About

David Cash is a Professor of Computer Science at the University of Chicago. The page does not provide specific details about his research focus, background, or key contributions.

Research topics

• Internal medicine
• Oncology
• Medicine
• Psychology
• Genetics
• Biology
• Pathology
• Nuclear medicine
• Bioinformatics
• Psychiatry
• Gastroenterology

Selected publications

• Examining the role of systemic inflammation as a mediator of the glycaemia-brain volume associations in women

  PLoS ONE · 2026-03-10

  articleOpen access

  Previous studies have found that diabetes and its mechanistic factors (e.g., glycaemia) are associated with poorer cognitive and brain health. There is also growing evidence of sex differences in how diabetes manifests itself and impacts the brain. The mechanisms through which this association manifests itself are still poorly understood, but the possible role of inflammation has been proposed. This study aims to explore whether the relationship between mid-life glycaemia and brain volumes in later-life in women is mediated by systemic inflammation. The sample consisted of female participants from the National Survey of Health and Development (NSHD) who underwent neuroimaging as part of the Insight 46 sub-study. Path analysis models were then constructed between glycaemic markers (age 60-64) and brain health outcomes (age 69-71) with adjustments for social and metabolic confounders (age 60-64). Although fasting glucose was associated with higher GlycA levels (β = 0.05 [0.01, 0.10], p = 0.005), associations with CRP and IL-6 were weaker and not statistically significant (e.g., IL-6: β = 0.10 [-0.04, 0.30], p = 0.102). However, we did not find evidence that inflammatory markers were associated with brain volume outcomes (e.g., IL-6 and whole brain volume: β = -3.4 [-8.1, 1.3], p = 0.092; IL-6 and grey matter volume: β = -0.4 [-1.9, 1.0], p = 0.512). Consequently, indirect (mediated) effects via systemic inflammation were not observed. This suggests that alternative mechanisms beyond inflammation may contribute to the relationship between mid-life glycaemia and later-life brain health.

  PublisherDOI

• Every Centiloid, from Everywhere, All at Once

  Alzheimer s & Dementia · 2025-12-01 · 1 citations

  articleOpen access

  Abstract Background Ten years after the original publication, the Centiloid framework is now broadly used to harmonize amyloid‐PET quantification, facilitate data sharing and comparison across cohorts, and even assist visual interpretation in clinical settings. We evaluated the global implementation of Centiloids by comparing their distribution and corresponding positivity thresholds across cohorts. Methods We gathered data from publicly available cohorts and reached out to investigators across the world to collect cross‐sectional Centiloids, demographic and clinical information, and visual read data. Gaussian mixture models (GMM, k=2) were fitted to Centiloid values for each cohort and cutoffs were calculated as mean + 2SD of the lower Gaussian. When visual reads were available, we determined Centiloid cutoffs that maximized correspondence with visual reads (Cohen’s kappa). Data was combined across cohorts using random effects meta‐analyses. Results As of January 2025, we included 37 cohorts ( n = 41,678 participants) with heterogeneous pipelines, radiotracers, and clinical and demographic characteristics (Table‐1). The low Gaussian peaks ranged from ‐9 to 10CL; the meta‐analysis identified a common peak at 1CL. The second peaks were more heterogeneous (range=38‐102CL; meta‐analysis outcome=64CL). Across cohorts, the proportion of cognitively unimpaired versus impaired participants impacted the position of both peaks, with better separation in cohorts enriched in impaired individuals (Figure‐1C). The meta‐analysis indicated a GMM‐based cutoff of 19CL (95%CI: 16‐21CL, Figure‐1B); subgroup analyses showed no evidence of significant effect between single versus multicenter settings (17 versus 20CL, p = 0.30), MRI‐based or PET‐only processing (18 versus 19CL, p = 0.88), and no evidence of difference across radiotracers (Flutemetamol: 16CL; PIB: 17CL, Flutafuranol: 18CL, Florbetaben: 19CL, Florbetapir: 20CL, p = 0.78). In a subset of 29,496 participants with visual reads available, binary visual reads corresponded well to Centiloids (common kappa=0.86, Figure‐2A). The visual read‐based cutoff of 24CL (95%CI: 21‐27CL, Figure‐2B) maximized correspondence between visual read and quantification and was slightly higher than the GMM‐based cutoff. All meta‐analysis models showed high non‐random heterogeneity (I 2 >80%) across studies, suggesting non‐random differences in peaks and cutoffs. Conclusions Meta‐analysis‐based cutoffs align well with thresholds from the existing literature. High heterogeneity among studies underscores the need to investigate contributing factors, raising concerns about applying common cutoffs.

