Complementary Center Without Walls
The center began in 1999 under the leadership of Barry Oken, M.D., with its first grant from the National Center for Complementary and Alternative Medicine at NIH focused around complementary medicine interventions that might reduce stress. The term stress was broadly used to include chronic psychological stress as well as metabolic oxidative stress and interventions were implemented in humans as well as animal models. The term complementary medicine is used similarly to the term integrative medicine.
Collaboration and Natural Antioxidants
The center initiated formal collaborations between Oregon Health & Science University (OHSU) and neighboring institutions: three CAM institutions – the National College of Natural Medicine, University of Western States, and the Oregon College of Oriental Medicine; the Linus Pauling Institute at Oregon State University; and the Portland Veteran Affairs Medical Center. One set of animal studies led by Dennis Bourdette, M.D., explored natural antioxidants in a mouse model of multiple sclerosis and found alpha lipoic acid significantly attenuated clinical signs and central nervous system inflammation in this model. Studies have teased apart the mechanism of this benefit of alpha lipoic acid (Maracci et al, 2002, Salinthone et al, 2008) and human trials have begun.
Age-Related Cerebral Degeneration
Joseph Quinn, M.D., and Balz Frei, Ph.D. led another project investigating mouse models of age-related cerebral degeneration, focusing on amyloid mouse models of Alzheimer’s disease. Initial results observed that ginkgo biloba extract and lipoic acid both improved the behavioral function of amyloid transgenic mice but that both produced no effect on the amyloid deposits in the brain (Stackman et al, 2003, Quinn et al, 2007). Follow-up studies extended the work to many other dietary supplements including coenzyme Q, fish oil, and docosahexaenoic acid. Jeffrey Kaye, M.D., led the first moderate-sized (133 subjects) primary prevention of dementia study in healthy over-84 year olds. Subjects who took ginkgo biloba extract for four years had a lower incidence of cognitive decline but the common intention to treat statistical analysis of all subjects fell just short of the common cutoff for significance, with a p value of 0.06. (Dodge et al, 2008).
Barry Oken, MD, led a project that included one of the earliest reasonably-sized, well-controlled trials of yoga in a clinical population. One study focused on those with Multiple Sclerosis and found that those randomised to six months of a yoga class or to an exercise class had significantly less fatigue than those randomised to a wait-list control group (Oken et al, 2004, see figure to right). Fatigue is a significant problem for those with Multiple Sclerosis and this important finding has been incorporated into standard clinical care. Another study with similar interventions in a group of healthy 65-85 year olds, also found that those randomised to yoga had significantly less fatigue (Oken et al, 2006). Both studies found no clear effects on cognitive function.
The follow-up NIH-funded centre grant to the original ORCCAMIND grant focused on mind-body medicine with an emphasis on expectancy and placebo effects, again with both animal and human projects. One project developed an animal model of a conditioned therapeutic response that had many features of a placebo effect (Jones et al, 2008). One project demonstrated the cognitive improvement in healthy seniors from simply the expectancy effect of taking a cognitive-enhancing agent (Oken et al, 2008). The two other projects examined the expectancy effect in humans with Parkinson’s disease and with metabolic syndrome. The expectancy or placebo effect, which is mediated through the brain and its connections, needs to be better understood in order to improve clinical research design and also to develop methods to clinically utilize the benefit of this mindbody effect (Oken, 2008).
Current ORCCAMIND Research
Current ORCCAMIND research has kept a focus on mind-body medicine (Wahbeh et al, Neurology 2008), using intervention techniques based on meditation and mindfulness training. Current projects have focused on clinical populations experiencing high psychological stress levels (e.g., caregivers and those with post-traumatic stress disorder). In addition to defining the clinical benefits of these therapies, there is a signifi cant effort to develop biomarkers of stress and of well-being. This is being done utilising serum markers (e.g., cytokines) and electrophysiologic measures (e.g., EEG and autonomic nervous system function) in addition to the more commonly used self-rated instruments. These physiologic markers utilize conventional methods (Wahbeh et al, Alz Disease and Related Disorders 2008) as well more innovative methods (Ellingson et al, 2008; Fonareva et al, 2009). In addition to ORCCAMIND’s mind-body focus, there continues to be a focus on diet and dietary supplements for age-related cognitive decline (Bowman et al, 2009; Shinto et al, 2008; Wadsworth et al, 2008; Calabrese et al, 2008).
ORCCAMIND has a major interest in collaboration with the Portland area CAM institutions mentioned above. This collaboration has been highlighted by the two NIH-funded centre grants that included project leaders and pilot grants at each of the three CAM institutions and has been extended to facilitation of faculty appointments and research interactions with OHSU faculty. ORCCAMIND supported research has extended to acupuncture and oriental medicine, naturopathy (Shinto et al, 2008a), and chiropractic (Haas et al, 2004). This collaboration with the CAM institutions extends to an annual invited CAM Distinguished Lectureship (sponsored by the Oregon Collaboration for Integrative Medicine), an annual Symposium for Portland-Area Research on Complementary and Alternative Medicine (SPARC), and the NIH research education grants awarded to the three Portland CAM institutions.
