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By Arline Kaplan
Psychiatric Times February 2005 Vol. XXII Issue 2

For Jeffrey L. Cummings, M.D., an interest in identifying and treating neuropsychiatric and neurodegenerative disorders, particularly Alzheimer's disease (AD) and other dementias, began early. After growing up in the rural town of Basin, Wyo., Cummings went to the University of Wyoming (graduating with high honors) and then on to medical school at the University of Washington (UW) in Seattle.

As an undergraduate student and even as a high school student, I was greatly attracted to philosophy, natural history and biology," he told Psychiatric Times. "So as I entered my undergraduate studies, the zoology and premedical courses attracted me to medicine, but the philosophical theme drew me to behavior, and to the choices of neurology or psychiatry. Undecided between the two, my career has been a union of those two disciplines."

At UW, Cummings worked with a neurologist, John Green, M.D. An epileptologist "committed to humanitarian care," Green encouraged Cummings "to think about the relationship between neuroscience and society and between neurological disease and the human mind and human spirit."

After his studies at UW, Cummings completed a rotating internship at Hartford Hospital in Hartford, Conn., followed by a residency in neurology and a fellowship in behavioral neurology at the Boston University School of Medicine in Massachusetts and another fellowship in neuropathology and neuropsychiatry at the National Hospital for Neurological Diseases in London.

It was at Boston University that Cummings met neurologist D. Frank Benson, M.D. Benson's 1975 book Psychiatric Aspects of Neurological Disease was a benchmark publication in which neurologists and psychiatrists contributed to discussions of brain diseases that produced psychiatric manifestations.

Cummings said, "Frank was very interested in behavioral neurology and was a wonderful mentor who was tremendously committed to education. [He] influenced me to go into behavioral neurology and to consider the dementing disorders and other neurocognitive illnesses."

Like his mentors, Cummings has continued the tradition of teaching and mentoring. In 1980, he became assistant professor of neurology at the School of Medicine at the University of California, Los Angeles (UCLA), and in 1992 became professor of neurology and of psychiatry and biobehavioral sciences. In 1996, he was made the Augustus S. Rose Professor of Neurology. Since 2002, he has served as executive vice chairperson in the department of neurology and, since 2003, as director of the Deane F. Johnson Center for Neurotherapeutics at UCLA.

Equally important, he has directed UCLA's Dementia and Neurobehavior Research Fellowship for over 15 years. Many of the approximately 50 fellows he has trained during that time currently hold leadership positions in dementia programs throughout the country. He has also supervised the training of some 19 international scholars and been a presenter or plenary speaker at numerous international conferences, including those in China, India, Indonesia and Egypt.

A prolific writer, Cummings has authored and/or edited 20 books, more than 450 peer-reviewed papers, some 170 chapters in books and several hundred abstracts. He is associate editor for several publications and is on the editorial board of several journals, including Dementia and Geriatric Cognitive Disorders and Alzheimer's Disease and Associated Disorders.

His relationship with Psychiatric Times began in the 1980s when he was lecturing in the Southern California area and John Schwartz, M.D., Psychiatric Times' founder and editor in chief, asked him to speak at Psychiatric Times'-sponsored meetings. In 1988, Cummings began writing his widely read "Brain and Behavior" column, which appeared four to six times a year until 1996. Since then, he occasionally contributes articles, such as "Advances in Alzheimer's Disease Research: Implications for New Treatments" in January of 2000 and "New Practice Parameters for Dementia" in October of 2001. He has served on the publication's editorial board since 1992 and helps as an occasional peer reviewer.

Because he is executive vice chairperson of UCLA's department of neurology, Cummings was asked about the major changes he has seen in the field during the last 20 years.

"The advent of imaging has been one of the major diagnostic advances and is increasingly playing a role in understanding the pathophysiology of neurological diseases. Imaging in all of its varying modalities has been one of the major developments in terms of neurology," he said.

Another major advance, he added, is the advent of neurotherapeutics. There has been the discovery and proliferation of new treatments for AD, Parkinson's disease, amyotrophic lateral sclerosis, epilepsy, multiple sclerosis and migraine. "There has been a remarkable paradigm shift in neurology from being a largely diagnostic specialty to being one that is largely a therapeutic specialty," he added.

Looking ahead, Cummings said, "The increasingly precise definition of the molecular mechanisms of neurological disease provides a variety of targets for pharmaceutical intervention. I think we are on the verge of seeing much more meaningful therapies for a number of neurological diseases, including neurodegenerative disorders."

The Deane F. Johnson Center for Neurotherapeutics that Cummings helped initiate will be at the forefront of identifying those meaningful therapies. "This is a multidisciplinary clinical trials program structured to treat multiple types of neurological illnesses and also to provide educational services to physicians, pharmaceutical company personnel and the public," he explained.

Because of his interest in developing and testing new treatments for AD, Cummings has long worked for expanding research in this field and was able to obtain federal funding from the National Institute on Aging (NIA) as well as funding from the state of California. In 1991, UCLA successfully competed for an Alzheimer's Disease Core Center under his leadership. In 1998, the Alzheimer Disease Research Center was established by a grant from NIA as a mechanism for integrating, coordinating and supporting new and ongoing research by established investigators in AD and aging. That same year, the center began receiving recurring funding from the state to be applied to new research efforts.

"The availability of this funding greatly augments our Alzheimer's research, giving us the ability to recruit patients; to study them in drug trials; to seriously study the brain when patients succumb to the illness; to collect imaging and genetic information on them; and to provide education to the community," Cummings said.