  PublisherOA PDFDOI

• Examining the role of systemic inflammation as a mediator of the glycaemia-brain volume associations in women

  medRxiv · 2025-08-05 · 1 citations

  preprintOpen access

  Abstract Previous studies have found that diabetes and its mechanistic factors (e.g. glycaemia) are associated with poorer cognitive and brain health. There is also growing evidence of sex differences in how diabetes manifests itself and impacts the brain. The mechanisms through which this association manifests itself are still poorly understood, but the possible role of inflammation has been proposed. This study aims to explore whether the relationship between mid-life glycaemia and brain volumes in later-life in women is mediated by systemic inflammation. The sample consisted of female participants from the National Survey of Health and Development (NSHD) who underwent neuroimaging as part of the Insight 46 sub-study. Path analysis models were then constructed between glycaemic markers (age 60-64) and brain health outcomes (age 69-71) with adjustments for social and metabolic confounders (age 60-64). Although glycaemia was mostly associated with a higher systemic inflammatory state in two of the three markers (e.g., HbA1c and interleukin-6: β = 0.05 [0.02. 0.01], p = 0.001 and glycoprotein A: β = 0.02 [=-0.01. 0.02], p = 0.001), we did not find a relationship between inflammation and our brain volume markers [whole brain, grey matter and white matter] (e.g. interleukin-6 and whole brain volume: β = -3.1 [=-7.7. 1.5], p = 0.2; interleukin-6 and grey matter: β = -0.3 [=-1.8. 1.2], p = 0.7), thus no mediated effect between the glycaemic markers and outcomes via the pathway of systematic inflammation. This raises the possibility alternative mechanistic pathway, to inflammation, playing a role in the relationship between hyperglycaemia and brain health outcomes.

  PublisherOA PDFDOI

• Visual modulation of vestibular‐evoked balance response disturbed by posterior cortical atrophy

  The Journal of Physiology · 2025-10-19 · 1 citations

  articleOpen access

  We have recently shown that perception of uprightness is disturbed in typical Alzheimer's disease (tAD) and posterior cortical atrophy (PCA; 'visual-variant Alzheimer's'); disturbances were attributed to disrupted spatial transformation of graviceptive information. Here, we extend investigations to the vestibular control of uprightness during stance using galvanic vestibular stimulation (GVS) under various proprioceptive and visual conditions. An appropriately directed response to GVS requires spatial transformation of the vestibular signal based on head orientation relative to the feet, while non-vestibular sensory information can modulate the magnitude of response. Balance responses were repeatedly evoked in healthy participants (n = 21) and participants with AD (tAD: n = 18; PCA: n = 18) under conditions evaluating proprioceptive-vestibular integration (head directed right, straight or left without vision), or visuo-vestibular integration (head directed straight with or without vision). Across head directions without vision, GVS-evoked response direction and magnitude were comparable across groups. These comparable responses without vision indicate sparing of vestibulo-motor systems and proprioceptive-vestibular integration predicated on transformations between head, body and leg coordinates. However, the modulating effect of vision on GVS-evoked response magnitude was decreased in PCA relative to control and tAD groups. This relatively decreased effect of vision in PCA was evident through the earliest mechanical indicator of response, consistent with reduced feedforward effects of vision on vestibularly driven balance response. Exaggerated response magnitude with vision was associated with occipito-thalamic volumetric and projection fibre abnormalities in PCA. The findings suggest candidate pathways for visual modulation of vestibular balance control and dissociations between systems responsible for perceiving uprightness versus rapid sensorimotor balance control. KEY POINTS: Accurate balance control relies on the integration of vestibular, proprioceptive and visual inputs, transformed across spatial reference frames. We examined whole-body balance responses to galvanic vestibular stimulation (GVS) under varying visual and proprioceptive conditions in people with posterior cortical atrophy (PCA), typical Alzheimer's disease (tAD) and controls. Without vision, GVS-evoked balance responses were comparable across groups with the head turned left, right or straight ahead, indicating spared proprioceptive-vestibular integration in patient groups. With vision, visual input had a reduced modulatory effect on GVS responses in PCA relative to tAD and control groups. This was evident at the earliest stage of mechanical response, suggesting reduced feedforward visual influences on balance control in PCA. Our findings implicate disrupted occipito-thalamic pathways in PCA-related balance disturbances. The findings reveal a dissociation between perceived uprightness and sensorimotor balance control, with implications for understanding disturbed spatial orientation and balance in dementia.

