Ryan O'Dell, MD, PhD
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About
Titles
Assistant Professor of Psychiatry
Biography
My passion for the pursuit of knowledge and scientific research has been a consistent and deep-rooted journey. As an undergraduate at the University of Rochester my scientific inquires took shape as a four-year research project in which I investigated how the primate brain coordinates complex muscle sets to achieve delicate hand and finger movements. As an MD/PhD candidate at SUNY Upstate, I used multiphoton live imaging techniques in an ex utero explant mouse model, investigating the role of the extracellular matrix protein Reelin in the dynamic properties of the emerging neurite arbor in early cortical development.
As a current PGY4 in the Yale Neuroscience Research Training Program, it is my ultimate goal to pursue a fellowship and eventual career in Geriatric Psychiatry, with a focus on Alzheimer’s disease and related neurocognitive disorders. Although it was my passion for the science that initially captivated me, it was not until I spent time in a Neurocognitive Clinic as a medical student and first sat with patients and their loved ones as they learned of this life-altering diagnosis, that I came to appreciate how the bench connects to the bedside.
To that end, throughout my time in the NRTP I have been working with Christopher van Dyck, MD and Adam Mecca, MD/PhD at the Alzheimer’s Disease Research Unit (ADRU), a clinical research unit specializing in Alzheimer’s disease, cognitive disorders, and aging research. Under this dual mentorship I have subsequently accumulated the technical tools, skills, and knowledge base necessary to collect, analyze, and interpret data gathered from the variety of ongoing multimodal neuroimaging studies (PET, MRI, fMRI) and clinical trials at the ADRU. Generally, I am interested in the investigation of novel neuroimaging biomarkers across the continuum of Alzheimer’s disease, spanning the preclinical to clinical stages of dementia. Such studies are essential for not only a more comprehensive understanding of disease pathogenesis and progression, but for the development of novel neuroimaging biomarkers for earlier diagnosis and intervention, tracking of disease progression, and monitoring of therapeutic efficacy in treatment studies.
I am currently involved in a variety of ongoing cross-sectional and longitudinal studies in the early stages of Alzheimer’s disease using a promising PET biomarker of synaptic density, [11C]UCB-J, which binds synaptic vesicle glycoprotein 2 (SV2A). Our goals include not only characterizing the spatiotemporal distribution of synaptic alterations across the continuum of disease (including preclinical, i.e. cognitively unimpaired but biomarker positive, cohorts), but determining the relationship of said synaptic alterations with other neuroimaging markers of disease progression, including amyloid/tau accumulation and glucose hypometabolism, respectively assessed by [11C]PiB, [18F]MK6240, and [18F]FDG PET.
My long-term career goals include becoming not only a competent and compassionate practicing Geriatric Psychiatrist, but an independently funded investigator in the fields of Alzheimer’s disease molecular neuroimaging and clinical trial design. In my free time I enjoy hiking the Connecticut trail systems and exploring the myriad craft breweries our state has to offer.
Appointments
Psychiatry
Assistant ProfessorPrimary
Other Departments & Organizations
Education & Training
- Geriatric Psychiatry Fellow
- Yale University School of Medicine (2022)
- Psychiatry Resident
- Yale University School of Medicine (2021)
- MD
- SUNY Upstate Medical University (2017)
- PhD
- SUNY Upstate Medical University (2017)
- BS
- University of Rochester, Neuroscience (2007)
- BA
- University of Rochester, Department of Modern Languages and Cultures/Spanish (2007)
Research
Publications
2025
Cerebrospinal fluid and brain positron emission tomography measures of synaptic vesicle glycoprotein 2A: Biomarkers of synaptic density in Alzheimer's disease
