Bio

Bio


Robert Cowan, MD, FAAN is Professor of Neurology and Chief of the Division of Headache Medicine at Stanford University. Prior to coming to Stanford he was ta senior clinical research scientist in molecular neurobiology at Huntington Medical Research Institutes (Pasadena, CA). Dr. Cowan attended University of Southern California, Keck Medical School, completed a residency program at USC Department of Neurology and served on faculty there until 2000. He is Board Certified in the areas of: Psychiatry and Neurology and Pain Medicine. He also holds subspecialty certification in Headache Medicine. Dr. Cowan is widely published in various scientific journals, including the Journal of the American Medical Association Cephalalgia, and Headache. He has authored book chapters lectures both nationally and internationally on a variety of headache topics, and has appeared on NBC, CBS and has been featured in articles ranging from the San Francisco Chronicle to Vogue Magazine.

Dr. Cowan has held several nationally elected positions, including chair of the sections on Chronic Daily Headache and In-office Patient Education for the American Headache Society. He is immediate past President of the Headache Cooperative of the Pacific, is a fellow of the American Academy of Neurology and the American Headache Society. He is on the boards of the Alliance for Headache Diseases Advocacy, the Headache Cooperative of the Pacific, the American Headache and Migraine Association, and the American Council for Headache Education. He is a reviewer for several peer-reviewed journals, including Headache and Cephalalgia. He is an editor for Headache Currents. Dr. Cowan is the author of The Keeler Migraine Method (Penguin/Avery, 2008).

Along with Dr. Alan Rapoport, Professor of Neurology at UCLA School of Medicine, Dr. Cowan co-founded BonTriage which develops computer-based tools to aid in the diagnosis, education, and care of people with chronic medical conditions. Dr. Cowan’s primary iresearch nterest is the pathophysiology of chronic daily headache, utilizing functional imaging, body fluid analysis and deep phenotyping. He has been the recipient of NIH, foundation, industry and individual grants and gifts for his research, .

Clinical Focus


  • Headache Medicine
  • Neurology

Academic Appointments


Administrative Appointments


  • Program Director, Headache Cooperative of the Pacific (2007 - 2011)
  • Vice President, Headache Cooperative of the Pacific (2007 - 2012)
  • Chair, Refractory Headache Special Interest Section, American Headache Society, American Headache Society (2012 - Present)
  • Director,Stanford Headache Program, Stanford University School of Medicine (2011 - Present)
  • President, Headache Cooperative of the Pacific (2012 - Present)

Honors & Awards


  • Magna Cum Laude, Clark University, Worcester, Massachusetts (1972)
  • Woodrow Wilson Scholar, Clark University, Worcester, Massachusetts (1972)
  • Chief Resident, LAC/USC, Los Angeles, California (1989)
  • Fellow, American Academy of Neurology (2006)
  • Fellow, American Headache Society (2010)

Boards, Advisory Committees, Professional Organizations


  • Member, Board of Directors, Alliance for Headache Disorders Advocacy (2009 - Present)
  • Member, Board of Directors, Headache Cooperative of the Pacific (2007 - Present)
  • Member, Advisory Committee, NCAA Select committee on headache in collegiate atheletes (2013 - Present)
  • Member,, American Headache Society (1995 - Present)
  • Member, American Academy of Neurology (1990 - Present)
  • Member, International Headache Society (2010 - Present)

Professional Education


  • Board Certification: Neurology, American Board of Psychiatry and Neurology (1994)
  • Residency:LAC and USC Medical Center (1990) CA
  • Internship:LAC and USC Medical Center (1987) CA
  • Medical Education:Keck School of Medicine University of Southern CA (1986) CA
  • Board Certification, Unified Council of Neurologic Subspecialties, Headache Medicine (2008)
  • Board Certification, American Academy of Pain Medicine (2000)

Community and International Work


  • AHDA

    Topic

    Funding for Headache Research

    Populations Served

    Headache Researchers, Clinicians, and Patients

    Location

    US

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • AHMA

    Topic

    Patient Advocacy

    Partnering Organization(s)

    American Headache Society

    Populations Served

    Patients with Headache

    Location

    US

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

Research & Scholarship

Current Research and Scholarly Interests


Current interest focus on patient education technology and patient/physician communication with a particular emphasis on tools which increase encounter efficiency and improve outcomes. Basic research focuses on mechanisms of action in Chronic Daily Headache, with a particular emphasis on New Daily Persistent Headache. Techniques include fMRI, biomarker investigation and evoked potentials. Clinical research includes clinical trials of novel treatments for episodic and chronic headache forms.

