720). Similarly, no significant correlation was found when stratifying by age group ( 0.26), indicating that FIQ was not significantly correlated with ALPS-indices in any subgroup. Detailed results are provided in Supporting Information Table S2. For the ASD group, we additionally assessed the association between ALPS-index and ADOS scores as a measure of the severity of core symptoms of autism. In the whole ASD sample, a weak negative, non-significant correlation was observed (r = − 0.161, p = 0.091). Subgroup analyses showed no significant associations in children/adolescents (< 18 years: r = 0.100, p = 0.390) or adults (≥ 18 years: r = 0.005, p = 0.975). We also examined the relationship between ALPS-index and depressive symptoms in adults using the BDI. BDI was only available in the Barrow cohort (N = 54), which only included adult participants (age range 18–64 years). In the whole adult sample, no significant association was observed (r = − 0.209, p = 0.129). However, when stratified by diagnosis, a significant negative correlation was identified in the adult ASD group (r = − 0.489, p = 0.013), whereas no significant correlation was found in NT adults (r = 0.005, p = 0.982). This suggests that the ALPS-index is largely unrelated to general cognitive ability (FIQ) or autism symptom severity (ADOS) in autistic individuals, whereas lower ALPS-indices in autistic adults show modest correlation with higher depressive symptom severity. Detailed correlation results are provided in Supporting Information Table S2. Discussion In this cross-sectional study spanning five independent cohorts, we observed that the ALPS-index was reduced in autistic compared to NT individuals. Notably, this group difference appeared to be modulated by age. When stratifying the sample into younger (< 18 years) and adult (≥ 18 years) participants, significantly lower ALPS-index values were only detected in autistic adults compared to NT adults, whereas no significant differences emerged between autistic and NT participants in the younger group. These findings stand in contrast to the three prior studies that have investigated ALPS-index in ASD, all of which focused exclusively on young children. Li et al. ( 2022 ) examined 30 autistic and 25 NT children (mean age 3.9 years, range 2–6 years) and reported significantly reduced ALPS-index in the ASD group (Li et al. 2022 ). Similarly, Wang et al. ( 2025 ) studied a larger pediatric sample (178 participants, mean age 4.9 years, range 3–7 years) and likewise found decreased ALPS-index in autistic compared to NT children (Wang et al. 2025 ). Lastly, Tian et al. ( 2025 ) included 89 autistic and 37 NT children (mean age 3.6 years, range 2–6 years) and demonstrated decreased ALPS-index in ASD (Tian et al. 2025 ). The discrepancy between our findings and prior reports may be explained by differences in participant age. The young group in our study had a substantially higher mean age (11.4 years, range 5–17 years) and did not include children as young as those examined in the prior studies. This age difference may have limited our ability to detect early developmental irregularities in glymphatic function. Given that ASD is a neurodevelopmental condition, glymphatic alterations may be most pronounced in the early years and then attenuate during later childhood, reflecting either delayed maturation or compensatory mechanisms. Supporting this notion, several studies have reported abnormalities in the glymphatic system in young children with ASD (Shen et al. 2018 ; Garic et al. 2023 ). In line with a developmental trajectory, glymphatic function (as indexed by ALPS) has been shown to increase with age across early childhood and adolescence (Wong et al. 2025 ). Consistently, Li et al. ( 2022 ) reported a positive correlation between ALPS-index and age in both ASD and NT children (Li et al. 2022 ). More broadly, evidence from a large cross-sectional study in NT individuals suggests that ALPS-index values continue to rise until approximately 40 years of age, followed by a gradual decline thereafter (Taoka et al. 2022 ). ASD is associated with an atypical developmental trajectory of brain volume, characterized by early brain overgrowth followed by reduced gray matter volume later in development (Levman et al. 2018 ; Prigge et al. 2021), this pattern also appears to involve changes in the choroid plexus. Several studies have reported increased choroid plexus volume during childhood and adulthood in ASD, although the magnitude of enlargement varies across ages (Levman et al. 2018 ; Tezcan et al. 2025 ) similarly to our results. The choroid plexus is a specialized epithelium within the brain’s ventricles that produces CSF and regulates the composition and circulation of the fluid that drives the glymphatic clearance system. Because choroid plexus enlargement has been associated with reduced glymphatic function (Gong et al. 2025 ), this may indicate that the glymphatic system is consistently, but in varying degrees dependent on age, affected in ASD. Taken together, these findings suggest that glymphatic function in ASD may change dynamically across development, with alterations most evident during specific age periods. However, longitudinal multimodal imaging studies are needed to clarify these developmental patterns and determine their relevance to the clinical and neurobiological features of autism. Glymphatic function in aging autistic individuals In our study, glymphatic function, assessed using the ALPS-index, was reduced in autistic adults. Prior work has shown that the ALPS-index correlates positively with sleep quality, memory performance, and neural communication in older adults (Ma et al. 2025 ), underscoring the importance of preserved glymphatic function for healthy brain aging (Benveniste et al. 2019 ). If ASD is indeed associated with reduced glymphatic function, as suggested by our findings, this could provide a mechanistic link to the increased risk of AD reported in autistic individuals (Vivanti et al. 2021 ; Sian-Hulsmann et al. 2026 ). Supporting this interpretation, postmortem studies have identified greater accumulation of amyloid-β in autistic brains (Wegiel et al. 2012 ). Considering that amyloid-β accumulates with increasing age (Knudsen et al. 2025 ) and is cleared by the glymphatic system, enhanced accumulation could be caused by reduced glymphatic function (Iliff et al. 2012 ). Furthermore, middle-aged and elderly autistic individuals have been shown to exhibit more severe reductions in both memory performance and hippocampal volume (Pagni et al. 2022 ; Walsh et al. 2022 ), both of which are indicators of AD. Interestingly, recent studies have reported positive correlations between glymphatic function and hippocampal volume (Chang et al. 2023 ), suggesting that impaired glymphatic clearance may contribute to the AD-like decline in hippocampal volume and memory performance observed in autistic individuals later in life. Another possible mechanism underlying reduced glymphatic function in ASD could be related to neuroinflammation and oxidative stress, which are frequently reported in autistic individuals (Thorsen et al. 2021 ; Than et al. 2023 ). Notably, both processes can damage astrocytic endfeet, causing a disruption of the AQP4 polarization, as well as vascular stiffening and impaired arterial pulsatility (Cai et al. 2024 ). These are all mechanisms that could cause reduced perivascular glymphatic function (Iliff et al. 2013 ; Cai et al. 2024 ). Taken together, these converging lines of evidence suggest that impaired glymphatic clearance in ASD may not only contribute to neurodevelopmental alterations but could also increase vulnerability to later-life neurodegenerative pathology. However, the underlying causes of reduced glymphatic function remains uncertain. Therefore, future work integrating longitudinal imaging, sleep assessment, measures of neuroinflammation, and biomarker studies will be essential to clarify the role of glymphatic dysfunction in linking autism with age-related neurological disorder. Correlation analyses In our correlation analysis, we observed a significant negative association between depressive symptoms (BDI score) and ALPS-index. This is noteworthy given that individuals with ASD are at increased risk for depression (Hudson et al. 2019 ), and depression in ASD is frequently accompanied by sleep disturbances (Stewart et al. 2020 ; Puzino et al. 2021 ). Because sleep quality has been closely linked to glymphatic function (Saito et al. 2023 ; Kikuta et al. 2024 ; Ma et al. 2025 ), it is plausible that disrupted sleep is linked to altered glymphatic clearance in ASD. Moreover, decreased ALPS-index have been demonstrated in patients with major depressive disorder (Bao et al. 2025 ). Consequently, the high prevalence of depression and anxiety in autism may, at least in part, be associated with limited glymphatic function. In contrast, we did not observe significant correlations between ALPS-index and either FIQ or autistic traits. This differs from the findings of Wang et al. ( 2025 ) and Tian et al. ( 2025 ) who both reported a negative correlation between ALPS-index and ASD severity measured by the Childhood Autism Rating Scale (CARS) (Schopler et al. 1980 ). Their result is consistent with prior studies linking autistic traits to sleep disturbances (Stewart et al. 2020 ). The discrepancy between our findings and prior studies may be explained by differences in study design, including our broader age range and the use of ADOS rather than CARS as the clinical measure. Limitations There are several limitations of our study that are worth discussing. First, the ALPS-index is an indirect proxy of glymphatic function, derived from the ratio of water diffusivity along PVS to that measured perpendicular to the PVS at the level of the lateral ventricles (Taoka et al. 2017 , 2024 ). As such, it primarily reflects left-right Brownian motion of water molecules in