Stanford Advisors


Current Research and Scholarly Interests


Genetic epidemiology, statistical genetics, omics data analysis, prostate cancer, Alzheimer's disease

All Publications


  • Cerebrospinal Fluid Sphingomyelins in Alzheimer's Disease, Neurodegeneration, and Neuroinflammation. Journal of Alzheimer's disease : JAD Morrow, A., Panyard, D. J., Deming, Y. K., Jonaitis, E., Dong, R., Vasiljevic, E., Betthauser, T. J., Kollmorgen, G., Suridjan, I., Bayfield, A., Van Hulle, C. A., Zetterberg, H., Blennow, K., Carlsson, C. M., Asthana, S., Johnson, S. C., Engelman, C. D. 2022

    Abstract

    BACKGROUND: Sphingomyelin (SM) levels have been associated with Alzheimer's disease (AD), but the association direction has been inconsistent and research on cerebrospinal fluid (CSF) SMs has been limited by sample size, breadth of SMs examined, and diversity of biomarkers available.OBJECTIVE: Here, we seek to build on our understanding of the role of SM metabolites in AD by studying a broad range of CSF SMs and biomarkers of AD, neurodegeneration, and neuroinflammation.METHODS: Leveraging two longitudinal AD cohorts with metabolome-wide CSF metabolomics data (n = 502), we analyzed the relationship between the levels of 12 CSF SMs, and AD diagnosis and biomarkers of pathology, neurodegeneration, and neuroinflammation using logistic, linear, and linear mixed effects models.RESULTS: No SMs were significantly associated with AD diagnosis, mild cognitive impairment, or amyloid biomarkers. Phosphorylated tau, neurofilament light, alpha-synuclein, neurogranin, soluble triggering receptor expressed on myeloid cells 2, and chitinase-3-like-protein 1 were each significantly, positively associated with at least 5 of the SMs.CONCLUSION: The associations between SMs and biomarkers of neurodegeneration and neuroinflammation, but not biomarkers of amyloid or diagnosis of AD, point to SMs as potential biomarkers for neurodegeneration and neuroinflammation that may not be AD-specific.

    View details for DOI 10.3233/JAD-220349

    View details for PubMedID 36155504

  • Principal components from untargeted cerebrospinal fluid metabolomics associated with Alzheimer's disease biomarkers. Neurobiology of aging Dong, R., Denier-Fields, D. N., Lu, Q., Suridjan, I., Kollmorgen, G., Wild, N., Betthauser, T. J., Carlsson, C. M., Asthana, S., Johnson, S. C., Zetterberg, H., Blennow, K., Engelman, C. D. 2022; 117: 12-23

    Abstract

    Studying the correlation between cerebrospinal fluid (CSF) metabolites and the Alzheimer's Disease (AD) biomarkers may offer a window to the alterations of the brain metabolome and unveil potential biological mechanisms underlying AD. In this analysis, 308 CSF metabolites from 338 individuals of Wisconsin Registry for Alzheimer's Prevention and Wisconsin Alzheimer's Disease Research Center were included in a principal component analysis (PCA). The resulted principal components (PCs) were tested for association with CSF total tau (t-tau), phosphorylated tau (p-tau), amyloid β 42 (Aβ42), and Aβ42/40 ratio using linear regression models. Significant PCs were further tested with other CSF NeuroToolKit (NTK) and imaging biomarkers. Using a Bonferroni corrected p < 0.05, 5 PCs were significantly associated with CSF p-tau and t-tau and 3 PCs were significantly associated with CSF Aβ42. Pathway analysis suggested that these PCS were enriched in 6 pathways, including metabolism of caffeine and nicotinate and nicotinamide. This study provides evidence that CSF metabolites are associated with AD pathology through core AD biomarkers and other NTK markers and suggests potential pathways to follow up in future studies.

    View details for DOI 10.1016/j.neurobiolaging.2022.04.009

    View details for PubMedID 35640460

  • CSF metabolites associate with CSF tau and improve prediction of Alzheimer's disease status. Alzheimer's & dementia (Amsterdam, Netherlands) Dong, R., Darst, B. F., Deming, Y., Ma, Y., Lu, Q., Zetterberg, H., Blennow, K., Carlsson, C. M., Johnson, S. C., Asthana, S., Engelman, C. D. 2021; 13 (1): e12167

    Abstract

    Cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) are biomarkers of Alzheimer's disease (AD), yet much is unknown about AD-associated changes in tau metabolism and tau tangle etiology.We assessed the variation of t-tau and p-tau explained by 38 previously identified CSF metabolites using linear regression models in middle-age controls from the Wisconsin Alzheimer's Disease Research Center, and predicted AD/mild cognitive impairment (MCI) versus an independent set of older controls using metabolites selected by the least absolute shrinkage and selection operator (LASSO).The 38 CSF metabolites explained 70.3% and 75.7% of the variance in t-tau and p-tau, respectively. Of these, seven LASSO-selected metabolites improved the prediction ability of AD/MCI versus older controls (area under the curve score increased from 0.92 to 0.97 and 0.78 to 0.93) compared to the base model.These tau-correlated CSF metabolites increase AD/MCI prediction accuracy and may provide insight into tau tangle etiology.

