Yuxin Zhu

Johns Hopkins University | JHU · Department of Neurology

Background Neuronal pentraxin 2 (NPTX2) is a synaptic protein involved in the homeostatic regulation of cortical network dynamics and synaptic plasticity. Prior cross‐sectional studies suggest that NPTX2 levels decline across the spectrum of Alzheimer’s disease (AD), and that NPTX2 levels can distinguish individuals with normal cognition vs. mild c...

Background Mounting evidence indicates that tau accumulation in the entorhinal cortex (EC) occurs early in the course of Alzheimer’s disease (AD). Recent advances in automated segmentation methods allow for the investigation of smaller regions of the medial temporal lobes (MTL), including subregions of the EC. This study examined tau deposition in...

Background Individual differences in brain connectivity have been associated with cognitive variability in older adults, making them ideal markers of early changes that may predict subsequent cognitive decline. Using MRI measures, we previously demonstrated that cross‐sectionally, both structural and functional connectivity each uniquely contribute...

Introduction The accumulation of neurofibrillary tau tangles, a neuropathological hallmark of Alzheimer’s disease (AD), occurs in medial temporal lobe (MTL) regions early in the disease process, with some of the earliest deposits localized to subregions of the entorhinal cortex. Although functional specialization of entorhinal cortex subregions has...

Background Diagnostic errors cause substantial preventable harms worldwide, but rigorous estimates for total burden are lacking. We previously estimated diagnostic error and serious harm rates for key dangerous diseases in major disease categories and validated plausible ranges using clinical experts. Objective We sought to estimate the annual US...

Objective: This study examined whether cerebrospinal fluid (CSF) baseline levels of the synaptic protein NPTX2 predict time to onset of symptoms of Mild Cognitive Impairment (MCI), both alone and when accounting for traditional CSF Alzheimer's disease (AD) biomarker levels. Longitudinal NPTX2 levels were also examined. Methods: CSF was collected...

Alzheimer's Disease (AD) research has shifted to focus on biomarker trajectories and their potential use in understanding the underlying AD-related pathological process. A conceptual framework was proposed in such modern AD research that hypothesized biomarker cascades as a result of underlying AD pathology. In this paper, we leverage the idea of b...

Diagnostic errors in medicine represent a significant public health problem but continue to be challenging to measure accurately, reliably, and efficiently. The recently developed Symptom-Disease Pair Analysis of Diagnostic Error (SPADE) approach measures misdiagnosis related harms using electronic health records or administrative claims data. The...

Investigating and monitoring misdiagnosis-related harm is crucial for improving health care. However, this effort has traditionally focused on the chart review process, which is labor intensive, potentially unstable, and does not scale well. To monitor medical institutes' diagnostic performance and identify areas for improvement in a timely fashion...

Introduction: Oxygen extraction fraction (OEF) reflects the balance between oxygen delivery and consumption. We longitudinally measured OEF in older adults to examine the relationship with markers of Alzheimer's disease (AD) and vascular pathology. Methods: One hundred thirty-seven participants were studied at two time-points at an interval of 2...

Cross-sectionally sampled data with binary disease outcome are commonly analyzed in observational studies to identify the relationship between covariates and disease outcome. A cross-sectional population is defined as a population of living individuals at the sampling or observational time. It is generally understood that binary disease outcome fro...

Objective This study examined the association of lifetime experiences, measured by a cognitive reserve (CR) composite score composed of years of education, literacy, and vocabulary measures, to level and rate of change in white matter microstructure, as assessed by diffusion tensor imaging (DTI) measures. We also examined whether the relationship b...

This cross-sectional study examined whether performance on the computerized Paired Associate Learning (PAL) task from the Cambridge Neuropsychological Test Automated Battery is associated with amyloid positivity as measured by Positron Emission Tomography, regional volume composites as measured by Magnetic Resonance Imaging, and cognitive impairmen...

Background: Neuropsychiatric symptoms (NPS) among cognitively normal older adults are increasingly recognized as risk factors for cognitive decline and impairment. However, the underlying mechanisms remain unclear. Objective: To examine whether biomarkers of Alzheimer's disease (amyloid burden) and cerebrovascular disease (white matter hyperinte...

Background The increased focus on preclinical Alzheimer’s disease (AD) necessitates an understanding of how general biomarkers of neuronal injury and AD‐specific biomarkers differentially contribute to the cognitive performance in cognitively normal individuals. It has been suggested that alterations in limbic white matter (WM) tracts may precede b...

This study examines the relationship of engagement in different lifestyle activities to connectivity in large-scale functional brain networks, and whether network connectivity modifies cognitive decline, independent of brain amyloid levels. Participants (N = 153, mean age = 69 years, including N = 126 with amyloid imaging) were cognitively normal w...

