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
Design and Analysis of N-Of-1 Trials That Incorporate Sequential Monitoring
AbstractJiang, S., Arnold, S. E., & Betensky, R. (n.d.).Publication year
2025Journal title
Statistics in MedicineVolume
44Issue
15-17AbstractFor many diseases and disorders, such as Alzheimer's disease, patients demonstrate considerable heterogeneity in their responses to treatment interventions. One treatment may be most effective for some patients, while another may be most effective for others, and neither may be effective for another subset of patients. This potentially renders the conventional parallel group design highly inefficient. An attractive alternative is the N-of-1 design, also called the multi-crossover randomized controlled trial. In this design, each participant serves as their own control in a series of randomized blocks of treatment assignments. We propose novel designs for both the single-person and multi-person N-of-1 trials that employ sequential monitoring. In particular, we allow for early stopping for a single participant as soon as there is sufficient evidence of a preferred treatment for them, and early stopping for the group of participants as soon as there is sufficient evidence of a preferred treatment for the population of patients. We provide sample size calculations and decision rules for terminating the trial early and illustrate their properties in simulation studies. We apply our proposed methods to N-of-1 studies of brain tumor excisions and of methylphenidate in mild cognitive impairment.Pseudo-observations for bivariate survival data
AbstractTravis-Lumer, Y., Mandel, M., & Betensky, R. (n.d.).Publication year
2025Journal title
BiometricsVolume
81Issue
1AbstractThe pseudo-observations approach has been gaining popularity as a method to estimate covariate effects on censored survival data. It is used regularly to estimate covariate effects on quantities such as survival probabilities, restricted mean life, cumulative incidence, and others. In this work, we propose to generalize the pseudo-observations approach to situations where a bivariate failure-time variable is observed, subject to right censoring. The idea is to first estimate the joint survival function of both failure times and then use it to define the relevant pseudo-observations. Once the pseudo-observations are calculated, they are used as the response in a generalized linear model. We consider 2 common nonparametric estimators of the joint survival function: the estimator of Lin and Ying (1993) and the Dabrowska estimator (Dabrowska, 1988). For both estimators, we show that our bivariate pseudo-observations approach produces regression estimates that are consistent and asymptotically normal. Our proposed method enables estimation of covariate effects on quantities such as the joint survival probability at a fixed bivariate time point or simultaneously at several time points and, consequentially, can estimate covariate-adjusted conditional survival probabilities. We demonstrate the method using simulations and an analysis of 2 real-world datasets.The association between measures of sleepiness and subjective cognitive decline symptoms in a diverse population of cognitively normal older adults
AbstractBriggs, A. Q., Boza-Calvo, C., Bernard, M. A., Rusinek, H., Betensky, R., & Masurkar, A. V. (n.d.).Publication year
2025Journal title
Journal of Alzheimer's DiseaseVolume
105Issue
3Page(s)
740-744AbstractSubjective cognitive decline (SCD) is associated with preclinical Alzheimer's disease (AD). Suboptimal sleep is also a risk factor for cognitive decline, but with unclear relationship to SCD. We conducted a retrospective cross-sectional study in a biracial research cohort of 148 cognitively normal older adults who underwent quantification of SCD (Cognitive Change Index; CCI), sleepiness (Epworth Sleepiness Scale; ESS), depression (Geriatric Depression Scale; GDS), and amyloid/tau PET. ESS score was associated with total, amnestic, and non-amnestic CCI scores, after adjustment for GDS, amyloid/tau burden, and race. This supports future longitudinal work on how sleepiness impacts SCD outcomes.15th Annual University of Pennsylvania conference on statistical issues in clinical trial/advances in time-to-event analyses in clinical trials (afternoon panel discussion)
AbstractBebu, I., Betensky, R., & Fay, M. P. (n.d.).Publication year
2024Journal title
Clinical TrialsVolume
21Issue
5Page(s)
612-622Abstract~Antidepressant exposure and long-term dementia risk in a nationwide retrospective study on US veterans with midlife major depressive disorder
