| 2017 Turken Research Award and Symposium | Dear Doc |
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The Mary S. Easton Center for Alzheimer's Disease Research at UCLA has very active teams working on basic research, drug discovery, biomarkers for early diagnosis and clinical activity including clinical trials, cognitive testing and patient care. [PDF Version]
The 2017 Turken Research Award and Symposium began with a morning tour of 2016 Turken Award recipient, Dr. Lin Jiang’s laboratory where he is using computer models to help design new drugs that block the formation of the toxic protein aggregates that most researchers believe cause Alzheimer’s disease (AD). He gave a presentation on this work entitled “New Approach to Treat Alzheimer's Disease and Others by Blocking Cell-to-Cell Spreading” where he talked about how he models the spread of tau peptide aggregates from one cell to another in a circuit. He also explained his recent discovery that amyloid-beta (Abeta or Aβ) peptides can accelerate this model of “tau pathology.” Dr. Jiang has designed highly specific new aggregation inhibitors and even found several aggregation inhibitor drug candidates that are already FDA approved and therefore much easier to try to move to the clinic.
Our Turken Day guests were also able to visit with Dr. Varghese John and learn how he and his Easton Drug Discovery team are developing new drugs in a multi-pronged approach to safely reduce beta-amyloid production. One of these Easton Drug Discovery strategies was revealed more fully in an oral presentation by a postdoctoral fellow in Dr. John’s laboratory, Dr. Asa Hatami. His talk was entitled “Differential Inhibition of the Alpha-Secretase ADAM10 by Abeta Variants Containing FAD Mutations.” Dr. Hatami explained that Alpha- Secretase is a protective enzyme that prevents Abeta from being produced and that some familial AD mutations appeared to cause AD by inhibiting this protective activity. This is a new and important finding that encourages further development of drugs that increase this protective alpha-secretase levels and activity. The Easton Drug Discovery team has other types of drug and novel approaches in their pipeline.
We were privileged to have opening remarks and the strong support of our Department Chair, Dr. S. Tom Carmichael. Dr. Carmichael is a world leader in the field of stroke research, particularly in efforts to understand the molecular pathways that enable recovery after strokes. Since it is very clear that small strokes can accelerate cognitive decline in people with Alzheimer’s pathology, Dr. Carmichael’s research can help inform AD researchers about how to counter that acceleration toward dementia produced from little strokes. This is not just a small theoretical concern because some 30-50 percent of Alzheimer’s patients have significant vascular disease and little strokes that appear to have accelerated and contributed to their dementia. Thus, a prevalent form of Alzheimer’s disease is not caused solely by pure AD or vascular disease, and is therefore called “mixed dementia”.
This year's Turken Award winner, Dr. Eric Hayden, informed us more about mixed dementia in the second half of his talk "Investigations into Pure Amyloid β-protein Oligomers and an Introduction to a Novel Mixed Dementia Model." But first, he spoke about small Abeta aggregates called Abeta oligomers that can be toxic to neurons and cause harmful neuroinflammation. While they may play a critical role in AD, they are very unstable and come in many different forms and sizes which makes them very difficult to study. As a project scientist with Dr. David Teplow, Dr. Hayden has created stable Abeta oligomers that don’t fall apart which has allowed their group to begin to define their individual physical, chemical and toxic properties. In a separate project, working with stoke researcher Dr. Jason Hinman, Dr. Hayden is developing a mixed dementia model by inducing small strokes in mice that develop Abeta plaques and also carry the major genetic risk factor, apolipoprotein E4 (ApoE4). While it is still early in their studies, these mice with combined pathology are revealing unexpected and novel interactions between stroke and AD pathology.
Of course, with so many UCLA researchers with exciting and interesting new work on Alzheimer’s disease, we had many Turken day participants sharing some of their findings in poster presentations. I am pleased to report that this was another successful event and would like to thank Ms. Beth Devermont, President and Director of the Sam and Ida Turken Charitable Foundation for her continuous support of this Award and our staff, particularly Nancy Osuch, for organizing the event.
”An Interview with Dr. Mario Mendez About Posterior Cortical Atrophy.”
Photo: Mario F. Mendez, M.D., Ph.D.
Mario F. Mendez, M.D., Ph.D., Professor of Neurology and of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA and the Director, Behavioral Neurology Program and VA Neurobehavior Unit.