this region. However, waste clearance from the brain parenchyma also follows radial pathways toward the cortical surface and ventricular walls, which are not fully captured by this measure. Consequently, the ALPS-index provides only an indirect approximation of glymphatic function. In principle, a lower ALPS-index reflects slower water diffusivity along perivascular pathways, which may indicate reduced solute clearance capacity and, to some extent, impaired glymphatic function. However, it does not capture the full complexity of glymphatic function across the brain. Future work employing diffusion MRI with multiple b-values, and combining ALPS with complementary imaging approaches (e.g., advanced CSF flow imaging), would provide a more comprehensive understanding of glymphatic function in ASD. Second, because our study is cross-sectional, we cannot directly assess longitudinal changes in glymphatic function across development or aging in ASD. Longitudinal studies spanning early childhood through adulthood will be necessary to establish developmental trajectories and clarify potential causal links with clinical outcomes. Third, although the ALPS-index equation includes an inherent normalization factor, as it is the ratio of internal references (Taoka et al. 2017 ), and our cohort comparisons did not indicate scanner-related differences (Supporting Information Table S1 and Fig. S1 ), we cannot entirely exclude the possibility that data from different scanners influenced the results. Fourth, while the overall sample size was relatively large, stratified subgroup analyses (e.g., adults only) reduced the effective sample size, which may have limited statistical power. Additionally, the limited number of female participants (n = 35) prevented us from assessing sex differences. Fifth, although interstitial solute clearance occurs during wakefulness, the interstitial space expands by approximately 60% during sleep, markedly enhancing glymphatic flow (Xie et al. 2013 ). Thus, glymphatic function is most accurately assessed during sleep, whereas in our study participants were imaged at rest while awake. This limitation highlights the importance of considering sleep–wake state in future glymphatic research. Sixth, we observed a significant difference in both comorbidity and medication use between groups, which was expected given the high prevalence of comorbidities in ASD (Simonoff et al. 2008 ). Nineteen participants in the ASD group had a comorbid condition (1 with anxiety, 18 with ADHD), whereas only one participant in the NT group had a comorbidity (thyrotoxicosis) (Fig. 3 ). Considering that approximately 40% of autistic individuals are diagnosed with ADHD (Rong et al. 2021 ), the comparatively lower prevalence of around 15% in our cohort suggests that our findings may not be fully generalizable to the broader autistic population. Accordingly, 25 participants in the ASD group reported medication use (2 amphetamine, 1 atomoxetine, 3 bupropion, 1 citalopram, 2 escitalopram, 1 fluoxetine, 2 lisdexamfetamine, 2 melatonin, 5 methylphenidate, 2 sertraline, 3 venlafaxine, and 1 ziprasidone), compared to only two participants in the NT group (1 levothyroxine and 1 antidepressant). How and whether these medications influence glymphatic function remains unknown and may therefore represent a potential source of bias. Conclusions In this multi-cohort cross-sectional study, we demonstrate that glymphatic function assessed using ALPS-index, is reduced in autistic individuals, with the effect most pronounced in adulthood. These findings may indicate that glymphatic alterations in autism evolve across development, appearing in early life, diminishing during later childhood, and re-emerging in adulthood, in a pattern that partly parallels the age-related trajectory of brain volume. Reduced glymphatic function in autistic adults may help explain their increased vulnerability to memory decline, hippocampal atrophy, and AD pathology, while also linking to the high prevalence of depression and sleep disturbances in this population. Taken together, our results support the hypothesis that glymphatic dysfunction may represent a common mechanistic pathway linking the neurodevelopmental features of autism with an increased risk of psychiatric and neurodegenerative diseases later in life. However, the causes of reduced glymphatic function remain uncertain. Future longitudinal and multimodal studies will be essential to clarify the role of glymphatic function in autism across the lifespan and to determine its clinical relevance for both early development and age-related outcomes. Declarations Conflict of interest statement The authors have no relevant financial or non-financial interests to disclose. Disclosures The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethic approval Alle data is from the ABIDE dataset. Details regarding recruitment, scanning information, diagnostic protocols, and ethics statements are provided here: https://fcon_1000.projects.nitrc.org/indi/abide/ Consent to participate Informed consent was not obtained by us, as we did not perform the data collection. Consent was obtained by the research team responsible for collecting the original data. Funding The author(s) received financial support for the research, from the Psychiatry Research Fund in the Region of Southern Denmark. Author Contribution Laust Vind Knudsen (LVK): Conceptualization; Methodology; Data curation; Formal analysis; Visualization (figure and table preparation); Writing – original draft; Writing – review & editing. Manouchehr Seyedi Vafaee (MSV): Conceptualization; Writing – review & editing. Abigail Jane Sheldrick‑Michel (AJSM): Conceptualization; Writing – review & editing. Tanja Maria Michel (TMM): Conceptualization; Writing – review & editing. Acknowledgement The author(s) would like to thank the Psychiatry Research Fund in the Region of Southern Denmark for financial support for the research. Data Availability Data is freely accessible at the Autism Brain Imaging Data Exchange[https://fcon_1000.projects.nitrc.org/indi/abide/](https:/fcon_1000.projects.nitrc.org/indi/abide) . References American Psychiatric Association. 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J Autism Dev Disord. https://doi.org/10.1007/s10803-021-04897-x Tian P, Xue Y, Zhu X, et al (2025) Abnormal glymphatic system function in children with autism spectrum disorder: a diffusion kurtosis imaging study. Eur J Pediatr 184:. https://doi.org/10.1007/s00431-025-06246-x Tournier JD, Smith R, Raffelt D, et al (2019) MRtrix3: A fast, flexible and open software framework for medical image processing and visualisation. Neuroimage 202 Vivanti G, Tao S, Lyall K, et al (2021) The prevalence and incidence of early-onset dementia among adults with autism spectrum disorder. Autism Research 14:2189–2199. https://doi.org/10.1002/aur.2590 Walsh MJM, Ofori E, Pagni BA, et al (2022) Preliminary findings of accelerated visual memory decline and baseline brain correlates in middle-age and older adults with autism: The case for hippocampal free-water. 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Magn Reson Imaging 120:. https://doi.org/10.1016/j.mri.2025.110398 Xie L, Kang H, Xu Q, et al (2013) Sleep Drives Metabolite Clearance from the Adult Brain. Science (1979) 342: Zhang W, Zhou Y, Wang J, et al (2021) Glymphatic clearance function in patients with cerebral small vessel disease. Neuroimage 238:. https://doi.org/10.1016/j.neuroimage.2021.118257 Additional Declarations No competing interests reported. Supplementary Files Supplemental.Information.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 14 Apr, 2026 Reviewers agreed at journal 10 Apr, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviewers invited by journal 18 Mar, 2026 Editor assigned by journal 09 Mar, 2026 Submission checks completed at journal 09 Mar, 2026 First submitted to journal 06 Mar, 2026 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-9047679","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":608441575,"identity":"ad0a3969-c056-4d75-820b-176f6c992720","order_by":0,"name":"Laust Vind Knudsen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAiElEQVRIiWNgGAWjYBACPgY2xgcMbEDWGWK1sDGwMRuQrIVNgkQtEmlplT/KDjPwnTlAvJZjt3nOHWaQPNtArBae4223GdsOMxicJ9phQC2FP0nTwt52jIEXpIV4h7G3JUvznEvnkSTa+/zMbIYff5RZy/GdSSDWZVDAQ6L6UTAKRsEoGAV4AQCEWSQ1PNBOjgAAAABJRU5ErkJggg==","orcid":"","institution":"Odense University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Laust","middleName":"Vind","lastName":"Knudsen","suffix":""},{"id":608441579,"identity":"9ef8d347-1e22-4c7b-8992-bd656e23f8c8","order_by":1,"name":"Manouchehr Seyedi Vafaee","email":"","orcid":"","institution":"Odense University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Manouchehr","middleName":"Seyedi","lastName":"Vafaee","suffix":""},{"id":608441580,"identity":"4d3c3083-3002-4f6a-bf31-ae28ffa2860d","order_by":2,"name":"Abigail Jane Sheldrick-Michel","email":"","orcid":"","institution":"Odense University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Abigail","middleName":"Jane","lastName":"Sheldrick-Michel","suffix":""},{"id":608441581,"identity":"253a5958-9d3d-45fd-9478-428ac305dd45","order_by":3,"name":"Tanja Maria Michel","email":"","orcid":"","institution":"Odense University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tanja","middleName":"Maria","lastName":"Michel","suffix":""}],"badges":[],"createdAt":"2026-03-06 07:56:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9047679/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9047679/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105195571,"identity":"daec65ff-ae6d-4d03-b6d8-459cda830bac","added_by":"auto","created_at":"2026-03-23 10:13:30","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":179519,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eWorkflow of ALPS-index Calculation and its Relation to Glymphatic Transport.