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
Cognitive resilience in clinical and preclinical Alzheimer’s disease: the Association of Amyloid and Tau Burden on cognitive performance
Correlation among baseline variables yields non-uniformity of p-values
Fluorodeoxyglucose metabolism associated with tau-amyloid interaction predicts memory decline
Is this significant?
Linear regression with a randomly censored covariate: application to an Alzheimer's study
Neurofibrillary tangle stage and the rate of progression of Alzheimer symptoms: Modeling using an autopsy cohort and application to clinical trial design
AbstractQian, J., Hyman, B. T., & Betensky, R. A. (n.d.).Publication year
2017Journal title
JAMA NeurologyVolume
74Issue
5Page(s)
540-548AbstractIMPORTANCE The heterogeneity of rate of clinical progression among patients with Alzheimer disease leads to difficulty in providing clinical counseling and diminishes the power of clinical trials using disease-modifying agents. OBJECTIVE To gain a better understanding of the factors that affect the natural history of progression in Alzheimer disease for the purpose of improving both clinical care and clinical trial design. DESIGN, SETTING, AND PARTICIPANTS A longitudinal cohort study of aging from 2005 to 2014 in the National Alzheimer Coordinating Center. Clinical evaluation of the participants was conducted in 31 National Institute on Aging's Alzheimer Disease Centers. Nine hundred eighty-four participants in the National Alzheimer Coordinating Center cohort study who died and underwent autopsy and met inclusion and exclusion criteria. MAIN OUTCOMES AND MEASURES We sought to model the possibility that knowledge of neurofibrillary tangle burden in the presence of moderate or frequent plaques would add to the ability to predict clinical rate of progression during the ensuing 2 to 3 years.We examined the National Alzheimer Coordinating Center autopsy data to evaluate the effect of different neurofibrillary tangle stages on the rates of progression on several standard clinical instruments: the Clinical Dementia Rating Scale sum of boxes, a verbal memory test (logical memory), and a controlled oral word association task (vegetable naming), implementing a reverse-time longitudinal modeling approach in conjunction with latent class estimation to adjust for unmeasured sources of heterogeneity. RESULTS Several correlations between clinical variables and neurocognitive performance suggest a basis for heterogeneity: Higher education level was associated with lower Clinical Dementia Rating Scale sum of boxes (β = -0.19; P < .001), and frequent vs moderate neuritic plaques were associated with higher Clinical Dementia Rating Scale sum of boxes (β = 1.64; P < .001) and lower logical memory score (β = -1.07; P = .005). The rate of change of the clinical and cognitive scores varied depending on Braak stage, when adjusting for plaques, age of death, sex, education, and APOE genotype. For example, comparing high vs low Braak stage with other variables fixed, the logical memory score decreased a substantial 0.38 additional units per year (95%CI, -0.70 to -0.06; P = .02). Using these data, we estimate that a 300-participant clinical trial with end point of a 20% improvement in slope in rate of change of Clinical Dementia Rating Scale sum of boxes has 89%power when all participants in the trial are from the high Braak stage, compared with 29% power if Braak stage had not used for eligibility. CONCLUSIONS AND RELEVANCE We found that knowledge of neurofibrillary tangle stage, modeled as the sort of information that could be available from tau positron-emission tomography scans and its use to determine eligibility to a trial, could dramatically improve the power of clinical trials and equivalently reduce the required sample sizes of clinical trials.Soluble oligomeric amyloid-β induces calcium dyshomeostasis that precedes synapse loss in the living mouse brain
AbstractArbel-Ornath, M., Hudry, E., Boivin, J. R., Hashimoto, T., Takeda, S., Kuchibhotla, K. V., Hou, S., Lattarulo, C. R., Belcher, A. M., Shakerdge, N., Trujillo, P. B., Muzikansky, A., Betensky, R. A., Hyman, B. T., & Bacskai, B. J. (n.d.).Publication year
2017Journal title
Molecular NeurodegenerationVolume
12Issue
1AbstractBackground: Amyloid-β oligomers (oAβ) are thought to mediate neurotoxicity in Alzheimer’s disease (AD), and previous studies in AD transgenic mice suggest that calcium dysregulation may contribute to these pathological effects. Even though AD mouse models remain a valuable resource to investigate amyloid neurotoxicity, the concomitant presence of soluble Aβ species, fibrillar Aβ, and fragments of amyloid precursor protein (APP) complicate the interpretation of the phenotypes. Method: To explore the specific contribution of soluble oligomeric Aβ (oAβ) to calcium dyshomeostasis and synaptic morphological changes, we acutely exposed the healthy mouse brain, at 3 to 6 months of age, to naturally occurring soluble oligomers and investigated their effect on calcium