Rebecca A Betensky
Rebecca Betensky
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Chair of the Department of Biostatistics
Professor of Biostatistics
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Professional overview
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Prior to NYU, Dr. Betensky was Professor of Biostatistics at the Harvard T.H. Chan School of Public Health. She was director of the Harvard Catalyst (Clinical and Translational Science Award) Biostatistics Program; director of the Data and Statistics Core for the Massachusetts Alzheimer’s Disease Research Center; and director of the Biostatistics Neurology Core at Massachusetts General Hospital. Previously, she was the Biostatistics Program Leader for the Dana-Farber/Harvard Cancer Center.
Dr. Betensky’s research focuses on methods for the analysis of censored and truncated outcomes and covariates, which frequently arise from the subsampling of cohort studies. She has a long-time interest in clinical trials, and has written on the evaluation of biomarkers and the use and interpretation of p-values. She has collaborated extensively in studies in neurologic diseases, and serves as statistical editor for Annals of Neurology.
Dr. Betensky was awarded, and directed for 15 years, an NIH T32 training program in neurostatistics and neuroepidemiology for pre- and post-doctoral students in biostatistics and epidemiology and for clinician-scientists. She previously directed Harvard’s Biostatistics programs to promote and support diversity at all levels in the field of quantitative public health. She was also a member of the BMRD Study Section for review of NIH statistical methodology grants; on committees for the Institute of Medicine; and a co-chair of the technical advisory committee for the scientific registry of transplant recipients.
Dr. Betensky an elected Fellow of the American Statistical Association and of the International Statistical Institute, and is a past recipient of the Spiegelman Award from the American Public Health Association. She currently serves as a member of the Board of Scientific Counselors for Clinical Science and Epidemiology at the National Cancer Institute.
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Education
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AB, Mathematics, Harvard University, Cambridge, MAPhD, Statistics, Stanford University, Stanford, CA
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Areas of research and study
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BiologyBiostatisticsNeuroepidemiologyNeurologyNeurostatisticsTranslational science
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Publications
Publications
Pseudo-observations for bivariate survival data
Antidepressant exposure and long-term dementia risk in a nationwide retrospective study on US veterans with midlife major depressive disorder
Association of Social Determinants of Health With Brain MRI Outcomes in Individuals With Pediatric Onset Multiple Sclerosis
AbstractRoss, R., O’Neill, K. A., Betensky, R. A., Billiet, T., Kenney, R., Lovett, J. T., Maletic-Savatic, M., Meeks, H. D., Sosa, A., Waltz, M., & Krupp, L. B. (n.d.).Publication year
2024Journal title
NeurologyVolume
103Issue
12AbstractBackground and ObjectivesAccumulating evidence points to worse clinical outcomes among adults with multiple sclerosis (MS) belonging to minority or poverty-affected groups. By contrast, little is known about the outcomes of these populations with pediatric-onset MS (POMS). Individuals with POMS represent 5% of the MS population and are more racially diverse yet have been understudied regarding socioeconomic environment or characteristics. In this study, we investigated the association between childhood social determinants of health (SDOH) and brain MRI outcomes in patients with POMS.MethodsThis is a retrospective single-site cohort study of patients with POMS with brain MRI quantitatively analyzed using icobrain software to yield total white matter lesion, black hole, whole brain, white matter, and gray matter volumes. All patients with POMS evaluated at New York University Langone MS Center and who underwent high-quality volumetric MRI scans were included in this study. SDOH indicators of race, ethnicity, health insurance type, parental education, and childhood neighborhood social vulnerability index (SVI) were examined for association with MRI outcomes using linear least absolute shrinkage selection operator penalized regression modeling. Disease-modifying therapy (DMT) timing and DMT efficacy were compared for each SDOH category.ResultsA total of 138 patients with POMS (70% female) were included with a mean age of 19.86 years and median disease duration of 4 years at time of scan. Public health insurance, Black race, Hispanic