Posterior cortical atrophy (PCA) is a progressive and disproportionate loss of visual functions associated with neurodegeneration of posterior cortical regions. This clinical syndrome was originally described by Dr. D. Frank Benson, the founder of Behavioral Neurology at UCLA. Today we know that the most common cause of PCA is a visual variant of Alzheimer’s disease (AD).
Most people think of Alzheimer’s disease (AD) as involving elderly individuals with memory difficulty. Although this is true in the vast majority of cases, about 5% of patients with AD have a young-onset (40’s to early 60’s) and often non-memory presentation. One of the most common young-onset forms of AD is the visual syndrome of Posterior Cortical Atrophy (PCA). Researchers believe that some unknown factors cause the changes of AD to shift backwards and concentrate in visual cortical areas.
1. How does a neurologist diagnose someone with PCA? Can you please explain the symptoms of PCA?
First, it is important to understand the distinction between PCA, which is a clinical syndrome and not a disease, and AD, which is a disease and a cause of PCA. Physicians diagnose clinical symptoms that go together as a “syndrome”. The doctor must then decide what is causing the syndrome. In the case of the clinical syndrome of PCA, the cause is AD in about three-quarters of cases.
In order to diagnose someone with PCA, the doctor takes a history of symptoms and concerns, does an examination, and evaluates a brain scan. A consortium of researchers have developed criteria for PCA that include the following:
- An insidious onset and gradual progression of early disturbances of visual and other posterior cortical functions.
- Problems in at least three of the following must be initially present:
- Localizing, such as finding buttons, nobs, words, or objects by sight.
- Seeing more than one item or a whole scene at a time.
- Recognizing known objects by sight.
- Drawing and copying simple figures.
- Getting around in familiar surroundings.
- Moving their eyes to see an object.
- Orienting body parts, such as arms and legs, so as to dress.
- Reaching out and touching an object by sight.
- Seeing well enough to read.
- Other specific associated posterior cognitive abilities.
- There must also be relative sparing of memory, language, organization and planning, and behavior and personality.
- Brain scan evidence of predominant disease involving the posterior cortex where complex visuospatial and visuoperceptual processing occur (occipito-parietal and occipto-temporal areas).
2. How do patients with PCA present to the doctor?
Patients with PCA usually present with visual complaints, most commonly involving spatial processing. These visuospatial problems affect the manipulation of controls (e.g., remote controls, buttons on phones or stoves, letters on keyboards), navigating their surroundings (getting lost, finding items in refrigerator or house, placing items correctly), getting dressed (finding clothes in closet and orienting arms and legs to the garment), and driving (staying in lanes, seeing traffic signals, parking the car). Many patients first notice PCA on reading, particularly in losing their visual place on the page or line. Others complain of the losing an object that they were looking at, loss of depth perception, problems with glare, and other unusual visual symptoms.
These visual complaints usually lead to consultations with eye doctors, either ophthalmologists or optometrists. These patients often undergo changes in glasses and other procedures, without benefit, before the suspicion is raised that the problem is from the visual brain and not the eyes. It is usually at this point that PCA patients are referred to a neurologist.
3. Are MRIs, PET scans, and other special tests used to help with diagnosis?
Yes. In the general evaluation, MRIs exclude other causes of posterior cortical injury and may show some atrophy in that region. A brain PET scan can reveal the characteristic PCA pattern of decreased activity in the posterior cortical region.
Additional important tests involve eye examinations and special Alzheimer tests. First, it is important to rule-out any problem with the eyes or primary vision that might be contributing to the problem. In particular, plotting the integrity of the patient’s visual fields can aid in determining degree of impairment. Second, it is also important to be as sure as possible that the PCA is due to AD and not to another condition. For this reason, the doctor may recommend Alzheimer biomarker tests, such as amyloid PET scans or spinal fluid analysis.
4. How does PCA affect a person’s activities of daily living?
If the patient has PCA, they behave, in many ways, as a visually impaired person does. In effect, they are partially sighted. This means that the focus is often on making the environment safe and more visually salient. Caregivers must consider problems with stairs, obstructing objects, visual clutter, and poor lighting. Simplifying, and sometimes color coding, the environment can be helpful. In addition, techniques and aids for the partially sighted, such as large print devices and audiobooks, benefit these patients.