Projects


  • Chronic Daily Headache Project, SunStar Foundation (8/15/2013)

    Investigation into the basic mechanisms and biomarkers associated with various form of chronic daily headache. Resting state and structural imaging, analysis of blood and CSF for biomarker identification, and evoked action potentials are utilized to better characterize the pathophysiology of chronic headache.

    Location

    Stanford University and other headache centers in U.S. and abroad.

Teaching

2018-19 Courses


Publications

All Publications


  • The Future of Migraine Prevention. Headache Cowan, R. P. 2018

    Abstract

    Barring unforeseen circumstances, we anticipate the arrival of the first mechanism-specific class of molecules for migraine prevention in 2018. Despite many ground-breaking advances in the field over the last several years, these agents, broadly identified as calcitonin gene-related peptide-based pharmaceuticals, have captured the imagination and attention of the lay press and much of the headache community. This paper will address the factors, both class-specific and systems-based, that are likely to affect the launch, access, compliance, and adherence related to this new class, as well as attempt to place these novel medications in context of the current state and anticipated changes in headache medicine.

    View details for DOI 10.1111/head.13418

    View details for PubMedID 30311219

  • Deep Brain Stimulation for Chronic Cluster Headache: A Review. Neuromodulation : journal of the International Neuromodulation Society Vyas, D. B., Ho, A. L., Dadey, D. Y., Pendharkar, A. V., Sussman, E. S., Cowan, R., Halpern, C. H. 2018

    Abstract

    OBJECTIVES: Cluster headaches are a set of episodic and chronic pain syndromes that are sources of significant morbidity for patients. The standard of care for cluster headaches remains medication therapy, however a minority of patients will remain refractory to treatment despite changes to dosage and therapeutic combinations. In these patients, functional neuromodulation using Deep Brain Stimulation (DBS) presents the opportunity to alleviate the significant pain that is experienced by targeting the neurophysiological substrates that mediate pain.MATERIAL AND METHODS: We review the literature on chronic cluster headache, including the growing number of DBS case reports and series that describe the alleviation of pain in a majority of patients through conventional or endoventricular targeting of the posterior hypothalamus and ventral tegmental area, with a minimal side effect profile.RESULTS: In this review, the history and outcomes of DBS use for medication-refractory cluster headaches are examined, with discussion on future directions for improving this novel treatment modality and providing efficacious, longer-lasting pain relief in headache patients.CONCLUSION: In patients with chronic cluster headache, functional neuromodulation using DBS presents the opportunity to alleviate the significant pain that is experienced by targeting the neurophysiological substrates that mediate pain.

    View details for DOI 10.1111/ner.12869

    View details for PubMedID 30303584

  • Migraine Action Plan (MAP). Headache Peretz, A. M., Minen, M. T., Cowan, R., Strauss, L. D. 2018; 58 (2): 355–56

    View details for DOI 10.1111/head.13255

    View details for PubMedID 29411363

  • Introducing the Migraine Action Plan HEADACHE Peretz, A. M., Minen, M. T., Cowan, R., Strauss, L. D. 2018; 58 (2): 195

    View details for DOI 10.1111/head.13256

    View details for Web of Science ID 000424352200001

    View details for PubMedID 29411373

  • Effect of Educating the Primary Care Physician About Headache to Help Reduce "Trivial" Referrals and Improve the Number and Quality of "Substantial" Referrals that Truly Need Subspecialty Headache Medicine Care. Current treatment options in neurology Cowan, R., Barad, M. 2017; 19 (7): 25-?

    Abstract

    Technology is likely to play an increasingly important role in the delivery of healthcare as the disparity between provider availability/expertise and patient numbers/needs increases. This article is intended to lend insight into the ways in which technology can facilitate the evaluation of patients with headache disorders and improve the ongoing monitoring of disease progression and response to therapy, following proper diagnosis. While it is not possible to prognosticate the impact of technologies not yet available, the article addresses potential novel usage of currently existing technology to standardize intake, expedite evaluations, ensure adequate history and documentation, and monitoring of patient care.