ORCCAMIND has always had a major emphasis on training academicians. The original ORCCAMIND centre grant provided four career development awards. Two awardees with clinical doctorates went on to obtain their own ﬁve-year NIH career development grants as a result. One of these clinicians, Lynne Shinto, ND, MPH, also began a Wellness Clinic within the Department of Neurology. Dr. Oken is principal investigator of an NIH-funded institutional training grant, “CAM Research Training in Neuroscience and Stress” that has been funded since 2005. There have been twelve post-doctoral fellows and one pre-doctoral fellow based at either OHSU (Departments of Neurology, Behavioral Neuroscience, or Psychiatry) or the Linus Pauling Institute at Oregon State University. Research by these fellows has extended from basic science to health services research. ORCCAMIND works closely with the OHSU Human Investigation Program, a certificate or masters degree program to educate clinical researchers beginning their post-doctoral careers. Dr Oken received funding for his own five-year NIH career development award that will further enhance his mentorship of junior academicians as well as advance his ability to utilize advanced signal analysis to improve mind-body medicine research.
Bowman GL, Frei B, Calabrese C, Dodge HH, Oken BS, Kaye JA, Quinn JF. Ascorbic acid and rates of cognitive decline in Alzheimer’s disease. Journal of Alzheimer’s Disease 2009, 16:93-98.
Calabrese C, Gregory WL, Leo M, Kraemer D, Groves M, Bone K, Oken B. Effects of a Standardised Bacopa monnieri Extract a on Cognitive Performance, Anxiety and Depression in the Elderly: A randomised Double-blind Placebo Controlled Trial. Journal of Alternative and Complementary Medicine 2008, 14:707-713.
Dodge HH, Zitzelberger T, Oken BS, Howieson D, Kaye J. A randomised placebo-controlled trial of ginkgo biloba for the prevention of cognitive decline. Neurology 2008, 70:1809-1817.
Ellingson RM, Eriksen KJ, Schaller JJ, Zajdel D, Kudura A, Oken B. Second generation complementary and alternative medicine physiologic data collection and monitoring research platform. Conference Proceedings IEEE Engineering in Medicine and Biology Society 2008, paper ThDPo07.1.
Fonareva I, Zajdel D, Herting M, McGee W, Oken B. Cognitive processes in older adults: potential impact of stress and physiologic function. Cognitive Neuroscience Society annual meeting, San Francisco 2009.
Haas M, Groupp E, Kraemer DF. Dose-response for chiropractic care of chronic low back pain. The Spine Journal 2004, 4:574–583.
Jones RE, Moes N, Zwickey H, Cunningham CL, Gregory WL, Oken B. Treatment of experimental autoimmune encephalomyelitis with alpha lipoic acid and associative conditioning. Brain, Behavior and Immunity 2008, 22:538-43.
Kaye JA, Dodge H, Zitzelberger T, Moore M, Oken B. MRI evidence for a disease modifying effect of Ginkgo Biloba extract in a dementia prevention trial. International Conference on Alzheimer’s disease. 2008. Presentation number IC-02-01.
Lovera J, Bagert B, Smoot K, Morris CD, Frank R, Bogardus K, Wild K, Oken B, Whitham R, Bourdette D. Ginkgo for improvement of cognitive performance in multiple sclerosis: a randomised, placebo-controlled trial. Multiple Sclerosis 2007. 13:376-385.
Marracci GH. Jones RE. McKeon GP. Bourdette DN. Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis. Journal of Neuroimmunology 2002, 131:104-14.
Oken BS, Kishiyama S, Zajdel D, Bourdette D, Carlsen J, Haas M, Hugos C, Kraemer DF, Lawrence J, Mass M. randomised controlled trial of yoga and exercise in multiple sclerosis. Neurology 2004; 62:2058-2064Oken, BS, Zajdel D, Kishiyama S, Flegal K, Dehen C, Haas M, Kraemer DF, Lawrence J, Leyva J. randomised controlled 6-month trial of yoga in healthy seniors: effects on cognition and quality of life. Alternative Therapies in Health and Medicine 2006, 12:40-49.
Oken BS, Flegal K, Zajdel D, Kishiyama S, Haas M, Peters D. Expectancy effect: impact of pill administration on cognitive performance in healthy seniors. Journal of Clinical and Experimental Neuropsychology 2008, 30:7-17.Oken BS. Placebo effects: Clinical aspects and neurobiology, Brain 2008, 131:2812-2823