ethnicity, low parental education, and high SVI (greater neighborhood disadvantage) were each associated with white matter lesion and black hole volume. SVI was the strongest individual predictor of total white matter lesion (β = 4.63, p = 0.002) and black hole volume (β = 2.91, p = 0.003). In models incorporating all SDOH variables, public health insurance was the strongest predictor of total lesion (β = 2.48, p = 0.01) and black hole volume (β = 1.50, p = 0.02), attenuating the effect of SVI (β = 1.66, p = 0.33 and β = 1.00, p = 0.39). There were no differences in DMT timing or efficacy between categories of social disadvantage.DiscussionIndividual-level and neighborhood-level indicators of social disadvantage are associated with worse brain MRI outcomes in POMS. Further investigation of race, ethnicity, and childhood disadvantage as risk factors of MS susceptibility and severity is needed to reduce MS health disparities.Autoimmune, Autoinflammatory Disease and Cutaneous Malignancy Associations with Hidradenitis Suppurativa: A Cross-Sectional Study
Comparison of comorbidities and adverse events in dermatology and rheumatology patients prescribed tofacitinib: A retrospective analysis
Needle, C. D., Klein, E. J., Gjonaj, J., Nohria, A., Karim, M., Liu, L., Shah, J., Betensky, R. A., Garshick, M., Lo Sicco, K., & Karagounis, T. K. (n.d.).Publication year
2024Journal title
Journal of the American Academy of DermatologyVolume
90Issue
3Page(s)
659-662Diffusion imaging markers of accelerated aging of the lower cingulum in subjective cognitive decline
AbstractFlaherty, R., Sui, Y. V., Masurkar, A. V., Betensky, R. A., Rusinek, H., & Lazar, M. (n.d.).Publication year
2024Journal title
Frontiers in NeurologyVolume
15AbstractIntroduction: Alzheimer’s Disease (AD) typically starts in the medial temporal lobe, then develops into a neurodegenerative cascade which spreads to other brain regions. People with subjective cognitive decline (SCD) are more likely to develop dementia, especially in the presence of amyloid pathology. Thus, we were interested in the white matter microstructure of the medial temporal lobe in SCD, specifically the lower cingulum bundle that leads into the hippocampus. Diffusion tensor imaging (DTI) has been shown to differentiate SCD participants who will progress to mild cognitive impairment from those who will not. However, the biology underlying these DTI metrics is unclear, and results in the medial temporal lobe have been inconsistent. Methods: To better characterize the microstructure of this region, we applied DTI to cognitively normal participants in the Cam-CAN database over the age of 55 with cognitive testing and diffusion MRI available (N = 325, 127 SCD). Diffusion MRI was processed to generate regional and voxel-wise diffusion tensor values in bilateral lower cingulum white matter, while T1-weighted MRI was processed to generate regional volume and cortical thickness in the medial temporal lobe white matter, entorhinal cortex, temporal pole, and hippocampus. Results: SCD participants had thinner cortex in bilateral entorhinal cortex and right temporal pole. No between-group differences were noted for any of the microstructural metrics of the lower cingulum. However, correlations with delayed story recall were significant for all diffusion microstructure metrics in the right lower cingulum in SCD, but not in controls, with a significant interaction effect. Additionally, the SCD group showed an accelerated aging effect in bilateral lower cingulum with MD, AxD, and RD. Discussion: The diffusion profiles observed in both interaction effects are suggestive of a mixed neuroinflammatory and neurodegenerative pathology. Left entorhinal cortical thinning correlated with decreased FA and increased RD, suggestive of demyelination. However, right entorhinal cortical thinning also correlated with increased AxD, suggestive of a mixed pathology. This may reflect combined pathologies implicated in early AD. DTI was more sensitive than cortical thickness to the associations between SCD, memory, and age. The combined effects of mixed pathology may increase the sensitivity of DTI metrics to variations with age and cognition.Early Detection of Amyloid-Related Changes in Memory among Cognitively Unimpaired Older Adults with Daily Digital Testing
KMstability: R tools to report the stability and precision of Kaplan–Meier estimates as well as measures of follow-up in time-to-event studies
AbstractErdmann, S., & Betensky, R. (n.d.).Publication year
2024Journal title
SoftwareXVolume
