Bio


Dr. Marks received an Honors Bachelor of Science degree in Biology from Marquette University and his Medical Degree from the Johns Hopkins University School of Medicine. He completed his neurology residency and fellowship at the University of California, San Francisco (UCSF). Dr. Marks also holds a Master of Science in Health Care Management degree from the Harvard School of Public Health.

Dr. Marks is Board Certified in Neurology and Clinical Neurophysiology. Prior to joining the Stanford Faculty, he served as Professor of Neurology at UCSF. His clinical and research interests include movement disorders, epilepsy, neuromodulation, health technology, and health care policy.

Dr. Marks also serves as Head of Clinical Neurology at Verily Life Sciences, formerly Google Life Sciences—a translational research and engineering organization focused on improving healthcare by applying scientific and technological advances to significant problems in health and biology. At Verily, Dr. Marks is responsible for developing and implementing strategies and initiatives that will advance the understanding of neurological disorders to ultimately improve patient outcomes.

All Publications


  • Biological and clinical correlates of the patient health questionnaire-9: exploratory cross-sectional analyses of the baseline health study. BMJ open Califf, R. M., Wong, C., Doraiswamy, P. M., Hong, D. S., Miller, D. P., Mega, J. L. 2022; 12 (1): e054741

    Abstract

    We assessed the relationship between the Patient Health Questionnaire-9 (PHQ-9) at intake and other measurements intended to assess biological factors, markers of disease and health status.We performed a cross-sectional analysis of 2365 participants from the Baseline Health Study, a prospective cohort of adults selected to represent major demographic groups in the USA. Participants underwent deep phenotyping on demographic, clinical, laboratory, functional and imaging findings.Despite extensive research on the clinical implications of the PHQ-9, data are limited on the relationship between PHQ-9 scores and other measures of health and disease; we sought to better understand this relationship.None.Cross-sectional measures of medical illnesses, gait, balance strength, activities of daily living, imaging and laboratory tests.Compared with lower PHQ-9 scores, higher scores were associated with female sex (46.9%-66.7%), younger participants (53.6-42.4 years) and compromised physical status (higher resting heart rates (65 vs 75 bpm), larger body mass index (26.5-30 kg/m2), greater waist circumference (91-96.5 cm)) and chronic conditions, including gastro-oesophageal reflux disease (13.2%-24.7%) and asthma (9.5%-20.4%) (p<0.0001). Increasing PHQ-9 score was associated with a higher frequency of comorbidities (migraines (6%-20.4%)) and active symptoms (leg cramps (6.4%-24.7%), mood change (1.2%-47.3%), lack of energy (1.2%-57%)) (p<0.0001). After adjustment for relevant demographic, socioeconomic, behavioural and medical characteristics, we found that memory change, tension, shortness of breath and indicators of musculoskeletal symptoms (backache and neck pain) are related to higher PHQ-9 scores (p<0.0001).Our study highlights how: (1) even subthreshold depressive symptoms (measured by PHQ-9) may be indicative of several individual- and population-level concerns that demand more attention; and (2) depression should be considered a comorbidity in common disease.NCT03154346.

    View details for DOI 10.1136/bmjopen-2021-054741

    View details for PubMedID 34983769

  • Predictors of multi-domain cognitive decline following DBS for treatment of Parkinson's disease. Parkinsonism & related disorders Rothlind, J. C., York, M. K., Luo, P., Carlson, K., Marks, W. J., Weaver, F. M., Stern, M., Follett, K. A., Duda, J. E., Reda, D. J., CSP-468 study group, Follett, K., Stern, M., Weaver, F., Ippolito, D., Stoner, G., Barnett, T., Bukowski, K., DeNicolo, R., Hur, K., Jimenez, J., Luo, P., Motyka, J., Reda, D., Simon, T., Thakkar, B., Woolson, R., Fye, C., Gagne, W., Harris, C., Heemskerk, J., Moy, C., Sheehy, P., O'Leary, T., Huang, G. D., Fiore, L., Hall, R., Stroupe, K., Burchiel, K., Follett, K., Fye, C., Harris, C., Heemskerk, J., Hur, K., Koller, W., Marks, W. J., Moy, C., Pahwa, R., Reda, D., Rothlind, J., Sagher, O., Sheehy, P., Stern, M., Weaver, F., Bakay, R., Chappell, R., Hart, R., Holloway, R. J., McCabe, G., Schenkman, M., Taha, J., Buckelew, J., Fye, C., Garin, M., Matzek, S., Smith, D., Bronstein, J., Duda, J., Hogarth, P., Holloway, K., Horn, S., Lai, E. C., Marks, W. J., Samii, A., Farah Atassi, Bello, C., Bunting-Perry, L., Conn, T., Cugley, A., Eubank, N., Fincher, L., Franks, R., Harris, T., Haselman, M., Heath, S., Hirsch, M., Janovsky, V., Lanier, E., Lloyd, M., Loehner, S., O'Connor, S., Ordonez, L., Maccarone, H., Massey-Makhoul, K., Matthews, M., Meyn, E., Mimura, K., Morrow, W., Searles, T., Valotta, J., Vasthare, U., Volz, M., Ward, C., Warker, R., Watson, H., Willson, P., Baron, M., Brodsky, M., Calabrese, V., Campbell, G., Colcher, A., Farag, E., Henry, E., Hou, J., Kang, G., Kleiner-Fisman, G., Kraakevik, J., Nutt, J., Ostrem, J., Sarwar, A., Subramanian, I., Vanek, Z., Baltuch, G., Burchiel, K., De Salles, A., Eller, J., Holloway, K., Larson, P., Simpson, R., Starr, P., Carne, W., Erikson, T., Kreutzer, J., Mendez, M., Moberg, P., Ragland, J., Rothlind, J., Seel, R., Storzbach, D., Troster, A., York, M., Jaggi, J. 1800; 95: 23-27