5. What is the prognosis for someone with PCA?
The prognosis for PCA is similar to that of other patients with Alzheimer’s Disease (AD), which includes a disease course often of a decade or more. Some studies suggest that the course can be long and slow. Unfortunately, as PCA progresses, patients develop the memory and other cognitive difficulties that are characteristic of typical AD.
6. What are the current treatments for PCA?
They are similar to AD with the addition of interventions to improve sight, as described above. There are drug and other management options for AD, from memory medications such as donepezil and memantine, to support groups and community services. Patient with PCA may benefit from these as well as those with typical AD. Additionally, caregivers may consider PCA as a visually-impaired form of AD. This involves that added task of seeking techniques and interventions focused on the partially sighted. Special services for visual impairment are applicable to PCA patients as well as those who are impaired from other causes of poor eyesight.
One added and important management in PCA is the treatment of depression. Investigators and clinicians have observed that, as PCA patients begin to lose the ability to see the world, they retain the ability to see themselves. This often leads to depression and further disengagement beyond the limitations caused by their vision. Vigorous treatment of depression can help these patients greatly, increasing their engagement and participation in activities with family and friends.
If you or a loved one is experiencing any of the symptoms of PCA and have yet to be diagnosed, please call the Easton Center, Dementia and Memory Disorders Clinic at (310) 794-6039 or UCLA Behavioral Neurology Clinic at (310) 794-1195 to schedule an appointment with Dr. Mendez and colleagues. Visit www.eastonad.ucla.edu or www.ftd.ucla.edu for more information on PCA and the other forms of dementia.
If you would like to advance Alzheimer's disease research, please consider participating at the Easton Center. Below are the current recruiting trials. For a complete list of enrolling studies, visit our website at www.eastonad.ucla.edu.
EASTON CENTER KAGAN CLINICAL TRIALS PROGRAM
- Alzheimer’s Disease Neuroimaging Initiative 3 (ADNI3) Protocol
- ENGAGE (221AD301 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer’s Disease) Study
- NEAT (Nicotinamide as an Early Alzheimer’s Disease Treatment) Study
- SUVN-502 Study with Donepezil and Memantine for the Treatment of Moderate Alzheimer’s Disease
BEHAVIORAL NEUROLOGY PROGRAM
- Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks
- Neuropsychological Test Measures in Behavioral Variant Frontotemporal Dementia (bvFTD) and Healthy Subjects
- Curcumin and Yoga Therapy for Those at Risk for Alzheimer’s Disease
- E2609 Study for MCI and Early Alzheimer’s Disease (MissionAD1)
- Effect of Grapes Dietary Supplement on Brain Metabolism and Cognition
- The UCLA Caregiver Sleep (CARES) Study
For information on other upcoming lectures and events, please visit the Easton Center Community Calendar.
South Bay Dementia Education Consortium
Date: Tuesday, March 20, 2018
Time: Reception 5:00 P.M. – 5:30 P.M. (PDT); Program 5:30 P.M. – 7:00 P.M. (PDT)
Location: Redondo Beach Main Public Library
303 N. Pacific Coast Hwy., 2nd Floor
Redondo Beach, CA 90277
Guest speaker, John M. Ringman, M.D., M.S., Professor of Clinical Neurology, Keck School of Medicine at USC will present “New Perspectives on Genetics: What is My Risk for Alzheimer’s Disease? Is Alzheimer’s in My Genes?”
Dr. Ringman will address how to assess one’s risk for developing Alzheimer’s disease based on current information regarding genetics. He will also discuss APOe, the newest developments in AD genetic risks, genetics of other causes of dementia, and important considerations for when considering genetic testing.
Monica Moore, Easton Center's Community Health Program Manager, will be available on site to answer any questions you might have.
Seating is limited. For RSVP, please call: (310) 374-3426 x256 [flyer]
23rd Annual UCLA Research Conference on Aging
Date: Wednesday, May 16, 2018
Time: 8:00 A.M. – 12:30 P.M. (PDT)
Location: Ackerman Grand Ballroom
308 Westwood Plaza
Los Angeles, CA 90095
The event provides opportunities for researchers and community members to network, be apprised of the latest research across a broad range of topics including aging biology, epidemiology, clinical research in older adults, public health, and health policy, and to spark new and innovative collaborations. The program includes one keynote lecture, two poster sessions, and plenary talks. http://geronet.ucla.edu/rcoa