AbstractRamos-Cejudo, J., Corrigan, J. K., Zheng, C., Swinnerton, K. N., Jacobson, S. R., La, J., Betensky, R., Osorio, R. S., Madanes, S., Pomara, N., Iosifescu, D., Brophy, M., Do, N. V., & Fillmore, N. R. (n.d.).Publication year
2024Journal title
Alzheimer's and DementiaAbstractINTRODUCTION: The use of antidepressants in major depressive disorder (MDD) has been reported to influence long-term risk of Alzheimer's disease (AD) and AD-related dementias (AD/ADRD), but studies are conflicting. METHODS: We used inverse probability weighted (IPW) Cox models with time-varying covariates in a retrospective cohort study among midlife veterans with MDD within the US Veterans Affairs healthcare system from January 1, 2000 to June 1, 2022. RESULTS: A total of 35,200 patients with MDD were identified. No associations were seen regarding the effect of being exposed to any antidepressant versus no exposure on AD/ADRD risk (events = 1,056, hazard ratio = 0.94, 95% confidence interval: 0.81 to 1.09) or the exposure to specific antidepressant classes versus no exposure. A risk reduction was observed for female patients in a stratified analysis; however, the number of cases was small. DISCUSSION: Our study suggests that antidepressant exposure has no effect on AD/ADRD risk. The association in female patients should be interpreted with caution and requires further attention. Highlights: We studied whether antidepressant use was associated with future dementia risk. We specifically focused on patients after their first-ever diagnosis of depression. We used IPW Cox models with time-varying covariates and a large observation window. Our study did not identify an effect of antidepressant use on dementia risk. A risk reduction was observed in female patients, but the number of cases was small.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., 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
AbstractBrydges, H. T., Onuh, O. C., Friedman, R., Barrett, J., Betensky, R., Lu, C. P., Caplan, A. S., Alavi, A., & Chiu, E. S. (n.d.).Publication year
2024Journal title
American Journal of Clinical DermatologyAbstractBackground: Hidradenitis suppurativa (HS) is a debilitating cutaneous disease characterized by severe painful inflammatory nodules/abscesses. At present, data regarding the epidemiology and pathophysiology of this disease are limited. Objective: To define the prevalence and comorbidity associations of HS. Methods: This was a cross-sectional study of EPICTM Cosmos© examining over 180 million US patients. Prevalences were calculated by demographic and odds ratios (OR) and identified comorbidity correlations. Results: All examined metabolism-related, psychological, and autoimmune/autoinflammatory (AI) diseases correlated with HS. The strongest associations were with pyoderma gangrenosum [OR 26.56; confidence interval (CI): 24.98–28.23], Down syndrome (OR 11.31; CI 10.93–11.70), and polycystic ovarian syndrome (OR 11.24; CI 11.09–11.38). Novel AI associations were found between HS and lupus (OR 6.60; CI 6.26–6.94) and multiple sclerosis (MS; OR 2.38; CI 2.29–2.48). Cutaneous malignancies were largely not associated in the unsegmented cohort; however, among Black patients, novel associations with melanoma (OR 2.39; CI 1.86–3.08) and basal cell carcinoma (OR 2.69; CI 2.15–3.36) were identified. Limitations: International Classification of Diseases (ICD)-based disease identification relies on coding fidelity and diagnostic accuracy. Conclusion: This is the first study to identify correlations between HS with melanoma and basal cell carcinoma (BCC) among Black patients as well as MS and lupus in all patients with HS.Autoimmune, Autoinflammatory Disease and Cutaneous Malignancy Associations with Hidradenitis Suppurativa : A Cross-Sectional Study
AbstractBrydges, H. T., Onuh, O. C., Friedman, R., Barrett, J., Betensky, R., Lu, C. P., Caplan, A. S., Alavi, A., & Chiu, E. S. (n.d.).Publication year
2024Journal title
American Journal of Clinical DermatologyAbstractBackground: Hidradenitis suppurativa (HS) is a debilitating cutaneous disease characterized by severe painful inflammatory nodules/abscesses. At present, data regarding the epidemiology and pathophysiology of this disease are limited. Objective: To define the prevalence and comorbidity associations of HS. Methods: This was a cross-sectional study of EPICTM Cosmos© examining over 180 million US patients. Prevalences were calculated by demographic and odds ratios (OR) and identified comorbidity correlations. Results: All examined metabolism-related, psychological, and autoimmune/autoinflammatory (AI) diseases correlated with HS. The strongest associations were with pyoderma gangrenosum [OR 26.56; confidence interval (CI): 24.98–28.23], Down syndrome (OR 11.31; CI 10.93–11.70), and polycystic ovarian syndrome (OR 11.24; CI 