Mecca A, Ashton N, Chen M, O'Dell R, Toyonaga T, Zhao W, Young J, Salardini E, Bates K, Ra J, Goodcase S, Silva‐Rudberg J, Nabulsi N, Brinkmalm A, Kvartsberg H, Schöll M, Nilsson J, Arnsten A, Huang Y, Hansson O, Zetterberg H, Carson R, Blennow K, van Dyck C. Cerebrospinal fluid and brain positron emission tomography measures of synaptic vesicle glycoprotein 2A: Biomarkers of synaptic density in Alzheimer's disease. Alzheimer's & Dementia 2025, 21: e70344. PMID: 40491249, PMCID: PMC12149441, DOI: 10.1002/alz.70344.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2APositron emission tomographyAlzheimer's diseaseSynaptic densityEnzyme-linked immunosorbent assayC]UCB-J positron emission tomographyPositron emission tomography measurementsEmission tomographyAxonal proteinsCN participantsImmunosorbent assaySymptomatic Alzheimer's diseaseAD groupProteinAssayParticipantsSV2AAlzheimerCerebrospinal fluidBrainInvestigate associationsCerebrospinal fluid assaysSV2A positron emission tomographyAssessment of the relationship between synaptic density and metabotropic glutamate receptors in early Alzheimer’s disease: a multi-tracer PET study
Salardini E, O’Dell R, Tchorz E, Nabulsi N, Huang Y, Carson R, van Dyck C, Mecca A. Assessment of the relationship between synaptic density and metabotropic glutamate receptors in early Alzheimer’s disease: a multi-tracer PET study. Alzheimer's Research & Therapy 2025, 17: 98. PMID: 40329311, PMCID: PMC12054321, DOI: 10.1186/s13195-025-01739-1.Peer-Reviewed Original ResearchConceptsDistribution volume ratioMedial temporal lobePositron emission tomographyTemporal lobeSynaptic densityMetabotropic glutamate receptor subtype 5Multi-tracer PET studiesAlzheimer's diseaseCerebellum reference regionAmyloid-positive participantsSynaptic lossSynaptic vesicle glycoprotein 2AMetabotropic glutamate receptorsPositron emission tomography scanNeocortical regionsSubtype 5MGluR5Entorhinal cortexAD groupReference regionGlutamate receptorsExploratory analysisWidespread reductionsLongitudinal studyReceptor bindingGenerating synthetic brain PET images of synaptic density based on MR T1 images using deep learning
Zheng X, Worhunsky P, Liu Q, Guo X, Chen X, Sun H, Zhang J, Toyonaga T, Mecca A, O’Dell R, van Dyck C, Angarita G, Cosgrove K, D’Souza D, Matuskey D, Esterlis I, Carson R, Radhakrishnan R, Liu C. Generating synthetic brain PET images of synaptic density based on MR T1 images using deep learning. EJNMMI Physics 2025, 12: 30. PMID: 40163154, PMCID: PMC11958861, DOI: 10.1186/s40658-025-00744-5.Peer-Reviewed Original ResearchCannabis use disorderStructural similarity indexPET imagingImages of higher qualityMR-T1 imagesMean square errorUse disorderEncoder-decoderDeep learningCross-validation processData-driven approachDiagnostic categoriesLow-dose scansPredicted imageTemporal regionsBrain disordersGround truthT1-weighted MRISynaptic densityHuman brainSimilarity indexDisordersSevere neurological disordersTranslation accuracyNoise reductionSUSCEPTIBLE PYRAMIDAL NEURONS IN PRIMATE DORSOLATERAL PREFRONTAL CORTEX EXPRESS AN ENRICHED CALCIUM INTERACTOME: CRITICAL ROLE OF CALBINDIN AND CAV1.2 IN HIGHER-ORDER COGNITION
Datta *, Yang S, Joyce M, Woo E, McCarroll S, Gonzalez-Burgos G, Perone I, Uchendu S, Ling E, Goldman R, Berretta S, Murray J, Morozov Y, Arellano J, Duque A, Rakic P, O'dell R, van Dyck C, Lewis D, Wang M, Krienen F, Arnsten A. SUSCEPTIBLE PYRAMIDAL NEURONS IN PRIMATE DORSOLATERAL PREFRONTAL CORTEX EXPRESS AN ENRICHED CALCIUM INTERACTOME: CRITICAL ROLE OF CALBINDIN AND CAV1.2 IN HIGHER-ORDER COGNITION. The International Journal Of Neuropsychopharmacology 2025, 28: i57-i58. PMCID: PMC11814899, DOI: 10.1093/ijnp/pyae059.100.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexMacaque dlPFCPrefrontal cortexWorking memoryLayer 3 pyramidal cellsAlzheimer s diseasePrefrontal cortex dysfunctionExpression of Grin2bPyramidal cellsHigher-order cognitionIncreased risk of mental disordersRisk of neuropsychiatric disordersDendritic spine pathologyRisk of mental disordersIncreased risk of neuropsychiatric disordersL-type calcium channel Cav1.2Primate dlPFCDLPFC functionCognitive deficitsLayer III pyramidal cellsMemory impairmentPsychiatric disordersBrain circuitryNeuropsychiatric disordersMental representations
2024
Connectivity as a universal predictor of tau spreading in typical and atypical Alzheimer’s disease