    View details for DOI 10.1007/s11940-017-0462-5

    View details for PubMedID 28536899

  • Migraine affects 1 in 10 people worldwide featuring recent rise: A systematic review and meta-analysis of community-based studies involving 6 million participants JOURNAL OF THE NEUROLOGICAL SCIENCES Woldeamanuel, Y. W., Cowan, R. P. 2017; 372: 307-315

    Abstract

    To study the weighted average global prevalence of migraine at the community level.A systematic review using advanced search strategies employing PubMed/MEDLINE, Scopus, and Web of Science was conducted for community-based and non-clinical studies by combining the terms "migraine", "community-based", and names of every country worldwide spanning all previous years from January 1, 1920 until August 31, 2015. Methods were in accordance with PRISMA and MOOSE guidelines. A meta-analysis with subgroup analysis was performed to identify pooled migraine prevalence and examine cohort heterogeneity.A total of 302 community-based studies involving 6,216,995 participants (median age 35years, male-to-female ratio of 0.91) were included. Global migraine prevalence was 11.6% (95% CI 10.7-12.6%; random effects); 10.4% in Africa, 10.1% in Asia, 11.4% in Europe, 9.7% in North America, 16.4% in Central and South America. When the pooled cohort was stratified, the prevalence was 13.8% among females, 6.9% among males, 11.2% among urban residents, 8.4% among rural residents, and 12.4% among school/college students. Our result showed a pattern of rising global migraine prevalence.Migraine affects one in ten people worldwide featuring recent rise. Higher prevalence was found among females, students, and urban residents.

    View details for DOI 10.1016/j.jns.2016.11.071

    View details for Web of Science ID 000393002500060

    View details for PubMedID 28017235

  • Migraine and Complex Regional Pain Syndrome: A Case-Referent Clinical Study. BioMed research international Woldeamanuel, Y. W., Cooley, C., Foley-Saldena, K., Cowan, R. P. 2017; 2017: 5714673

    Abstract

    We studied clinical phenotype differences between migraineurs with CRPS (Mig + CRPS) and those without (Mig - CRPS). Mig + CRPS cases and Mig - CRPS referents aged ≥18 years were enrolled. Diagnosis was made in accordance with International Classification of Headache Disorders-3 beta (ICHD-3 beta) for migraine and Budapest Criteria for CRPS. Migraines both with and without aura were included. A total of 70 Mig + CRPS cases (13% males, mean age 48 years) and 80 Mig - CRPS referents (17% males, mean age 51 years) were included. 33% of Mig + CRPS and 38% of Mig - CRPS exhibited episodic migraine (EM) while 66% of Mig + CRPS and 62% of Mig - CRPS had chronic migraine (CM) (OR = 0.98, CI 0.36, 2.67). Median duration of CRPS was 3 years among EM + CRPS and 6 years among CM + CRPS cohort (p < 0.02). Mig + CRPS (57%) carried higher psychological and medical comorbidities compared to Mig - CRPS (6%) (OR 16.7, CI 10.2, 23.6). Higher migraine frequency was associated with longer CRPS duration. Migraineurs who developed CRPS had higher prevalence of psychological and medical disorders. Alleviating migraineurs' psychological and medical comorbidities may help lower CRPS occurrence.

    View details for DOI 10.1155/2017/5714673

    View details for PubMedID 29214172

    View details for PubMedCentralID PMC5682894

  • Spontaneous extracranial hemorrhagic phenomena in primary headache disorders: A systematic review of published cases CEPHALALGIA Peretz, A. M., Woldeamanuel, Y. W., Rapoport, A. M., Cowan, R. P. 2016; 36 (13): 1257-1267
  • Journal Club: Change in brain network connectivity during PACAP38-induced migraine attacks. Neurology DeSouza, D. D., O'Hare, M., Woldeamanuel, Y. W., Cowan, R. P. 2016; 87 (16): e199-e202

    View details for PubMedID 27754916

  • Journal Club: Exacerbation of headache during dihydroergotamine for chronic migraine does not alter outcome. Neurology Woldeamanuel, Y. W., O'Hare, M., DeSouza, D. D., Cowan, R. P. 2016; 87 (16): e196-e198

    Abstract

    Transient headache exacerbation during IV dihydroergotamine (DHE) therapy of migraine may prompt clinicians to prematurely discontinue DHE therapy, potentially depriving patients of the full benefit of DHE infusion. In a recent Neurology® article, Eller et al. evaluated whether or not worsening headache during DHE infusion was associated with suboptimal medium-term headache outcomes.