    Abstract

    BACKGROUND: Statistically and clinically significant cognitive declines are observed in a small subset of individuals with Parkinson's Disease (PD) following treatment with Deep Brain Stimulation (DBS).OBJECTIVES: We examine the association between multi-domain cognitive decline (MCD) and demographic and baseline clinical variables and the incidence of serious adverse events (SAE) arising within a six-month interval following DBS for PD.METHOD: Study participants with PD who displayed MCD at 6-month follow-up evaluation after DBS (n=18) were contrasted with individuals with PD from the same study who did not show cognitive decline after DBS (n=146). Logistic regression analyses were employed to assess relationship between predictors, including age (>70 years old), pre-DBS cognitive screening test performance, SAE, and MCD. MCD+ and MCD-groups were also compared on other baseline clinical and demographic variables.RESULTS: MCD showed modest association with older age and lower baseline neurocognitive screening performance, whereas the groups did not differ on most other baseline clinical and demographic variables. SAEs during the study interval were the most robust predictor of MCD in the DBS group. A variety of SAEs were documented in study participants experiencing MCD after DBS surgery, including, but not limited to, infections and small intracranial hemorrhages.CONCLUSIONS: Older age and lower baseline cognition measured prior to treatment are associated with MCD measured at six-months after DBS. SAE occurring following DBS surgery are also predictive of MCD. These predictors may reflect aspects of "frailty" in advanced PD. Risk factors for SAE warrant careful consideration in clinical trials.

    View details for DOI 10.1016/j.parkreldis.2021.12.011

    View details for PubMedID 34974395

  • 10 Year Clinical Outcomes of Subthalamic Nucleus versus Pallidal Deep Brain Stimulation for Parkinson's Disease: VA/ NINDS CSP #468F Ostrem, J., Luo, P., Weaver, F., Follett, K., Galifianakis, N., Lai, E., Bronstein, J., Duda, J., Holloway, K., Sarwar, A., Brodsky, M., Chung, K., Spindler, M., Reda, D., Rothland, J., Snodgrass, A., Marks, W. LIPPINCOTT WILLIAMS & WILKINS. 2021
  • The Project Baseline Health Study: a step towards a broader mission to map human health NPJ DIGITAL MEDICINE Arges, K., Assimes, T., Bajaj, V., Balu, S., Bashir, M. R., Beskow, L., Blanco, R., Califf, R., Campbell, P., Carin, L., Christian, V., Cousins, S., Das, M., Dockery, M., Douglas, P. S., Dunham, A., Eckstrand, J., Fleischmann, D., Ford, E., Fraulo, E., French, J., Gambhir, S. S., Ginsburg, G. S., Green, R. C., Haddad, F., Hernandez, A., Hernandez, J., Huang, E. S., Jaffe, G., King, D., Koweek, L. H., Langlotz, C., Liao, Y. J., Mahaffey, K. W., Marcom, K., Marks, W. J., Maron, D., McCabe, R., McCall, S., McCue, R., Mega, J., Miller, D., Muhlbaier, L. H., Munshi, R., Newby, L., Pak-Harvey, E., Patrick-Lake, B., Pencina, M., Peterson, E. D., Rodriguez, F., Shore, S., Shah, S., Shipes, S., Sledge, G., Spielman, S., Spitler, R., Schaack, T., Swamy, G., Willemink, M. J., Wong, C. A. 2020; 3 (1): 84

    Abstract

    The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum. Enrolled participants will be evaluated serially using clinical, molecular, imaging, sensor, self-reported, behavioral, psychological, environmental, and other health-related measurements. An initial deeply phenotyped cohort will inform the development of a large, expanded virtual cohort. The PBHS will contribute to precision health and medicine by integrating state of the art testing, longitudinal monitoring and participant engagement, and by contributing to the development of an improved platform for data sharing and analysis.

