Yael Shrager (yshrager@ucsd.edu)

Lab PI: Larry Squire
Undergraduate Institution: Stanford University
Med-into-Grad clinical training area: Neurodegenerative Disease – Alzheimer’s
Main clinical mentors: James Brewer jbrewer@ucsd.edu

Quote:  “The most important insight my training gave me was the realization that dementia manifests in various ways, and it is often quite difficult to make a diagnosis without autopsy details.  I also came to understand how ineffective the current treatments are for Alzheimer’s disease.”

Rationale for Med-inito-Grad training:
Medical Training and Identification of medically-relevant research issues:
Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs:
Diagnostic, therapeutic, and Research collaborations:
Long term impact.:
Advice for new trainees--Autumn preparatory quarter:
Advice for new trainees--Winter clinical training quarter:
Take home perspective on Med-into-Grad at UCSD:

Rational for Med-into-Grad training: My thesis research aims to understand the cognitive function of the medial temporal lobe, which comprises the hippocampus and entorhinal, perirhinal, and parahippocampal cortices.  The medial temporal lobe is known to support declarative memory – that is, memory for facts and events.  Traditionally, it has been thought the medial temporal lobe is not required for other perceptual or cognitive functions, so that damage to the medial temporal lobe results in a circumscribed memory impairment, leaving other cognitive functions intact.  My thesis work has further tested whether other cognitive functions depend on the medial temporal lobe.  In a number of experiments, I have tested patients with lesions limited to the hippocampus as well as patients with larger lesions that extend throughout the hippocampus and include additional medial temporal lobe structures for their visual perceptual, working memory, and path integration abilities.  These abilities are intact in the patients as long as demands are not made on long-term memory (a capacity which is known to be impaired in these patients).
The damage associated with Alzheimer’s disease is thought to first occur in the medial temporal lobe, specifically in entorhinal cortex.  At more advanced stages of the disease, perhaps the most extensive damage is found in the medial temporal lobe.  Consistent with the anatomy of the damage, patients with Alzheimer’s disease show, even at early stages, significant memory impairment.  I thought that my research on medial temporal lobe function might help inform understanding of Alzheimer’s disease, or conversely, that studying patients with Alzheimer’s might give insight into medial temporal lobe function.

Medical training and identification of medically-relevant research issues: I attended the core meetings of the Alzheimer’s Disease Research Center, where the clinicians described cases each week and would try to agree on a diagnosis based on the available information (sometimes only functional information, sometimes also autopsy details).  I also attended clinic sessions, where I sat in on the patient interviews and the neurological exam.  I attended psychological testing sessions.  And lastly, I attended an Alzheimer’s disease journal club.  I learned how the disease manifests itself and how it affects patients in terms of task performance and also on a psychological and emotional level.
The most important insight my training gave me was the realization that dementia manifests in various ways, and it is often quite difficult to make a diagnosis without autopsy details.  I also came to understand how ineffective the current treatments are for Alzheimer’s disease.

Research collaborations:  One of my experiments from early in graduate school involved visual perceptual tests that might help to functionally detect damage just lateral to the medial temporal lobe.  I learned that two forms of dementia (Alzheimer’s and Lewy Body) can be difficult to dissociate from one another based on the current test battery.  Dr. Jim Brewer thought that by using my tests, he might be able to differentiate between the two conditions.  Testing has not yet begun for this project. 

Long term impact: This training acted as an introduction to the effects of Alzheimer’s disease and brought to mind the possibility of having one line of research that is clinically oriented.  The laboratory I will join as a postdoctoral researcher pursues as one research direction the study of Alzheimer’s, so I might be a part of that endeavor.

Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs: I have acquired some understanding of diagnostics and therapeutics of Alzheimer’s disease and other forms of dementia.  Diagnostics, while the patient is alive, are based on functional tests – a psychological test battery and a neurological exam, as well as an interview with the patient and with a witness (relative, caregiver, etc.).  The ultimate diagnosis is postmortem and is based on brain damage.  Therapeutics include various drugs, at various levels of strength, that are relatively ineffective.  There is currently no cure.

Advice for new trainees: In the autumn, read up on the disease you will be studying.  It would be best if you can get your MSP advisor to direct you.  Also, agree on an overall plan for your clinical training quarter.  Specifically, discuss the activities you will participate in, how often each one will occur, etc.
You should have your MSP advisor explain to you what is involved in each activity.  For example, you advisor might think that telling you that Wednesday is ‘clinic day’ is self-explanatory, but you should ask (if you don’t know) how this is structured and what actually happens in each clinic session and what the goal is.  It is also a good idea either now or at the outset of the clinical training quarter to talk to your advisor and to understand what your role is, and how that role changes in each activity you are involved in.  That is, should you just sit quietly and observe, saving questions for after the patient has gone, or can you ask questions throughout the process. 
Also, if you work with different individuals on different days (and you likely will), you should likewise ask them what is involved in each session and what your role should be in each session (as this can change from one session to another and from one clinician to another).  For example, should you just sit quietly and observe, saving questions for after the patient has gone (if this is a clinical session), or can you ask questions throughout the process.

Take home perspective on Med-into-Grad at UCSD: I would recommend this program to students who feel they can work this out with their lab schedule and who have a strong interest in the topic.  Regardless of whether one continues to pursue translational research, it gives one perspective about different paths one can take in a research career and also opens up dialogue between researchers and clinicians.