11.09–11.38). Novel AI associations were found between HS and lupus (OR 6.60; CI 6.26–6.94) and multiple sclerosis (MS; OR 2.38; CI 2.29–2.48). Cutaneous malignancies were largely not associated in the unsegmented cohort; however, among Black patients, novel associations with melanoma (OR 2.39; CI 1.86–3.08) and basal cell carcinoma (OR 2.69; CI 2.15–3.36) were identified. Limitations: International Classification of Diseases (ICD)-based disease identification relies on coding fidelity and diagnostic accuracy. Conclusion: This is the first study to identify correlations between HS with melanoma and basal cell carcinoma (BCC) among Black patients as well as MS and lupus in all patients with HS.Basic Science and Pathogenesis
AbstractAlzheimer’s Disease Neuroimaging Initiative (ADNI), A., Jacobs, T., Jacobson, S. R., Fortea, J., Berger, J. S., Vedvyas, A., Marsh, K., Gonzalez, M., Figueredo, L. F., Plaska, C. R., Blessing, E. M., Betensky, R., Rusinek, H., Glodzik, L., Wisniewski, T., Osorio, R. S., de Leon, M. J., & Cejudo, J. R. (n.d.).Publication year
2024Journal title
Alzheimer's and DementiaVolume
20Page(s)
e092957AbstractBACKGROUND: An elevated neutrophil-lymphocyte ratio (NLR) 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. METHOD: 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 NYU Center for Brain Health (CBH). Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-β42 (Aβ42), total tau (t-tau), and phosphorylated tau181 (p-tau181), as well as the trajectories of these CSF measures obtained longitudinally. RESULT: 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, pCapturing learning curves with the multiday Boston Remote Assessment of Neurocognitive Health (BRANCH): Feasibility, reliability, and validity
AbstractBetensky, R., Weizenbaum, E. L., Soberanes, D., Hsieh, S., Molinare, C. P., Buckley, R. F., Betensky, R. A., Properzi, M. J., Marshall, G. A., Rentz, D. M., Johnson, K. A., Sperling, R. A., Amariglio, R. E., & Papp, K. V. (n.d.).Publication year
2024Journal title
NeuropsychologyVolume
38Issue
2Page(s)
198-210AbstractUnsupervised remote digital cognitive assessment makes frequent testing feasible and allows for measurement of learning over repeated evaluations on participants' own devices. This provides the opportunity to derive individual multiday learning curve scores over short intervals. Here, we report feasibility, reliability, and validity, of a 7-day cognitive battery from the Boston Remote Assessment for Neurocognitive Health (Multiday BRANCH), an unsupervised web-based assessment.Capturing learning curves with the multiday Boston Remote Assessment of Neurocognitive Health (BRANCH): Feasibility, reliability, and validity
AbstractBetensky, R., Weizenbaum, E. L., Soberanes, D., Hsieh, S., Molinare, C. P., Buckley, R. F., Betensky, R. A., Properzi, M. J., Marshall, G. A., Rentz, D. M., Johnson, K. A., Sperling, R. A., Amariglio, R. E., & Papp, K. V. (n.d.).Publication year
2024Journal title
NeuropsychologyVolume
38Issue
2Page(s)
198-210AbstractUnsupervised remote digital cognitive assessment makes frequent testing feasible and allows for measurement of learning over repeated evaluations on participants' own devices. This provides the opportunity to derive individual multiday learning curve scores over short intervals. Here, we report feasibility, reliability, and validity, of a 7-day cognitive battery from the Boston Remote Assessment for Neurocognitive Health (Multiday BRANCH), an unsupervised web-based assessment.Clinical Manifestations
AbstractBriggs, A. Q., Betensky, R., Bernard, M. A., & Masurkar, A. V. (n.d.).Publication year
2024Journal title
Alzheimer's and DementiaVolume
20Page(s)
e091665AbstractBACKGROUND: Subjective cognitive decline (SCD) is a preclinical stage of Alzheimer's disease (AD), with correlations to cerebral amyloid and tau and accelerated cognitive decline. Studies have also revealed an association between sleep fragmentation and such AD biomarkers and cognitive decline, suggesting that cognitive function should be monitored in individuals experiencing excessive sleepiness. It is unclear if and how sleep dysfunction relates to SCD apart from AD biomarkers, as well as symptoms related to SCD and sleep dysfunction, such as depression. Furthermore, studies of SCD and sleep dysfunction have primarily focused on non-Hispanic Whites. Hence, a better understanding of how sleep impacts preclinical AD risk in SCD is needed in more diverse cohorts. We investigated the cross-sectional relationship between excessive sleepiness in cognitively normal older adults and SCD symptoms linked to cognitive domains in a cohort consisting of NHWs and Black/African Americans (B/AA). METHOD: This retrospective cross-sectional study