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Thursday, February 20, 2014

Citalopram May Help Reduce Agitation in AD Patients

Dear Readers,

Data from the the Citalopram for Agitation in Alzheimer Disease(CitAD)study was recently published in the Journal of the American Medical Association. The study enrolled 186 patients with probable AD, with an average age of 78, and followed them for nine weeks. None of the participants had major depression or psychosis requiring treatment. Researchers randomly assigned the participants to citalopram or placebo. All participants also received psychosocial interventions that included education materials, crisis management, and individual counseling sessions. At the conclusion of the nine week study, researchers found a statistically significant improvement in the citalopram group compared with the placebo group on the Neurobehavioral Rating Scale-Agitation, which assesses symptoms such as agitation, hostility, and disinhibition, with higher scores indicating more severe symptoms.

Moreover, 40% of the patients receiving citalopram had moderate or marked improvement from baseline severity on the modified Alzheimer's Disease Cooperative Study–Clinical Global Impression of Change score, which assesses items specific to agitation in AD. This compared to 26% of the patients taking placebo. The fact that 26% of patients on placebo improved is important to note, and resulted from the benefits associated with the psychosocial interventions offered as part of the study.

Interestingly, the effect of citalopram on agitation is about the same as that reported for the atypical anti-psychotic drugs, such as olanzapine and risperidon.

What do the results of this study mean? Citalopram is one of many selective serotonin reuptake inhibitors, which are primarily used as anti-depressants. However, in patients with AD, where multiple neurotransmitter systems are becoming disrupted and leading to behavioral symptoms, the use of anti-depressants may provide some benefit. Additional studies should determine the duration of benefits beyond nine weeks of treatment. And, physicians should also continue to emphasize non-pharmacologic strategies to manage agitation. However, this study is a very important first step in looking at new therapies for a very challenging aspect of AD.

Thanks for reading,

Michael Rafii, MD, PhD
Director, Memory Disorders Clinic
Medical Core Director
Alzheimer’s Disease Cooperative Study
University of California San Diego

Author: Michael Rafii MD,PhD at 11:50 AM 0 Comments

Tuesday, February 11, 2014

Increasing Diversity in Clinical Trial Participation in Upcoming ADCS Trials

Over the last few years, increased attention has focused on disparities in health that exist between white Americans and other racial and ethnic minorities. Data from national health surveys has consistently shown that racial and ethnic minorities have higher rates and greater severity of disease than whites, for most, if not all leading causes of morbidity and mortality in the US. These include heart disease, cancer, stroke, diabetes and dementia. Yet, the majority of persons who continue to participate in medical research (including both prevention and treatment trials), often represent the well educated, middle class, married, white population.

Major reasons given for under-representation of minorities in clinical trials include mistrust of researchers and health insitutions, lack of awareness of clinical trials by minorities, inadequate involvement of minority investigators in the recruitment process, cultural differences, economic limitations, less access to both health care and to research facilities. Existing data has shown that minority participation in clinical trials is especially low among older persons.

The major barriers to recruitment and and participation in clinical trials, has traditionally centered around the physician’s concern for the patient, concerns about the conduct of studies, and concerns about the role as both physician care manager and trial researcher. In surveys conducted with physicians, they have often expressed that there a is intellectual and emotional tension between the role they have defined as a physician, which places the health interests of the individual patient first, and the role they define as a researcher, which places the benefit to humanity in general, second. As physicians have not received formal training in either medical school or residency regarding the roles and duties that are associated with that of a Principal Investigator/ Trial Researcher, many are unclear and uneasy about recommending participation in trials to their patients.

Since the ultimate goal of any clinical trial is to recruit and retain study participants, barriers to subject participation must also be understood and minimized. Patient concerns have often related to time commitments needed for participation, negative personal and family attitude regarding trials and their safety, and inadequate evidence of benefits from trial participation.