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA) Diffusion MRI data were preprocessed (topup, eddy, and DTIFIT) to generate fractional anisotropy (FA) maps. At the level of the body of the lateral ventricle, regions of interest (ROIs) were placed in projection and association fibers to derive diffusivity measures along the x-, y-, and z-axes. These measures were used to calculate the ALPS-index, providing an indirect marker of perivascular diffusivity. B) Schematic representation of glymphatic transport, which the ALPS-index is thought to reflect. CSF enters the brain parenchyma along para-arterial perivascular spaces (Step 1), mixes with interstitial fluid to facilitate solute clearance (Step 2, mediated by AQP4 water channels on astrocytic endfeet), and drains along paravenous pathways into the bloodstream (Step 3). Aβ = amyloid-β. AQP4 = aquaporin-4. CSF = cerebrospinal fluid. ISF = interstitial fluid.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9047679/v1/542f725fdc8796d7881b8053.jpg"},{"id":105195562,"identity":"7c459567-4a18-4906-918a-19ec14a03b5e","added_by":"auto","created_at":"2026-03-23 10:13:27","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":103107,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eParticipant Inclusion and Exclusion Flowchart.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe flowchart illustrates the inclusion and exclusion process of participants across cohorts, leading to the final study sample.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9047679/v1/ad4c6d5b3d1e7d797f5d1179.jpg"},{"id":105195566,"identity":"d2a11e92-e913-440a-9238-734873d02447","added_by":"auto","created_at":"2026-03-23 10:13:28","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":80628,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOverview of The Study Participant and Cohort Characteristics.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA) Number of participants in each diagnostic group (ASD and NT).\u003cstrong\u003e \u003c/strong\u003eB) Distribution of participants across the five contributing cohorts.\u003cstrong\u003e \u003c/strong\u003eC) Age distribution of all included participants.\u003cstrong\u003e \u003c/strong\u003eD) Sex distribution across diagnostic groups.\u003cstrong\u003e \u003c/strong\u003eE) Proportion of participants using medication.\u003c/p\u003e\n\u003cp\u003eF) Proportion of participants with comorbid conditions.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9047679/v1/74c9b516effe62487d9d9022.jpg"},{"id":105195568,"identity":"b87b8670-dfd9-4abf-a522-4375748a626b","added_by":"auto","created_at":"2026-03-23 10:13:29","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":46440,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGroup Differences in ALPS-index by Diagnosis and Age group.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBoxplots show the distribution of ALPS-index values in neurotypical (NT, blue) and autistic (ASD, orange) participants stratified by age group (\u0026lt;18 years, ≥18 years). Individual data points are overlaid. Error bars indicate group means ± standard deviation. A significant group difference was observed in adults (≥18 years, N = 99), with lower ALPS-index in the ASD group compared to NT (p = 0.0004).\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9047679/v1/d8878bc9cbe5aec63abd2f70.jpg"},{"id":105195599,"identity":"dbe4ea4a-dbe0-4e53-bc61-299a20be03ec","added_by":"auto","created_at":"2026-03-23 10:13:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1528808,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9047679/v1/3f7be13d-a041-41c1-ab36-171eee301d2c.pdf"},{"id":105195578,"identity":"84895a4e-f552-487d-aac1-88fe29037a56","added_by":"auto","created_at":"2026-03-23 10:13:35","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":120000,"visible":true,"origin":"","legend":"","description":"","filename":"Supplemental.Information.docx","url":"https://assets-eu.researchsquare.com/files/rs-9047679/v1/f595873c699a995decb4d806.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Reduced Glymphatic Function in Autism Revealed by the Diffusion Tensor Analysis Along the Perivascular Space Index","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAutism spectrum disorder (ASD) is a neurodevelopmental condition affecting more than 2.3% of 8-year-old children (Maenner et al. \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). ASD is characterized by difficulties in social interaction and communication, along with restricted, repetitive behaviors and atypical sensory processing (American Psychiatric Association. 2013). In addition to these core features, sleep disturbances are highly prevalent in children with ASD, with reported rates ranging from 50% to 80%, compared to 9% to 50% in neurotypical (NT) children (Richdale and Schreck \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2009\u003c/span\u003e; Burman et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Furthermore, sleep-related problems often persist into adulthood, with some studies reporting that up to 86% of autistic adults experience at least one form of sleep disturbance (Lampinen et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). The most frequently reported sleep disturbances include difficulties initiating and maintaining sleep, as reported subjectively, and objectively measured patterns such as prolonged sleep onset latency, reduced total sleep duration, and decreased sleep efficiency (Lampinen et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Burman et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). These sleep disturbances are associated with impairments in daytime functioning, increased behavioral challenges, and cognitive deficits, particularly in children with ASD (Carnett et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Moreover, ASD is coupled with higher rates of depression and anxiety (Hudson et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2019\u003c/span\u003e), both of which have been linked to sleep disturbances in autistic individuals (Stewart et al. \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Puzino et al. \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBeyond its effects on cognitive abilities and mental health, sleep plays a critical role in clearing metabolic waste from the brain through the glymphatic system (Iliff et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2012\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). The glymphatic system facilitates clearance of metabolic waste from the brain by directing cerebrospinal fluid (CSF) into the parenchyma along specialized perivascular spaces (PVSs) that surround cerebral blood vessels (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). These spaces are bordered by astrocytic endfeet, which are densely enriched with aquaporin-4 (AQP4) water channels and form the structural barrier known as the glia limitans. Through this arrangement, CSF entering along arterial PVSs mixes with interstitial fluid (ISF), promoting solute exchange and supporting the removal of neurotoxic proteins and other metabolites. The mixture is then directed toward venous PVSs for clearance from the brain, making AQP4-mediated water transport at astrocytic endfeet a key driver of glymphatic function. Impaired glymphatic function has been associated with reduced cognitive performance (Kamagata et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), whereas an efficient glymphatic system may protect against age-related cognitive decline (Wang et al. \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). This link between glymphatic activity and cognition is thought to be partially mediated by the accumulation of neurotoxic proteins, such as amyloid-β and tau neurofibrillary tangles, which are key neuropathological hallmarks of Alzheimer\u0026rsquo;s disease (AD) (Binette et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Indeed, amyloid-β accumulation has been linked to impaired glymphatic function in both rodents (Iliff et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Harrison et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) and humans (Park et al. \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Okazawa et al. \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Moreover, the role of the glymphatic system in clearance of amyloid-β and tau has been well established (Iliff et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2012\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eConsequently, reduced glymphatic function may play a role in age-related cognitive decline and neurodegeneration, potentially facilitating brain atrophy and the development of AD. Notably, although ASD is a neurodevelopmental disorder, it persists throughout life and has recently been linked with a 2.6-fold increased risk of developing AD (Vivanti et al. \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Supporting this, postmortem studies have reported significantly greater amyloid-β accumulation in autistic individuals compared to NT individuals (Wegiel et al. \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). These findings suggest that impaired glymphatic function may contribute to the elevated risk of AD observed in ASD (Vivanti et al. \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Evidence suggests that glymphatic dysfunction in ASD may begin early in life. Studies report excessive CSF in the subarachnoid space surrounding the cortical surface, thought to reflect impaired CSF circulation, in autistic children as early as 6 months and up to 3 years of age (Shen et al. \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Garic et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Enlarged PVS at 24 months have been linked to a 2.2-fold higher likelihood of ASD diagnosis and an increased risk of sleep problems by the age of 8 years (Garic et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Such early alterations support the view that impaired glymphatic function may represent a core component of ASD neuropathology.