Memory and Cognitive Disorders Program


With the rapid aging of our society, cognitive impairment (CI) due to Alzheimer’s disease (AD) and related disorders is posing a huge socioeconomic pressure. Orange County (OC) is not an exception. Those over 65 represent the only growing age group, one projected to increase in the next 25 years from 14% in 2015 to 24% in 2040. In addition, while four of the five leading causes of death in OC have decreased by between 16% and 40% in the past 10 years, AD has increased by 125%, urging innovative and pragmatic management of cognitive health in our community.

Our 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 AD and related disorders (ADRD), including biomarker analysis, which includes quantitative volumetric MRI, functional MRI, Amyvid PET imaging, and cerebrospinal fluid assessment.

    In selected patients with abnormal objective memory testing in the earliest stages of cognitive impairment, quantitative measurement of the hippocampal volume provides a bio-marker that can establish the diagnosis. Serial testing can demonstrate disease progression, and/or response to therapy.

    Scanned Brain
    Figure 1

    Selected coronal MRI slice with the cortical segmentation algorithm shows the hippocampal atrophy (olive green region in Figure 1) as well as enlargement of lateral ventricles and inferior lateral ventricles. The quantitative measure for the hippocampal region is shown in Figure 2.

    Brain Structure Volume (cm2) % of ICV (5%-95% Normative Percentile)Normative
			 Percentile Hippocampi 7.33 0.40 (0.41-0.58) < 5 0.7 0.6 0.5 0.4 0.3 95%
			 5 25 50 75 50 60 70 80 90 100 Volume 1% of ICVI Age (Years)
    Figure 2

    Another promising application of PET/MR is combining a PET Tau tracer with the quantitative MRI study in one sitting for an even more specific diagnosis, enabling targeted Tau- reducing therapy to appropriate patients (Figure 3). Note the bright green areas in the hippocampus.

    Scanned Brain
    Figure 3
  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 more manageable, reversible conditions, including cerebrovascular disease, hypertension, diabetes, cardiac, pulmonary, and renal diseases, depression, obesity, and certain lifestyles. AD, which accounts for about 45% of all CI cases, can also 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 education and other 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.


William R. Shankle, MS, MD, FACP
William R. Shankle, MS, MD, FACP

The team is led by William R. Shankle, M.S., M.D., F.A.C.P., 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. Greg Whitman, M.D., joined the team in 2018, expanding access to the Irvine community. All the Hoag neurologists participate in the best practice care pathways of the program. Celine Keeble and Betsey Olver coordinate the OCVBAP’s education, assessment, and outreach efforts. Junko Hara, Ph.D., 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 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.

Figure 4: Online Self-Assessment Utilization (2016-2018)
Risk Factor Depression Memory
Assessment Self-Screen Self-Screen
Figure 4: Online Self-Assessment Utilization (2016-2018)

OCVBAP provides the public with online self assessment and in-person formal memory testing (screening) services. For online self-assessments, 5,110 community members have taken advantage of them to learn about their memory, depression, and ADRD risk factors for CI (Figure 4). The OCVBAP website has attracted steady use by community members each year.

OCBVAP’s in-person formal memory testing (screening) service is provided in both English and Spanish at five testing 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, 4,940 individuals have participated in the In-person formal memory testing (screening) and many have returned for annual formal re-testing. (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 5).

# Assessments
2,397 (36%)
4,223 (64%)
6,620 (100%)
Average Age
72.1 +/- 10.1
69.2 +/- 10.8
70.3 +/- 10.7
# Below Normal
744 (31%)
764 (18%)
1,508 (23%)
Table 1. Assessment Summary

Figure 5: Number of Participants by Age Group

Figure 5: Number of Participants by Age Group

Figure 5: Number of Participants by Age Group

The program’s effort to reach the younger at-risk population is evident. At the time of the assessment, almost 26% of all assessments were for participants under 65 years old, and 37% were for 65 to 74 years old (Figure 6). In addition, approximately 24% of assessments were referred by their primary care physician, and 23% by family and friends, reflecting the program’s education and outreach effort in our community.

Figure 6: % Assessment by Age Group
Figure 6: % Assessment by Age Group

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 2018, 21 public seminars were provided in either English, Spanish, or Japanese addressing a proactive approach to maintaining a healthy brain. Also OCVBAP has participated in 7 public events including senior health fairs. For healthcare professionals, 2 CME/CEU programs and ongoing online CME events were offered.

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 collaboration with affiliated partner Institute for Systems Biology, our team continues to conduct a trial 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.

F. Hoffman-La Roche BN29552 “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.

Biogen 221AD302 “EMERGE”: A Phase III 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.

Biogen 251AD201 “TANGO”: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Safety, Tolerability, and Efficacy of BIIB092 in Subjects with Mild Cognitive Impairment due to Alzheimer’s Disease or with Mild Alzheimer’s Disease.

COCOA: Coaching for Cognition in Alzheimer’s Disease. Two-year study evaluating lifestyle changes and how they affect cognition with persons Stages 2-4 with AD.

Eli Lilly Protocol I5T-MC-AACG “TRAILBLAZER-ALZ”: Assessment of Safety, Tolerability and Efficacy of LY3002813 Alone and in Combination with LY3202626 in Early Symptomatic Alzheimer’s Disease.

Janssen 54861911ALZ2003 “EARLY”: A Phase 2b/3 Randomized, Double-blind, Placebo-Controlled, Parallel Group, Multicenter Study Investigating the Efficacy and Safety of JNJ-54861911 in Subjects Who Are Asymptomatic At Risk for Developing Alzheimer’s Dementia.

Avid F18-AV1451-A16: A Clinico-Pathological Study of the Correspondence Between 18F-AV-1451 PET Imaging and Post-Mortem Assessment of Tau Pathology.

F. Hoffman-La Roche Protocol BN40031: A Multicenter, Open-Label, Long-Term Extension Of Phase Iii Studies (Bn29552/Bn29553) Of Crenezumab In Patients With Alzheimer’s Disease.

Publications, Lectures, Book Chapters

Peer-Reviewed Journal Articles

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.

Conference Presentations

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.

Shankle WR, Bock JR, Hara J, Mangrola T, Fortier D, Lee MD, Kremers W, Petersen RC. Measuring Latent Cognitive Processes To Detect The Earliest Changes in Alzheimer’s Disease. AAIC 2018. Poster Presentation. Chicago, July 2018.

Shankle WR, Hara J, Mangrola M, Fortier D. Gender Differences in Memory Across the Human Lifespan. AAIC 2018. Oral Presentation. Chicago, July 2018.

Bock JR, Shankle WR, Hara J, Keeble K, Olver B, Fortier D, Porter S, Guillen Nguyen N, Brant-Zawadzki M. Addressing Depression in Seniors: Evaluation and Support in the Orange County Vital Brain Aging Program. AAIC 2018. Poster Presentation. Chicago, July 2018.

Shankle WR, Hara J, Mangrola T, Fortier D. Gender Differences in Memory Across the Human Lifespan. AAIC 2018. Oral Presentation. Chicago, July 2018.

Shankle WR, Hara J, Bock JR, Fortier D, Mangrola T, Lee MD, Alexander GE, Batchelder WH, Petersen RC, Kremers W. Using Graphical Hierarchical Bayesian Cognitive Process Models Applied to Common Memory Tests to Predict AD Pathology within Normal Subjects. CTAD 2018. Poster Presentation. Barcelona, November 2018.

To learn more, visit the Memory & Cognitive Disorders Program section or call 949-764-4430.