de Bruin H, Groot C, ADNI, Barthel H, Bischof G, Boellaard R, Brendel M, Cash D, Coath W, Day G, Dickerson B, Doering E, Drzezga A, van Dyck C, van Eimeren T, van der Flier W, Fredericks C, Fryer T, van de Giessen E, Gordon B, Graff‐Radford J, Hobbs D, Höglinger G, Hönig M, Irwin D, Jones P, Josephs K, Katsumi Y, Lee E, Levin J, Malpetti M, McGinnis S, Mecca A, Nasrallah I, O'Brien J, O'Dell R, Palleis C, Perneczky R, Phillips J, Pijnenburg Y, Putcha D, Rahmouni N, Rosa‐Neto P, Rowe J, Rullmann M, Sabri O, Saur D, Schildan A, Schott J, Schroeter M, Servaes S, Sintini I, Stevenson J, Therriault J, Touroutoglou A, Trainer A, Visser D, Weston P, Whitwell J, Wolk D, Franzmeier N, Ossenkoppele R. Connectivity as a universal predictor of tau spreading in typical and atypical Alzheimer’s disease. Alzheimer's & Dementia 2024, 20: e085869. PMCID: PMC11714601, DOI: 10.1002/alz.085869.Peer-Reviewed Original ResearchAlzheimer's diseaseTau spreadingProgression of Alzheimer's diseaseTau-PETFunctional proximityPosterior patterningAD variantsTauPersonalized medicineTau-PET standardized uptake value ratiosVariantsWidespread patternAtypical ADDominant patternAtypical Alzheimer's diseaseRegionNeurodegenerationPositive probabilityPatternsConnectivity as a universal predictor of tau spreading in typical and atypical Alzheimer’s disease
de Bruin H, Groot C, ADNI, Barthel H, Bischof G, Boellaard R, Brendel M, Cash D, Coath W, Day G, Dickerson B, Doering E, Drzezga A, van Dyck C, van Eimeren T, van der Flier W, Fredericks C, Fryer T, van de Giessen E, Gordon B, Graff‐Radford J, Hobbs D, Höglinger G, Hönig M, Irwin D, Jones P, Josephs K, Katsumi Y, Lee E, Levin J, Malpetti M, McGinnis S, Mecca A, Nasrallah I, O'Brien J, O'Dell R, Palleis C, Perneczky R, Phillips J, Pijnenburg Y, Putcha D, Rahmouni N, Rosa‐Neto P, Rowe J, Rullmann M, Sabri O, Saur D, Schildan A, Schott J, Schroeter M, Servaes S, Sintini I, Stevenson J, Therriault J, Touroutoglou A, Trainer A, Visser D, Weston P, Whitwell J, Wolk D, Franzmeier N, Ossenkoppele R. Connectivity as a universal predictor of tau spreading in typical and atypical Alzheimer’s disease. Alzheimer's & Dementia 2024, 20: e093663. PMCID: PMC11713789, DOI: 10.1002/alz.093663.Peer-Reviewed Original ResearchAlzheimer's diseaseTau spreadingProgression of Alzheimer's diseaseTau-PETFunctional proximityPosterior patterningAD variantsTauPersonalized medicineTau-PET standardized uptake value ratiosVariantsWidespread patternAtypical ADDominant patternAtypical Alzheimer's diseaseRegionNeurodegenerationPatternsSelf‐reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort
Miller A, Sharp E, Wang S, Zhao Y, Mecca A, van Dyck C, O'Dell R, Initiative F. Self‐reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort. Alzheimer's & Dementia 2024, 20: 7847-7858. PMID: 39324520, PMCID: PMC11567835, DOI: 10.1002/alz.14252.Peer-Reviewed Original ResearchSelf-reported hearing lossFunctional Activities QuestionnaireHearing lossMild cognitive impairmentModifiable risk factorsMild cognitive impairment participantsFunctional declineImpairment diagnosisModified Preclinical Alzheimer Cognitive CompositeRate of functional declineRate of cognitive declinePreclinical Alzheimer Cognitive CompositeRisk factorsCognitive impairmentSignificant longitudinal associationsActivity QuestionnaireLongitudinal associationsAlzheimer's Disease Neuroimaging InitiativeLongitudinal relationshipCognitive compositeCN participantsIncreased riskCognitive declineParticipantsDiagnostic conversionValidation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET
Young J, O’Dell R, Naganawa M, Toyonaga T, Chen M, Nabulsi N, Huang Y, Cooper E, Miller A, Lam J, Bates K, Ruan A, Nelsen K, Salardini E, Carson R, van Dyck C, Mecca A. Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET. Journal Of Nuclear Medicine 2024, 65: jnumed.124.267419. PMID: 39299782, PMCID: PMC11533916, DOI: 10.2967/jnumed.124.267419.Peer-Reviewed Original ResearchDistribution volume ratioSUV ratioSynaptic densityEffect sizeAlzheimer's diseaseLongitudinal study of Alzheimer's diseaseMethods:</b> ParticipantsLongitudinal studyMeasure synaptic densityAD participantsStudy of Alzheimer's diseaseNormal cognitionReference regionOlder adultsMulticenterDensity alterationsKey Roles of CACNA1C/Cav1.2 and CALB1/Calbindin in Prefrontal Neurons Altered in Cognitive Disorders