26AbstractIn order to appropriately report time-to-event analyses by means of Kaplan–Meier estimates, its precision and stability should be described. The precision is often reported by confidence intervals. For reporting the stability, various measures of the follow-up time distribution are used. However, these do not provide the intended insight. Recently, a new stability measure was presented. We have developed the software KMstability for calculation and display of this stability measure, including a user-friendly R shiny application and an open-source R package. The software enables informative reporting of time-to-event analysis. This is essential for reporting time-to-event analyses at interim-analyses of clinical trials and for observational (real-world-data) studies.Pathways to personalized medicine—Embracing heterogeneity for progress in clinical therapeutics research in Alzheimer's disease
Phenoconversion in pure autonomic failure: a multicentre prospective longitudinal cohort study
Predictors for the use of systemic therapy in stage IB Mycosis fungoides
AbstractRodriguez, E., Needle, C. D., Martinez, M. J., Nohria, A., Xing, Y., Song, C., Betensky, R., Latkowski, J. A., & Adotama, P. (n.d.). In Archives of Dermatological Research (1–).Publication year
2024Volume
316Issue
6AbstractBackground: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is aprospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) inpatients with newly diagnosed mycosis fungoides (MF). Objectives: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB)staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. Methods: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centresin 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. Results: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smallerpercentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariateanalysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA,20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs.T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%,while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improvedsignificantly both in patients with responsive disease and in those with stable disease. Conclusions: Disease characteristics such as presence of plaques and FMF influence physician treatment choices,and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, futuretreatment guidelines for early-stage MF need to address these issues.The neutrophil to lymphocyte ratio associates with markers of Alzheimer’s disease pathology in cognitively unimpaired elderly people
AbstractJacobs, T., Jacobson, S. R., Fortea, J., Berger, J. S., Vedvyas, A., Marsh, K., He, T., Gutierrez-Jimenez, E., Fillmore, N. R., Gonzalez, M., Figueredo, L., Gaggi, N. L., Plaska, C. R., Pomara, N., Blessing, E., Betensky, R., Rusinek, H., Zetterberg, H., Blennow, K., … Ramos-Cejudo, J. (n.d.).Publication year
2024Journal title
Immunity and AgeingVolume
21Issue
1AbstractBackground: An elevated neutrophil–lymphocyte ratio (NLR) in blood has been associated with Alzheimer’s disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. Herein, we explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the M.J. de Leon CSF repository at NYU. Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-β42 (Aβ42), total tau (t-tau), and phosphorylated tau181 (p-tau), as well as the trajectories of these CSF measures obtained longitudinally. Results: A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p < 0.001), and a greater percentage of Aβ-positivity (34.2% vs. 20.0%, p = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aβ42 (β = -12.193, p = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (β = 26.812, p = 0.019) and p-tau (β = 3.441, p = 0.015), but not Aβ42. In the NYU cohort alone, subjects classified as Aβ + (n = 38) displayed a stronger association between the NLR and t-tau (β = 100.476, p = 0.037) compared to Aβ- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data. Conclusions: We report associations between the NLR and Aβ42 in the older ADNI cohort, and between the NLR and t-tau and p-tau in the younger NYU cohort. Associations persisted after adjusting for comorbidities, suggesting a direct link between the NLR and AD. However, changes in associations between the NLR and specific AD biomarkers may occur as part of immunosenescence.Trajectories of Inflammatory Markers and Post-COVID-19 Cognitive Symptoms: A Secondary Analysis of the CONTAIN COVID-19 Randomized Trial
Capturing Learning Curves With the Multiday Boston Remote Assessment of Neurocognitive Health (BRANCH): Feasibility, Reliability, and Validity
Genomic and Transcriptomic Analyses of NF1-Mutant Melanoma Identify Potential Targeted Approach for Treatment
Internet usage and the prospective risk of dementia: A population-based cohort study
Neuropathology-Independent Association between APOE Genotype and Cognitive Decline Rate in the Normal Aging-Early Alzheimer Continuum
Nonparametric and semiparametric estimation with sequentially truncated survival data