In terms of his own research on cognitive problems, Cummings said, "We have recently been looking at the neuropsychiatric symptoms that occur in patients with mild cognitive impairment to help us understand whether the behavioral changes might help us predict which patients with mild cognitive impairment are going on to Alzheimer's disease. There is substantial evidence that patients who have mild cognitive impairment plus depression or plus apathy are those who are going to progress relatively soon to a full-blown diagnosis of Alzheimer's disease."

In the search for a cure for AD, research efforts at multiple centers have focused on preventing or reversing amyloid deposition in the brain. Efficacy evaluation of these anti-amyloid therapies would greatly benefit from tools that enable in-vivo detection and quantitation of amyloid deposits in the brain. Cummings' colleague John M. Ringman, M.D., in conjunction with Jorge Barnos, Ph.D., and Gary Small, M.D., is engaged in amyloid imaging. Ringman is studying patients who have an inherited form of AD. At this point, Cummings explained, one of the mysteries is how long before the disease becomes manifest does the protein accumulate in the brain.

"We are imaging those patients with amyloid imaging to determine when the protein that accumulates in the brain of the Alzheimer's patient is laid down," he explained. "Is it only a few years or 20 years? Dr. Ringman's population along with this novel form of imaging will help us answer that [question]."

Cummings is also enthusiastic about a study by colleague Il-Seon Shin, which was first presented as a poster at the International Psychogeriatric Association meeting in Seoul, South Korea, last September, and now is in press at the American Journal of Geriatric Psychiatry. The study involved some 40 patients with AD, who were evaluated at UCLA using both the Quality of Life - Alzheimer's Disease (QoL-AD) instrument and the Neuropsychiatric Inventory (NPI). The article discusses the relationship between neuropsychiatric symptoms in AD and their impact on quality of life for patients and their caregivers.

"What we can show is that agitation is a major negative influence on quality of life for the caregiver, and depression has a major negative influence on both the quality of life for the caregiver and the patient," Cummings said. "Our message ... is that neuropsychiatric symptoms are a very important part of the dementing illnesses, and they have major impact on quality of life for both the patients and the family members who care for them."

As immediate past president of the board of directors for the Alzheimer's Association of Los Angeles, Cummings is attuned to the needs of caregivers and patients with dementia. According to the Alzheimer's Association, in Los Angeles County alone there are more than 150,000 people afflicted with AD or related dementias.

Cummings pointed out that assistance to the caregiver can improve the life of both the patient and the caregiver. He explained that referral to the Alzheimer's Association and other caregiver groups; use of educational materials, so caregivers can understand the disease better; and the provision of some interventions (e.g., support groups) that can reduce the burdens on caregivers all have an effect on both patients and caregivers.

Another aid is individual therapy for caregivers who are having more substantial psychological struggles, he said. Additionally, specific educational programs can inform caregivers on how to better manage behavioral disturbances or how to better manage the lack of cooperation that patients may manifest.

With regard to how care for patients with dementia can be improved, Cummings talked about multiple approaches.

"Patients are both underdiagnosed and undertreated once they are identified," he said. "Certainly a patient cannot receive treatment and a caregiver cannot receive services unless it is recognized and discussed that a patient is suffering from a dementing illness. It is very critical that caregivers draw attention to memory deficits in the person that they are concerned about. Similarly, it is very important that practitioners hear these complaints and not just ascribe the deficits to normal aging. They need to do the careful assessments to determine whether the deficits go beyond normal aging and then either evaluate the patients themselves or initiate a referral to a dementia specialist if that is appropriate."

Because primary care physicians are often the first line of medical services that caregivers and patients seek, Cummings explained, "It is very important that they take those complaints seriously and refer [patients] to a dementia specialist, for example, if the complaints are substantive."

Improved pharmacotherapy is a major way to benefit patients, according to Cummings. "We need better drug therapies that are more powerful and that are truly disease modifying and will reduce the progression of the illness or the risk of developing the illness," he said.

"A more systematic use of the available agents may be of benefit to patients," he added. "The cholinesterase inhibitors such as Aricept [donepezil], Reminyl [galantamine] and Exelon [rivastigmine] all have been shown to improve patients' cognition, function and behavior. Similarly, Namenda [memantine] has been shown to improve patients' behavior, cognition and activities of daily living in the advanced phase of the disease. The thoughtful, systematic and persistent use of these drugs would be of benefit to patients."

Reviewing his career, Cummings said the combining of neurology and psychiatry has proven beneficial and is a harbinger of the future:

"Every day these two disciplines become more integrated on both a conceptual and therapeutic basis. One example, the drugs that we use to treat dementia now, such as the cholinesterase inhibitors and Namenda, although developed for their cognitive impact, have been shown to reduce the behavioral disturbances that accompany Alzheimer's disease, so they also have a psychiatric impact. On the other hand, drugs such as Prozac [fluoxetine] have been shown to be not only antidepressants but also to increase the rate of nerve cell generation in the medial temporal lobes of individuals to whom the drug is given. Therefore, there is a neurological impact of psychiatric drugs and a psychiatric impact of neurological drugs that is forcing us to the increasingly obvious conclusion that behavioral disturbances are a product of brain disorders and that neuropsychiatry is a unified field that includes both the neurological basis of psychiatry and the psychiatric manifestations of brain disorders."

Source: 2005 Psychiatric Times.

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