A Set of FMRI Quality Control Tools in AFNI: Systematic, in-depth, and interactive QC with afni_proc.py and more.

Quality control (QC) assessment is a vital part of FMRI processing and analysis, and a typically underdiscussed aspect of reproducibility. This includes checking datasets at their very earliest stages (acquisition and conversion) through their processing steps (e.g., alignment and motion correction) to regression modeling (correct stimuli, no collinearity, valid fits, enough degrees of freedom, etc.) for each subject. There are a wide variety of features to verify throughout any single-subject processing pipeline, both quantitatively and qualitatively. We present several FMRI preprocessing QC features available in the AFNI toolbox, many of which are automatically generated by the pipeline-creation tool, afni_proc.py. These items include a modular HTML document that covers full single-subject processing from the raw data through statistical modeling, several review scripts in the results directory of processed data, and command line tools for identifying subjects with one or more quantitative properties across a group (such as triaging warnings, making exclusion criteria, or creating informational tables). The HTML itself contains several buttons that efficiently facilitate interactive investigations into the data, when deeper checks are needed beyond the systematic images. The pages are linkable, so that users can evaluate individual items across a group, for increased sensitivity to differences (e.g., in alignment or regression modeling images). Finally, the QC document contains rating buttons for each "QC block," as well as comment fields for each, to facilitate both saving and sharing the evaluations. This increases the specificity of QC, as well as its shareability, as these files can be shared with others and potentially uploaded into repositories, promoting transparency and open science. We describe the features and applications of these QC tools for FMRI.

Cerebellar Atrophy and Language Processing in Chronic Left-Hemisphere Stroke.

Chronic stroke results in significant downstream changes at connected cortical sites. However, less is known about the impact of cortical stroke on cerebellar structure. Here, we examined the relationship between chronic stroke, cerebellar volume, cerebellar symmetry, language impairment, and treatment trajectories in a large cohort (N = 249) of chronic left hemisphere (LH) stroke patients with aphasia, using a healthy aging cohort (N = 244) as control data. Cerebellar gray matter volume was significantly reduced in chronic LH stroke relative to healthy control brains. Within the chronic LH stroke group, we observed a robust relationship between cerebellar volume, lesion size, and days post-stroke. Notably, the extent of cerebellar atrophy in chronic LH patients, particularly in the contralesional (right) cerebellar gray matter, explained significant variability in post-stroke aphasia severity, as measured by the Western Aphasia Battery-Revised, above and beyond traditional considerations such as cortical lesion size, days post-stroke, and demographic measures (age, race, sex). In a subset of participants that took part in language treatment studies, greater cerebellar gray matter volume was associated with greater treatment gains. These data support the importance of considering both cerebellar volume and symmetry in models of post-stroke aphasia severity and recovery.

Long-range white matter fibres and post-stroke verbal and non-verbal cognition.

Among stroke survivors, linguistic and non-linguistic impairments exhibit substantial inter-individual variability. Stroke lesion volume and location do not sufficiently explain outcomes, and the neural mechanisms underlying the severity of aphasia or non-verbal cognitive deficits remain inadequately understood. Converging evidence supports the idea that white matter is particularly susceptible to ischaemic injury, and long-range fibres are commonly associated with verbal and non-verbal function. Here, we investigated the relationship among post-stroke aphasia severity, cognition, and white matter integrity. Eighty-seven individuals in the chronic stage of stroke underwent diffusion MRI and behavioural testing, including language and cognitive measures. We used whole-brain structural connectomes from each participant to calculate the ratio of long-range fibres to short-range fibres. We found that a higher proportion of long-range fibres was associated with lower aphasia severity, more accurate picture naming, and increased performance on non-verbal semantic memory/processing and non-verbal reasoning while controlling for lesion volume, key damage areas, age, and years post stroke. Our findings corroborate the hypothesis that, after accounting for age and lesion anatomy, inter-individual differences in post-stroke aphasia severity, verbal, and non-verbal cognitive outcomes are related to the preservation of long-range white matter fibres beyond the lesion.

A Rose by Any Other Name: Mapping Taxonomic and Thematic Naming Errors Poststroke.

