Aging; Alzheimer Disease; Drug Therapy; Genetics; Neurobiology; Neurology; Psychiatry; Neuroimaging
Dr Christopher H. van Dyck is a graduate of Yale College and Northwestern University Medical School. He completed his residency in psychiatry, fellowship in geriatric psychiatry, and research fellowship in neuroimaging at Yale University School of Medicine. He subsequently joined the faculty at Yale where he is Professor of Psychiatry, Neurology, and Neurobiology, Director of the Alzheimer's Disease Research Unit, and Director of the Division of Aging and Geriatric Psychiatry.
Dr. van Dyck is a recognized leader in the neuroimaging of Alzheimer’s disease and healthy aging. His research interests also include the pharmacologic treatment of Alzheimer’s disease and Mild Cognitive Impairment, and he serves as Steering Committee member and Yale site Principal Investigator for the Alzheimer’s Disease Cooperative Study (National Institute of Aging). He is also Principal Investigator on grants from the National Institutes of Health and a number of private foundations, including the Alzheimer’s Association.
He received the prestigious Junior Investigator Award from the American Association for Geriatric Psychiatry (1996) and serves on the Editorial Board for the Journal of Nuclear Medicine and Brain Imaging and Behavior. He has participated in several invited presentations at national and international meetings and has authored over 100 papers, abstracts, and reviews. Finally, Dr. van Dyck is extremely committed to advancing the cause of Alzheimer’s patients and their families on the local and national level. As Chairman of the Medical Scientific Advisory Committee for the Connecticut Chapter of the Alzheimer’s Association, he is intimately involved with local program development, advocacy, and education.
Specialized Terms: Alzheimer's disease; Healthy aging; Cognitive aging; Pharmacotherapy; Neuroimaging; Genetics
Extensive Research Description
Christopher H. van Dyck, MD, is Professor of Psychiatry, Neurology, and Neuroscience; Director, Division of Aging and Geriatric Psychiatry; Director of the Alzheimer's Disease Research Unit; Director, Yale Alzheimer's Disease Research Center. His research interests include therapeutic, neuroimaging and genetic studies of Alzheimer's disease (AD) and healthy aging. Dr. van Dyck and the Yale ADRU are very active in national and international research in the treatment of AD.
Since 1992 he has participated in 80+ multicenter clinical trials for AD and the prodromal condition of Mild Cognitive Impairment (MCI) and has authored several of the trial publications. Since 1996 he has been a member of the Alzheimer's Disease Cooperative Study (ADCS), the principal academic consortium for AD therapeutic studies funded by NIH. Dr. van Dyck’s other significant scholarly contributions have included:
Dopamine Transporter (DAT) Imaging in Aging.
He has used SPECT imaging to demonstrate a 50% loss of DATs over the lifespan and has further shown that this loss of dopamine is associated with the slowing of reaction time that is characteristic of the normal aging process.
The Apolipoprotein E e4 (ApoE e4) Phenotype of AD.
He has combined genetics and neuroimaging to characterize the role of the most common genetic risk factor, ApoE e4, in structural and cognitive changes in AD. He has found that patients who carry the ApoE e4 allele are at greater risk for psychosis and for loss of medial temporal lobe tissue. He is now using the PET ligand [11C]PIB to assess amyloid plaques in asymptomatic first-degree relatives as a function of ApoE e4 genotype.
- Guanfacine Treatment for Prefrontal Cognitive Dysfunction in Elderly Subjects (funded by NIA). The major goal of this project is to test the hypothesis that low doses of the alpha-2A-adrenoceptor agonist guanfacine can improve deficits in prefrontally-mediated working memory and executive control functions in healthy elderly subjects.
- Amyloid Binding In Subjects At Risk For Alzheimer’s Disease (funded by Alzheimer's Association). The major goal of this project is to test the hypothesis that in vivo brain Aß burden as measured using [11C]PIB and PET is increased in healthy subjects with a family history of AD who are homozygous or heterozygous for the ApoE e4 allele compared to subjects who lack this allele.
