Memory and Cognitive Disorders Program

Overview

Cognitive Impairment (CI) imposes a major health and socioeconomic concern to all aging communities.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. Such population shift will require a comprehensive community-wide approach to address brain health.

Almost half of CI cases are due to manageable, treatable 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.

“Prevention through Delay” characterizes the philosophical approach of the Memory and Cognitive Disorders program. This approach involves the use of sensitive monitoring tools, advanced diagnostic methods, state-of-the-art treatment approaches, and disease management integrated with the best community services. This coordinated approach among physicians, patients, and community organizations is critical to prevent or delay CI and dementia.

The Hoag Neuroscience Institute Memory and Cognitive Disorders program has three main functions:

  1. Provides accurate diagnostic assessment and monitoring of AD and related disorders (ADRD), by studying biomarkers measured at the Advanced Technology Pavilion, which include quantitative MRI (Neuroquant®), functional MRI, Amyvid® PET, and cerebrospinal fluid.
  2. Engages in FDA Phase I, II, and III clinical trials for ADRD patients, as well as conducts research in behavior and healthcare outcomes to improve measurement in ADRD healthcare.
  3. Spearheads the Orange County Vital Brain Aging Program (OCVBAP), a population cognitive health initiative to promote healthy brain aging in the Orange County community.

Team

The Memory and Cognitive Disorders program is led by Dr. William R. Shankle, the Judy & Richard Voltmer Endowed Chair. He is also OCVBAP’s director, and is teamed with neurology and cognitive psychiatry colleagues including Drs. Teryn Clarke with support from multi-disciplinary talent in education, research, and outreach. Celine Keeble and Betsey Olver coordinate the Orange County Vital Brain Aging Program’s education, assessment, and outreach efforts.

Orange County Vital Brain Aging Program

As an extension of the “Prevention through Delay” philosophy, the Memory and Cognitive Disorders Program leads OCVBAP (www.OCBrain.org). OCVBAP, in its sixth year, is a community-wide, multi-disciplinary program, supported by prior grants and philanthropy, promoting brain health through public and physician education, self-education and self-assessment tools, memory screening 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’s lead by HHS, and the action items of the Healthy Brain Initiative lead by the Alzheimer’s Association and CDC. The program facilitates memory and cognition management pathways for primary care physicians, and collaborates with Hoag’s other institutes, including the Hoag Family Cancer Institute and Hoag Orthopedic Institute, to mitigate threats to cognition caused by treatment and/or surgery.

OCVBAP educates the public through online self- assessment and in-person memory assessment services. To date, 3,900 community members have used OCVBAP’s online services to learn about their memory, depression, and ADRD risk factors for CI. The OCVBAP website has attracted steady use by community members each year.

OCBVAP’s in-person memory assessment service is provided at five assessment locations (Hoag Newport, Hoag Irvine, Oasis Senior Center, Hoag Medical Center at Huntington Beach, Florence Sylvester Senior Center). To date, 4,387 assessments have been provided to community participants. Over 25% of participants were referred by their primary care physician; the referral rate is increasing as OCVBAP’s physician education and outreach effort continues.

The program’s effort to reach the at-risk population is evident: almost 25% of all participants were under 65 years old, and 38% were 65 to 74 years old.

Cognitively normal individuals learn about maintaining their cognitive health through managing existing medical conditions, modifying their lifestyle, and engaging in regular physical, cognitive and social activity. When community members are identified with CI, they 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 45 years old.

Among Orange County community participants in the OCVBAP cognitive assessment service, the rate of CI was 23%, which is consistent with nationally published data in primary care settings. The CI rate increases with age.

Support and Education

The Memory and Cognitive Disorders Program provides ongoing public and physician lecture series,and works with community organizations serving seniors and persons with AD and related disorders.

From July 2015 to June 2016, OCVBAP provided 10 public seminars and six CME programs, educating over 1,000 community members and 170 physicians on maintaining cognitive health and effective cognitive healthcare delivery.

Clinical Research

Lilly & Company H8A-MC-LZAX: Effect of Passive Immunization on the Progression of Mild Alzheimer’s Disease: Solanezumab (LY2062430) Versus Placebo (Shankle


TauRx TRx-237-015: Randomized, Double-Blind, PlaceboControlled, Parallel-Group, 12-Month Trial of Leucomethylthioninium bis(hydromethanesulfonate) in Subjects with Mild to Moderate Alzheimer’s Disease October 2013-(Shankle)


TauRx TRx-237-007 - A Double-Blind, Placebo-Controlled, Randomized, Parallel Group, 12-Month Safety and Efficacy Trial of Leuco-methylthioninium bis(hydromethanesulfonate) in Subjects with Behavioral Variant Frontotemporal Dementia (bvFTD) (Shankle)


Avid Radiopharmaceuticals, Inc 18F-AV-1451-A05 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 (Shankle)


TRx-237-020: An Open-Label, Extension Study of the Effects of Leuco-methylthioninium bis(hydromethanesulfonate) in Subjects with Alzheimer’s Disease or Behavioral Variant Frontotemporal Dementia (Shankle)


Biogen 221AD302: 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 - (Shankle)


Avid F18-AV1451-A16: A Clinico-Pathological Study of the Correspondence Between 18F-AV-1451 PET Imaging and PostMortem Assessment of Tau Pathology (Shankle)


F. Hoffman-La Roche Protocol BN29552: A PHASE III, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBOCONTROLLED, PARALLEL-GROUP, EFFICACY AND SAFETY STUDY OF CRENEZUMAB IN PATIENTS WITH PRODROMALTO-MILD ALZHEIMER’S DISEASE (Shankle)


American College of Radiology: Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) Study: A Coverage with Evidence Development Longitudinal Cohort Study (Shankle)

Publication, Lectures, Book Chapters

PEER-REVIEWED JOURNAL PUBLICATIONS

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. 2015 Oct 28. [Epub ahead of print]


Alexander GE, Satalitch TA, Shankle WR, Batchelder WH. A Cognitive Psychometric Model for Psychodiagnostic Assessment of Memory Deficit Disorders. Psych Assessment. 2016;28(3):279-93.


Hara J, Shankle WR, Barrentine L, Curole M. Treatment of Hyperhomocysteinemia in Mild Cognitive Impairment, Alzheimer’s Disease, and Other Dementing Disorders. JNHA. (in press)


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. JAD. (in press)


Chien DT, Szardenings AK, Bahri S, Walsh JC, Mu F, Xia C, Shankle WR, Lerner AJ, Su MY, Elizarov A, Kolb HC. Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808. JAD. 2014; 38(1):171-184.

CONFERENCE PRESENTATIONS

Shankle WR. Hoag Neurosciences Symposium. Oral Presentation. Newport Beach, CA, March 27, 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.