Understanding the neurobiology of semantic knowledge is a major goal of cognitive neuroscience. Taxonomic and thematic semantic knowledge are represented differently within the brain's conceptual networks, but the specific neural mechanisms remain unclear. Some neurobiological models propose that the anterior temporal lobe is an important hub for taxonomic knowledge, whereas the TPJ is especially involved in the representation of thematic knowledge. However, recent studies have provided divergent evidence. In this context, we investigated the neural correlates of taxonomic and thematic confrontation naming errors in 79 people with aphasia. We used three complementary lesion-symptom mapping (LSM) methods to investigate how structure and function in both spared and impaired brain regions relate to taxonomic and thematic naming errors. Voxel-based LSM mapped brain damage, activation-based LSM mapped BOLD signal in surviving tissue, and network-based LSM mapped white matter subnetwork integrity to error type. Voxel- and network-based lesion symptom mapping provided converging evidence that damage/disruption of the left mid-to-anterior temporal lobe was associated with a greater proportion of thematic naming errors. Activation-based lesion symptom mapping revealed that higher BOLD signal in the left anterior temporal lobe during an in-house naming task was associated with a greater proportion of taxonomic errors on the Philadelphia Naming Test administered outside of the scanner. A lower BOLD signal in the bilateral angular gyrus, precuneus, and right inferior frontal cortex was associated with a greater proportion of taxonomic errors. These findings provide novel evidence that damage to the anterior temporal lobe is especially related to thematic naming errors.

Brain-Hand Function Relationships Based on Level of Grasp Function in Chronic Left-Hemisphere Stroke.

BACKGROUND AND OBJECTIVE: The biomarkers of hand function may differ based on level of motor impairment after stroke. The objective of this study was to determine the relationship between resting state functional connectivity (RsFC) and unimanual contralesional hand function after stroke and whether brain-behavior relationships differ based on level of grasp function. METHODS: Sixty-two individuals with chronic, left-hemisphere stroke were separated into three functional levels based on Box and Blocks Test performance with the contralesional hand: Low (moved 0 blocks), Moderate (moved >0% but <90% of blocks relative to the ipsilesional hand), and High (moved ≥90% of blocks relative to the ipsilesional hand). RESULTS: RsFC in the ipsilesional and interhemispheric motor networks was reduced in the Low group compared to the Moderate and High groups. While interhemispheric RsFC correlated with hand function (grip strength and Stroke Impact Scale Hand) across the sample, contralesional RsFC correlated with hand function in the Low group and no measures of connectivity correlated with hand function in the Moderate and High groups. Linear regression modeling found that contralesional RsFC significantly predicted hand function in the Low group, while no measure correlated with hand function in the High group. Corticospinal tract integrity was the only predictor of hand function for the Moderate group and in an analysis across the entire sample. CONCLUSIONS: Differences in brain-hand function relationships based on level of motor impairment may have implications for predictive models of treatment response and the development of intervention protocols aimed at improving hand function after stroke.

The stroke outcome optimization project: Acute ischemic strokes from a comprehensive stroke center.

Stroke is a leading cause of disability, and Magnetic Resonance Imaging (MRI) is routinely acquired for acute stroke management. Publicly sharing these datasets can aid in the development of machine learning algorithms, particularly for lesion identification, brain health quantification, and prognosis. These algorithms thrive on large amounts of information, but require diverse datasets to avoid overfitting to specific populations or acquisitions. While there are many large public MRI datasets, few of these include acute stroke. We describe clinical MRI using diffusion-weighted, fluid-attenuated and T1-weighted modalities for 1715 individuals admitted in the upstate of South Carolina, of whom 1461 have acute ischemic stroke. Demographic and impairment data are provided for 1106 of the stroke survivors from this cohort. Our validation demonstrates that machine learning can leverage the imaging data to predict stroke severity as measured by the NIH Stroke Scale/Score (NIHSS). We share not only the raw data, but also the scripts for replicating our findings. These tools can aid in education, and provide a benchmark for validating improved methods.

Tractometry of the Human Connectome Project: resources and insights.

