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Memory Medication: Today and Tomorrow

How neurons interact over time and space may be the key to the brain's secrets.

The recent announcement of a novel cognitive enhancer, J147, has generated excitement among patients and families affected by Alzheimer’s Disease, a devastating neurodegenerative dementia that affects more than 5 million people in the United States already. As baby boomers age, estimated to be between 74 and 79 million, memory loss will become an even greater public health concern than it is today.  Future medications in clinical trials are aimed at staving off Alzheimer's, which may develop years before symptoms are noticeable.  While available medication is primarily aimed at attenuating symptoms of the established disease, some physicians question its value for nursing home patients. 

Alzheimer’s Medication: Dr. Ellison

James M. Ellison, M.D., M.P.H., is a proponent of appropriate integration of cognitive enhancing medications into a comprehensive treatment program for patients with Alzheimer’s Disease and some other dementias.

He says that “As a result of brilliant research during recent decades, we now recognize that Alzheimer’s Disease is actively destroying the brain for many years before our patients develop clinical signs of dementia.  We should do all that we can to identify those at risk earlier and intervene as early as possible. These interventions are beneficial even after cognitive changes are present, but may be of greatest importance during the so-called pre-symptomatic phase of Alzheimer’s Disease. Research has shown a very long presymptomatic course before cognitive impairment becomes manifest in the later decades.”  

Dr. Ellison, who pointed out that there is no medication as yet approved for use in the pre-symptomatic phase, is an Associate Professor of Psychiatry, Harvard Medical School, as well as Director of the Geriatric Psychiatry Program and the Memory Disorders Clinic at McLean Hospital in Belmont, MA.

New Clinical Trials: Dr. Salloway

At Brown University, Stephen Salloway, M.D., M.S., says that there are new clinical trials underway at Butler Hospital in Providence,RI, to address prevention. “The biggest impact over time will be with medications that modify the risk so as to delay onset. With new brain imaging, we can detect the amyloid plaque.”

Beta-amyloid is from a larger protein found in fatty membrane that surrounds nerve cells. It is considered a sticky chemical that builds into damaging groups, plaques, that clump together and block cell-to-cell activity.

“We are currently working on a prevention trial for people 70 to 85 -- those with amyloid plaque and those without.  And we are expecting to be able to offer a vaccine to people whose brain imaging identifies amyloid plaque.”

The team from Brown and at Butler Hospital is involved in a National Institute of Health public-private partnership.  And Dr. Salloway added, “We will be doing another prevention trial for families with early indications of Alzheimer’s so that we may begin treating this population years prior to the onset.  Over time, early detection will yield the biggest payoff.”  At Butler, Dr. Salloway is Director of Neurology and the Memory and Aging Department and a Professor of Neurology and Psychiatry at the Warren Alpert Medical School of Brown University. 

Physican Agreement on Early Stages

With mild forms of dementia, there seems to be agreement among physicians that medications work.  However, Dr. Ellison cautions that “the appearance of mild cognitive symptoms, usually in the form of short-term memory difficulties or executive dysfunction, does not mean medications should be given.”

There are two categories of cognitive enhancers currently available in the United States. The cholinesterase inhibitors are Food and Drug Administration approved for mild dementia and beyond. Donepezil (Aricept™), Galantamine (Reminyl™), and Rivastigmine (Exelon™).  Memantine (Namenda) is indicated for moderate dementia and beyond.

Dr. Ellison noted, “Our new psychiatric diagnostic manual, the DSM 5, will affect our diagnostic terminology and change the name of dementia to Major Neurocognitive Disorder, but for the diagnosis, it will still require a significant impairment in social or occupational functioning related to the cognitive changes. “

He added, “While cognitive enhancers have been shown to be moderately beneficial, for many patients the benefits are significant in sustaining cognitive function and also activities of daily living.”

With patients who take medication, researchers have found a small but significant reduction in the burden carried by caregivers.

However, Dr. Ellison stressed that these medications are not given in isolation. “These contribute to a larger care program that includes patient and family psychoeducation, problem-solving, psychotherapy as indicated, information about supportive resources, help with advance-stage planning, supervision for safety and stimulation, and, when possible, participation in a cognitively engaging program of activities.”

Later Stage Medication Opinions Differ

There appears to be a movement to cut down on medication in nursing homes, especially drugs that over-sedate or the antipsychotics.  But this debate differs from the memory drugs.  However, there are physicians today who believe that once a patient is in a nursing home, there is no longer a need for memory enhancing drugs.

Dr. Ellison said, “Withdrawing cognitively enhancing medications is often an individualized decision that takes many factors into account including the patient’s previous response to the medication, the current stage of dementia, as well as the patient’s previously expressed wishes about prolonged treatment, side effects, and cost of the medications.” 

The Medication Future

With J147, developed by Salk Institute for Biological Studies, LaJolla, CA, scientists  tested a hybrid molecule derived in part from a component of curry, a spice known to have some anti-Alzheimer’s effects. The medication they developed was then tested in mice specifically bred to develop an Alzheimer’s-like brain disease and the results are promising. These initial findings were published in Alzheimer’s Research and Therapy on May 14, 2014.  Salk scientists develop drug that slows Alzheimer's in mice 

Dr. Salloway said that “With millions being affected by Alzheimer’s, we must add to the treatment that we currently have as some of these work on modifying the underlying illness.  We are trying to lower the amyloid and improve cognitive function, which is one reason for these our trials.” 

With regard to the dementia and Alzheimer’s, Dr. Salloway expressed what he calls a need for “open-mindedness.”  He said, “For Alzheimer’s, it is going to require a combination of treatments both medical and psychological and we need to be very open to innovation that comes down the pike. We need to be planning combination treatment trials to maximize the therapeutic impact.  Researchers will have to be creative and collaborate in order to foster an innovative environment.”

Prevention of Memory Loss Today

In the world of memory, many people are concerned about the here and now.  At the American Psychiatric Association conference last month, Gary Small, MD, Professor of Psychiatry and Biobehavioral Sciences at UCLA, and director of the Memory Clinic and Director Center on Aging talked about the need to maintain one's brain health. Live-Blogging the 2013 APA Annual Meeting: Sunday 

For those who wonder what can be done today, Dr. Ellison has these suggestions: “Make healthy lifestyle choices including good medical care, physical exercise, good nutrition, cognitive stimulation, and adequate sleep.  Take advantage of leisure time, socializing and connecting with others.  Develop a sense of purpose.  These suggestions are valuable for all of us and especially for those at risk of later life dementia.”

BRAINfeedback

In May it was announced that there will be a new Advisory Committee Working Group on the new BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative. The focus is on new technologies to enable scientists to create a picture of brain function and “the interaction of circuits involving large numbers of neurons interacting with each other over time and space, and will ultimately advance understanding of brain diseases like epilepsy, schizophrenia, autism, and Alzheimer’s disease.” BRAINfeedback.nih.gov

Rita Watson, MPH, is a MetLife Foundation 2013 Journalist in Aging Program of the Gerontological Society of America and New America Media

Copyright 2013 Rita Watson/ All Rights Reserved

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Rita Watson is an Associate Fellow at Yale's Ezra Stiles College and a columnist for The Providence Journal.

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