- Alzheimer’s Disease Cooperative Study Unit (ADCS, funded by NIA). The major goal of this multicenter consortium is to conduct clinical trial research in Alzheimer’s disease that would not otherwise be conducted by private pharmaceutical corporations. Role: Principal Investigator for Yale Site (PI: Paul Aisen, University of California, San Diego)
- Alzheimer’s Disease Neuroimaging Initiative (ADNI, funded by NIA) The major goals of this project are to: 1. Develop improved methods which will lead to uniform standards for acquiring longitudinal, multi-site MRI and PET data on patients with Alzheimer’s disease, mild cognitive impairment, and elderly controls. 2. Acquire a generally accessible data repository, which describes longitudinal changes in brain structure and metabolism. In parallel, acquire clinical cognitive and biomarker data for validation of imaging surrogates. Role: Principal Investigator for Yale Site (PI: University of California, San Francisco)
- Mitsis EM, Cosgrove KP, Staley JK, Bois F, Frohlich EB, Tamagnan GD, Estok KM, Seibyl JP, van Dyck CH. Age-related decline in nicotinic receptor availability with [123I]5-IA-85380 SPECT. Neurobiol Aging 2009;30(9):1490-7.
- Santhosh L, Estok KM, Vogel RS, Tamagnan GD, Baldwin RM, Mitsis EM, MacAvoy MG, Staley JK, van Dyck CH. Regional distribution and behavioral correlates of 5-HT2A receptors in Alzheimer’s disease with [18F]deuteroaltanserin and PET. Psychiatry Res Neuroimaging 2009;173:212-7.
- van Dyck CH, Avery RA, MacAvoy MG, Marek KL, Quinlan DM, Baldwin RM, Seibyl JP, Innis RB, Arnsten AFT. Striatal dopamine transporters correlate with simple reaction time in elderly subjects. Neurobiol Aging 2008;29(8):1237-46.
- Zdanys KF , Kleiman TG, MacAvoy MG, Black BT, Rightmer TE, Grey M, Garman KS, Tampi RR, Gelernter J, van Dyck CH. Apolipoprotein E e4 allele increases risk for psychotic symptoms in Alzheimer’s disease. Neuropsychopharmacology 2007;32(1):171-9.
- Basso M, Gelernter J, Yang J, MacAvoy MG, Varma P, Bronen RA, van Dyck CH. Apolipoprotein E e4 is associated with atrophy of the amygdala in Alzheimer's disease. Neurobiol Aging 2006;27(10):1416-24.
- van Dyck CH, Newhouse P, Falk WE, Mattes JA: Extended-release physostigmine in Alzheimer's disease: a multicenter, double-blind, 12-week study with dose-enrichment. Arch Gen Psychiatry, 2000;57:157-164.
- Nygaard HB, Wagner A, Bowen G, Good S, MacAvoy M, Strittmatter KA, Kaufman AC, Rosenberg BJ, Sekine-Konno T, Varma P, Chen K, Koleske AJ, Reiman EM, Strittmatter SM, van Dyck CH. A Phase Ib Multiple Ascending Dose Study of the Safety, Tolerability, and CNS Availability of AZD0530 (Saracatinib) in Alzheimer's disease. Alzheimer's Research & Therapy, 2015;7(1):35.
- Coric V, van Dyck CH, Salloway S, Andreasen N, Brody M, Richter RW, Soininen H, Thein S, Shiovitz T, Pilcher G, Colby S, Rollin L, Dockens R, Pachai C, Portelius E, Andreasson U, Blennow K, Soares H, Albright C, Feldman HF, Berman RM. Safety and tolerability of the gamma secretase inhibitor avagacestat in a Phase 2 study in mild-to-moderate Alzheimer’s disease. Arch Neurol. 2012 Nov;69(11):1430-40.