Introduction: The Human Connectome Project (HCP) has become a keystone dataset in human neuroscience, with a plethora of important applications in advancing brain imaging methods and an understanding of the human brain. We focused on tractometry of HCP diffusion-weighted MRI (dMRI) data. Methods: We used an open-source software library (pyAFQ; https://yeatmanlab.github.io/pyAFQ) to perform probabilistic tractography and delineate the major white matter pathways in the HCP subjects that have a complete dMRI acquisition (n = 1,041). We used diffusion kurtosis imaging (DKI) to model white matter microstructure in each voxel of the white matter, and extracted tract profiles of DKI-derived tissue properties along the length of the tracts. We explored the empirical properties of the data: first, we assessed the heritability of DKI tissue properties using the known genetic linkage of the large number of twin pairs sampled in HCP. Second, we tested the ability of tractometry to serve as the basis for predictive models of individual characteristics (e.g., age, crystallized/fluid intelligence, reading ability, etc.), compared to local connectome features. To facilitate the exploration of the dataset we created a new web-based visualization tool and use this tool to visualize the data in the HCP tractometry dataset. Finally, we used the HCP dataset as a test-bed for a new technological innovation: the TRX file-format for representation of dMRI-based streamlines. Results: We released the processing outputs and tract profiles as a publicly available data resource through the AWS Open Data program's Open Neurodata repository. We found heritability as high as 0.9 for DKI-based metrics in some brain pathways. We also found that tractometry extracts as much useful information about individual differences as the local connectome method. We released a new web-based visualization tool for tractometry-"Tractoscope" (https://nrdg.github.io/tractoscope). We found that the TRX files require considerably less disk space-a crucial attribute for large datasets like HCP. In addition, TRX incorporates a specification for grouping streamlines, further simplifying tractometry analysis.

Under pressure: the interplay of hypertension and white matter hyperintensities with cognition in chronic stroke aphasia.

While converging research suggests that increased white matter hyperintensity load is associated with poorer cognition, and the presence of hypertension is associated with increased white matter hyperintensity load, the relationship among hypertension, cognition and white matter hyperintensities is not well understood. We sought to determine the effect of white matter hyperintensity burden on the relationship between hypertension and cognition in individuals with post-stroke aphasia, with the hypothesis that white matter hyperintensity load moderates the relationship between history of hypertension and cognitive function. Health history, Fazekas scores for white matter hyperintensities and Wechsler Adult Intelligence Scale Matrix Reasoning subtest scores for 79 people with aphasia collected as part of the Predicting Outcomes of Language Rehabilitation study at the Center for the Study of Aphasia Recovery at the University of South Carolina and the Medical University of South Carolina were analysed retrospectively. We found that participants with a history of hypertension had increased deep white matter hyperintensity severity (P < 0.001), but not periventricular white matter hyperintensity severity (P = 0.116). Moderation analysis revealed that deep white matter hyperintensity load moderates the relationship between high blood pressure and Wechsler Adult Intelligence Scale scores when controlling for age, education, aphasia severity and lesion volume. The interaction is significant, showing that a history of high blood pressure and severe deep white matter hyperintensities together are associated with poorer Matrix Reasoning scores. The overall model explains 41.85% of the overall variation in Matrix Reasoning score in this group of participants. These findings underscore the importance of considering cardiovascular risk factors in aphasia treatment, specifically hypertension and its relationship to brain health in post-stroke cognitive function.

Regional brain aging: premature aging of the domain general system predicts aphasia severity.

Premature brain aging is associated with poorer cognitive reserve and lower resilience to injury. When there are focal brain lesions, brain regions may age at different rates within the same individual. Therefore, we hypothesize that reduced gray matter volume within specific brain systems commonly associated with language recovery may be important for long-term aphasia severity. Here we show that individuals with stroke aphasia have a premature brain aging in intact regions of the lesioned hemisphere. In left domain-general regions, premature brain aging, gray matter volume, lesion volume and age were all significant predictors of aphasia severity. Increased brain age following a stroke is driven by the lesioned hemisphere. The relationship between brain age in left domain-general regions and aphasia severity suggests that degradation is possible to specific brain regions and isolated aging matters for behavior.

Verbal working memory and syntactic comprehension segregate into the dorsal and ventral streams.

