DIMENSIONS Spring 2010

Focus on Research: Old Drugs Are New Weapons in the Fight against Alzheimer's Disease

by Murray Raskind, MD

UW ADRC Investigators Awarded Grants from National Institute on Aging to Study Drugs Used in
General Medicine for Prevention and Treatment of Alzheimer's Disease

Gail Li, MD, PhD

Gail Li, MD, PhD

“I knew about lowering cholesterol with statins to prevent heart disease, but can it prevent Alzheimer’s disease?”

One of the most important advances in preventive medicine has been the use of the cholesterol-lowering statin drugs to reduce the risk of heart disease. These drugs are taken by millions of healthy middle-aged Americans to help prevent heart attack decades later.

Recent studies suggest that too much cholesterol in healthy middle age may also increase the risk of Alzheimer’s disease in later life. Building on these studies, UW ADRC investigator Gail Li, MD, PhD, and our group performed a preliminary pilot study of the cholesterol lowering statin called simvastatin (“Zocor”) to see if it could slow “pre-Alzheimer’s” processes in healthy adults years or decades before they might develop Alzheimer’s disease. (We now know that early Alzheimer’s changes often begin decades before any symptoms appear.) Simvastatin was chosen because it easily enters the brain. Simvastatin is a safe and widely used medication for the treatment of high cholesterol.

The only way to see if a statin slows the very early changes of Alzheimer’s disease is to measure the “biomarker” indicators of the earliest Alzheimer’s changes in cerebrospinal fluid (CSF). Dr. Li and colleagues gave simvastatin to a small number of volunteers for 14 weeks and measured its effects on (1) the Alzheimer’s disease volunteers’ tau and p-tau (the major chemicals in Alzheimer’s neurofibrillary tangles) and (2) the brain protection factor BDNF.

The Results were Extremely Encouraging.

As Dr. Li hoped, simvastatin decreased CSF tau and p-tau, and increased CSF BDNF. These findings suggest that simvastatin could decrease brain cell damage and improve brain cell survival.

Conclusion.

Perhaps simvastatin in middle age can prevent Alzheimer’s disease in later life.

The National Institute on Aging was so impressed by Dr. Li’s pilot study results that they awarded her a three-year $1.2 million grant to perform a larger definitive study of the effects of simvastatin on Alzheimer’s disease biomarkers in normal middle aged persons. Healthy middle aged volunteers will receive 12 months of simvastatin or placebo.

The pressing need now is for volunteers to participate in Dr. Li’s pioneering study.

To participate in this study research volunteers must:

  • Be age 45-64
  • Have normal memory
  • Not be on medication for high cholesterol or lipids
  • Able to come to the research center for nine visits over one year
  • Have a “study companion” who can answer questions by phone
  • Willing to have two lumbar punctures to obtain cerebral spinal fluid for measurement of tau, p-tau, BDNF and other important brain chemicals

One half of study participants will receive simvastatin and the other half will receive placebo (a pill without any medication in it.)

1-800-317-5382 or 206-764-2069 for more information.

Elaine R. Peskind, MD

Elaine R. Peskind, MD

“How can adrenaline-blocking drugs used for high blood pressure or prostate symptoms calm agitated Alzheimer’s disease patients with no sedation or sleepiness?”

Agitation and aggressive behaviors are the most common reason an exhausted family finally places their loved ones with Alzheimer’s disease into long-term care. Irritability, uncooperativeness with necessary care, anger outbursts, pressured pacing and sleep disruption can exhaust even the most devoted family. The antipsychotic drugs (such as quetiapine and olanzapine) most commonly used to treat agitation/aggression in Alzheimer’s disease often are not effective. In addition, these antipsychotics produce side effects such as excessive sedation symptoms similar to those experienced by persons with Parkinson’s disease, and increase the risk of stroke and death. Clearly, research is needed to develop new treatments for these life altering behavioral problems of the later stages of Alzheimer’s disease that plague patients.

Elaine Peskind, MD, and ADRC investigators have taken a novel approach to discovering effective treatments for agitation/aggression in Alzheimer’s disease. Working with ADRC neuroscientist Patti Szot, PhD, they discovered a cause of agitation in Alzheimer’s disease: over activity of the brain “adrenaline” arousal system that uses the messenger chemical norepinephrine.

Decades ago, drugs had been developed to lower high blood pressure without producing sedation by blocking excess effects of norepinephrine on blood vessels. Dr. Peskind reasoned that if one of these “adrenaline blocker” drugs could enter the brain it might reduce agitation/ aggression in Alzheimer’s disease. Prazosin (formerly marketed as “Minipress”) is just such an inexpensive generic drug – and it worked! In a small pilot study in 22 persons with Alzheimer’s disease agitation/aggression, prazosin was markedly more effective than placebo for reducing these distressing symptoms and did not produce sedation or other problem side effects.

The National Institute on Aging was so impressed with Dr. Peskind’s pilot study results that they awarded her a one million dollar grant to perform a larger definitive study of prazosin in one hundred Alzheimer’s disease patients living with a caregiver in the community who have problematic behaviors such as uncooperativeness with care, irritability/anger, physically aggressive behavior or restlessness which occur at least two times per week.

For more information please call: 1-800 317-5382 or 206 764-2069.


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