Joshua D. Grill
Associate Professor, Psychiatry & Human Behavior
|Alzheimer's disease, clinical trials, recruitment and retention|
For any new Alzheimer’s disease drug to achieve FDA approval and widespread clinical use, it must be tested in human beings and demonstrated as both safe and efficacious. Studies to test the safety and efficacy of new treatments are called clinical trials. Clinical testing now represents the most costly and difficult phase of developing improved therapies. A major challenge of completing human clinical trials is the timely enrollment of participants who will enable adequate examination of therapeutic hypotheses. Alzheimer’s disease clinical trials now enroll people with Alzheimer’s dementia, people with mild cognitive impairment, and people with healthy memories but who are at increased risk to some day develop dementia. We are engaged in a variety of studies that aim to
• Identify means to improve Alzheimer’s disease clinical trial designs to enable adequate testing in fewer participants,
• Elucidate barriers to clinical trial enrollment in each Alzheimer’s disease population, so that trials and recruitment campaigns can be designed in a manner that maximizes the speed of accrual,
• Understand better which participants are at risk to be lost to follow-up, to guide clinician scientists when enrolling participants in Alzheimer’s disease trials, and
• Investigate the ethical challenges in clinical trials, especially those related to Alzheimer’s disease disclosure, including the disclosure of diagnosis, biomarker results, and genetic testing.
|Publications||Grill JD, Cox CG, Kremen S, Mendez MF, Teng E, Shapira J, Ringman JM, Apostolova LG. Patient and caregiver reactions to clinical amyloid imaging. Alzheimer’s & Dementia. 2017 Feb 4. pii: S1552-5260(17)30005-5. doi: 10.1016/j.jalz.2017.01.001. [Epub ahead of print].|
|Grill JD, Holbrook A, Pierce A, Hoang D, Gillen D. Attitudes toward potential participant registries. Journal of Alzheimer’s Disease. 2017;56(3):939-946. doi: 10.3233/JAD-160873. PMID: 28106553.|
|Lin Y, Brook J, Grill JD, Teng E. Participant-informant relationships affect quality of life ratings in incipient and clinical Alzheimer disease. Am J Geriatr Psychiatry. 2016: S1064-7481(16)30273-1. PMID: 27818119.|
|Zhou Y, Elashoff D, Kremen S, Teng E, Karlawish J, Grill JD. African Americans are less likely to enroll in preclinical Alzheimer's disease clinical trials. Alzheimer’s & Dementia: Translational Research and Clinical Interventions. Accepted.|
Chang T, Teng E, Grill JD for the Alzheimer’s Disease Neuroimaging Initiative. Optimizing effect sizes with imaging enrichment and outcome choices for mild Alzheimer’s disease clinical trials. Alzheimer’s Disease and Associated Disorders. Accepted.
Grill JD, Zhou Y, Elsashoff D, Karlawish, J. Disclosure of amyloid status is not a barrier to recruitment in preclinical Alzheimer’s disease clinical trials. Neurobiol Aging. Accepted.
Coric V, Salloway S, van Dyck CH, Dubois B, Andreasen N, Brody M, Curtis C, Soininen H, Thein S, Shiovitz T, Pilcher G, Ferris S, Colby S, Kerselaers W, Dockens R, Soares H, Kaplita S, Luo F, Pachai C, Bracoud L, Mintun M, Grill JD, Marek K, Seibyl J, Cedarbaum JM, Albright C, Feldman HH, Berman RM. Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial. JAMA Neurology. 2015. Epub ahead of print. PMID: 26414022.
Grill JD, Karlawish, J. Consider the source: the implications of informant type on outcome assessments. Alzheimer’s Disease Associated Disorders. Accepted. PMID: 26485500.
Grill JD, Bateman RJ, Buckles V, Oliver A, Morris JC, Masters CL, Klunk WE, Ringman, JM for the Dominantly Inherited Alzheimer’s Network. A survey of attitudes toward clinical trials and genetic disclosure in autosomal dominant Alzheimer's disease. Alzheimer’s Research and Therapy. 2015;7(1):50.