levels using in vivo multiphoton imaging. Results: We observed a dramatic increase in the levels of neuronal resting calcium, which was dependent upon extracellular calcium influx and activation of NMDA receptors. Ryanodine receptors, previously implicated in AD models, did not appear to be primarily involved using this experimental setting. We used the high resolution cortical volumes acquired in-vivo to measure the effect on synaptic densities and observed that, while spine density remained stable within the first hour of oAβ exposure, a significant decrease in the number of dendritic spines was observed 24 h post treatment, despite restoration of intraneuronal calcium levels at this time point. Conclusions: These observations demonstrate a specific effect of oAβ on NMDA-mediated calcium influx, which triggers synaptic collapse in vivo. Moreover, this work leverages a method to quantitatively measure calcium concentration at the level of neuronal processes, cell bodies and single synaptic elements repeatedly and thus can be applicable to testing putative drugs and/or other intervention methodologies.A concept-wide association study of clinical notes to discover new predictors of kidney failure
Comparison of urine output among patients treated with more intensive versus less intensive RRT: Results from the acute renal failure trial network study
Decreased hippocampal metabolism in high-amyloid mild cognitive impairment
Episodic memory of odors stratifies Alzheimer biomarkers in normal elderly
AbstractDhilla Albers, A., Asafu-Adjei, J., Delaney, M. K., Kelly, K. E., Gomez-Isla, T., Blacker, D., Johnson, K. A., Sperling, R. A., Hyman, B. T., Betensky, R. A., Hastings, L., & Albers, M. W. (n.d.).Publication year
2016Journal title
Annals of NeurologyVolume
80Issue
6Page(s)
846-857AbstractObjective: The objective of this study was to relate a novel test of identifying and recalling odor percepts to biomarkers of Alzheimer's disease (AD) in well-characterized elderly individuals, ranging from cognitively normal to demented. Methods: One hundred eighty-three participants (cognitively normal: n = 70; subjective cognitive concerns: n = 74; mild cognitive impairment [MCI]: n = 29, AD dementia: n = 10) were administered novel olfactory tests: the Odor Percept IDentification (OPID) and the Percepts of Odor Episodic Memory (POEM) tests. Univariate cross-sectional analyses of performance across diagnoses; logistic regression modeling, including covariates of age, sex, education, APOE genotype, and neuropsychological test scores; and linear mixed modeling of longitudinal cognitive scores were performed. Amyloid deposition and MRI volumetrics were analyzed in a subset of participants. Results: Accuracy of identification and episodic memory of odor percepts differed significantly across diagnosis and age, with progressively worse performance across degrees of impairment. Among the participants who were cognitively normal or had subjective cognitive concerns, poorer than expected performance on the POEM test (based on the same individual's performance on the OPID and odor discrimination tests) was associated with higher frequencies of the APOE ε4 allele, thinner entorhinal cortices, and worse longitudinal trajectory of Logical Memory scores. Interpretation: Selective impairment of episodic memory of odor percepts, relative to identification and discrimination of odor percepts revealed by this novel POEM battery, is associated with biomarkers of AD in a well-characterized pre-MCI population. These affordable, noninvasive olfactory tests offer potential to identify clinically normal individuals who have greater likelihood of future cognitive decline. Ann Neurol 2016;80:846–857.Maternal dementia age at onset in relation to amyloid burden in non-demented elderly offspring
Multiple imputation of a randomly censored covariate improves logistic regression analysis
Optimization of Signal Decomposition Matched Filtering (SDMF) for Improved Detection of Copy-Number Variations
Plaque-associated local toxicity increases over the clinical course of Alzheimer disease
Retinal Dystrophy and Optic Nerve Pathology in the Mouse Model of Mucolipidosis IV
Tau positron emission tomographic imaging in aging and early Alzheimer disease
Thal amyloid stages do not significantly impact the correlation between neuropathological change and cognition in the Alzheimer disease continuum
Thioesterase superfamily member 1 suppresses cold thermogenesis by limiting the oxidation of lipid droplet-derived fatty acids in brown adipose tissue
A Pairwise Naïve Bayes Approach to Bayesian Classification
Accuracy of digital versus conventional implant impressions
APOEε2 is associated with milder clinical and pathological Alzheimer disease
Clinical pertinence metric enables hypothesis-independent genome-phenome analysis for neurologic diagnosis
Computationally simple analysis of matched, outcome-based studies of ordinal disease states
Matrix metalloproteinase 9-mediated intracerebral hemorrhage induced by cerebral amyloid angiopathy