  PublisherDOI

• Executive Function Deficits in Genetic Frontotemporal Dementia

  Neurology Genetics · 2025-07-21 · 1 citations

  articleOpen access

  Background and Objectives: Executive dysfunction is a core feature of frontotemporal dementia (FTD). While there has been extensive research into such impairments in sporadic FTD, there has been little research in the familial forms. Methods: mutation carriers, stratified into asymptomatic, prodromal, and fully symptomatic; and 247 mutation-negative controls. Attention and executive function were measured using the Weschler Memory Scale-Revised (WMS-R) Digit Span Backwards (DSB), Wechsler Adult Intelligence Scale-Revised Digit Symbol task, Trail Making Test Parts A and B, and the Delis-Kaplan Executive Function System Color Word Interference Test. Linear regression models with bootstrapping were used to assess differences between groups. Correlation of task score with disease severity was also performed, as well as an analysis of the neuroanatomical correlates of each task. Results: < 0.001). Discussion: mutation carriers. This differential performance across the genetic groups will be important in neuropsychological task selection in upcoming clinical trials.

  PublisherDOI

• Longitudinal trajectories of advanced cortical diffusion‐weighted imaging measures of tissue microstructure in pre‐symptomatic autosomal dominant Alzheimer’s disease

  Alzheimer s & Dementia · 2025-12-01

  articleOpen access

  BACKGROUND: In Alzheimer's disease, quantitative biomarkers of early subtle neurodegeneration are needed to identify individuals at greatest risk of imminent cognitive decline. Advanced cortical diffusion-weighted imaging (DWI) probes biologically specific tissue microstructural features, which may enable earlier detection of neurodegeneration than macrostructural measures (e.g., cortical thickness). Previous studies have examined neurodegeneration in symptomatic AD cross-sectionally. Here, we analyse a longitudinal cohort of individuals with autosomal dominant AD (ADAD), spanning the full disease spectrum, to explore changes in advanced cortical DWI metrics throughout the pre-symptomatic period. METHOD: -weighted imaging, plasma collection and neuropsychological testing. Region-averaged advanced cortical DWI measures of orientation dispersion index (ODI), a proxy measure of dendritic complexity, and the intra-voxel neuronal tissue fraction (TF); and cortical thickness, were extracted for 6 cortical regions previously reported to undergo pre-symptomatic cortical thinning in ADAD. Longitudinal trajectories were characterised with mixed effects models. Associations with plasma biomarkers of pathology and cognitive measures were assessed with Pearson correlations adjusted for estimated years to symptom onset (EYO). RESULT: Longitudinal models show widespread significant associations between EYO and advanced cortical DWI microstructure metrics of ODI and TF in all regions in mutation carriers (p <0.05). Carrier temporal trajectories diverged from non-carriers up to 3.7 years before symptom onset (Figure 1). No associations were found in non-carriers. Significant associations were observed between TF and plasma markers of neuronal damage (NFL) and synaptic integrity (NPTXR); and with tests of memory and cognition (Figure 2). Cortical thickness (CT) associations were weaker and less consistent. CONCLUSION: Longitudinal analysis shows pre-symptomatic changes in advanced cortical DWI metrics, suggesting sensitivity to early neurodegeneration. Regional differences in TF and ODI trajectories highlight potential spatiotemporal variation in microstructural breakdown. Associations between TF and plasma markers suggest close correspondence between this measure and early neuronal and synaptic loss. Stronger associations between cortical DWI measures and EYO, plasma and neuropsychological test scores, compared to cortical thickness measures, demonstrate the potential added value of advanced quantitative microstructure imaging for the early detection and characterisation of AD neurodegeneration.