included cognitively normal older participants (n = 147, age> 60 years, 61 B/AA, 86 NHW) evaluated at the NYU Alzheimer's Disease Research Center. Participants underwent Uniform Data Set 3.0 psychometric testing to confirm normal cognition, Epworth Sleepiness Scale (ESS), Geriatric Depression Scale (GDS), and the Cognitive Change Index (CCI) as a measure of SCD. The CCI was further divided into subscores of non-amnestic (i.e. executive) and amnestic domains (i.e. memory). Participants underwent amyloid (florbetaben) and tau (PI-2620 or MK-6240) PET MRI, with composite SUVR calculated by averaging key cortical regions. Multivariable linear regression models tested the association of ESS and covariates (GDS, amyloid SUVR, tau SUVR, race) to the three CCI outcome measures (total, non-amnestic, amnestic). RESULT: ESS (excessive sleepiness) was significantly positively associated with total CCI (p = 0.01042) as well as non-amnestic (0.00771) and amnestic CCI subgroups (0.02583), after full covariate adjustment, as was GDS. Race did not show an independent statistically significant association. CONCLUSION: These results suggest that excessive sleepiness, independent of depression and amyloid and tau burdens, may be a significant contributor to SCD severity. Furthermore, these contributions impact both amnestic and non-amnestic domains. Future studies are needed to investigate the longitudinal impact of excessive sleepiness on SCD outcomes.Comparison of comorbidities and adverse events in dermatology and rheumatology patients prescribed tofacitinib: A retrospective analysis
AbstractBetensky, R., 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)
659-662Abstract~Correction to : Predictors for the use of systemic therapy in stage IB Mycosis fungoides (Archives of Dermatological Research, (2024), 316, 6, (337), 10.1007/s00403-024-03005-0)
AbstractRodriguez, E., Needle, C. D., Martinez, M. J., Nohria, A., Xing, Y., Song, C., Betensky, R., Latkowski, J. A., & Adotama, P. (n.d.).Publication year
2024Journal title
Archives of Dermatological ResearchVolume
316Issue
8AbstractThe abstract was incorrect in this article and should have read as follows. Cutaneous T Cell Lymphoma (CTCL) is an increasingly prevalent condition that impacts patients of all skin types. The most common subtype of CTCL is Mycosis Fungoides (MF), an indolent non-Hodgkin lymphoma of T cell origin that primarily develops in the skin. Most patients with Stage IB MF receive phototherapy as a first-line treatment; however, some require additional systemic therapy. We conducted an institutional review board (IRB)-approved single-center retrospective study of 172 patients diagnosed with Stage IB MF at NYU Langone Health from January 1990 to April 2021. Our study identified demographic and clinical parameters that may indicate which Stage IB patients will require systemic therapy in order to guide clinical decision making and ensure that these treatments can be offered earlier in the disease course. Of 172 total patients enrolled, 129 (75.0%) received phototherapy only, 33 (19.2%) received phototherapy and a systemic agent, and 10 (5.8%) were excluded for lack of documented treatment modality. Univariate statistical analysis demonstrated that advanced age at diagnosis (p < 0.005) and elevated LDH (p < 0.001) were statistically significant markers in the systemic therapy group. There were no significant differences in anatomical regions involved for patients on systemic agents. Other variables including ethnicity, Fitzpatrick skin type, and health insurance status were not statistically significant predictors of receiving systemic therapy. These results suggest that clinicians should routinely order LDH upon diagnosis for all patients with Stage IB MF. If elevated, patients should be more closely monitored for earlier initiation of systemic agents. Patients with Stage IB MF with an advanced age of diagnosis are also at higher risk of requiring systemic therapy. The original article has been corrected.Diffusion imaging markers of accelerated aging of the lower cingulum in subjective cognitive decline
AbstractFlaherty, R., Sui, Y. V., Masurkar, A. V., Betensky, R., 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.Estimation and regression for partially truncated data
AbstractBetensky, R., & Qian, J. (n.d.).Publication year
2024Journal title
Journal of Nonparametric StatisticsAbstractJournal of Nonparametric StatisticsKMstability : 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.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
AbstractArnold, S. E., Hyman, B. T., Betensky, R., & Dodge, H. H. (n.d.).Publication year
2024Journal title
Alzheimer's and DementiaVolume
20Issue
10Page(s)