\u003c/p\u003e \u003cp\u003eInitially, human glymphatic function was assessed using invasive intrathecal injections of gadolinium, a technique referred to as glymphatic imaging. More recently, non-invasive methods such as diffusion tensor image (DTI) analysis along the perivascular space (ALPS-index) have been developed (Taoka et al. \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). The ALPS-index utilizes diffusion imaging to quantify water diffusivity along perivascular spaces, thereby serving as an indirect proxy of glymphatic function. Glymphatic activity is believed to depend strongly on water movement within these spaces, particularly in regions adjacent to the lateral ventricles. Accordingly, the ALPS-index is derived from diffusivity in the radial direction (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), which represents the most direct route for solute clearance from the ventricular bodies toward the brain surface or ventricular walls (Taoka et al. \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2017\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Histological changes within the glymphatic pathway are expected to alter water diffusivity, especially along the right-left axis. Thus, the ALPS-index offers a highly reproducible (Liu et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2024\u003c/span\u003e) non-invasive alternative to gadolinium-based glymphatic imaging (Taoka et al. \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2024\u003c/span\u003e), with the two methodologies demonstrating strong correlation (Zhang et al. \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite the well-established association between ASD and sleep disturbances (Lampinen et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Burman et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), the increased risk of AD (Vivanti et al. \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e2021\u003c/span\u003e), and evidence of glymphatic abnormalities in autistic infants and young children (Shen et al. \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Garic et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), only a few studies to date have examined the ALPS-index in autistic individuals. All reported significantly lower ALPS-index values in autistic children aged 2\u0026ndash;7 years compared to NT children (Li et al. \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Wang et al. \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Tian et al. \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e2025\u003c/span\u003e), suggesting reduced glymphatic function in this population.\u003c/p\u003e \u003cp\u003eBecause previous investigations were limited to young children and modest sample sizes, the present study aimed to: 1) test whether ALPS-index is reduced in autistic compared to NT individuals, 2) examine whether this reduction is present in autistic adults, and 3) evaluate whether prior reports of reduced ALPS-index in autistic children could be replicated in a larger sample.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eGiven the limited number of studies applying the ALPS-index in autistic individuals, and that the existing studies focused exclusively on young children (\u0026lt;\u0026thinsp;7 years), we did not restrict participant age. Instead, participants were stratified into two groups: youth (\u0026lt;\u0026thinsp;18 years) and adults (\u0026ge;\u0026thinsp;18 years), enabling evaluation of ALPS-index across age ranges not previously examined.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eData for the present study were obtained from the publicly available Autism Brain Imaging Data Exchange (ABIDE) repository (Di Martino et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). Sites were included if their datasets contained diffusion MRI scans for both autistic and neurotypical participants. This resulted in the inclusion of five cohorts: Barrow Neurological Institute (n\u0026thinsp;=\u0026thinsp;58), Institute Pasteur and Robert Debr\u0026eacute; Hospital (n\u0026thinsp;=\u0026thinsp;56), NYU Langone Medical Center \u0026ndash; Sample 1 (n\u0026thinsp;=\u0026thinsp;78), Trinity Centre for Health Sciences (n\u0026thinsp;=\u0026thinsp;42), and San Diego State University (n\u0026thinsp;=\u0026thinsp;58).\u003c/p\u003e \u003cp\u003eParticipants in the ASD group had a prior clinical diagnosis of ASD, which was confirmed at each site using gold-standard diagnostic instruments, including the Autism Diagnostic Observation Schedule (ADOS) and/or the Autism Diagnostic Interview\u0026ndash;Revised (ADI-R), in accordance with DSM-IV-TR or DSM-5 criteria (American Psychiatric Association. 2013). NT participants had no history of neurological, psychiatric, or developmental disorders. Exclusion criteria included: 1) missing T1-weighted or diffusion-weighted images, 2) full-scale IQ\u0026thinsp;\u0026lt;\u0026thinsp;70 when available, and 3) poor imaging quality, determined through visual inspection and site-specific quality control procedures. After applying these criteria, the final sample comprised 250 participants: 128 with ASD and 122 NT (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). All MRI data were acquired on 3 Tesla scanners. Detailed information on scanner models, sequence parameters, and site-specific acquisition protocols is available on the ABIDE project website (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://fcon_1000.projects.nitrc.org/indi/abide/\u003c/span\u003e\u003cspan address=\"https://fcon_1000.projects.nitrc.org/indi/abide/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDiffusion Tensor Imaging Preprocessing\u003c/h3\u003e\n\u003cp\u003eThe 4D DTI datasets were converted from DICOM to NIfTI format using \u003cem\u003edcm2niix\u003c/em\u003e (Li et al. \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2010\u003c/span\u003e). Image preprocessing included artifact correction via the Marchenko-Pastur principal component analysis (MP-PCA) denoising algorithm and Gibbs ringing removal, implemented with the Mrtrix3 (Tournier et al. \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e2019\u003c/span\u003e) commands dwidenoise and mrdegibbs, respectively. Susceptibility-induced distortion, eddy current, and motion corrections were performed using the FMRIB Software Library (FSL) version 6.0.1 commands \u003cem\u003etopup\u003c/em\u003e and \u003cem\u003eeddy\u003c/em\u003e (Andersson et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2003\u003c/span\u003e). Fractional anisotropy (FA) maps and diffusivity maps along the x-, y-, and z-axes were generated with the FSL command \u003cem\u003edtifit\u003c/em\u003e (Jenkinson et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). Each subject\u0026rsquo;s FA map was co-registered to the JHU-ICBM-FA template in FSL, and the resulting transformation matrix was applied to all diffusivity maps using the FSL command flirt.\u003c/p\u003e\n\u003ch3\u003eALPS-index\u003c/h3\u003e\n\u003cp\u003eThe ALPS-index was used to assess glymphatic function following the methods described by Taoka et al. (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). This approach quantifies water diffusivity along the PVS at the level of the lateral ventricle bodies, where perivascular flow is oriented predominantly along the right-left axis, corresponding to the x-axis in the diffusion image (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Diffusivity coefficients were extracted from two major fiber systems traversing this region: projection fibers adjacent to the ventricular wall (craniocaudal, z-axis) and association fibers located more laterally (anteroposterior, y-axis). The x-axis diffusivity in projection (Dx_proj​) and association (Dx_assoc​) fiber ROIs was normalized by the y-axis diffusivity in projection fibers (Dy_proj​) and z-axis diffusivity in association fibers (Dz_assoc​). We utilized an automatic pipeline to reduce subjectivity in placement of the regions of interest (ROIs) as described by Zhang et al. (\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). ROIs (5 mm diameter) were defined using an atlas-based approach (ICBM-DTI-81 template) (Hua et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2008\u003c/span\u003e) and restricted to regions perpendicular to the lateral ventricles. Voxels with FA\u0026thinsp;\u0026le;\u0026thinsp;0.2 were excluded to avoid cerebrospinal fluid contamination.\u003c/p\u003e \u003cp\u003eThe ALPS-index was determined according to previously described methods (Taoka et al. \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Specifically, it was calculated as:\u003c/p\u003e \u003cp\u003e \u003cb\u003eALPS-index\u003c/b\u003e = \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\frac{\\text{m}\\text{e}\\text{a}\\text{n}(\\text{D}\\text{x}.\\text{p}\\text{r}\\text{o}\\text{j}+\\text{D}\\text{x}.\\text{a}\\text{s}\\text{s}\\text{o}\\text{c})}{\\text{m}\\text{e}\\text{a}\\text{n}(\\text{D}\\text{y}.\\text{p}\\text{r}\\text{o}\\text{j}+\\text{D}\\text{z}.\\text{a}\\text{s}\\text{s}\\text{o}\\text{c})}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003cp\u003eThe computation was performed separately for the left and right hemispheres. The resulting values were then averaged to obtain a single bilateral ALPS-index, which was subsequently used for statistical analyses.