Henley DB, Dowsett SA, Chen YF, Liu-Seifert H, Grill JD, Doody RS, Aisen P, Raman R, Miller DS, Hake AM, Cummings JL. Alzheimer’s disease progression by geographical region in a clinical trial setting. Alzheimer’s Research and Therapy. 2015;7:43. PMID: 26120369. PMCID: PMC4481070
Grill JD, Raman R, Ernstrom K, Aisen P, Dowsett SA, Chen YF, Liu-Seifert H, Hake AM, Miller DS, Doody RS, Henley DB, Cummings JL. Comparing recruitment, retention, and safety reporting among geographic regions in multinational Alzheimer’s disease clinical trials. Alzheimer’s Research and Therapy. 2015;7:39. PMID: 26120368. PMCID: PMC4481112
Harkins K, Healy M, Sankar P, Sperling R, Grill JD, Green RC, Karlawish J. Development of a Process to Disclose Amyloid Imaging Results to Cognitively Normal Older Adult Research Participants. Alzheimer’s Research and Therapy. 2015:7;26. PMID: 2596999.
Grill JD, Vinters H, Monsell S. Does Alzheimer's disease pathologic change underlie subjective cognitive complaints? Alzheimer’s Disease Associated Disorders. 2015 Epub ahead of print. PMID: 25973910.
Grill JD, Zhou Y, Karlawish J, Elashoff D. Frequency and impact of informant replacement in Alzheimer's disease research. Alzheimer’s Disease Associated Disorders. 2014 Dec 3 Epub ahead of print. PMID: 25551863.
Jennings LA, Reuben DB, Evertson LC, Serrano KS, Ercoli L, Grill J, Chodosh J, Tan Z, Wenger NS. Unmet Needs of Caregivers of Patients Referred to a Dementia Care Program. Journal of the American Geriatric Society. 2015;63:282-289. PMID: 25688604. PMCID: PMC4332558.
Hsiao J, Lu P, Grill JD, Teng E. Longitudinal Declines in Instrumental Activities of Daily Living in Stable and Progressive Mild Cognitive Impairment. Dementia & Geriatric Cognitive Disorders. 2015;39:12-24. PMID: 25300404.
Cary MS, Rubright JD, Grill JD, Karlawish J. Why are spouse caregivers more prevalent than nonspousal caregivers as study partners in AD dementia clinical trials? Alzheimer’s Disease and Associated Disorders. May 6. Epub ahead of print. PMID: 24805971.
Grill JD, Galvin J. Facilitating Alzheimer’s disease research recruitment. Alzheimer’s Disease and Associated Disorders. 2014;28(1):1-8. PMID: 24322484. PMCID: PMC3945167.
Grill JD, Monsell SE. Choosing Alzheimer’s disease prevention clinical trial populations. Neurobiol Aging. 2014;35(3):466-71. PMID: 241195446. PMCID: PMC3864603.
Grill JD, Zhou Y, Karlawish J, Elashoff D. Does study partner type impact the rate of Alzheimer’s disease progression? Journal of Alzheimer’s Disease. 2014;38(3):507-14. PMID: 23985417. PMCID: PMC3842422
Kohannim O, Hua X, Rajagopolan P, Hibar DP, Jahanshad N, Grill JD, Apostolova L, Toga AW, Jack CR, Weiner MW, Thompson PM, for the Alzheimer’s Disease Neuroimaging Initiative. Multilocus genetic profiling to empower drug trials and predict brain atrophy. NeuroImage: Clinical. 2013;2:827-35. PMCID: PMC3777716.
Hooper M, Grill JD, Rodriguez-Agudelo Y, Medina LD, Fox M, Alvarez-Retuerto AI, Wharton D, Brook J, Ringman JM. The Impact of the Availability of Prevention Studies on the Desire to Undergo Predictive Testing in Persons at-risk for Autosomal Dominant Alzheimer's Disease. Contemp Clin Trials. 2013;36(1):256-62. PMID: 23876673. PMCID: PMC3858206.