    View details for PubMedID 27754915

  • The impact of regular lifestyle behavior in migraine: a prevalence case-referent study JOURNAL OF NEUROLOGY Woldeamanuel, Y. W., Cowan, R. P. 2016; 263 (4): 669-676

    Abstract

    Regular lifestyle behaviors (RLBs) of sleep, exercise, mealtime pattern and hydration status independently affect migraine occurrence. We aimed herein to evaluate the differences in migraine occurrence among participants who do and do not maintain the RLB triumvirate. Cases of chronic migraine (CM) and referents of episodic migraine (EM) ≥aged 15 years with charts regularly documenting RLB notes were continuously enrolled from a retrospective case-referent cohort study performed on electronic chart review from January 1, 2014 to January 1, 2015 at the Stanford Headache and Facial Pain Program. Association between RLB prevalence and migraine occurrence was studied. 175 CM and 175 EM patients were enrolled (mean age 44.4 years, 22 % males). Migraine was diagnosed according to the ICHD-3 beta criteria, and was confirmed by a Headache Specialist attending the Clinic. The CM cohort (22 %) exhibited less RLB than the EM cohort (69 %), with crude odds ratio of 0.13 (95 % confidence interval or CI 0.08-0.21). The adjusted odds ratio and adjusted relative risk between RLB+, Meds+ (those taking medication) and CM were 0.67 (95 % CI 0.32-1.40) and 0.74 (95 % CI 0.43-1.28), indicating no significant effect modification. Engaging in regular lifestyle behavior helps quell chronic migraine.

    View details for DOI 10.1007/s00415-016-8031-5

    View details for Web of Science ID 000373742600006

    View details for PubMedID 26810728

  • Severe Headache or Migraine History Is Inversely Correlated With Dietary Sodium Intake: NHANES 1999-2004 HEADACHE Pogoda, J. M., Gross, N. B., Arakaki, X., Fonteh, A. N., Cowan, R. P., Harrington, M. G. 2016; 56 (4): 688-698

    Abstract

    We investigated whether dietary sodium intake from respondents of a national cross-sectional nutritional study differed by history of migraine or severe headaches.Several lines of evidence support a disruption of sodium homeostasis in migraine.Our analysis population was 8819 adults in the 1999-2004 National Health and Nutrition Examination Survey (NHANES) with reliable data on diet and headache history. We classified respondents who reported a history of migraine or severe headaches as having probable history of migraine. To reduce the diagnostic conflict from medication overuse headache, we excluded respondents who reported taking analgesic medications. Dietary sodium intake was measured using validated estimates of self-reported total grams of daily sodium consumption and was analyzed as the residual value from the linear regression of total grams of sodium on total calories. Multivariable logistic regression that accounted for the stratified, multistage probability cluster sampling design of NHANES was used to analyze the relationship between migraine and dietary sodium.Odds of probable migraine history decreased with increasing dietary sodium intake (odds ratio = 0.93, 95% confidence interval = 0.87, 1.00, P = .0455). This relationship was maintained after adjusting for age, sex, and body mass index (BMI) with slightly reduced significance (P = .0505). In women, this inverse relationship was limited to those with lower BMI (P = .007), while in men the relationship did not differ by BMI. We likely excluded some migraineurs by omitting frequent analgesic users; however, a sensitivity analysis suggested little effect from this exclusion.This study is the first evidence of an inverse relationship between migraine and dietary sodium intake. These results are consistent with altered sodium homeostasis in migraine and our hypothesis that dietary sodium may affect brain extracellular fluid sodium concentrations and neuronal excitability.