Syntactic processing and verbal working memory are both essential components to sentence comprehension. Nonetheless, the separability of these systems in the brain remains unclear. To address this issue, we performed causal-inference analyses based on lesion and connectome network mapping using MRI and behavioral testing in 103 individuals with chronic post-stroke aphasia. We employed a rhyme judgment task with heavy working memory load without articulatory confounds, controlling for the overall ability to match auditory words to pictures and to perform a metalinguistic rhyme judgment, isolating the effect of working memory load. We assessed noncanonical sentence comprehension, isolating syntactic processing by incorporating residual rhyme judgment performance as a covariate for working memory load. Voxel-based lesion analyses and structural connectome-based lesion symptom mapping controlling for total lesion volume were performed, with permutation testing to correct for multiple comparisons (4,000 permutations). We observed that effects of working memory load localized to dorsal stream damage: posterior temporal-parietal lesions and frontal-parietal white matter disconnections. These effects were differentiated from syntactic comprehension deficits, which were primarily associated with ventral stream damage: lesions to temporal lobe and temporal-parietal white matter disconnections, particularly when incorporating the residual measure of working memory load as a covariate. Our results support the conclusion that working memory and syntactic processing are associated with distinct brain networks, largely loading onto dorsal and ventral streams, respectively.

Exploring the link between tooth loss, cognitive function, and brain wellness in the context of healthy aging.

AIMS: The aim of this study was to evaluate the utility of using MRI-derived tooth count, an indirect and nonspecific indicator of oral/periodontal health, and brain age gap (BAG), an MRI-based measure of premature brain aging, in predicting cognition in a population of otherwise healthy adults. METHODS: This retrospective study utilized data from 329 participants from the University of South Carolina's Aging Brain Cohort Repository. Participants underwent neuropsychological testing including the Montreal Cognitive Assessment (MoCA), completed an oral/periodontal health questionnaire, and submitted to high-resolution structural MRI imaging. The study compared variability on cognitive scores (MoCA) accounted for by MRI-derived BAG, MRI-derived total tooth count, and self-reported oral/periodontal health. RESULTS: We report a significant positive correlation between the total number of teeth and MoCA total scores after controlling for age, sex, and race, indicating a robust relationship between tooth count and cognition, r(208) = .233, p < .001. In a subsample of participants identified as being at risk for MCI (MoCA <= 25, N = 36) inclusion of MRI-based tooth count resulted in an R2 change of .192 (H0 = 0.138 → H1 = 0.330), F(1,31) = 8.86, p = .006. Notably, inclusion of BAG, a valid and reliable measure of overall brain health, did not significantly improve prediction of MoCA scores in similar linear regression models. CONCLUSIONS: Our data support the idea that inclusion of MRI-based total tooth count may enhance the ability to predict clinically meaningful differences in cognitive abilities in healthy adults. This study contributes to the growing body of evidence linking oral/periodontal health with cognitive function.

A Set of FMRI Quality Control Tools in AFNI: Systematic, in-depth and interactive QC with afni_proc.py and more.

Quality control (QC) assessment is a vital part of FMRI processing and analysis, and a typically under-discussed aspect of reproducibility. This includes checking datasets at their very earliest stages (acquisition and conversion) through their processing steps (e.g., alignment and motion correction) to regression modeling (correct stimuli, no collinearity, valid fits, enough degrees of freedom, etc.) for each subject. There are a wide variety of features to verify throughout any single subject processing pipeline, both quantitatively and qualitatively. We present several FMRI preprocessing QC features available in the AFNI toolbox, many of which are automatically generated by the pipeline-creation tool, afni_proc.py. These items include: a modular HTML document that covers full single subject processing from the raw data through statistical modeling; several review scripts in the results directory of processed data; and command line tools for identifying subjects with one or more quantitative properties across a group (such as triaging warnings, making exclusion criteria or creating informational tables). The HTML itself contains several buttons that efficiently facilitate interactive investigations into the data, when deeper checks are needed beyond the systematic images. The pages are linkable, so that users can evaluate individual items across a group, for increased sensitivity to differences (e.g., in alignment or regression modeling images). Finally, the QC document contains rating buttons for each "QC block", as well as comment fields for each, to facilitate both saving and sharing the evaluations. This increases the specificity of QC, as well as its shareability, as these files can be shared with others and potentially uploaded into repositories, promoting transparency and open science. We describe the features and applications of these QC tools for FMRI.

Discourse- and lesion-based aphasia quotient estimation using machine learning.

