Memory and Cognitive Disorders Program


An increase in prevalence of cognitive impairment (CI) due to rapid aging of our society poses a major health and socioeconomic concern. Orange County (OC) is not an exception. From 2013-2018, OC will experience the fastest population increase in persons over 65 years old, even compared to that of California or of the United States (Figure 1). Such population shift requires our comprehensive community-wide approach to address brain health.

Hoag Memory and Cognitive Disorders program focuses on three main goals:

  1. Community education, risk factor analysis and early annual assessment of memory, using the Orange County Vital Brain Aging Program (OCVBAP), a population cognitive health initiative to promote healthy brain aging in our community and beyond.
  2. Accurate diagnostic assessment and monitoring of Alzheimer’s disease (AD) and related disorders (ADRD), including biomarker analysis, which includes quantitative volumetric MRI, functional MRI, Amyvid PET imaging, and cerebrospinal fluid assessment.
  3. Clinical research in FDA ADRD Phase I, II, and III clinical trials and prevention trials, as well as research in behavior and healthcare outcomes to improve measurement in ADRD healthcare.

Almost half of CI cases are due to manageable, reversible conditions, including cerebrovascular disease, hypertension, diabetes, cardiac, pulmonary, and renal diseases, depression, obesity, and certain lifestyles. Alzheimer’s disease (AD), which accounts for about 45% of all CI cases, can be significantly delayed at all severity stages with proper medication, better management of existing medical conditions, lifestyle modification, and appropriate caregiver support. And as is the case for any medical condition, prevention and early detection are the keys to effective management of CI or dementia.

“Prevention through Delay” characterizes the philosophical approach of the Memory and Cognitive Disorders program. Our sensitive monitoring tools, advanced diagnostic methods, state-of-the-art treatment approaches, and disease management works with optimal community services coordinated among physicians, patients, and community organizations. This approach is critical to slow progression of CI, prevent full blown dementia that incapacitates people, and raises health care costs.


The team is led by William R. Shankle, MS, MD, FACP, the Judy & Richard Voltmer Endowed Chair, Memory and Cognitive Disorders Program. He also serves as a director of OCVBAP, and is teamed with neurology and psychiatry colleagues with support from multi-disciplinary talent in education, research, and outreach. Celine Keeble and Betsey Olver coordinate the OCVBAP’s education, assessment, and outreach efforts. Junko Hara, PhD leads its research and academic development, as well as grant procurement effort.

Orange County Vital Brain Aging Program

Since 2010, OCVBAP ( has led a community-wide, multi-disciplinary program, supported by prior grants and philanthropy, promoting brain health aging in our community. Targeting persons over 45 years old, this effort is disseminated through public and healthcare professional education seminars, self-education and self-assessment tools, in-person memory assessment services, plus triaging community resources and healthcare services when indicated. The program and its components are consistent with the goals of the National Alzheimer’s Project Act, and the tactics of the Healthy Brain Initiative lead by the Alzheimer’s Association and CDC. The program also facilitates memory and cognition management pathways for primary care physicians, and collaborates with Hoag’s other institutes to mitigate threats to cognition caused by routine medical treatment and/or surgery.

OCVBAP provides the public with online self-assessment and in-person memory assessment services. To date, 4,700 community members have taken advantage of OCVBAP’s online services to learn about their memory, depression, and ADRD risk factors for CI (Figure 2). The OCVBAP website has attracted steady use by community members each year.

OCBVAP’s in-person formal memory assessment service is provided in both English and Spanish at five assessment locations (Hoag Hospital Newport Beach, Hoag Health Center Irvine, Oasis Senior Center, Senior Center Huntington Beach, Melinda Hoag Smith Center for Healthy Living).

At the assessment, those found cognitively normal learn about maintaining their cognitive health through managing existing medical conditions, modifying their lifestyle, and engaging in regular physical, cognitive and social activity. Those identified with CI, are assisted in finding the right healthcare professionals to diagnose the underlying causes, to treat, and to manage them. All participants are encouraged to monitor their memory annually after age 45.

To date, 4,350 individuals have participated in the assessment, and many have returned for annual assessment, OCVBAP conducting over 5,600 assessments (Table 1). The overall rate of CI was 23%, which is consistent with nationally published data in primary care settings. There were close to twice as many assessments of females (64%) than males (36%), although males had higher impairment rate (31%) than females (18%). This is partly due to older average age for male participants as the CI rate increases with age (Figure 3).

The program’s effort to reach the younger at-risk population is evident. Almost 25% of all participants were under 65 years old, and 37% were 65 to 74 years old. In addition, over 25 % of participants were referred by their primary care physician reflecting the program’s education effort in physician community.

Support and Education

The Memory and Cognitive Disorders Program provides ongoing public and healthcare professional education seminars, and works with community organizations serving seniors and persons with ADRD.

In 2017, 20 public seminars were provided addressing proactive approach to maintaining healthy brain. For healthcare professionals, 3 CME/CEU programs were offered, and OCVBAP participated in 3 conferences presenting on effective cognitive health management. In addition, with the grant from UniHealth foundation and philanthropy support, OCVBAP has undertaken the development of online CME to address discrepancy in management of cognitive health in primary care settings.

Clinical Research

Clinical research provides a great opportunity to better understand the ADRD disease mechanisms and to provide treatment options for our patients. The Memory and Cognitive Disorders Program engages not only in FDA ADRD clinical trials, but also prevention trials where healthy participants are studied to understand how to prevent or delay ADRD. In late 2017, in collaboration with affiliated partner Institute for Systems Biology, our team launched a new study called Coaching for Cognition in Alzheimer’s (COCOA) to determine how health coaching affects the cognitive function in early stage AD. This study will also analyze longitudinal, metabolomic data to explore transitions in cognitive function over time. As the focus of scientific and clinical research shifts toward prevention and early detection of AD, especially before symptoms develop, understanding non-pharmacologic approaches to treat AD will become more important.