    View details for DOI 10.1111/head.12792

    View details for Web of Science ID 000374696100006

    View details for PubMedID 27016121

  • Spontaneous extracranial hemorrhagic phenomena in primary headache disorders: A systematic review of published cases. Cephalalgia Peretz, A. M., Woldeamanuel, Y. W., Rapoport, A. M., Cowan, R. P. 2015

    Abstract

    Head pain is a cardinal feature of primary headache disorders (PHDs) and is often accompanied by autonomic and vasomotor symptoms and/or signs. Spontaneous extracranial hemorrhagic phenomena (SEHP), including epistaxis, ecchymosis, and hematohidrosis (a disorder of bleeding through sweat glands), are poorly characterized features of PHDs.To critically appraise the association between SEHP and PHDs by systematically reviewing and pooling all reports of SEHP associated with headaches.Advanced searches using the PubMed/MEDLINE, Web of Science, Cochrane Library, Google Scholar, and ResearchGate databases were carried out for clinical studies by combining the terms "headache AND ecchymosis", "headache AND epistaxis", and "headache AND hematohidrosis" spanning all medical literature prior to October 10, 2015. Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines were applied.A total of 105 cases of SEHP associated with PHDs (83% migraine and 17% trigeminal autonomic cephalgias) were identified (median age 27 years, male to female ratio 1:2.3); 63% had epistaxis, 33% ecchymosis, and 4% hematohidrosis. Eighty-three percent of studies applied the International Classification of Headache Disorders diagnostic criteria. Eighty percent of the reported headaches were episodic and 20% were chronic. Twenty-four percent of studies reported recurrent episodes of SEHP.Our results suggest that SEHP may be rare features of PHDs. Future studies would benefit from the systematic characterization of these phenomena.

    View details for PubMedID 26611681

  • Comparison of parenteral treatments of acute primary headache in a large academic emergency department cohort. Cephalalgia McCarthy, L. H., Cowan, R. P. 2015; 35 (9): 807-815

    Abstract

    The objective of this article is to compare acute primary headache patient outcomes in those initially treated with parenteral opiates or non-opiate recommended headache medications in a large academic medical emergency department (ED).Many acute primary headache patients are not diagnosed with a specific headache type and are treated with opiates and nonspecific pain medications in the ED setting. This is inconsistent with multiple expert recommendations.Electronic charts were reviewed from 574 consecutive patients who visited the ED for acute primary headache (identified by chief complaint and ICD9 codes) and were treated with parenteral medications.Non-opiate recommended headache medications were given first line to 52.6% and opiates to 22.8% of all participants. Patients given opiates first had significantly longer length of stays (median 5.0 vs. 3.9 hours, p < 0.001) and higher rates of return ED visits within seven days (7.6% vs. 3.0%, p = 0.033) compared with those given non-opiate recommended medications in univariate analysis. Only the association with longer length of stay remained significant in multivariable regression including possible confounding variables.Initial opiate use is associated with longer length of stay compared with non-opiate first-line recommended medications for acute primary headache in the ED. This association remained strong and significant even after multivariable adjustment for headache diagnosis and other possible confounders.

    View details for DOI 10.1177/0333102414557703

    View details for PubMedID 25366551

  • Prevalence of migraine headache and its weight on neurological burden in Africa: a 43-year systematic review and meta-analysis of community-based studies. Journal of the neurological sciences Woldeamanuel, Y. W., Andreou, A. P., Cowan, R. P. 2014; 342 (1-2): 1-15

    Abstract

    Headache burden is not adequately explored in Africa. Here, we measured weighted migraine prevalence from community-based studies in Africa.PubMed search was employed using terms 'headache in Africa' AND/OR 'migraine in Africa' for published literature from 1970 until January 31, 2014. PRISMA was applied for systematic review. Forest-plot meta-analysis, inter-study heterogeneity, and odds ratio were used to measure weighted prevalence, inter-gender, and urban-rural differences. Disability adjusted life years (DALYs) for migraine and other neurologic disorders in Africa were extracted from Global Burden of Diseases (GBD) 2000-2030.Among 21 community-based studies included (n=137,277), pooled migraine prevalence was 5.61% (95% CI 4.61, 6.70; random effects) among general population; while 14.89% (14.06, 15.74; fixed effects) among student cohorts. Female students had weighted OR of 2.13 (1.34, 3.37; p=0.0013). Prevalence of migraine was higher among urban population compared to rural settings. Migraine burden is bound to increase by more than 10% DALYs within the next decade.Africa has a crude estimate of 56 million people suffering from migraine. By virtue of mainly afflicting the younger working-age group, migraine disability has wider socioeconomic implications. Improving early headache management access points at community-level, training and research at facility-level, and healthy lifestyle modification among urban residents can help reduce this costly and disabling chronic progressive health problem.