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll analyses were performed in R (version 2025.05.1\u0026thinsp;+\u0026thinsp;513). Continuous variables were summarized as means and standard deviations, and group differences in demographic and clinical characteristics between ASD and NT participants were assessed using independent-samples \u003cem\u003et\u003c/em\u003e-tests. Categorical variables were compared using χ\u0026sup2; tests. The primary analysis examined whether the ALPS-index differed by diagnosis (ASD vs. NT), by age group (younger participants\u0026thinsp;\u0026lt;\u0026thinsp;18 years vs. adults\u0026thinsp;\u0026ge;\u0026thinsp;18 years), and by their interaction, using a two-way analysis of variance (ANOVA). Partial eta squared (ηp\u0026sup2;) with 95% confidence intervals (CI) was calculated as an effect size measure for the ANOVA. When significant main effects or interactions were detected, we performed post hoc pairwise comparisons using estimated marginal means (\u003cem\u003eemmeans\u003c/em\u003e), applying Bonferroni adjustments to control for multiple comparisons within each family of tests. Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e was reported for effect size of post hoc tests. Due to the high reproducibility of the ALPS-index, even between scanner vendors (Liu et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2024\u003c/span\u003e) we did not correct for scanner albeit the use of data acquired from different scanners. However, a cohort-wise comparison is available in Supporting Information Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e and Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e. Associations between ALPS-index and continuous clinical or cognitive measures were examined using Pearson correlation coefficients (\u003cem\u003er\u003c/em\u003e), computed in the whole sample, and stratified by diagnosis and age group. Correlations were performed for Full-scale Intelligence Quotient (FIQ), ADOS total scores, and Beck Depression Inventory (BDI) scores (BDI was assessed only in the Barrow Neurological Institute cohort). Two-tailed p\u003cem\u003e-\u003c/em\u003evalues\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. Effect sizes for correlations were interpreted according to conventional benchmarks (small: |\u003cem\u003er\u003c/em\u003e| \u0026ge; 0.10, medium: |\u003cem\u003er\u003c/em\u003e| \u0026ge; 0.30, large: |\u003cem\u003er\u003c/em\u003e| \u0026ge; 0.50).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe final sample comprised 250 participants, including 128 autistic and 122 NT individuals (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). No significant differences were observed between the ASD and NT groups in terms of age or gender distribution, either in the overall sample or when stratified by age (\u0026lt;\u0026thinsp;18 vs. \u0026ge;18 years). However, the ASD group exhibited significantly higher proportions of comorbidity and medicine use, as well as lower FIQ scores and higher BDI scores compared to the NT group (Table\u0026nbsp;1).\u003c/p\u003e \u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e \u003cstrong\u003eDemographic and Clinical Characteristics of The ASD and NT Group.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"670\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"8\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eASD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"8\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"10\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnalysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u003cstrong\u003et\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003edf\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003eWhole sample\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e18.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e13.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e21.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e14.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e1.538\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e246\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026lt;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e11.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e3.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e11.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e3.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e1.394\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e143.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.166\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026ge;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e33.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e14.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e32.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e14.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.594\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e88.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.554\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003edf\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003eWhole sample\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e12.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e15.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.489\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.484\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026lt;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e12.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e10.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.699\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026ge;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e11.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e21.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e1.421\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003edf\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003eComorbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003eWhole sample\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e14.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e14.841\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026gt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026lt;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e12.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e1.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e7.358\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026ge;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e7.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e2.112\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.145\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003edf\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003eMedicine use\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003eWhole sample\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e19.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e1.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e19.307\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026gt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026lt;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e19.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e1.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e10.232\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026ge;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e19.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e1.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e6.936\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u003cstrong\u003et\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003edf\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003eFIQ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003eWhole sample\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e104.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e15.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e111.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e14.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp; 3.353\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 44px;\"\u003e\n \u003cp\u003e216.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026lt;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e103.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e16.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e110.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e16.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp; 2.526\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 44px;\"\u003e\n \u003cp\u003e133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026ge;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e107.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e13.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e113.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e11.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp; 2.202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 44px;\"\u003e\n \u003cp\u003e75.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003eADOS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003eWhole sample\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e12.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e4.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026lt;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e12.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e4.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026ge;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e11.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e3.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003eBDI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003eWhole sample\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e11.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e10.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e5.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e6.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;2.595\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;39.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026lt;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026ge;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003e11.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e10.