    View details for DOI 10.1038/s41746-020-0290-y

    View details for Web of Science ID 000538242900001

    View details for PubMedID 32550652

    View details for PubMedCentralID PMC7275087

  • The Project Baseline Health Study: a step towards a broader mission to map human health. NPJ digital medicine Arges, K., Assimes, T., Bajaj, V., Balu, S., Bashir, M. R., Beskow, L., Blanco, R., Califf, R., Campbell, P., Carin, L., Christian, V., Cousins, S., Das, M., Dockery, M., Douglas, P. S., Dunham, A., Eckstrand, J., Fleischmann, D., Ford, E., Fraulo, E., French, J., Gambhir, S. S., Ginsburg, G. S., Green, R. C., Haddad, F., Hernandez, A., Hernandez, J., Huang, E. S., Jaffe, G., King, D., Koweek, L. H., Langlotz, C., Liao, Y. J., Mahaffey, K. W., Marcom, K., Marks, W. J., Maron, D., McCabe, R., McCall, S., McCue, R., Mega, J., Miller, D., Muhlbaier, L. H., Munshi, R., Newby, L. K., Pak-Harvey, E., Patrick-Lake, B., Pencina, M., Peterson, E. D., Rodriguez, F., Shore, S., Shah, S., Shipes, S., Sledge, G., Spielman, S., Spitler, R., Schaack, T., Swamy, G., Willemink, M. J., Wong, C. A. 2020; 3 (1): 84

    Abstract

    The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum. Enrolled participants will be evaluated serially using clinical, molecular, imaging, sensor, self-reported, behavioral, psychological, environmental, and other health-related measurements. An initial deeply phenotyped cohort will inform the development of a large, expanded virtual cohort. The PBHS will contribute to precision health and medicine by integrating state of the art testing, longitudinal monitoring and participant engagement, and by contributing to the development of an improved platform for data sharing and analysis.

    View details for DOI 10.1038/s41746-020-0290-y

    View details for PubMedID 33597683

  • Cost-Effectiveness of Deep Brain Stimulation for Advanced Parkinson's Disease in the United States NEUROMODULATION Pietzsch, J. B., Garner, A. M., Marks, W. J. 2016; 19 (7): 689-697

    Abstract

    Deep brain stimulation (DBS), which uses an implantable device to modulate brain activity, is clinically superior to medical therapy for treating advanced Parkinson's disease (PD). We studied the cost-effectiveness of DBS in conjunction with medical therapy compared to best medical therapy (BMT) alone, using the latest clinical and cost data for the U.S. healthcare system.We used a decision-analytic state-transition (Markov) model to project PD progression and associated costs for the two treatment strategies. We estimated the discounted incremental cost-effectiveness ratio (ICER) in U.S. dollars per quality-adjusted life-year (QALY) from the Medicare payer perspective, considering a ten-year horizon, and evaluated the robustness of our projections through extensive deterministic sensitivity analyses.Over ten years, DBS treatment led to discounted total costs of $130,510 compared to $91,026 for BMT and added 1.69 QALYs more than BMT, resulting in an ICER of $23,404 per QALY. This ICER was relatively insensitive to variations in input parameters, with neurostimulator replacement, costs for DBS implantation, and costs for treatment of disease-related falls having the greatest effects. Across all investigated scenarios, including a five-year horizon, ICERs remained under $50,000 per QALY. Longer follow-up periods and younger treatment age were associated with greater cost-effectiveness.DBS is a cost-effective treatment strategy for advanced PD in the U.S. healthcare system across a wide range of assumptions. DBS yields substantial improvements in health-related quality of life at a value profile that compares favorably to other well-accepted therapies.

