About

Sharon Xiangwen Xie, Ph.D., is a Professor of Biostatistics in the Department of Biostatistics and Epidemiology at the Hospital of the University of Pennsylvania and a Senior Scholar at the Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine. She serves as the Director of the Data Management and Statistical Core for the University of Pennsylvania Alzheimer's Disease Research Center and is the Deputy Director of the Center for Clinical Epidemiology and Biostatistics. Her research focuses on developing new statistical methods for survival analysis, missing data, measurement error problems, high dimensional data, biomarker evaluations, and longitudinal analysis, particularly in the context of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis. She applies these methods to real-world epidemiological studies and her work is supported by NIH grants where she acts as principal investigator. Dr. Xie is actively involved in collaborative research efforts and serves in various leadership and review roles within the scientific community. Her educational background includes degrees in Applied Mathematics from Beijing University of Technology, and advanced degrees in Statistics and Biostatistics from the University of Texas and University of Washington, respectively.

Research topics

• Medicine
• Pathology
• Biology
• Psychology
• Neuroscience
• Internal medicine
• Family medicine
• Oncology
• Radiology
• Bioinformatics
• Psychiatry
• Surgery
• Virology

Selected publications

• Repeated Administration of Social and Structural Determinants of Health (SSDOH) Questions in an Alzheimer’s Disease Research Center: The Aging Brain Study (ABC) Life Experience Survey

  Sage Open Aging · 2026-03-01

  articleOpen access

  Social and structural determinants of health (SSDOH) must be measured longitudinally to understand how lived experiences shape trajectories of Alzheimer's disease and related dementias (ADRD). This study evaluated the feasibility of administering an SSDOH survey to cognitively unimpaired older adults, examining response consistency, changes over time, and missing data patterns. A follow-up survey was conducted with participants in the UPenn Alzheimer's Disease Research Center clinical cohort an average of 1.7 years after the initial survey. The 225-item questionnaire covered domains including education, social networks, and stressors. At follow-up, markers of feasibility included a 60% completion rate (81 of 135 participants), high item completion (>93%), and minimal missing data (<3% missed more than 10% of data). Logistic regression identified gender, social network size, and social readjustment experiences as predictors of nonrandom missingness. Response changes between administrations were likely due to ambiguity in item phrasing, instructions, or changes in participants' experiences. Overall, repeated administration of the SSDOH survey was feasible. The response rate was reasonable but lower than expected for a volunteer research sample, suggesting multiple modes of completion may increase engagement. Repeated administration also helped identify ambiguous items and methods for improving the validity and reliability of SSDOH measures.

  PublisherDOI

• Idiotypic-susceptible Alzheimer’s disease: a clinically relevant, neurofibrillary tangle subtype

  Acta Neuropathologica · 2026-05-02

  articleOpen access

  Neurofibrillary tangles in Alzheimer's disease (AD) stereotypically spread from the medial temporal lobe to association areas and then to idiotypic areas (i.e., primary motor, somatosensory, auditory, and visual). Previous studies have reported variable and clinically relevant tangle densities across the hippocampus and association cortices, but the idiotypic tangle burden is understudied. In this study, we measured tangle density using immunohistochemistry in three idiotypic cortices (primary motor, somatosensory, and visual), three association cortices (middle frontal, superior temporal, and inferior parietal), and two hippocampal sectors (CA1 and subiculum) in 144 cases with a high level of AD neuropathologic change. Clinical diagnoses included late-onset AD (LOAD, n = 50), early-onset AD (EOAD, n = 21), behavioral variant frontotemporal dementia (bvFTD, n = 19), corticobasal syndrome (CBS, n = 18), logopenic primary progressive aphasia (lvPPA, n = 21), and posterior cortical atrophy (PCA, n = 15). We algorithmically assigned cases outside the interquartile ranges of mean tangle ratios of association:hippocampal, idiotypic:association, and idiotypic:hippocampal to mutually exclusive subtypes: idiotypic-susceptible, associative-predominant, limbic-predominant, or typical Braak (for all remaining cases). Regional tangle burdens differentiated subtypes, while female sex, younger ages, and longer disease durations also influenced tangle severity. Compared to typical Braak cases, idiotypic-susceptible and associative-predominant cases exhibited shorter disease duration and younger age at death while limbic-predominant cases were older. The MAPT H1H1 haplotype also differed by subtype, being most prevalent in limbic-predominant and least common in idiotypic-susceptible and associative-predominant subtypes. Clinically, the idiotypic-susceptible subtype associated with CBS (56%), the associative-predominant subtype with bvFTD (53%), and the limbic-predominant subtype with LOAD (14%). The typical Braak subtype characterized 74-76% of amnestic AD cases and 32-53% of non-amnestic AD cases. Moreover, k-means clustering corroborated four clusters including the idiotypic-susceptible and associative-predominant patterns. Our results confirm previously described tau subtypes and describe an idiotypic-predominant subtype with clinical relevance and distinct demographic and genetic characteristics in AD.