    View details for DOI 10.1002/dad2.12167

    View details for PubMedID 33969169

    View details for PubMedCentralID PMC8087982

  • Metabolic Profiling of Cognitive Aging in Midlife. Frontiers in aging neuroscience Huo, Z., Rana, B. K., Elman, J. A., Dong, R., Engelman, C. D., Johnson, S. C., Lyons, M. J., Franz, C. E., Kremen, W. S., Zhao, J. 2020; 12: 555850

    Abstract

    Alzheimer's dementia (AD) begins many years before its clinical symptoms. Metabolic dysfunction represents a core feature of AD and cognitive impairment, but few metabolomic studies have focused on cognitive aging in midlife. Using an untargeted metabolomics approach, we identified metabolic predictors of cognitive aging in midlife using fasting plasma sample from 30 middle-aged (mean age 57.2), male-male twin pairs enrolled in the Vietnam Era Twin Study of Aging (VETSA). For all twin pairs, one twin developed incident MCI, whereas his co-twin brother remained to be cognitively normal during an average 5.5-year follow-up. Linear mixed model was used to identify metabolites predictive of MCI conversion or cognitive change over time, adjusting for traditional risk factors. Results from twins were replicated in an independent cohort of middle-aged adults (mean age 59.1) in the Wisconsin Registry for Alzheimer's Prevention (WRAP). Results in twins showed that higher baseline levels of four plasma metabolites, including sphingomyelin (d18:1/20:1 and d18:2/20:0), sphingomyelin (d18:1/22:1, d18:2/22:0, and d16:1/24:1), DAG (18:2/20:4), and hydroxy-CMPF, were significantly associated with a slower decrease in one or more domains of cognitive function. The association of sphingomyelin (d18:1/20:1 and d18:2/20:0) was replicated in WRAP. Our results support that metabolic perturbation occurs many years before cognitive impairment and plasma metabolites may serve as early biomarkers for prediction or monitoring of cognitive aging and AD in midlife.

    View details for DOI 10.3389/fnagi.2020.555850

    View details for PubMedID 33250761

    View details for PubMedCentralID PMC7674168

  • Acculturation and Adherence to Physical Activity Recommendations Among Chinese American and Non-Hispanic White Breast Cancer Survivors. Journal of immigrant and minority health Le, Y., Gao, Z., Gomez, S. L., Pope, Z., Dong, R., Allen, L., Chang, M. W., Wang, J. H. 2019; 21 (1): 80-88

    Abstract

    Chinese American breast cancer survivors' adherence to recommended physical activity (PA) guidelines has been understudied. This study investigated their PA adherence by acculturation level (vs. non-Hispanic White (NHW) survivors). One hundred ninety five Chinese and 202 NHW breast cancer survivors (stage 0-III) responded to a cross-sectional survey including a self-reported PA questionnaire. PA adherence referred to meeting PA recommendations for cancer survivors. Acculturation among Chinese was defined by proxies of U.S. residency, English proficiency, and interview language. Logistic regression was performed to examine factors associated with PA adherence. More-acculturated Chinese survivors' PA adherence rate was 76%. Less-acculturated Chinese survivors' adherence rate (60%) was significantly lower than that of NHWs (80%) (OR 0.38, 95%CI 0.19, 0.75). Less-acculturated Chinese survivors were also less likely to engage in vigorous-intensity PA than NHWs (p < 0.01). Future research on less-acculturated Chinese survivors' motivation for PA to promote their adherence is needed.

    View details for DOI 10.1007/s10903-018-0721-x

    View details for PubMedID 29569102

    View details for PubMedCentralID PMC6151158

  • Physician Intervention and Chinese Americans' Colorectal Cancer Screening. American journal of health behavior Huei-Yu Wang, J., Ma, G. X., Liang, W., Tan, Y., Makambi, K. H., Dong, R., Vernon, S. W., Tu, S. P., Mandelblatt, J. S. 2018; 42 (1): 13-26

    Abstract

    We conducted a cluster-randomized trial evaluating an intervention that trained Chinese-American primary care physicians to increase their Chinese patients' colorectal cancer (CRC) screening.Twenty-five physicians (13 randomized to the intervention arm and 12 to the control arm) and 479 of their patients (aged 50-75 and nonadherent to CRC screening guidelines) were enrolled. The intervention, guided by Social Cognitive Theory, included a communication guide and 2 in-office training sessions to enhance physicians' efficacy in com- municating CRC screening with patients. Patients' CRC screening rates (trial outcome) and rating of physician communication before intervention and at 12-month follow-up were assessed. Intention-to-treat analysis for outcome evaluation was conducted.Screening rates were slightly higher in the intervention vs. the control arm (24.4% vs. 17.7%, p = .24). In post hoc analyses, intervention arm patients who perceived better communication were more likely to be screened than those who did not (OR = 1.09, 95% CI: 1.03, 1.15). This relationship was not seen in the control arm.This physician-focused intervention had small, non-significant effects in increasing Chinese patients' CRC screening rates. Physician communication appeared to explain intervention efficacy. More intensive interventions are needed to enhance Chinese patients' CRC screening.

    View details for DOI 10.5993/AJHB.42.1.2

    View details for PubMedID 29320335

    View details for PubMedCentralID PMC5765879