  PublisherOA PDFDOI

• Cerebrovascular Reactivity at Rest and Its Association With Cognitive Function in People With Genetic Frontotemporal Dementia

  Neurology · 2025-09-04 · 1 citations

  articleOpen access

  BACKGROUND AND OBJECTIVES: Cerebrovascular reactivity (CVR) is an indicator of cerebrovascular health, and its signature in familial frontotemporal dementia (FTD) remains unknown. The primary aim was to investigate CVR in genetic FTD using an fMRI index of vascular contractility termed resting-state fluctuation amplitudes (RSFAs) and to assess whether RSFA differences are moderated by age. A secondary aim was to study the relationship between RSFA and cognition. METHODS: < 0.05. RESULTS: = 0.008, 95% CI 0.04-0.15), particularly in the prefrontal cortex, in sequence variation carriers across the sample, independent of disease stage. DISCUSSION: CVR impairment in genetic FTD has a predilection for the middle frontal and posterior cortex, and its preservation may yield a cognitive benefit for at-risk individuals. Although findings do not provide causality and warrant replication, they support the notion that vascular dysfunction in familial FTD may be a target for biomarker identification and disease-modifying efforts.

  PublisherOA PDFDOI

• Associations of Echocardiographic Biomarkers with White Matter Hyperintensities: Insights from the British 1946 Birth Cohort

  Alzheimer s & Dementia · 2025-12-01

  articleOpen access

  BACKGROUND: White matter hyperintensities (WMH) are established markers of presumed cerebrovascular disease and are associated with cognitive decline. Despite growing recognition of heart-brain interactions, longitudinal evidence linking cardiac function to WMH development remains limited, partly due to reliance on cross-sectional designs. This study investigates whether midlife echocardiographic parameters were linked to subsequent WMH burden 5-7 years later in participants from the National Survey for Health and Development (NSHD) Neuroimaging sub-study (Insight46). METHOD: ) quantification globally and across regions/depths. Key demographical and clinical details are provided in Table 1. Missing data (7%) were imputed with the MICE method. Associations between echocardiographic parameter and WMH volumes were examined using generalised linear models with gamma distribution, adjusting for demographic, cardiovascular, and socioeconomic factors. We applied the Benjamini-Hochberg procedure for multiple comparison correction. Potential non-linear relationships were explored using quadratic models and generalised additive models. RESULT: increase. Figure 1 presents the forest plot summarising these associations across all echocardiographic biomarkers. Regional analyses indicated pronounced frontal lobe effects for both LAV/BSA (2.4% increase, p = 0.005) and E/e' ratio (7.9% increase, p = 0.017); LAV/BSA was associated with WMH across all white matter layers, whereas E/e' ratio was most evident in intermediate layers. Figure 2 provides a heat-map illustrating these spatial patterns. End systolic volume showed a non-linear association with WMH (quadratic term, p = 0.001), suggesting complex interactions CONCLUSION: In this study, echocardiographic parameters, particularly left atrial measures, demonstrated significant associations with subsequent WMH burden over 5-7 years. Although these findings remain observational and do not confirm causality, they support the integration of cardiac assessments into comprehensive risk profiling for age-related brain changes. Future work should clarify whether interventions aiming to optimise cardiac health can mitigate WMH accumulation and related cognitive risks in later life.