  • AVID AVID-A05 (Phase III): An open label, multicenter study, evaluating the safety and imaging characteristics of 18F-AV-1451 in cognitively healthy volunteers, subjects with Mild Cognitive Impairment, and subjects with Alzheimer's Disease
  • AVID AVID-A16 (Phase III): A Clinico-Pathological Study of the Correspondence Between 18F-AV-1451 PET Imaging and Post-Mortem Assessment of Tau Pathology
  • AVID AVID-A18 (Phase III): An open label, multicenter study evaluating the imaging characteristics of a follow up 18F-AV-1451 scan in subjects that participated in the confirmatory cohort of 18F-AV-1451-A05
  • Biogen BIIB037 (Phase III): A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Aducanumab (BIIB037) in Subjects with Early Alzheimer's Disease
  • Genentech-Roche CREAD: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy And Safety Study Of Crenezumab In Patients With Prodromal To Mild Alzheimer’s Disease
  • Janssen EARLY (Phase IIb/III): A Phase 2b/3 Randomized, Double-blind, Placebo-Controlled, Parallel Group, MulticenterStudy Investigating the Efficacy and Safety of JNJ-54861911 in Subjects who areAsymptomatic At Risk for Developing Alzheimer’s Dementia
  • Providence St. Joseph Health: Coaching for Cognition in Alzheimer's (COCOA)

Publication, Lectures, Book Chapters


  • Alexander GE, Satalitch TA, Shankle WR, Batchelder WH. A Cognitive Psychometric Model for Psychodiagnostic Assessment of Memory Deficit Disorders. Psych Assessment. 2016;28(3):279-293.

  • Lee MD, Abramyan MD, Shankle WR. Semantic Structure and Memory Impairment: New Methods, Measures, and Models for Analyzing Triadic Comparisons. Behavior Research Methods. Behav Res Methods. 2016; 48(4):1492-1507.
  • Hara J, Shankle WR, Barrentine L, Curole M. Novel Therapy of Hyperhomocysteinemia in Mild Cognitive Impairment, Alzheimer's Disease, and Other Dementing Disorders. J Nutr Health Aging. 2016; 20(8):825-834.
  • Shankle WR, Hara J, Barrentine L, Curole M. CerefolinNAC Therapy of Hyperhomocysteinemia Delays Cortical and White Matter Atrophy in Alzheimer's Disease and Cerebrovascular Disease. J Alzheimers Dis. 2016; 54(3):1073-1084.


  • Shankle WR. Hoag Neurosciences Symposium. Oral Presentation. Newport Beach, CA, March, 2015.

  • Lee MD, Abramyan M, Shankle WR. Quantifying Judgment and Semantic Memory Using a Triadic Comparison Task. AAIC 2015. Poster Presentation. Washington DC, July 2015.
  • Alexander GE, Batchelder WH, Shankle WR, Petersen RC. Characterizing Cognitive Processes Affected By Alzheimer’s Disease Using Markov Models. AAIC 2015. Poster Presentation. Washington DC, July 2015.
  • Barrentine L, Hara J, Curole M, Shankle WR. Management of Hyperhomocysteinemia Delays Regional Brain Atrophy in Patients with Cognitive Impairment. AAIC 2015. Poster Presentation. Washington DC, July 2015.
  • Barrentine L, Hara J, Curole M, Shankle WR. Treatment of Hyperhomocysteinemia Slows Cognitive Decline in Patients with Alzheimer's Disease and Related Disorders. AAIC 2015. Poster Presentation. Washington DC, July 2015.
  • Alexander GE, Batchelder WH, Shankle WR, Petersen RC. Measuring Cognitive Processes Affected by Alzheimer’s Disease Using Markov Models. CTAD 2015. Oral Presentation. Barcelona. November 2015.
  • Shankle WR, Bock BR, Hara J, Brant-Zawadski M, Keeble C, Olver O, Fortier D, Mangrola T. Combining Subjective and Objective Cognitive Assessments for Pre-Clinical Detection: A Population Based Study. AAIC 2016. Poster Presentation. Toronto, Canada, July 2016.
  • Hara J, Shankle WR, Brant-Zawadzki M, Fortier D, Keeble C, Olver B, Porter S, Clarke T, Bock J, Nyugen N. Population Based Cognitive Health Program: Learnings from the Orange County Vital Brain Aging Program - 6 Year Report. AAIC 2016. Poster Presentation. Toronto, Canada, July 2016.
  • Shankle WR, Alexander GE, Batchelder WH, Petersen R. Predicting Alzheimer’s Disease in Asymptomatic Subjects Using A Hierarchical Hidden Markov Model, A Wordlist Memory Task, And The Mayo Aging Study. AAIC 2016. Poster Presentation. Toronto, Canada, July 2016.
  • Shankle WR, Hara J, Fortier D, Batchelder WH, Alexander GE, Petersen RC. Stability of Bayesian Cognitive Process Parameters Across Wordlist Memory Tasks and Study Populations. CTAD 2016. Poster Presentation. San Diego, December 2016.
  • Shankle WR. Cognitive Impairment and Delirium in Critical Care Medicine. Hoag Critical Care and Cardiovascular Nursing Conference. Newport Beach, January 2017.
  • Shankle WR. The Cardiac Connection of Cognitive Impairment: Detection, Treatment and Management. The Cardiology Update / ACC California Chapter Conference. Newport Beach, September 2017.

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To learn more, visit the Memory & Cognitive Disorders Program section or call 949-764-6288.