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 42px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e5.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 48px;\"\u003e\n \u003cp\u003e6.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;2.595\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;39.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eContinuous variables are reported as mean \u0026plusmn; standard deviation (SD), and group differences were assessed with independent-samples t-tests, applying Welch\u0026rsquo;s correction when appropriate. Categorical variables (gender) are presented as counts and percentages, and group differences were assessed using Chi-squared tests (\u0026chi;\u0026sup2;). Autism Diagnostic Observation Schedule (ADOS); Degrees of freedom (df); Full-scale Intelligence Quotient (FIQ); Beck Depression Inventory (BDI).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eALPS-index\u003c/h2\u003e \u003cp\u003eWe first examined the effects of diagnosis (ASD vs. NT) and age group (\u0026lt;\u0026thinsp;18 vs. \u0026ge;18 years) on the ALPS-index using a two-way ANOVA (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The analysis revealed a significant main effect of diagnosis, \u003cem\u003eF\u003c/em\u003e(1, 246)\u0026thinsp;=\u0026thinsp;10.44, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0014, η\u0026sup2;ₚ = 0.041, indicating overall lower ALPS-indices in the ASD group compared to NT. A significant diagnosis \u0026times; age group interaction was also observed, \u003cem\u003eF\u003c/em\u003e(1, 246)\u0026thinsp;=\u0026thinsp;4.71, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031, η\u0026sup2;ₚ = 0.019, suggesting that the effect of diagnosis differed by age group. This indicates that the diagnostic effect (ASD vs NT) varied across age groups (\u0026lt;\u0026thinsp;18 vs. \u0026ge;18 years), suggesting an age-dependent difference in ALPS-index. Post hoc pairwise comparisons showed no significant ALPS-index difference between ASD and NT participants in the young (\u0026lt;\u0026thinsp;18-year) group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.342, Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.16, N\u0026thinsp;=\u0026thinsp;151), whereas the adult (\u0026ge;\u0026thinsp;18-year) ASD group demonstrated significantly lower ALPS-indices compared with age-matched NT participants (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0004, Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.72, N\u0026thinsp;=\u0026thinsp;99) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). In contrast, no significant main effect of age group was detected in the ANOVA, \u003cem\u003eF\u003c/em\u003e(1, 246)\u0026thinsp;=\u0026thinsp;1.98, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.123, η\u0026sup2;ₚ = 0.010. Overall, these results indicate that the reduction in ALPS-index is primarily driven by autistic adults.\u003c/p\u003e \n\u003cp\u003e\u003cstrong\u003eTable 2. ALPS-index Two-way ANOVA and Post-hoc Comparisons\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cimg 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\" width=\"724\" height=\"372\"\u003e\u003c/strong\u003e\u003cbr\u003e\u003c/p\u003e\u003cp\u003eThe upper portion displays the two-way ANOVA results, including F-statistics, p-values, and Partial eta squared (\u0026eta;p\u0026sup2;) for the effects of \u003cstrong\u003ediagnosis\u003c/strong\u003e (ASD vs NT), \u003cstrong\u003eage group\u003c/strong\u003e (\u0026lt;18 vs \u0026ge;18 years), and their interaction (Diagnosis \u0026times; Age Group). The lower panel provides ALPS-index group means \u0026plusmn; standard deviation (SD) with 95% confidence intervals (CI), \u003cstrong\u003eASD-NT group differences (\u0026Delta;)\u003c/strong\u003e, post-hoc p-values, and \u003cstrong\u003eCohen\u0026rsquo;s d\u003c/strong\u003e effect sizes, where negative values indicate \u003cstrong\u003elower ALPS-index in ASD than NT.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eCorrelation between ALPS-index and clinical measures\u003c/h3\u003e\n\u003cp\u003eGiven that FIQ differed significantly between ASD and NT groups (Table\u0026nbsp;1), we examined the relationship between the ALPS-index and FIQ. In the whole sample, no significant correlation was observed (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.060, p\u0026thinsp;=\u0026thinsp;0.372). Stratified analyses revealed no significant correlations in either the ASD (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.101, p\u0026thinsp;=\u0026thinsp;0.267) or NT group (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.037, p\u0026thinsp;=\u0026thinsp;0.720). Similarly, no significant correlation was found when stratifying by age group (\u0026lt;\u0026thinsp;18 years: r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.088, p\u0026thinsp;=\u0026thinsp;0.294; \u0026ge;18 years: r\u0026thinsp;=\u0026thinsp;0.014, p\u0026thinsp;=\u0026thinsp;0.903). Fully stratified analyses by both diagnosis and age group also revealed no significant correlations (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.26), indicating that FIQ was not significantly correlated with ALPS-indices in any subgroup. Detailed results are provided in Supporting Information Table S2.\u003c/p\u003e \u003cp\u003eFor the ASD group, we additionally assessed the association between ALPS-index and ADOS scores as a measure of the severity of core symptoms of autism. In the whole ASD sample, a weak negative, non-significant correlation was observed (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.161, p\u0026thinsp;=\u0026thinsp;0.091). Subgroup analyses showed no significant associations in children/adolescents (\u0026lt;\u0026thinsp;18 years: r\u0026thinsp;=\u0026thinsp;0.100, p\u0026thinsp;=\u0026thinsp;0.390) or adults (\u0026ge;\u0026thinsp;18 years: r\u0026thinsp;=\u0026thinsp;0.005, p\u0026thinsp;=\u0026thinsp;0.975). We also examined the relationship between ALPS-index and depressive symptoms in adults using the BDI. BDI was only available in the Barrow cohort (N\u0026thinsp;=\u0026thinsp;54), which only included adult participants (age range 18\u0026ndash;64 years). In the whole adult sample, no significant association was observed (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.209, p\u0026thinsp;=\u0026thinsp;0.129). However, when stratified by diagnosis, a significant negative correlation was identified in the adult ASD group (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.489, p\u0026thinsp;=\u0026thinsp;0.013), whereas no significant correlation was found in NT adults (r\u0026thinsp;=\u0026thinsp;0.005, p\u0026thinsp;=\u0026thinsp;0.982). This suggests that the ALPS-index is largely unrelated to general cognitive ability (FIQ) or autism symptom severity (ADOS) in autistic individuals, whereas lower ALPS-indices in autistic adults show modest correlation with higher depressive symptom severity. Detailed correlation results are provided in Supporting Information Table S2.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this cross-sectional study spanning five independent cohorts, we observed that the ALPS-index was reduced in autistic compared to NT individuals. Notably, this group difference appeared to be modulated by age. When stratifying the sample into younger (\u0026lt;\u0026thinsp;18 years) and adult (\u0026ge;\u0026thinsp;18 years) participants, significantly lower ALPS-index values were only detected in autistic adults compared to NT adults, whereas no significant differences emerged between autistic and NT participants in the younger group. These findings stand in contrast to the three prior studies that have investigated ALPS-index in ASD, all of which focused exclusively on young children. Li et al. (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) examined 30 autistic and 25 NT children (mean age 3.9 years, range 2\u0026ndash;6 years) and reported significantly reduced ALPS-index in the ASD group (Li et al. \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Similarly, Wang et al. (\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) studied a larger pediatric sample (178 participants, mean age 4.9 years, range 3\u0026ndash;7 years) and likewise found decreased ALPS-index in autistic compared to NT children (Wang et al. \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Lastly, Tian et al. (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) included 89 autistic and 37 NT children (mean age 3.6 years, range 2\u0026ndash;6 years) and demonstrated decreased ALPS-index in ASD (Tian et al. \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). The discrepancy between our findings and prior reports may be explained by differences in participant age. The young group in our study had a substantially higher mean age (11.4 years, range 5\u0026ndash;17 years) and did not include children as young as those examined in the prior studies. This age difference may have limited our ability to detect early developmental irregularities in glymphatic function. Given that ASD is a neurodevelopmental condition, glymphatic alterations may be most pronounced in the early years and then attenuate during later childhood, reflecting either delayed maturation or compensatory mechanisms. Supporting this notion, several studies have reported abnormalities in the glymphatic system in young children with ASD (Shen et al. \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Garic et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). In line with a developmental trajectory, glymphatic function (as indexed by ALPS) has been shown to increase with age across early childhood and adolescence (Wong et al. \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Consistently, Li et al. (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) reported a positive correlation between ALPS-index and age in both ASD and NT children (Li et al. \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). More broadly, evidence from a large cross-sectional study in NT individuals suggests that ALPS-index values continue to rise until approximately 40 years of age, followed by a gradual decline thereafter (Taoka et al. \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). ASD is associated with an atypical developmental trajectory of brain volume, characterized by early brain overgrowth followed by reduced gray matter volume later in development (Levman et al. \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Prigge et al. 2021), this pattern also appears to involve changes in the choroid plexus. Several studies have reported increased choroid plexus volume during childhood and adulthood in ASD, although the magnitude of enlargement varies across ages (Levman et al. \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Tezcan et al. \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) similarly to our results. The choroid plexus is a specialized epithelium within the brain\u0026rsquo;s ventricles that produces CSF and regulates the composition and circulation of the fluid that drives the glymphatic clearance system. Because choroid plexus enlargement has been associated with reduced glymphatic function (Gong et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2025\u003c/span\u003e), this may indicate that the glymphatic system is consistently, but in varying degrees dependent on age, affected in ASD.