7384-7394AbstractBiological and clinical heterogeneity is a major challenge in research for developing new treatments for Alzheimer's disease (AD). AD may be defined by its amyloid beta and tau pathologies, but we recognize that mixed pathologies are common, and that diverse genetics, central nervous system (CNS) and systemic pathophysiological processes, and environmental/experiential factors contribute to AD's diverse clinical and neuropathological features. All these factors are rational targets for therapeutic development; indeed, there are hundreds of candidate pharmacological, dietary, neurostimulation, and lifestyle interventions that show benefits in homogeneous laboratory models. Conventional clinical trial designs accommodate heterogeneity poorly, and this may be one reason that progress in translating candidate interventions has been so difficult. We review the challenges of AD's heterogeneity for the clinical trials enterprise. We then discuss how advances in repeatable biomarkers and digital phenotyping enable novel “single-case” and adaptive trial designs to accelerate therapeutics development, moving us closer to personalized research and medicine for AD. Highlights: Alzheimer's disease is diverse in its clinical features, course, risks, and biology. Typical randomized controlled trials are exclusive and necessarily large to attain arm comparability with broad outcomes. Repeated blood biomarkers and digital tracking can improve outcome measure precision and sensitivity. This enables the use of novel “single-case” and adaptive trial designs for inclusivity, rigor, and efficiency.Phenoconversion in pure autonomic failure : a multicentre prospective longitudinal cohort study
AbstractVernetti, P. M., Norcliffe-Kaufmann, L., Palma, J. A., Biaggioni, I., Shibao, C. A., Peltier, A., Freeman, R., Gibbons, C., Goldstein, D. S., Low, P. A., Singer, W., Coon, E. A., Miglis, M. G., Wenning, G. K., Fanciulli, A., Vernino, S., Betensky, R., & Kaufmann, H. (n.d.).Publication year
2024Journal title
BrainVolume
147Issue
7Page(s)
2440-2448AbstractWe aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain. Patients diagnosed with PAF were evaluated at eight centres (seven US-based and one European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson's disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features. A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3-10) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB and 23% to MSA). Faster phenoconversion from study enrolment to any diagnosis was associated with urinary and sexual dysfunction [hazard ratio (HR) 5.9, 95% confidence interval (CI): 1.6-22 and HR: 3.6, 95% CI: 1.1-12] followed by subtle motor signs (HR: 2.7, 95% CI: 1.2-6), trouble swallowing (HR 2.5, 95% CI: 1.4-4.5) and changes in speech (HR:2.4, 95% CI:1.1-4.8) at enrolment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95% CI: 1.1-5.9) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95% CI: 1.2-38). Patients with a younger age of PAF onset (HR: 11, 95% CI: 2.6-46), preserved olfaction (HR: 8.7, 95% CI: 1.7-45), anhidrosis (HR: 1.8, 95% CI: 1-3.1, P = 0.042) and severe urinary problems (HR 1.6, 95% CI: 1-2.5, P = 0.033) were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95% CI: 1.4-26). Patients with PAF have an estimated 12% (95% CI: 9-15%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy.Phenoconversion in pure autonomic failure: a multicentre prospective longitudinal cohort study
AbstractBetensky, R., Millar Vernetti, P., Norcliffe-Kaufmann, L., Palma, J.- A., Biaggioni, I., Shibao, C. A., Peltier, A., Freeman, R., Gibbons, C., Goldstein, D. S., Low, P. A., Singer, W., Coon, E. A., Miglis, M. G., Wenning, G. K., Fanciulli, A., Vernino, S., Betensky, R. A., & Kaufmann, H. (n.d.).Publication year
2024Journal title
Brain : a journal of neurologyAbstractWe aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain. Patients diagnosed with PAF were evaluated at 8 Centers (7-US based and 1 European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive, and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features. A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3-10) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB, and 23% to MSA). Faster phenoconversion from study enrollment to any diagnosis was associated with urinary and sexual dysfunction [HR 5.9, 95%CI: 1.6-22, and HR: 3.6, 95%CI: 1.1-12] followed by subtle motor signs [HR: 2.7, 95%CI: 1.2-6], trouble swallowing [HR 2.5, 95%CI: 1.4-4.5], and changes in speech [HR:2.4, 95%CI:1.1-4.8] at enrollment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95%CI: 1.1-5.9, ) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95%CI: 1.2-38). Patients with a younger age of PAF onset [HR: 11, 95%CI: 2.6-46], preserved olfaction [HR: 8.7, 95%CI: 1.7-45], anhidrosis [HR: 1.8, 95%CI: 1-3.1, p=0.042], and severe urinary problems [HR 1.6, 95%CI: 1-2.5, p=0.033] were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95%CI: 1.4-26). Patients with PAF have an estimated 12% (95% CI: 9%-15%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy.Phenoconversion in pure autonomic failure: a multicentre prospective longitudinal cohort study