  PublisherDOI

• Clinical correlates of perfusion and diffusion MRI metrics in cognitively unimpaired older adults

  Journal of Cerebral Blood Flow & Metabolism · 2025-12-07

  articleOpen access

  Cerebral small vessel disease (CSVD) is associated with vascular risk factors (VRFs) and early executive function (EF) decline. Because periventricular white matter (PVWM) is the most weakly perfused brain region, it may be particularly sensitive to early manifestations of CSVD. Among 101 cognitively unimpaired adults, we assessed the cross-sectional correlations of arterial spin-labeled derived absolute and relative cerebral blood flow (CBF and rCBF, respectively) and diffusion tensor imaging (DTI) metrics in normal-appearing WM (NA-WM) and normal-appearing PVWM (NA-PVWM) with VRFs and EF, and evaluated the mediation and moderation relationships between these variables in amyloid β negative (Aβ−) subjects. CBF, rCBF, and DTI metrics were significantly different in NA-PVWM compared to NA-WM ( p &lt; 0.001). In multivariate analysis of the Aβ− group, NA-PVWM rCBF was associated with VRFs ( p = 0.012), while NA-PVWM rCBF ( p = 0.035) and mean diffusivity (MD) in NA-WM ( p = 0.022) and NA-PVWM ( p = 0.029) were associated with EF. The association between VRF and EF was not mediated by rCBF and/or MD. However, increased MD was significantly associated with poorer EF for NA-PVWM CBF ⩽16.3 mL/100 g/min and NA-PVWM rCBF ⩽0.35. NA-PVWM rCBF is associated with VRFs and EF and might be an early biomarker for CSVD, especially in the absence of amyloid pathology.

  PublisherDOI

• Higher neighborhood deprivation is associated with accelerated disease progression in behavioral-variant frontotemporal degeneration

  medRxiv · 2025-05-13

  preprintOpen access

  INTRODUCTION: Neighborhood deprivation is associated with shorter survival, cognitive impairment and neurodegeneration in aging and Alzheimer's disease. However, the association of neighborhood deprivation with disease progression in behavioral-variant frontotemporal degeneration (bvFTD) is unknown. METHODS: We examined associations between tertiles of neighborhood deprivation, using the Area Deprivation Index (ADI), and survival in 311 individuals clinically diagnosed with bvFTD from the Penn FTD Center. In a subset (n=161) with complete baseline data across measures of global cognition, executive function, and language, we examined the association of ADI with longitudinal change. RESULTS: Compared to adults living in the least deprived neighborhoods, those living in the most deprived neighborhoods showed shorter survival after symptom onset and faster decline in global cognition, executive and language functions, independent of genetic risk. DISCUSSION: Living in more deprived neighborhoods was associated with an accelerated disease course in bvFTD, highlighting an important socioeconomic disparity in disease prognosis.

  PublisherOA PDFDOI

• Robust inverse probability weighted estimators for doubly truncated Cox regression with closed-form standard errors

  Lifetime Data Analysis · 2025-04-01

  articleOpen accessSenior author

  Survival data is doubly truncated when only participants who experience an event during a random interval are included in the sample. Existing methods typically correct for double truncation bias in Cox regression through inverse probability weighting via the nonparametric maximum likelihood estimate (NPMLE) of the selection probabilities. This approach relies on two key assumptions, quasi-independent truncation and positivity of the sampling probabilities, yet there are no methods available to thoroughly assess these assumptions in the regression context. Furthermore, these estimators can be particularly sensitive to extreme event times. Finally, current double truncation methods rely on bootstrapping for variance estimation. Aside from the unnecessary computational burden, there are often identifiability issues with the NPMLE during bootstrap resampling. To address these limitations of current methods, we propose a class of robust Cox regression coefficient estimators with time-varying inverse probability weights and extend these estimators to conduct sensitivity analysis regarding possible non-positivity of the sampling probabilities. Also, we develop a nonparametric test and graphical diagnostic for verifying the quasi-independent truncation assumption. Finally, we provide closed-form standard errors for the NPMLE as well as for the proposed estimators. The proposed estimators are evaluated through extensive simulations and illustrated using an AIDS study.