In longitudinal event data, a crude rate is a simple quantification of the event rate, defined as the number of events during an evaluation window, divided by the at‐risk population size at the beginning or mid‐time point of that window. The crude rate recently received revitalizing interest from medical researchers who aimed to improve measurement...

In biomedical practices, multiple biomarkers are often combined using a pre‐specified classification rule with tree structure for diagnostic decisions. The classification structure and cutoff point at each node of a tree are usually chosen on an ad‐hoc basis, depending on decision makers' experience. There is a lack of analytical approaches that le...

Objectives Diagnostic error is a serious public health problem. Measuring diagnostic performance remains elusive. We sought to measure misdiagnosis-related harms following missed acute myocardial infarctions (AMI) in the emergency department (ED) using the symptom-disease pair analysis of diagnostic error (SPADE) method. Methods Retrospective admi...

Objective Examine whether cognitive reserve moderates the association of 1) vascular risk factors and 2) white matter hyperintensity burden with risk of clinical progression and longitudinal cognitive decline. Methods BIOCARD Study participants were cognitively normal and primarily middle‐aged (M = 57 years) at baseline and have been followed with...

Introduction: Identifying cognitively normal individuals at high risk for progression to symptomatic Alzheimer's disease (AD) is critical for early intervention. Methods: An AD risk score was derived using unsupervised machine learning. The score was developed using data from 226 cognitively normal individuals and included cerebrospinal fluid, m...

Background Missed vascular events, infections, and cancers account for ~75% of serious harms from diagnostic errors. Just 15 diseases from these “Big Three” categories account for nearly half of all serious misdiagnosis-related harms in malpractice claims. As part of a larger project estimating total US burden of serious misdiagnosis-related harms,...

Objective: Recent studies suggest that white matter hyperintensities (WMH) on MRI, which primarily reflect small vessel cerebrovascular disease, may play a role in the evolution of Alzheimer disease (AD). In a longitudinal study, we investigated whether WMH promote the progression of AD pathology, or alter the association between AD pathology and...

We examined whether cognitive reserve (CR) impacts level of, or rate of change in, biomarkers of Alzheimer's disease (AD) and small-vessel cerebrovascular disease in >250 individuals who were cognitively normal and middle-aged and older at the baseline. The four primary biomarker categories commonly examined in studies of AD were measured longitudi...

Background Diagnostic errors cause substantial preventable harm, but national estimates vary widely from 40,000 to 4 million annually. This cross-sectional analysis of a large medical malpractice claims database was the first phase of a three-phase project to estimate the US burden of serious misdiagnosis-related harms. Methods We sought to identi...

Background: Few studies have examined the relationship between lifestyle activity engagement and cognitive trajectories among individuals who were cognitively normal at baseline. Objective: To examine the relationship of current engagement in lifestyle activities to previous cognitive performance among individuals who were cognitively normal at...

Recent evidence indicates that measures from cerebrospinal fluid, MRI scans and cognitive testing obtained from cognitively normal individuals can be used to predict likelihood of progression to mild cognitive impairment several years later, for groups of individuals. However, it remains unclear whether these measures are useful for predicting like...

Purpose: Docetaxel has a demonstrated survival benefit for patients with metastatic castration-resistant prostate cancer (mCRPC); however, 10% to 20% of patients discontinue docetaxel prematurely because of toxicity-induced adverse events, and the management of risk factors for toxicity remains a challenge. Patients and methods: The comparator a...

Consider the partially linear model (PLM) with random design: $Y=X^T\beta^*+g(W)+u$, where $g(\cdot)$ is an unknown real-valued function, $X$ is $p$-dimensional, $W$ is one-dimensional, and $\beta^*$ is $s$-sparse. Our aim is to efficiently estimate $\beta^*$ based on $n$ i.i.d. observations of $(Y,X,W)$ with possibly $n<p$. The popular approaches...

This study examined whether cognitive reserve (CR) alters the relationship between magnetic resonance imaging (MRI) measures of cortical thickness and risk of progression from normal cognition to the onset of clinical symptoms associated with mild cognitive impairment (MCI). The analyses included 232 participants from the BIOCARD study. Participant...

Background: Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an ope...

In this paper, we present our winning method for survival time prediction in the 2015 Prostate Cancer DREAM Challenge, a recent crowdsourced competition focused on risk and survival time predictions for patients with metastatic castration-resistant prostate cancer (mCRPC). We are interested in using a patient's covariates to predict his or her time...

Supplementary material. Additional information about the characteristics of the subjects in the analyses.

Mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia are preceded by a phase of disease, referred to as ‘preclinical AD’, during which cognitively normal individuals have evidence of AD pathology in the absence of clinical impairment. This study examined whether a magnetic resonance imaging (MRI) measure of cortical thickness in br...