- Sano M, Bell KL, Galasko D, Galvin JE, Thomas RG, van Dyck CH, Aisen PS. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology. 2011 Aug 9;77(6):556-63.
- Harrington C, Sawchak S, Chiang C, Davies J, Donovan C, Saunders AM, Irizarry M, Jeter B, Zvartau-Hind M, van Dyck CH, Gold M. Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: Two Phase 3 studies. Curr Alzheimer Res. 2011 Aug 1;8(5):592-606.
- Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, van Dyck CH, Galvin JE, Emond J, Jack CR Jr, Weiner M, Shinto L, Aisen PS. Docosahexaenoic Acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA 2010 Nov 3;304(17):1903-11
- Hannestad J, Gallezot JD, Planeta-Wilson B, Lin SF, Williams WA, van Dyck CH, Malison RT, Carson RE, Ding YS. Clinically relevant doses of methylphenidate significantly occupy norepinephrine transporters in humans in vivo. Biol Psychiatry 2010 Nov 1;68(9):854-60.
- Chapman SB, Cotman CW, Fillit HM, Gallagher M, van Dyck CH. Clinical trials: new opportunities. J Gerontol A Biol Sci Med Sci. 2012 Jun;67(7):773-80.
- Farlow M, Arnold SE, van Dyck CH, Aisen PS, MD, Snider BJ, Porsteinsson AP, Friedrich S, Dean RA, Gonzales C, Sethuraman G, DeMattos RB, Mohs R, Paul SM, Siemers ER. Safety and biomarker effects of solanezumab in patients with Alzheimer’s disease. Alzheimers Dement. 2012 Jul;8(4):261-71.
- Nygaard HB, van Dyck CH, Strittmatter SM. Fyn kinase inhibition as a novel therapy for Alzheimer's disease. Alzheimers Res Ther. 2014 Feb 5;6(1):8.
- Galasko D, Bell J, Mancuso JY, Kupiec JW, Sabbagh MN, van Dyck CH, Thomas RG, Aisen PS; Alzheimer's Disease Cooperative Study. Clinical trial of an inhibitor of RAGE-Aβ interactions in Alzheimer disease. Neurology 2014 Apr 29;82(17):1536-42.
- Isaias IU, Spiegel J, Brumberg J, Cosgrove KP, Marotta G, Oishi N, Higuchi T, Küsters S, Schiller M, Dillmann U, van Dyck CH, Buck A, Herrmann K, Schloegl S, Volkmann J, Lassmann M, Fassbender K, Lorenz R, Samnick S. Nicotinic acetylcholine receptor density in cognitively intact subjects at an early stage of Parkinson's disease. Front Aging Neurosci. 2014 Aug 14;6:213.
- 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’s Disease: Methodology and Results from a Phase 2 Global Trial with Avagacestat. JAMA Neurology, 2015 Sep 28:1-10. [Epub ahead of print]
- Turner RS, Thomas RG, Craft S, van Dyck CH, Mintzer J, Reynolds BA, Brewer JB, Rissman RA, Raman R, Aisen PS, A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer’s disease. Neurology, 2015 Sep 11. pii: 10.1212/WNL.0000000000002035. [Epub ahead of print]
- Kaufman AC, Salazar SV, Haas LT, Yang J, Kostylev MA, Jeng AT, Robinson SA, Gunther EC, van Dyck CH, Nygaard HB, Strittmatter SM. Fyn inhibition rescues established memory and synapse loss in Alzheimer mice. Ann Neurol. 2015 Jun;77(6):953-71.
- A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer's disease. Nygaard HB, Wagner AF, Bowen GS, Good SP, MacAvoy MG, Strittmatter KA, Kaufman AC, Rosenberg BJ, Sekine-Konno T, Varma P, Chen K, Koleske AJ, Reiman EM, Strittmatter SM, van Dyck CH. Alzheimers Res Ther. 2015 Apr 14;7(1):35.