  PublisherOA PDFDOI

• An online vignette study of diagnostic testing: Racial and ethnic differences in Alzheimer's disease diagnosis confidence and stigma

  Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · 2025-10-01

  articleOpen access

  INTRODUCTION: Understanding how biomarker testing affects Alzheimer's disease (AD) diagnosis confidence and AD stigma among race and ethnicity groups is essential for supporting early diagnosis and treatment. METHODS: = 3548) rated confidence in an AD diagnosis based on four diagnostic evaluations and answered questions about AD stigma based on a clinical vignette. The sample reflects response and completion rates of 53% and 91.3%, respectively. Bivariate and multivariable regression analyses were conducted. RESULTS: Black participants showed the smallest increase (11.86 points) in diagnosis confidence of all race groups when a brain scan was included in the diagnostic evaluation. AD diagnosis confidence changed across diagnostic evaluation categories based on level and type of AD stigma domain and race group. DISCUSSION: Use of brain scans in evaluations can heighten diagnosis confidence in all race groups. Yet, no group had 100% confidence in an AD diagnosis with any evaluation. Recommendations are discussed. Highlights: Confidence in an Alzheimer's disease (AD) diagnosis varies across racial groups.Within racial groups, AD diagnosis confidence differs with diagnostics.Even with cutting-edge biomarker testing, no racial group had 100% confidence in an AD diagnosis.Patient-centered care and systemic changes are needed to widen distribution of diagnostic technologies and improve access to care.

  PublisherDOI

• Remote, Automated Gamification and Community-Based Physical Activity in Parkinson Disease

  JAMA Neurology · 2025-11-03

  articleOpen access

  This nonrandomized clinical trial tests the efficacy of a remote, automated gamification intervention for increasing daily steps in people with Parkinson disease.

  PublisherOA PDFDOI

• Bias and Efficiency Comparison Between Multiple Imputation and Available-Case Analysis for Missing Data in Longitudinal Models

  Statistics in Biosciences · 2025-06-12 · 2 citations

  articleOpen accessSenior author

  In this paper, we compare the performance of available-case analysis (ACA) and several multiple imputation (MI) approaches for handling missing data problems in longitudinal analysis through estimation bias and relative efficiency. When the missingness of covariates depends on observed responses, ACA produces estimation bias, but it is preferred when there are only missing values in longitudinal responses. Multilevel MI methods are not always a solution to longitudinal data analysis. Single-level MI methods, like fully conditional specification (FCS), provide unbiased estimates under a variety of missing data scenarios, and improve efficiency gain in certain scenarios. The general assumption of missing data mechanism is missing at random (MAR). We carry out a systematic synthetic data analysis where missing data exist in longitudinal outcomes or/and covariates under different kinds of missing data generation procedures. The analysis model is a linear mixed-effects model. For each of the missing data scenarios, we give our recommendation (between ACA and a specific MI method) based on theoretical justifications and extensive simulations. In addition, a longitudinal neurodegenerative disease dataset is used as a real case study.

  PublisherOA PDFDOI

• Seizure characteristics and outcomes in patients with pleomorphic xanthoastrocytoma