    View details for DOI 10.1111/ner.12474

    View details for Web of Science ID 000385723600003

    View details for PubMedID 27491661

  • Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: A double-blind, randomized, controlled trial ANNALS OF NEUROLOGY Olanow, C. W., Bartus, R. T., Baumann, T. L., Factor, S., Boulis, N., Stacy, M., Turner, D. A., Marks, W., Larson, P., Starr, P. A., Jankovic, J., Simpson, R., Watts, R., Guthrie, B., Poston, K., Henderson, J. M., Stern, M., Baltuch, G., Goetz, C. G., Herzog, C., Kordower, J. H., Alterman, R., Lozano, A. M., Lang, A. E. 2015; 78 (2): 248-257

    Abstract

    A 12-month double-blind sham-surgery-controlled trial assessing adeno-associated virus type 2 (AAV2)-neurturin injected into the putamen bilaterally failed to meet its primary endpoint, but showed positive results for the primary endpoint in the subgroup of subjects followed for 18 months and for several secondary endpoints. Analysis of postmortem tissue suggested impaired axonal transport of neurturin from putamen to substantia nigra. In the present study, we tested the safety and efficacy of AAV2-neurturin delivered to putamen and substantia nigra.We performed a 15- to 24-month, multicenter, double-blind trial in patients with advanced Parkinson disease (PD) who were randomly assigned to receive bilateral AAV2-neurturin injected bilaterally into the substantia nigra (2.0 × 10(11) vector genomes) and putamen (1.0 × 10(12) vector genomes) or sham surgery. The primary endpoint was change from baseline to final visit performed at the time the last enrolled subject completed the 15-month evaluation in the motor subscore of the Unified Parkinson's Disease Rating Scale in the practically defined off state.Fifty-one patients were enrolled in the trial. There was no significant difference between groups in the primary endpoint (change from baseline: AAV2-neurturin, -7.0 ± 9.92; sham, -5.2 ± 10.01; p = 0.515) or in most secondary endpoints. Two subjects had cerebral hemorrhages with transient symptoms. No clinically meaningful adverse events were attributed to AAV2-neurturin.AAV2-neurturin delivery to the putamen and substantia nigra bilaterally in PD was not superior to sham surgery. The procedure was well tolerated, and there were no clinically significant adverse events related to AAV2-neurturin. Ann Neurol 2015;78:248-257.

    View details for DOI 10.1002/ana.24436

    View details for Web of Science ID 000358501600009

  • Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: A double-blind, randomized, controlled trial. Annals of neurology Warren Olanow, C., Bartus, R. T., Baumann, T. L., Factor, S., Boulis, N., Stacy, M., Turner, D. A., Marks, W., Larson, P., Starr, P. A., Jankovic, J., Simpson, R., Watts, R., Guthrie, B., Poston, K., Henderson, J. M., Stern, M., Baltuch, G., Goetz, C. G., Herzog, C., Kordower, J. H., Alterman, R., Lozano, A. M., Lang, A. E. 2015; 78 (2): 248-57

    Abstract

    A 12-month double-blind sham-surgery-controlled trial assessing adeno-associated virus type 2 (AAV2)-neurturin injected into the putamen bilaterally failed to meet its primary endpoint, but showed positive results for the primary endpoint in the subgroup of subjects followed for 18 months and for several secondary endpoints. Analysis of postmortem tissue suggested impaired axonal transport of neurturin from putamen to substantia nigra. In the present study, we tested the safety and efficacy of AAV2-neurturin delivered to putamen and substantia nigra.We performed a 15- to 24-month, multicenter, double-blind trial in patients with advanced Parkinson disease (PD) who were randomly assigned to receive bilateral AAV2-neurturin injected bilaterally into the substantia nigra (2.0 × 10(11) vector genomes) and putamen (1.0 × 10(12) vector genomes) or sham surgery. The primary endpoint was change from baseline to final visit performed at the time the last enrolled subject completed the 15-month evaluation in the motor subscore of the Unified Parkinson's Disease Rating Scale in the practically defined off state.Fifty-one patients were enrolled in the trial. There was no significant difference between groups in the primary endpoint (change from baseline: AAV2-neurturin, -7.0 ± 9.92; sham, -5.2 ± 10.01; p = 0.515) or in most secondary endpoints. Two subjects had cerebral hemorrhages with transient symptoms. No clinically meaningful adverse events were attributed to AAV2-neurturin.AAV2-neurturin delivery to the putamen and substantia nigra bilaterally in PD was not superior to sham surgery. The procedure was well tolerated, and there were no clinically significant adverse events related to AAV2-neurturin. Ann Neurol 2015;78:248-257.