Datta D, Yang S, Joyce M, Woo E, McCarroll S, Gonzalez-Burgos G, Perone I, Uchendu S, Ling E, Goldman M, Berretta S, Murray J, Morozov Y, Arellano J, Duque A, Rakic P, O’Dell R, van Dyck C, Lewis D, Wang M, Krienen F, Arnsten A. Key Roles of CACNA1C/Cav1.2 and CALB1/Calbindin in Prefrontal Neurons Altered in Cognitive Disorders. JAMA Psychiatry 2024, 81: 870-881. PMID: 38776078, PMCID: PMC11112502, DOI: 10.1001/jamapsychiatry.2024.1112.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexPrefrontal cortexLayer III pyramidal cellsWorking memoryCognitive disordersNeuronal firingPrimate dorsolateral prefrontal cortexPyramidal cellsSpatial working memoryWorking memory performanceRisk of mental disordersCalcium-related proteinsReduced neuronal firingL-type calcium channel Cav1.2GluN2B-NMDA receptorsL-type calcium channel activityPrefrontal neuronsL-type calcium channel blockerMemory performanceL-type calcium channelsMental disordersRisk of cognitive disordersCognitive behaviorProtein expressionAssociated with increased riskCommentary on “Study Partner Report of Apathy in Older Adults is Associated With AD Biomarkers: Findings From the Harvard Aging Brain Study”
Khasnavis S, O'Dell R, van Dyck C, Mecca A. Commentary on “Study Partner Report of Apathy in Older Adults is Associated With AD Biomarkers: Findings From the Harvard Aging Brain Study”. American Journal Of Geriatric Psychiatry 2024, 32: 920-921. PMID: 38658231, DOI: 10.1016/j.jagp.2024.03.017.Peer-Reviewed Original Research
Academic Achievements & Community Involvement
Clinical Care
Overview
Ryan O’Dell, MD, PhD, is a geriatric psychiatrist who specializes in the evaluation and management cognitive disorders, particularly Alzheimer’s disease.
He says he was drawn to the field of Alzheimer’s disease and related dementias because there is still much to learn about them. Recent breakthroughs, such as the Food and Drug Administration’s approval of lecanemab (brand name: Leqembi), a medication shown to slow the progression of the early stages of Alzheimer’s disease, has been an exciting new development in this field, he adds.
Dr. O’Dell says he practices a family-centered approach. “I think the involvement of families and their support systems in the evaluation and management of cognitive disorders is a very important part of the process, whether it’s a spouse or an adult child, or whoever the patient is comfortable bringing to an appointment,” he says. “Another important aspect of the evaluation of cognitive disorders is addressing any changes in mood and behavior, such as anxiety and depression, which are frequently seen with advancing neurodegenerative disease, and sometimes may even precede cognitive or functional decline.”
He says it’s also important for him to take things slow and develop rapport when he first meets a patient and their family.
“Unless someone is coming to me who is transferring care and there’s a clear-cut, pre-established workup, we don’t jump to conclusions surrounding a diagnosis,” he says. “If someone is experiencing new memory changes, we need to first do a comprehensive diagnostic workup. I am transparent and take a gentle approach. I do share what I’m worried about and keep everyone in the loop. I might say, ‘We don’t have a diagnosis yet, but here’s what we have to do to get one.’”
In addition, Dr. O’Dell says he keeps the patient’s and family’s perspectives, values, and goals of care in mind throughout the evaluation and treatment process.
“It’s important to consider that some diagnostic procedures may be too invasive or not tolerated because of age, active medical conditions, or even significant anxiety or agitation, and we should therefore take a different approach to the workup, one that both the patient and their family feel most comfortable with,” he says.
Dr. O’Dell’s research interests include using brain imaging (PET and MRI) to study the underlying pathophysiological changes in people with symptomatic and pre-symptomatic Alzheimer’s disease. He is also involved in several Alzheimer’s disease clinical trials through the Yale Alzheimer’s Disease Research Unit (ADRU). For more information surrounding ongoing clinical trials and observational neuroimaging studies in Alzheimer’s disease, call (203) 764-8100.
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Alzheimer's Disease Research Unit
Yale School of Medicine, One Church Street
New Haven, CT 06510
United States
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New Haven, CT 06510
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