  Neuro-Oncology Advances · 2025-01-01

  articleOpen access

  Abstract Background Pleomorphic xanthoastrocytomas (PXAs) are rare brain tumors that are often associated with seizures. There are limited data characterizing epilepsy phenotypes in relation to PXA tumor biology and survival outcomes. Methods This is a retrospective observational study of 35 patients with PXA who received treatment at the University of Pennsylvania or Dana-Farber Cancer Institute. Demographic and clinical features were assessed in PXA patients with or without seizures and with respect to seizure freedom following tumor resection. Results During their clinical course, 27 (77%) developed tumor-related epilepsy (TRE), with 25 (71%) initially presenting with a seizure. Compared to those without TRE, patients with TRE were more likely to have a BRAF-mutated PXA and less likely to have frontal lobe tumor localization. Patients with TRE who became seizure-free after the initial resection up to the time of progressive disease were found to have a lower age of seizure onset, smaller tumor diameter, and more likely to have BRAF-mutated tumors compared to those who were not seizure-free. However, following the last tumor resection and accounting for tumor recurrences, there were no significant differences in clinical features between those who were seizure-free and those who were not. Overall survival was 88% after 5 years and 59% after 10 years, with similar survival rates between patients with and without TRE. Conclusion These findings indicate that BRAF-mutated and BRAF-wildtype PXAs have distinct epilepsy phenotypes. Further investigation of the interplay between tumor biology and seizures may help guide counseling and targeted therapeutic strategies for PXA-related epilepsy.

  PublisherOA PDFDOI

• Blood α‐Synuclein Separates Parkinson's Disease from Dementia with Lewy Bodies

  Annals of Neurology · 2025-06-16 · 4 citations

  articleOpen access

  OBJECTIVE: Aggregation of misfolded α-synuclein (aSyn) within the brain is the pathologic hallmark of Lewy body diseases (LBDs), including Parkinson's disease (PD), and dementia with Lewy bodies (DLB) disease. Although evidence exists for aSyn "strains," conformations with distinct biological properties, biomarkers for PD versus DLB are lacking. Here, we used monoclonal antibodies selective for two different in vitro aSyn species - termed strain A and B - to evaluate human brain tissue, cerebrospinal fluid (CSF), and plasma. METHODS: Using these antibodies, we characterized specific aSyn species in human specimens from neurologically normal individuals and individuals with LBD using enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemistry. We also characterized aSyn species immunoprecipitated from brain lysate or plasma with these antibodies using seed amplification assays (SAAs) and a cellular model. RESULTS: Surprisingly, levels of strain A and B aSyn species were higher in plasma from individuals with PD compared to DLB in 2 independent cohorts. Lower levels of plasma aSyn strain A species predicted a faster rate of cognitive decline in individuals with PD. Furthermore, strain A and strain B aSyn species were undetectable in CSF, and their levels in brain versus plasma did not correlate. Moreover, plasma aSyn species isolated by aSyn strain antibodies could template aSyn fibrillization, and they could seed formation of aSyn inclusions in cells. INTERPRETATION: Our findings suggest that circulating plasma aSyn strains may impact LBD clinical presentation, particularly cognition. The enrichment of these aSyn species in plasma but not CSF also suggests a potential source outside the brain. ANN NEUROL 2025;98:682-698.

  PublisherOA PDFDOI

Recent grants

• NIH Grant P50NS053488

  NIH · $33.7M · 2018

• Efficient statistical methods for assessing dementia risk in Parkinson's disease

  NIH · $1.3M · 2017–2024

• Frontotemporal Dementias: Genotypes and Phenotypes

  NIH · $61.9M · 2000–2022

• Project II "aSyn Strains & Diverse Synucleinopathies"

  NIH · $16.0M · 2019–2025

• Penn Alzheimer's Disease Research Center (ADRC)

  NIH · $30.9M · 2021–2026

Frequent coauthors

• John Q. Trojanowski

  University of Pennsylvania

  338 shared

• Virginia M.‐Y. Lee

  California University of Pennsylvania

  187 shared

• Murray Grossman

  180 shared

• John Robinson

  University of Pennsylvania

  171 shared

• Vivianna M. Van Deerlin

  University of Pennsylvania

  169 shared

• Edward B. Lee

  159 shared

• David J. Irwin

  University of Pennsylvania

  152 shared

• Daniel Weintraub

  Veterans Health Administration

  121 shared

Labs

• Sharon Xiangwen Xie Research LabPI

Education

• PhD in Biostatistics

  University of Washington

  1997

Awards & honors

• Elected Fellow of the American Statistical Association
• 2011 Young Investigator Award of Statistics in the Epidemiol…
• 2012 ENAR Distinguished Student Paper Award
• 2011 Young Investigator Award from Statistics in Epidemiolog…
• W. Edwards Deming Student Scholar Award from the 2017 Annual…