Grill JD, Johnson DK, Burns JM. Should we disclose amyloid imaging results to cognitively normal individuals? Neurodegenerative Disease Management. 2013;3(1)43-51.
Grill JD, Raman R, Ernstrom K, Aisen P, Karlawish J. Study partner impact on Alzheimer’s disease clinical trials. Neurology. 2013;80(3):282-8. PMID:23255824. PMCID: PMC3589183.
Grill JD, Karlawish J, Elashoff D, Vickrey BG. Risk disclosure and preclinical Alzheimer’s disease clinical trial enrollment. Alzheimer’s & Dementia: Journal of the Alzheimer’s Association. 2013;9(3):356-359. PMID: 23141383. PMCID: PMC3572336.
Grill JD, Di L, Lu P, Lee C, Ringman J, Apostolova L, Chow N, Kohannim O, Cummings JL, Thompson P, Elashoff D, for the Alzheimer’s Disease Neuroimaging Initiative. Estimating sample sizes for pre-dementia Alzheimer’s trials based on the Alzheimer’s Disease Neuroimaging Initiative. Neurobiol Aging. 2013;34(1):62-72. PMID: PMC3412892
Grill JD, Monsell S, Karlawish J. Are patients whose study partners are spouses more likely to eligible for Alzheimer’s disease clinical trials? Dementia & Geriatric Cognitive Disorders. 2012;33(5):334-340. PMID: 22759982. PMCID: PMC3477789.
Grill JD, Ringman JM. Should persons with autosomal dominant AD be included in clinical trials? Alzheimer’s Research and Therapy. 2011;3 (3):18. PMID: 21609419. PMCID: PMC3226307.
Grill JD, Karlawish J. Addressing the challenges to successful recruitment and retention in Alzheimer’s disease clinical trials. Alzheimer’s Research and Therapy. 2010;2:34. PMID: 21172069. PMCID: PMC3031880.
Grill JD, Cummings JL. Current therapeutic targets for Alzheimer’s disease. Expert Reviews in Neurotherapeutics. 2010;10(5):711-728. PMID: 20420492
Ringman JM, Grill J, Rodriguez-Agudelo Y, Chavez M, Xiong C. Commentary on "a roadmap for the prevention of dementia II: Leon Thal Symposium 2008." Prevention trials in persons at risk for dominantly inherited Alzheimer's disease: opportunities and challenges. Alzheimer’s and Dementia: Journal of the Alzheimer’s Association. 2009;5:166-171. PMID: 19328453
Grill JD, Cummings JL. “My patient can’t stop laughing”: Involuntary Emotional Expression Disorder. Current Psychiatry. 2008;7:101-111.
Robinson-Smith GR, Grill JD. (2007) Recognizing involuntary emotional expression disorder. Journal of Neuroscience Nursing. 2007;39:202-207. PMID: 17847666
Grill JD, Sonntag WE, Riddle DR. Dendritic regulation in a model of adult-onset IGF-1 deficiency. Growth Hormone and IGF-1 Research. 2005;15(5):337-348. PMID: 16143551
Grill JD, Riddle DR. Age-related and laminar-specific dendritic changes in the medial frontal cortex of the rat, Brain Research. 2002;937(1-2):8-21. PMID: 12020857
Grill JD, Coghill RC. Transient analgesia evoked by noxious stimulus offset, Journal of Neurophysiology. 2002;87:2205-2208. PMID: 11929939
|Grant||“A Phase II, Proof-of-Concept, Double-Blind-Randomized, Placebo-Controlled Adaptive Design Trial of Nicotinamide.” University of California Office of the President|
|Research Centers||Associate Director, Alzheimer's Disease Research Center|
|Director of Education, Institute for Memory Impairments and Neurological Disorders|
|Accrual and Retention, Institute for Clinical and Translational Science|
|Co-Director, Institute for Memory Impairments and Neurological Disorders|
|Link to this profile||http://www.faculty.uci.edu/profile.cfm?faculty_id=6201|