    View details for DOI 10.1016/j.jns.2014.04.019

    View details for PubMedID 24814950

  • Prevalence of migraine headache and its weight on neurological burden in Africa: A 43-year systematic review and Meta-analysis of community-based studies JOURNAL OF THE NEUROLOGICAL SCIENCES Woldeamanuel, Y. W., Andreou, A. P., Cowan, R. P. 2014; 342 (1-2): 1-15
  • CAM in the Real World: You May Practice Evidence-Based Medicine, But Your Patients Don't. Headache Cowan, R. P. 2014; 54 (6): 1097-1102

    Abstract

    Complementary and Alternative Medicine (CAM) approaches are widely used among individuals suffering from headache. The medical literature has focused on the evidence base for such use and has largely ignored the fact that these approaches are in wide use despite that evidence base.This article focuses on the uses of CAM by patients and suggests strategies for understanding and addressing this use without referring back to the evidence base. The rationale for this discussion pivots on the observation that patients are already using these approaches, and for many there are anecdotal and historical bases for use which patients find persuasive in the absence of scientific evidence.Until such time as the body of scientific literature adequately addresses non-conventional approaches, physicians must acknowledge and understand, as best as possible, CAM approaches which are in common use by patients. This is illustrated with a case study and examples from practice. This article does not review the evidence base for various CAM practices as this has been done well elsewhere.

    View details for DOI 10.1111/head.12364

    View details for PubMedID 24766436

  • Does exercise make migraines worse and tension type headaches better? Current pain and headache reports Hindiyeh, N. A., Krusz, J. C., Cowan, R. P. 2013; 17 (12): 380-?

    Abstract

    Many non-pharmacological treatments have been implicated in the treatment of primary headache, with exercise being a common recommendation. In this review we first provide an overview of the relationship between exercise and primary headaches. We then review the physiology of pain modulation, with focus on the endogenous opioids, endocannabinoids, and neuropeptides calcitonin gene-related peptide (CGRP) and brain-derived neurotrophic factor (BDNF), and their associations with primary headache and exercise. Finally, we summarize current literature evaluating effects of exercise on primary headache in an effort to understand the benefits and disadvantages of exercise in primary headaches.

    View details for DOI 10.1007/s11916-013-0380-5

    View details for PubMedID 24234818

  • Does exercise make migraines worse and tension type headaches better? Current pain and headache reports Hindiyeh, N. A., Krusz, J. C., Cowan, R. P. 2013; 17 (12): 380-?

    View details for DOI 10.1007/s11916-013-0380-5

    View details for PubMedID 24234818

  • Executive Function Changes before Memory in Preclinical Alzheimer's Pathology: A Prospective, Cross-Sectional, Case Control Study PLOS ONE Harrington, M. G., Chiang, J., Pogoda, J. M., Gomez, M., Thomas, K., Marion, S. D., Miller, K. J., Siddarth, P., Yi, X., Zhou, F., Lee, S., Arakaki, X., Cowan, R. P., Thao Tran, T., Charleswell, C., Ross, B. D., Fonteh, A. N. 2013; 8 (11)

    Abstract

    Early treatment of Alzheimer's disease may reduce its devastating effects. By focusing research on asymptomatic individuals with Alzheimer's disease pathology (the preclinical stage), earlier indicators of disease may be discovered. Decreasing cerebrospinal fluid beta-amyloid42 is the first indicator of preclinical disorder, but it is not known which pathology causes the first clinical effects. Our hypothesis is that neuropsychological changes within the normal range will help to predict preclinical disease and locate early pathology.We recruited adults with probable Alzheimer's disease or asymptomatic cognitively healthy adults, classified after medical and neuropsychological examination. By logistic regression, we derived a cutoff for the cerebrospinal fluid beta amyloid42/tau ratios that correctly classified 85% of those with Alzheimer's disease. We separated the asymptomatic group into those with (n = 34; preclinical Alzheimer's disease) and without (n = 36; controls) abnormal beta amyloid42/tau ratios; these subgroups had similar distributions of age, gender, education, medications, apolipoprotein-ε genotype, vascular risk factors, and magnetic resonance imaging features of small vessel disease. Multivariable analysis of neuropsychological data revealed that only Stroop Interference (response inhibition) independently predicted preclinical pathology (OR = 0.13, 95% CI = 0.04-0.42). Lack of longitudinal and post-mortem data, older age, and small population size are limitations of this study.Our data suggest that clinical effects from early amyloid pathophysiology precede those from hippocampal intraneuronal neurofibrillary pathology. Altered cerebrospinal fluid beta amyloid42 with decreased executive performance before memory impairment matches the deposits of extracellular amyloid that appear in the basal isocortex first, and only later involve the hippocampus. We propose that Stroop Interference may be an additional important screen for early pathology and useful to monitor treatment of preclinical Alzheimer's disease; measures of executive and memory functions in a longitudinal design will be necessary to more fully evaluate this approach.