Discourse is a fundamentally important aspect of communication, and discourse production provides a wealth of information about linguistic ability. Aphasia commonly affects, in multiple ways, the ability to produce discourse. Comprehensive aphasia assessments such as the Western Aphasia Battery-Revised (WAB-R) are time- and resource-intensive. We examined whether discourse measures can be used to estimate WAB-R Aphasia Quotient (AQ), and whether this can serve as an ecologically valid, less resource-intensive measure. We used features extracted from discourse tasks using three AphasiaBank prompts involving expositional (picture description), story narrative, and procedural discourse. These features were used to train a machine learning model to predict the WAB-R AQ. We also compared and supplemented the model with lesion location information from structural neuroimaging. We found that discourse-based models could estimate AQ well, and that they outperformed models based on lesion features. Addition of lesion features to the discourse features did not improve the performance of the discourse model substantially. Inspection of the most informative discourse features revealed that different prompt types taxed different aspects of language. These findings suggest that discourse can be used to estimate aphasia severity, and provide insight into the linguistic content elicited by different types of discourse prompts.

Dissociating reading and auditory comprehension in persons with aphasia.

Language comprehension is often affected in individuals with post-stroke aphasia. However, deficits in auditory comprehension are not fully correlated with deficits in reading comprehension and the mechanisms underlying this dissociation remain unclear. This distinction is important for understanding language mechanisms, predicting long-term impairments and future development of treatment interventions. Using comprehensive auditory and reading measures from a large cohort of individuals with aphasia, we evaluated the relationship between aphasia type and reading comprehension impairments, the relationship between auditory versus reading comprehension deficits and the crucial neuroanatomy supporting the dissociation between post-stroke reading and auditory deficits. Scores from the Western Aphasia Battery-Revised from 70 participants with aphasia after a left-hemisphere stroke were utilized to evaluate both reading and auditory comprehension of linguistically equivalent stimuli. Repeated-measures and univariate ANOVA were used to assess the relationship between auditory comprehension and aphasia types and correlations were employed to test the relationship between reading and auditory comprehension deficits. Lesion-symptom mapping was used to determine the dissociation of crucial brain structures supporting reading comprehension deficits controlling for auditory deficits and vice versa. Participants with Broca's or global aphasia had the worst performance on reading comprehension. Auditory comprehension explained 26% of the variance in reading comprehension for sentence completion and 44% for following sequential commands. Controlling for auditory comprehension, worse reading comprehension performance was independently associated with damage to the inferior temporal gyrus, fusiform gyrus, posterior inferior temporal gyrus, inferior occipital gyrus, lingual gyrus and posterior thalamic radiation. Auditory and reading comprehension are only partly correlated in aphasia. Reading is an integral part of daily life and directly associated with quality of life and functional outcomes. This study demonstrated that reading performance is directly related to lesioned areas in the boundaries between visual association regions and ventral stream language areas. This behavioural and neuroanatomical dissociation provides information about the neurobiology of language and mechanisms for potential future treatment interventions.

Improving 3D edge detection for visual inspection of MRI coregistration and alignment.

BACKGROUND: Visualizing edges is critical for neuroimaging. For example, edge maps enable quality assurance for the automatic alignment of an image from one modality (or individual) to another. NEW METHOD: We suggest that using the second derivative (difference of Gaussian, or DoG) provides robust edge detection. This method is tuned by size (which is typically known in neuroimaging) rather than intensity (which is relative). RESULTS: We demonstrate that this method performs well across a broad range of imaging modalities. The edge contours produced consistently form closed surfaces, whereas alternative methods may generate disconnected lines, introducing potential ambiguity in contiguity. COMPARISON WITH EXISTING METHODS: Current methods for computing edges are based on either the first derivative of the image (FSL), or a variation of the Canny Edge detection method (AFNI). These methods suffer from two primary limitations. First, the crucial tuning parameter for each of these methods relates to the image intensity. Unfortunately, image intensity is relative for most neuroimaging modalities making the performance of these methods unreliable. Second, these existing approaches do not necessarily generate a closed edge/surface, which can reduce the ability to determine the correspondence between a represented edge and another image. CONCLUSION: The second derivative is well suited for neuroimaging edge detection. We include this method as part of both the AFNI and FSL software packages, standalone code and online.

Neurodesk: an accessible, flexible and portable data analysis environment for reproducible neuroimaging.

Neuroimaging research requires purpose-built analysis software, which is challenging to install and may produce different results across computing environments. The community-oriented, open-source Neurodesk platform ( https://www.neurodesk.org/ ) harnesses a comprehensive and growing suite of neuroimaging software containers. Neurodesk includes a browser-accessible virtual desktop, command-line interface and computational notebook compatibility, allowing for accessible, flexible, portable and fully reproducible neuroimaging analysis on personal workstations, high-performance computers and the cloud.