AbstractBetensky, R., Millar Vernetti, P., Norcliffe-Kaufmann, L., Palma, J.- A., Biaggioni, I., Shibao, C. A., Peltier, A., Freeman, R., Gibbons, C., Goldstein, D. S., Low, P. A., Singer, W., Coon, E. A., Miglis, M. G., Wenning, G. K., Fanciulli, A., Vernino, S., Betensky, R. A., & Kaufmann, H. (n.d.).Publication year
2024Journal title
Brain : a journal of neurologyAbstractWe aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain. Patients diagnosed with PAF were evaluated at 8 Centers (7-US based and 1 European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive, and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features. A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3-10) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB, and 23% to MSA). Faster phenoconversion from study enrollment to any diagnosis was associated with urinary and sexual dysfunction [HR 5.9, 95%CI: 1.6-22, and HR: 3.6, 95%CI: 1.1-12] followed by subtle motor signs [HR: 2.7, 95%CI: 1.2-6], trouble swallowing [HR 2.5, 95%CI: 1.4-4.5], and changes in speech [HR:2.4, 95%CI:1.1-4.8] at enrollment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95%CI: 1.1-5.9, ) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95%CI: 1.2-38). Patients with a younger age of PAF onset [HR: 11, 95%CI: 2.6-46], preserved olfaction [HR: 8.7, 95%CI: 1.7-45], anhidrosis [HR: 1.8, 95%CI: 1-3.1, p=0.042], and severe urinary problems [HR 1.6, 95%CI: 1-2.5, p=0.033] were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95%CI: 1.4-26). Patients with PAF have an estimated 12% (95% CI: 9%-15%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy.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.).Publication year
2024Journal title
Archives of Dermatological ResearchVolume
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
AbstractFrontera, J. A., Betensky, R., Pirofski, L. A., Wisniewski, T., Yoon, H., & Ortigoza, M. B. (n.d.).Publication year
2024Journal title
Neurology: Neuroimmunology and NeuroInflammationVolume
11Issue
3Page(s)
e200227AbstractBACKGROUND AND OBJECTIVES: Chronic systemic inflammation has been hypothesized to be a mechanistic factor leading to post-acute cognitive dysfunction after COVID-19. However, little data exist evaluating longitudinal inflammatory markers. METHODS: We conducted a secondary analysis of data collected from the CONTAIN randomized trial of convalescent plasma in patients hospitalized for COVID-19, including patients who completed an 18-month assessment of cognitive symptoms and PROMIS Global Health questionnaires. Patients with pre-COVID-19 dementia/cognitive abnormalities were excluded. Trajectories of serum cytokine panels, D-dimer, fibrinogen, C-reactive peptide (CRP), ferritin, lactate dehydrogenase (LDH), and absolute neutrophil counts (ANCs) were evaluated over 18 months using repeated measures and Friedman nonparametric tests. The relationships between the area under the curve (AUC) for each inflammatory marker and 18-month cognitive and global health outcomes were assessed. RESULTS: A total of 279 patients (N = 140 received plasma, N = 139 received placebo) were included. At 18 months, 76/279 (27%) reported cognitive abnormalities and 78/279 (28%) reported fair or poor overall health. PROMIS Global Mental and Physical Health T-scores were 0.5 standard deviations below normal in 24% and 51% of patients, respectively. Inflammatory marker levels declined significantly from hospitalization to 18 months for all markers (IL-2, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, INFγ, TNFα, D-dimer, fibrinogen, ferritin, LDH, CRP, neutrophils; all p < 0.05), with the exception of IL-1β, which remained stable over time. There were no significant associations between the AUC for any inflammatory marker and 18-month cognitive symptoms, any neurologic symptom, or PROMIS Global Physical or Mental health T-scores. Receipt of convalescent plasma was not associated with any outcome measure. DISCUSSION: At 18 months posthospitalization for COVID-19, cognitive abnormalities were reported in 27% of patients, and below average PROMIS Global Mental and Physical Health scores occurred in 24% and 51%, respectively. However, there were no associations with measured inflammatory markers, which decreased over time.