New drug options for dementia and Parkinson's disease

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Inhibiting cholinesterase (blue) can make more acetylcholine available to neurons in the brain.
Inhibiting cholinesterase (blue) can make more acetylcholine available to neurons in the brain.

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At a glance:

  • Acetylcholinesterase inhibitors are not cures for dementia but provide significant symptom relief.
  • N-methyl-D-aspartate receptor antagonists can slow the rate of progression of Alzheimer's disease.
  • Carbidopa/levodopa is the gold standard for treatment of Parkinson's disease symptoms.
  • Monoamine oxidase type B inhibitors work by increasing intracellular dopamine.

When the Decade of the Brain began in 1990, there was little new to offer patients and families dealing with dementia. At the time, the gold standard for Parkinson's disease treatment was carbidopa/levodopa (Sinemet, Parcopa). There has since been an explosion of new drugs for neurologic disorders. Nowhere has this advancement had a greater impact than on the treatment of patients with dementia or Parkinson's disease (PD).

Dementia

Estimated to affect approximately 4.5 million older adults in the United States and about 15 million worldwide, dementia is now a major public health concern. As our population ages, these numbers will continue to rise. It is estimated that by age 85 years, 50% of adults will have some memory difficulty, including dementia.1 Not long ago, there were no options considered useful to help manage these patients. There are now two classes of drugs for the management and treatment of dementia.

There continues to be a fair amount of controversy regarding treatment and/or management of Alzheimer disease (AD). A 2005 placebo-controlled study looked at the rate of conversion from mild cognitive impairment to frank AD.2 This study compared donepezil (Aricept), vitamin E, and placebo in cases in which the primary outcome was clinically probable AD. There was a statistically significant decreased rate of conversion in the first twelve months in the donepezil group compared with the other two. After three years, the rate of conversion for donepezil was the same as placebo. In those patients with one or more apolipo­protein E4 alleles, the benefit was sustained throughout the three-year study. If one only considers the impact of 12 months of improved cognition on families, this is truly significant.

A second placebo-controlled study compared primarily community-dwelling patients with dementia on donepezil with a placebo group.3 Criteria for study inclusion was a Mini-Mental Status Examination score below 12 and Functional Assessment Staging scores of six or higher. The donepezil group had significantly improved cognition as well as improved global functioning, including improved activities of daily living (ADL) ability. If one considers that incontinence and inability to perform ADLs are the primary reasons for nursing home admission in this group, the cost savings and improved outcomes for patients who remain at home can be significant.

There are two mechanisms thought to be involved in AD. Amyloid plaques, found mostly in the hippocampus, are accumulations of protein material and cellular components. Neurofibrillary tangles are intracellular collections of abnormal filaments.4

Changes in the brain's neurotransmitters—particularly acetylcholine—also contribute to AD. Acetylcholine is involved in the transmission of neuronal messages across the synaptic junction in the areas of the brain that are devoted to memory formation (primarily the hippocampus). In patients who have AD, cellular loss in the basal forebrain reduces the amount of acetylcholine available. What is left is broken down in increasing amounts by acetylcholinesterase, thus impairing memory. By blocking this process, acetylcholinesterase inhibitors (Table 1) make more acetylcholine available at the synaptic junction, thereby improving memory.

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