  PublisherOA PDFDOI

• MRI measures of cortical microstructural damage associate with tau accumulation in presymptomatic Alzheimer’s disease

  medRxiv · 2025-12-16

  articleOpen access

  Abstract Objectives Amyloid lowering therapies for Alzheimer’s disease are most effective in those without significant neocortical tau spread. Currently, the only method for anatomically staging tau is through PET scanning, which is largely unavailable in clinical settings. We assessed whether advanced MRI biomarkers of cortical microstructure may provide a more accessible option for assessing early neocortical tau accumulation. Methods 217 asymptomatic individuals underwent amyloid-β PET, tau PET and multi-shell diffusion 3T MRI. Neurite orientation dispersion and density imaging (NODDI) metrics including orientation dispersion index (ODI; a proxy measure of dendritic complexity), and free water fraction (FWF) were calculated. Analysis focused on a meta-temporal cortical composite region, the first site of neocortical tau beyond the medial temporal lobe (MTL). Results Meta-temporal tau burden was associated with meta-temporal ODI (Pearson’s r=-0.24, p=0.001), with a weaker association also seen with meta-temporal FWF (r=-0.14, p=0.07). Within the amyloid-β positive group, ODI discriminated between those with and without meta-temporal tau positivity (area under the curve=0.86). Discussion NODDI-derived ODI is associated with tau PET signal, even in preclinical disease and may discriminate individuals with-and without tau beyond the MTL. NODDI represents a potential alternative imaging tool for staging tau spread, aiding future treatment stratification and delivery.

  PublisherOA PDFDOI

• Recent advances in neuroimaging of Alzheimer's disease and related dementias

  Alzheimer s & Dementia · 2025-09-01 · 9 citations

  reviewOpen access

  This review covers recent advances (2023-2024) in neuroimaging research into the pathophysiology, progression, and treatment of Alzheimer's disease (AD) and related dementias (ADRD). Despite the rapid emergence of blood-based biomarkers, neuroimaging continues to be a vital area of research in ADRD. Here, we discuss neuroimaging as a powerful tool to topographically visualize and quantify amyloid, tau, neurodegeneration, inflammation, and vascular disease in the brain. We examine the utility of neuroimaging for (1) tracking the spatiotemporal progression of pathology, (2) serving as the reference standard for validating novel fluid biomarkers, (3) characterizing disease heterogeneity, (4) exploring the role of brain networks in ADRD progression, and (5) evaluating biomarkers for better individualized estimates of treatment benefit. Finally, we discuss advances in radiotracer development and AD risk factors. By reviewing the most promising breakthroughs in the neuroimaging field, we hope to spark new ideas for future discoveries that will deepen our understanding of ADRD. HIGHLIGHTS: The diagnostic and staging criteria for Alzheimer's disease (AD) were updated in 2024. Despite robust harmonization methods for amyloid beta positron emission tomography (PET), parallel efforts for tau PET remain challenging. Larger anti-amyloid drug effects were seen at lower levels of amyloid and tau PET. Phosphorylated tau217 (p-tau217) is currently the most promising plasma biomarker to detect AD pathology. There are new tracer developments for alpha-synuclein, primary tauopathies, and inflammation.

  PublisherOA PDFDOI

Recent grants

• CAREER: Cryptography for Secure Outsourcing

  NSF · $447k · 2015–2019

• CAREER: Cryptography for Secure Outsourcing

  NSF · $287k · 2018–2021

• SaTC: CORE: Medium: Collaborative: Cryptographic Data Protection in Modern Systems

  NSF · $366k · 2018–2022

Frequent coauthors

• Nick C. Fox

  National Hospital for Neurology and Neurosurgery

  1252 shared

• Ian B. Malone

  855 shared

• Martina Bocchetta

  University College London

  690 shared

• Jonathan M. Schott

  UK Dementia Research Institute

  668 shared

• David L. Thomas

  University College London

  659 shared

• Jonathan D. Rohrer

  UK Dementia Research Institute

  643 shared

• Carole H. Sudre

  University College London

  547 shared

• Sébastien Ourselin

  544 shared

Labs

• Research Labs & GroupsPI

Education

• Ph.D., Computer Science

  University of Chicago

  2005

• M.S., Computer Science

  University of Chicago

  2002

• B.S., Computer Science

  University of Illinois at Urbana-Champaign

  1999

Awards & honors

• 2025 Quantrell Award for Undergraduate Teaching
• 2019 Keynote Speaker, NSS
• 2015 CAREER Award Research Fellow at Simons Institute
• 2011 Best Paper, Eurocrypt
• 2010 Best Paper, Eurocrypt