Nonparametric bounds for the survivor function under general dependent truncation
AbstractQian, J., & Betensky, R. A. (n.d.).Publication year
2023Journal title
Scandinavian Journal of StatisticsVolume
50Issue
1Page(s)
327-357AbstractTruncation occurs in cohort studies with complex sampling schemes. When truncation is ignored or incorrectly assumed to be independent of the event time in the observable region, bias can result. We derive completely nonparametric bounds for the survivor function under truncation and censoring; these extend prior nonparametric bounds derived in the absence of truncation. We also define a hazard ratio function that links the unobservable region in which event time is less than truncation time, to the observable region in which event time is greater than truncation time, under dependent truncation. When this function can be bounded, and the probability of truncation is known approximately, it yields narrower bounds than the purely nonparametric bounds. Importantly, our approach targets the true marginal survivor function over its entire support, and is not restricted to the observable region, unlike alternative estimators. We evaluate the methods in simulations and in clinical applications.Simulation of New York City's Ventilator Allocation Guideline during the Spring 2020 COVID-19 Surge
AbstractWalsh, B. C., Zhu, J., Feng, Y., Berkowitz, K. A., Betensky, R. A., Nunnally, M. E., & Pradhan, D. R. (n.d.).Publication year
2023Journal title
JAMA network openVolume
6Issue
10Page(s)
E2336736AbstractImportance: The spring 2020 surge of COVID-19 unprecedentedly strained ventilator supply in New York City, with many hospitals nearly exhausting available ventilators and subsequently seriously considering enacting crisis standards of care and implementing New York State Ventilator Allocation Guidelines (NYVAG). However, there is little evidence as to how NYVAG would perform if implemented. Objectives: To evaluate the performance and potential improvement of NYVAG during a surge of patients with respect to the length of rationing, overall mortality, and worsening health disparities. Design, Setting, and Participants: This cohort study included intubated patients in a single health system in New York City from March through July 2020. A total of 20000 simulations were conducted of ventilator triage (10000 following NYVAG and 10000 following a proposed improved NYVAG) during a crisis period, defined as the point at which the prepandemic ventilator supply was 95% utilized. Exposures: The NYVAG protocol for triage ventilators. Main Outcomes and Measures: Comparison of observed survival rates with simulations of scenarios requiring NYVAG ventilator rationing. Results: The total cohort included 1671 patients; of these, 674 intubated patients (mean [SD] age, 63.7 [13.8] years; 465 male [69.9%]) were included in the crisis period, with 571 (84.7%) testing positive for COVID-19. Simulated ventilator rationing occurred for 163.9 patients over 15.0 days, 44.4% (95% CI, 38.3%-50.0%) of whom would have survived if provided a ventilator while only 34.8% (95% CI, 28.5%-40.0%) of those newly intubated patients receiving a reallocated ventilator survived. While triage categorization at the time of intubation exhibited partial prognostic differentiation, 94.8% of all ventilator rationing occurred after a time trial. Within this subset, 43.1% were intubated for 7 or more days with a favorable SOFA score that had not improved. An estimated 60.6% of these patients would have survived if sustained on a ventilator. Revising triage subcategorization, proposed improved NYVAG, would have improved this alarming ventilator allocation inefficiency (25.3% [95% CI, 22.1%-28.4%] of those selected for ventilator rationing would have survived if provided a ventilator). NYVAG ventilator rationing did not exacerbate existing health disparities. Conclusions and Relevance: In this cohort study of intubated patients experiencing simulated ventilator rationing during the apex of the New York City COVID-19 2020 surge, NYVAG diverted ventilators from patients with a higher chance of survival to those with a lower chance of survival. Future efforts should be focused on triage subcategorization, which improved this triage inefficiency, and ventilator rationing after a time trial, when most ventilator rationing occurred..APOE ε4 and late-life cognition: mediation by structural brain imaging markers
Association between lower body temperature and increased tau pathology in cognitively normal older adults
Causal inference in medical records and complementary systems pharmacology for metformin drug repurposing towards dementia
Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia
Nonparametric estimation of the survival distribution under covariate-induced dependent truncation