Progressive lesion necrosis is related to increasing aphasia severity in chronic stroke.

BACKGROUND: Volumetric investigations of cortical damage resulting from stroke indicate that lesion size and shape continue to change even in the chronic stage of recovery. However, the potential clinical relevance of continued lesion growth has yet to be examined. In the present study, we investigated the prevalence of lesion expansion and the relationship between expansion and changes in aphasia severity in a large sample of individuals in the chronic stage of aphasia recovery. METHODS: Retrospective structural MRI scans from 104 S survivors with at least 2 observations (k = 301 observations; mean time between scans = 31 months) were included. Lesion demarcation was performed using an automated lesion segmentation software and lesion volumes at each timepoint were subsequently calculated. A linear mixed effects model was conducted to investigate the effect of days between scan on lesion expansion. Finally, we investigated the association between lesion expansion and changes on the Western Aphasia Battery (WAB) in a group of participants assessed and scanned at 2 timepoints (N = 54) using a GLM. RESULTS: Most participants (81 %) showed evidence of lesion expansion. The mixed effects model revealed lesion volumes significantly increase, on average, by 0.02 cc each day (7.3 cc per year) following a scan (p < 0.0001). Change on language performance was significantly associated with change in lesion volume (p = 0.025) and age at stroke (p = 0.031). The results suggest that with every 10 cc increase in lesion size, language performance decreases by 0.9 points, and for every 10-year increase in age at stroke, language performance decreases by 1.9 points. CONCLUSIONS: The present study confirms and extends prior reports that lesion expansion occurs well into the chronic stage of stroke. For the first time, we present evidence that expansion is predictive of longitudinal changes in language performance in individuals with aphasia. Future research should focus on the potential mechanisms that may lead to necrosis in areas surrounding the chronic stroke lesion.

Improved naming in patients with Broca's aphasia with tDCS.

BACKGROUND: Language impairment (aphasia) is a common neurological deficit after strokes. For individuals with chronic aphasia (beyond 6 months after the stroke), language improvements with speech therapy (ST) are often limited. Transcranial direct current stimulation (tDCS) is a promising approach to complement language recovery but interindividual variability in treatment response is common after tDCS, suggesting a possible relationship between tDCS and type of linguistic impairment (aphasia type). METHODS: This current study is a subgroup analysis of a randomised controlled phase II futility design clinical trial on tDCS in chronic post-stroke aphasia. All participants received ST coupled with tDCS (n=31) vs sham tDCS (n=39). Confrontation naming was tested at baseline, and 1, 4, and 24 weeks post-treatment. RESULTS: Broca's aphasia was associated with maximal adjunctive benefit of tDCS, with an average improvement of 10 additional named items with tDCS+ST compared with ST alone at 4 weeks post-treatment. In comparison, tDCS was not associated with significant benefits for other aphasia types F(1)=4.23, p=0.04. Among participants with Broca's aphasia, preservation of the perilesional posterior inferior temporal cortex was associated with higher treatment benefit (R=0.35, p=0.03). CONCLUSIONS: These results indicate that adjuvant tDCS can enhance ST to treat naming in Broca's aphasia, and this may guide intervention approaches in future studies.

White matter hyperintensity load mediates the relationship between age and cognition.

To elucidate the relationship between age and cognitive decline, it is important to consider structural brain changes such as white matter hyperintensities (WMHs), which are common in older age and may affect behavior. Therefore, we aimed to investigate if WMH load is a mediator of the relationship between age and cognitive decline. Healthy participants (N = 166, 20-80 years) completed the Montreal Cognitive Assessment (MoCA). WMHs were manually delineated on FLAIR scans. Mediation analysis was conducted to determine if WMH load mediates the relationship between age and cognition. Older age was associated with worse cognition (p < 0.001), but this was an indirect effect: older participants had more WMHs, and, in turn, increased WMH load was associated with worse MoCA scores. WMH load mediates the relationship between age and cognitive decline. Importantly, this relationship was not moderated by age (i.e., increased WMH severity is associated with poorer MoCA scores irrespective of age). Across all ages, high cholesterol was associated with increased WMH severity.