    View details for DOI 10.1002/ana.24436

    View details for PubMedID 26061140

  • Inclusion and Exclusion Criteria for DBS in Dystonia MOVEMENT DISORDERS Bronte-Stewart, H., Taira, T., Valldeoriola, F., Merello, M., Marks, W. J., Albanese, A., Bressman, S., Moro, E. 2011; 26: S5-S16

    Abstract

    When considering a patient with dystonia for deep brain stimulation (DBS) surgery several factors need to be considered. Level B evidence has shown that all motor features and associated pain in primary generalized and segmental dystonia are potentially responsive to globus pallidus internus (GPi) DBS. However, improvements in clinical series of ≥ 90% may reflect methods that need improvement, and larger prospective studies are needed to address these factors. Nevertheless, to date the selection criteria for DBS-specifically in terms of patient features (severity and nature of symptoms, age, time of evolution, or any other demographic or disease aspects)--have not been assessed in a systematic fashion. In general, dystonia patients are not considered for DBS unless medical therapies have been previously and extensively tested. The vast majority of reported patients have had DBS surgery when the disease was provoking important disability, with loss of independence and impaired quality of life. There does not appear to be an upper age limit or a minimum age limit, although there are no published data regarding the outcome of GPi DBS for dystonia in children younger than 7 years of age. There is currently no enough evidence to prove that subjects with primary--generalized dystonia who undergo DBS at an early age and sooner rather than later after disease onset may gain more benefit from DBS than those undergoing DBS after the development of fixed skeletal deformities. There is no enough evidence to refuse or support consideration of DBS in patients with previous ablative procedures.

    View details for DOI 10.1002/mds.23482

    View details for Web of Science ID 000291866500003

    View details for PubMedID 21692112

  • Deep Brain Stimulation for Parkinson Disease An Expert Consensus and Review of Key Issues ARCHIVES OF NEUROLOGY Bronstein, J. M., Tagliati, M., Alterman, R. L., Lozano, A. M., Volkmann, J., Stefani, A., Horak, F. B., Okun, M. S., Foote, K. D., Krack, P., Pahwa, R., Henderson, J. M., Hariz, M. I., Bakay, R. A., Rezai, A., Marks, W. J., Moro, E., Vitek, J. L., Weaver, F. M., Gross, R. E., DeLong, M. R. 2011; 68 (2): 165-171

    Abstract

    To provide recommendations to patients, physicians, and other health care providers on several issues involving deep brain stimulation (DBS) for Parkinson disease (PD).An international consortium of experts organized, reviewed the literature, and attended the workshop. Topics were introduced at the workshop, followed by group discussion.A draft of a consensus statement was presented and further edited after plenary debate. The final statements were agreed on by all members.(1) Patients with PD without significant active cognitive or psychiatric problems who have medically intractable motor fluctuations, intractable tremor, or intolerance of medication adverse effects are good candidates for DBS. (2) Deep brain stimulation surgery is best performed by an experienced neurosurgeon with expertise in stereotactic neurosurgery who is working as part of a interprofessional team. (3) Surgical complication rates are extremely variable, with infection being the most commonly reported complication of DBS. (4) Deep brain stimulation programming is best accomplished by a highly trained clinician and can take 3 to 6 months to obtain optimal results. (5) Deep brain stimulation improves levodopa-responsive symptoms, dyskinesia, and tremor; benefits seem to be long-lasting in many motor domains. (6) Subthalamic nuclei DBS may be complicated by increased depression, apathy, impulsivity, worsened verbal fluency, and executive dysfunction in a subset of patients. (7) Both globus pallidus pars interna and subthalamic nuclei DBS have been shown to be effective in addressing the motor symptoms of PD. (8) Ablative therapy is still an effective alternative and should be considered in a select group of appropriate patients.

    View details for DOI 10.1001/archneurol.2010.260

    View details for Web of Science ID 000287330300003

    View details for PubMedID 20937936

  • Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy EPILEPSIA Fisher, R., Salanova, V., Witt, T., Worth, R., Henry, T., Gross, R., Oommen, K., Osorio, I., Nazzaro, J., Labar, D., Kaplitt, M., Sperling, M., Sandok, E., Neal, J., Handforth, A., Stern, J., DeSalles, A., Chung, S., Shetter, A., Bergen, D., Bakay, R., Henderson, J., French, J., Baltuch, G., Rosenfeld, W., Youkilis, A., Marks, W., Garcia, P., Barbaro, N., Fountain, N., Bazil, C., Goodman, R., McKhann, G., Krishnamurthy, K. B., Papavassiliou, S., Epstein, C., Pollard, J., Tonder, L., Grebin, J., Coffey, R., Graves, N. 2010; 51 (5): 899-908

    Abstract

    We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy.Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation.One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and "most severe" seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events.Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.

    View details for DOI 10.1111/j.1528-1167.2010.02536.x

    View details for PubMedID 20331461