\u003c/p\u003e \u003cp\u003eTaken together, these findings suggest that glymphatic function in ASD may change dynamically across development, with alterations most evident during specific age periods. However, longitudinal multimodal imaging studies are needed to clarify these developmental patterns and determine their relevance to the clinical and neurobiological features of autism.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eGlymphatic function in aging autistic individuals\u003c/h2\u003e \u003cp\u003eIn our study, glymphatic function, assessed using the ALPS-index, was reduced in autistic adults. Prior work has shown that the ALPS-index correlates positively with sleep quality, memory performance, and neural communication in older adults (Ma et al. \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2025\u003c/span\u003e), underscoring the importance of preserved glymphatic function for healthy brain aging (Benveniste et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). If ASD is indeed associated with reduced glymphatic function, as suggested by our findings, this could provide a mechanistic link to the increased risk of AD reported in autistic individuals (Vivanti et al. \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Sian-Hulsmann et al. \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2026\u003c/span\u003e). Supporting this interpretation, postmortem studies have identified greater accumulation of amyloid-β in autistic brains (Wegiel et al. \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). Considering that amyloid-β accumulates with increasing age (Knudsen et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) and is cleared by the glymphatic system, enhanced accumulation could be caused by reduced glymphatic function (Iliff et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2012\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurthermore, middle-aged and elderly autistic individuals have been shown to exhibit more severe reductions in both memory performance and hippocampal volume (Pagni et al. \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Walsh et al. \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), both of which are indicators of AD. Interestingly, recent studies have reported positive correlations between glymphatic function and hippocampal volume (Chang et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), suggesting that impaired glymphatic clearance may contribute to the AD-like decline in hippocampal volume and memory performance observed in autistic individuals later in life.\u003c/p\u003e \u003cp\u003eAnother possible mechanism underlying reduced glymphatic function in ASD could be related to neuroinflammation and oxidative stress, which are frequently reported in autistic individuals (Thorsen et al. \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Than et al. \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Notably, both processes can damage astrocytic endfeet, causing a disruption of the AQP4 polarization, as well as vascular stiffening and impaired arterial pulsatility (Cai et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). These are all mechanisms that could cause reduced perivascular glymphatic function (Iliff et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Cai et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTaken together, these converging lines of evidence suggest that impaired glymphatic clearance in ASD may not only contribute to neurodevelopmental alterations but could also increase vulnerability to later-life neurodegenerative pathology. However, the underlying causes of reduced glymphatic function remains uncertain. Therefore, future work integrating longitudinal imaging, sleep assessment, measures of neuroinflammation, and biomarker studies will be essential to clarify the role of glymphatic dysfunction in linking autism with age-related neurological disorder.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eCorrelation analyses\u003c/h2\u003e \u003cp\u003eIn our correlation analysis, we observed a significant negative association between depressive symptoms (BDI score) and ALPS-index. This is noteworthy given that individuals with ASD are at increased risk for depression (Hudson et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2019\u003c/span\u003e), and depression in ASD is frequently accompanied by sleep disturbances (Stewart et al. \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Puzino et al. \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Because sleep quality has been closely linked to glymphatic function (Saito et al. \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Kikuta et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Ma et al. \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2025\u003c/span\u003e), it is plausible that disrupted sleep is linked to altered glymphatic clearance in ASD. Moreover, decreased ALPS-index have been demonstrated in patients with major depressive disorder (Bao et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Consequently, the high prevalence of depression and anxiety in autism may, at least in part, be associated with limited glymphatic function.\u003c/p\u003e \u003cp\u003eIn contrast, we did not observe significant correlations between ALPS-index and either FIQ or autistic traits. This differs from the findings of Wang et al. (\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) and Tian et al. (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) who both reported a negative correlation between ALPS-index and ASD severity measured by the Childhood Autism Rating Scale (CARS) (Schopler et al. \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e1980\u003c/span\u003e). Their result is consistent with prior studies linking autistic traits to sleep disturbances (Stewart et al. \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). The discrepancy between our findings and prior studies may be explained by differences in study design, including our broader age range and the use of ADOS rather than CARS as the clinical measure.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThere are several limitations of our study that are worth discussing. First, the ALPS-index is an indirect proxy of glymphatic function, derived from the ratio of water diffusivity along PVS to that measured perpendicular to the PVS at the level of the lateral ventricles (Taoka et al. \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2017\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). As such, it primarily reflects left-right Brownian motion of water molecules in this region. However, waste clearance from the brain parenchyma also follows radial pathways toward the cortical surface and ventricular walls, which are not fully captured by this measure. Consequently, the ALPS-index provides only an indirect approximation of glymphatic function. In principle, a lower ALPS-index reflects slower water diffusivity along perivascular pathways, which may indicate reduced solute clearance capacity and, to some extent, impaired glymphatic function. However, it does not capture the full complexity of glymphatic function across the brain. Future work employing diffusion MRI with multiple b-values, and combining ALPS with complementary imaging approaches (e.g., advanced CSF flow imaging), would provide a more comprehensive understanding of glymphatic function in ASD.\u003c/p\u003e \u003cp\u003eSecond, because our study is cross-sectional, we cannot directly assess longitudinal changes in glymphatic function across development or aging in ASD. Longitudinal studies spanning early childhood through adulthood will be necessary to establish developmental trajectories and clarify potential causal links with clinical outcomes.\u003c/p\u003e \u003cp\u003eThird, although the ALPS-index equation includes an inherent normalization factor, as it is the ratio of internal references (Taoka et al. \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2017\u003c/span\u003e), and our cohort comparisons did not indicate scanner-related differences (Supporting Information Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e and Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e), we cannot entirely exclude the possibility that data from different scanners influenced the results.