The challenge facing many large scale trials is to recruit diverse populations to participate in a wide range of prevention and treatment studies. In doing so one must carefully consider how we define diversity in trials. One set of guidelines put forth by the National Institute of Health, was developed to ensure that women and minorities are included in trials, and utilizes purely demographic categories. On the other end of the spectrum are the epidemiologists and social sciences researchers, who define diversity based on descriptors such as age, marital status, sex, race, ethnicity, religious affiliation, education level, socioeconomic status and other socio-cultural attributes. Despite all these efforts for characterization it is very important to recognize that diversity within ethnic and racial group will exist. No group is entirely homogeneous, and as such, many socio-cultural factors can converge and influence the individual’s behavior when a person considers participating in a trial.

Another area that has been shown to impact participation in trials in both minority and non-minority populations is the concept of health and disease. Health and illness concerns vary widely within and across ethnic populations. Chronic illness and disability are not always viewed as problems that are appropriate for intervention. For some groups, illness may be a burden that the individual or family is expected to bear. Such beliefs have shown to alter and affect the probability that people will participate in trials.

With the changes in the healthcare delivery underway, and the emergence of “population health” as a discipline within itself, it is becoming apparent that biomedical research and specifically, clinical trials, can have a prominent role in determining the most effective method of prevention and treatment of chronic conditions for all segments of the population. Encouraging and involving physicians and patients to consider participating in clinical trials should be viewed as opportunities to enhance our understanding of treatment and prevention outcomes.

Dr. Neelum Aggarwal is a cognitive neurologist at the Rush Alzheimer’s Disease Center and Rush University Medical Center, and serves on the clinical trial Steering Committee for the NIH-funded Alzheimer’s Disease Cooperative Study (ADCS).

Author: Neelum Aggarwal MD at 9:31 AM 0 Comments

Thursday, February 06, 2014

Watching Memories Form

Dear Readers,

In a technological tour de force, researchers at Albert Einstein College of Medicine of Yeshiva University have published two studies in the January 24 2014 issue of the journal, Science, that provide an unparalleled window into how the brain makes memories. Such insights into the molecular basis of memory formation have never before been achieved in animals.

Einstein researchers developed a mouse in which they fluorescently tagged all molecules of messenger RNA (mRNA) that code for the beta-actin protein – a key structural protein found in large amounts in neurons and considered a key player in making memories. mRNA is a family of RNA molecules that copy DNA's genetic information and translate it into the proteins that make life possible.

The researchers then stimulated neurons in the mouse's hippocampus, where memories are made and stored, and watched fluorescently glowing beta-actin mRNA molecules form in the nuclei of neurons and travel within dendrites, the neuron's branched projections. They discovered that mRNA in neurons is regulated through a novel process described as "masking" and "unmasking," which allows beta-actin protein to be synthesized from the mRNA.

As readers of this blog will recall, neurons communicate with each other at synapses. Studies over the past 30 years have demonstrated that repeated stimulation increases the strength of synaptic connections by changing the shape of synapses. Beta-actin protein plays an important role in physically strengthening these connections. Memories are thought to be encoded when stable, long-lasting synaptic connections form between neurons in contact with each other.

The relevance of such research in the field of AD cannot be overstated. By seeing the physical nature of memory formation, we can now look at this process in various disease states, including memory robbing diseases such as AD. Further, we can better understand how beta-amyloid may perhaps interfere with the brain’s memory machinery.

Thanks for reading,

Michael Rafii, MD, PhD
Director, Memory Disorders Clinic
Medical Core Director
Alzheimer’s Disease Cooperative Study
University of California San Diego

Author: Michael Rafii MD,PhD at 2:12 PM 0 Comments

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About Us

The Alzheimer's Disease Cooperative Study (ADCS) was formed in 1991 as a cooperative agreement between the National Institute on Aging (NIA) and the University of California, San Diego. The ADCS is a major initiative for Alzheimer's disease (AD) clinical studies in the Federal government, addressing treatments for both cognitive and behavioral symptoms. This is part of the NIA Division of Neuroscience's effort to facilitate the discovery, development and testing of new drugs for the treatment of AD and also is part of the Alzheimer's Disease Prevention Initiative.

The ADCS was developed in response to a perceived need to advance research in the development of drugs that might be useful for treating patients with Alzheimer's disease (AD), particularly drugs that might not be developed by industry.