    View details for DOI 10.1371/journal.pone.0079378

    View details for Web of Science ID 000327308500055

    View details for PubMedID 24260210

    View details for PubMedCentralID PMC3832547

  • Phospholipase C activity increases in cerebrospinal fluid from migraineurs in proportion to the number of comorbid conditions: a case-control study JOURNAL OF HEADACHE AND PAIN Fonteh, A. N., Pogoda, J. M., Chung, R., Cowan, R. P., Harrington, M. G. 2013; 14

    Abstract

    Migraineurs are more often afflicted by comorbid conditions than those without primary headache disorders, though the linking pathophysiological mechanism(s) is not known. We previously reported that phosphatidylcholine-specific phospholipase C (PC-PLC) activity in cerebrospinal fluid (CSF) increased during migraine compared to the same individual's well state. Here, we examined whether PC-PLC activity from a larger group of well-state migraineurs is related to the number of their migraine comorbidities.In a case-control study, migraineurs were diagnosed using International Headache Society criteria, and controls had no primary headache disorder or family history of migraine. Medication use, migraine frequency, and physician-diagnosed comorbidities were recorded for all participants. Lumbar CSF was collected between the hours of 1 and 5 pm, examined immediately for cells and total protein, and stored at -80°C. PC-PLC activity in thawed CSF was measured using a fluorometric enzyme assay. Multivariable logistic regression was used to evaluate age, gender, medication use, migraine frequency, personality scores, and comorbidities as potential predictors of PC-PLC activity in CSF.A total of 18 migraineurs-without-aura and 17 controls participated. In a multivariable analysis, only the number of comorbidities was related to PC-PLC activity in CSF, and only in migraineurs [parameter estimate (standard error) = 1.77, p = 0.009].PC-PLC activity in CSF increases with increasing number of comorbidities in migraine-without-aura. These data support involvement of a common lipid signaling pathway in migraine and in the comorbid conditions.

    View details for DOI 10.1186/1129-2377-14-60

    View details for Web of Science ID 000321647800001

    View details for PubMedID 23826990

  • Cerebrospinal fluid phosopholipase C activity increases in migraine. Cephalalgia Alfred N Fonteh, Rainbow Chung, Tara L Sharma, R Danielle Fisher, Janice M Pogoda, Robert Cowan, Michael G Harrington 2011; 31 (4): 456-462
  • Capillary Endothelial Na+, K+, ATPase Transporter Homeostasis and a New Theory for Migraine Pathophysiology. Headache Harrington, M.G., Fonteh, A.N., Arakaki, X., Cowan, R.P., Ecke, L.E., Foster, H., Huhmer, A.F., & Biringer, R. 2010; 50 (3): 459-78
  • The morphology and biochemistry of nanostructures provide evidence for synthesis and signaling functions in human cerebrospinal fluid. Cerebrospinal Fluid Res. Harrington MG, Fonteh AN, Oborina E, Liao P, Cowan RP, McComb G, Chavez JN, Rush J, Biringer RG, Huhmer AF. 2009: 6:10
  • Prostaglandin D Synthase Isoforms from Cerebrospinal Fluid Vary with Brain Physiology. Disease Markers Harrinton MG, Fonteh AN, Biringer RG, Huhmer AF, Cowan RP. 2006; 22 (1-2): 73-81
  • Cerebrospinal Fluid Sodium Increases in Migraine Headache Harrington MG, Fonteh AN, Cowan RP, Perrine K, Pogoda JM, Biringer, RG, Huhmer AFR. 2006; 46 (7): 1128-1135