\u003c/p\u003e \u003cp\u003eFourth, while the overall sample size was relatively large, stratified subgroup analyses (e.g., adults only) reduced the effective sample size, which may have limited statistical power. Additionally, the limited number of female participants (n\u0026thinsp;=\u0026thinsp;35) prevented us from assessing sex differences.\u003c/p\u003e \u003cp\u003eFifth, although interstitial solute clearance occurs during wakefulness, the interstitial space expands by approximately 60% during sleep, markedly enhancing glymphatic flow (Xie et al. \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Thus, glymphatic function is most accurately assessed during sleep, whereas in our study participants were imaged at rest while awake. This limitation highlights the importance of considering sleep\u0026ndash;wake state in future glymphatic research.\u003c/p\u003e \u003cp\u003eSixth, we observed a significant difference in both comorbidity and medication use between groups, which was expected given the high prevalence of comorbidities in ASD (Simonoff et al. \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2008\u003c/span\u003e). Nineteen participants in the ASD group had a comorbid condition (1 with anxiety, 18 with ADHD), whereas only one participant in the NT group had a comorbidity (thyrotoxicosis) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Considering that approximately 40% of autistic individuals are diagnosed with ADHD (Rong et al. \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2021\u003c/span\u003e), the comparatively lower prevalence of around 15% in our cohort suggests that our findings may not be fully generalizable to the broader autistic population. Accordingly, 25 participants in the ASD group reported medication use (2 amphetamine, 1 atomoxetine, 3 bupropion, 1 citalopram, 2 escitalopram, 1 fluoxetine, 2 lisdexamfetamine, 2 melatonin, 5 methylphenidate, 2 sertraline, 3 venlafaxine, and 1 ziprasidone), compared to only two participants in the NT group (1 levothyroxine and 1 antidepressant). How and whether these medications influence glymphatic function remains unknown and may therefore represent a potential source of bias.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this multi-cohort cross-sectional study, we demonstrate that glymphatic function assessed using ALPS-index, is reduced in autistic individuals, with the effect most pronounced in adulthood. These findings may indicate that glymphatic alterations in autism evolve across development, appearing in early life, diminishing during later childhood, and re-emerging in adulthood, in a pattern that partly parallels the age-related trajectory of brain volume. Reduced glymphatic function in autistic adults may help explain their increased vulnerability to memory decline, hippocampal atrophy, and AD pathology, while also linking to the high prevalence of depression and sleep disturbances in this population. Taken together, our results support the hypothesis that glymphatic dysfunction may represent a common mechanistic pathway linking the neurodevelopmental features of autism with an increased risk of psychiatric and neurodegenerative diseases later in life. However, the causes of reduced glymphatic function remain uncertain. Future longitudinal and multimodal studies will be essential to clarify the role of glymphatic function in autism across the lifespan and to determine its clinical relevance for both early development and age-related outcomes.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eConflict of interest statement\u003c/strong\u003e \u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eDisclosures\u003c/strong\u003e \u003cp\u003eThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eEthic approval\u003c/h2\u003e \u003cp\u003eAlle data is from the ABIDE dataset. Details regarding recruitment, scanning information, diagnostic protocols, and ethics statements are provided here: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://fcon_1000.projects.nitrc.org/indi/abide/\u003c/span\u003e\u003cspan address=\"https://fcon_1000.projects.nitrc.org/indi/abide/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConsent to participate\u003c/h2\u003e \u003cp\u003eInformed consent was not obtained by us, as we did not perform the data collection. Consent was obtained by the research team responsible for collecting the original data.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe author(s) received financial support for the research, from the Psychiatry Research Fund in the Region of Southern Denmark.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eLaust Vind Knudsen (LVK): Conceptualization; Methodology; Data curation; Formal analysis; Visualization (figure and table preparation); Writing \u0026ndash; original draft; Writing \u0026ndash; review \u0026amp; editing. Manouchehr Seyedi Vafaee (MSV): Conceptualization; Writing \u0026ndash; review \u0026amp; editing. Abigail Jane Sheldrick‑Michel (AJSM): Conceptualization; Writing \u0026ndash; review \u0026amp; editing. Tanja Maria Michel (TMM): Conceptualization; Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe author(s) would like to thank the Psychiatry Research Fund in the Region of Southern Denmark for financial support for the research.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData is freely accessible at the Autism Brain Imaging Data Exchange[https://fcon_1000.projects.nitrc.org/indi/abide/](https:/fcon_1000.projects.nitrc.org/indi/abide) .\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAmerican Psychiatric Association. (2013) Diagnostic and Statistical Manual of Mental Disorders (DSM-5). 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Neuroimage 238:. https://doi.org/10.1016/j.neuroimage.2021.118257\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":false,"email":"","identity":"journal-of-neural-transmission","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Journal of Neural Transmission","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"VoR Journals","inReviewEnabled":false,"inReviewRevisionsEnabled":false},"keywords":"Autism, ASD, Glymphatic system, ALPS-index, Diffusion tensor imaging, MRI","lastPublishedDoi":"10.21203/rs.3.rs-9047679/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9047679/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe glymphatic system supports brain homeostasis by clearing interstitial solutes via perivascular pathways. Alterations in glymphatic function have been linked to neurodevelopmental and neurodegenerative disorders, but its role in autism spectrum disorder (ASD) remains unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe analyzed diffusion tensor imaging (DTI) magnetic resonance imaging data from five cohorts in the Autism Brain Imaging Data Exchange (ABIDE) project. Glymphatic function was estimated using the DTI analysis along the perivascular space (ALPS) index. ASD diagnoses were confirmed according to DSM-IV-TR or DSM-5 criteria, and neurotypical (NT) participants had no history of neurological, psychiatric, or developmental disorders.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe final sample comprised 250 participants (128 ASD, mean age\u0026thinsp;=\u0026thinsp;18.57\u0026thinsp;\u0026plusmn;\u0026thinsp;13.81; 122 NT, mean age\u0026thinsp;=\u0026thinsp;21.32\u0026thinsp;\u0026plusmn;\u0026thinsp;14.37). Two-way analysis of variance (ANOVA) revealed a significant main effect of diagnosis, F(1, 246)\u0026thinsp;=\u0026thinsp;10.44, p\u0026thinsp;=\u0026thinsp;0.0014, with lower ALPS-indices in ASD. A diagnosis-by-age interaction was also observed, F(1, 246)\u0026thinsp;=\u0026thinsp;4.71, p\u0026thinsp;=\u0026thinsp;0.031. Post hoc tests demonstrated that autistic adults (\u0026ge;\u0026thinsp;18 years) had significantly lower ALPS-indices than NT adults (p\u0026thinsp;=\u0026thinsp;0.0004), whereas no group differences were demonstrated between younger ASD and NT (\u0026lt;\u0026thinsp;18 years). In ASD adults, the ALPS-index correlated negatively with depressive symptoms (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.489, p\u0026thinsp;=\u0026thinsp;0.013), but not with IQ or autistic traits.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThese findings suggest that glymphatic dysfunction in ASD may follow a developmental trajectory, with alterations becoming most evident in adulthood, potentially contributing to an increased risk of developing neurodegenerative disorder in autistic individuals.\u003c/p\u003e","manuscriptTitle":"Reduced Glymphatic Function in Autism Revealed by the Diffusion Tensor Analysis Along the Perivascular Space Index","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-23 10:12:27","doi":"10.21203/rs.3.rs-9047679/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-14T18:44:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"53645729618929272570864225306420944558","date":"2026-04-10T11:50:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"321058707535705789926302861842506193740","date":"2026-03-18T18:03:15+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-18T11:01:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-09T12:36:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-09T07:27:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Neural Transmission","date":"2026-03-06T07:42:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":false,"email":"","identity":"journal-of-neural-transmission","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Journal of Neural Transmission","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"VoR Journals","inReviewEnabled":false,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"edf9f950-16fd-4a27-b108-810db4819f48","owner":[],"postedDate":"March 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-23T10:12:27+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-23 10:12:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9047679","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9047679","identity":"rs-9047679","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}