Medications for Dementia

Chapter 42


Medications for Dementia






INDICATIONS



Alzheimer’s disease (AD) is a chronic neurodegenerative illness characterized by cognitive and functional decline, as well as emergent behavioral disturbances. Currently, cholinesterase (ChE) inhibitors (e.g., donepezil, rivastigmine, and galantamine) are the standard therapy for AD. The three cholinesterase inhibitors are medications that are currently available specifically for the treatment of mild to moderate dementia of the Alzheimer’s type, with donepezil also approved for severe Alzheimer’s disease. These drugs do not cure the disease, but they may slow the progression of the disease and at best may modestly improve function. These medications often are initiated by primary care practitioners for patients who meet the criteria for mild to moderate Alzheimer’s-type dementia, or they may be initiated after consultation with a provider who specializes in geriatrics or with a neurologist or psychiatrist.


Memantine hydrochloride is available for moderate to severe dementia. It is the first N-methyl-d-aspartate (NMDA) receptor antagonist, a subclass of medications that have a different mechanism of action from the cholinesterase inhibitors. Memantine may slightly improve function, reduce care dependency (in one study by as much as 40 minutes a day of provider time), and may slow clinical decline in patients with moderate to severe dementia (those who are stage 5 through 7 on the Global Deterioration Scale, or who have a Mini Mental State Exam score <10; see “How to Monitor”). It may be given in addition to the cholinesterase inhibitors or as monotherapy.


Medication treatment for AD is a topic of intense research that is limited by our lack of understanding of the cause and pathology of the disease. No drugs have been found that prevent or reverse degeneration of neurons.



Therapeutic Overview


Pathophysiology


In patients with AD, loss of neurons occurs in the nucleus basalis of Meynert, the origin of the cholinergic neurons. A decrease in cholinergic activity results from loss of neurons and from a decrease in the activity of choline acetyl transferase, the enzyme responsible for acetylcholine synthesis.


The brain of a patient with AD often shows marked atrophy, with widened sulci and shrinkage of the gyri. In the great majority of cases, every part of the cerebral cortex is involved; however, the occipital pole often is relatively spared. The cortical ribbon may be thinned and ventricular dilation apparent, especially in the temporal horn, as the result of atrophy of the amygdala and hippocampus. Microscopically, significant loss of neurons is apparent, in addition to shrinkage of large cortical neurons. Many investigators believe that loss of synapses, in association with shrinkage of the dendritic arbor of large neurons, is the critical pathologic substrate. The neuropathologic hallmarks of AD are neuritic plaques and neurofibrillary tangles. Classic neuritic plaques are spherical structures that consist of a central core of fibrous protein known as amyloid that is surrounded by degenerating or dystrophic nerve endings (neurites). Two other types of amyloid-related plaques are recognized in the brains of patients with AD: diffuse plaques, which contain poorly defined amyloid but no well-circumscribed amyloid core, and “burnt-out” plaques, which consist of an isolated dense amyloid core.



Disease Process


More than 50 causes of dementia—a syndrome of impaired cognition involving memory, language, and reasoning—have been identified. AD and vascular dementia are the most common causes of dementia. Mixed vascular dementia and AD commonly occur together. In the United States, 5.4 million people have an Alzheimer’s diagnosis. By 2050, that number is expected to more than triple. The incidence of AD varies from 5% in those older than 65 years of age to 30% to 50% in those older than age 85. Some evidence suggests that women who drink more caffeine and people with higher education have some neuroprotection from AD, perhaps because of some cognitive reserve; however, people with higher education seem to have AD in which symptoms progress rapidly. Diagnosis of AD is based on exclusionary and inclusionary data. The criteria for dementia are listed in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).


Alzheimer’s disease begins long before people notice differences in the patient’s memory and behavior. By the time an official diagnosis is made, the person’s function is often significantly impaired, and treatment rarely helps. The aim of identifying the disease earlier is to get patients in the pipeline for research for future treatment. When the disease is not identified until later in its progression, patients are more impaired and treatments are even less effective.


Researchers from the Alzheimer’s Association and the National Institutes of Health believe that Alzheimer’s disease should be considered a spectrum of disorders and be regarded as having three stages ranging from lesser to greater severity in hopes that the devastating neurologic condition could be detected earlier. The three phases of Alzheimer’s are as follows:



Workup includes CBC, chemistries, vitamin B12, folate, thyroid profile, VDRL test, and, if relevant, CT scans or MRIs to rule out treatable causes of impaired cognition.



Mechanism of Action


Cholinesterase Inhibitors


Cholinesterase inhibitors act by blocking the enzyme that degrades acetylcholine in the brain. This results in more acetylcholine in the synaptic cleft and may enhance cholinergic transmission. The intended effect is to diminish signs and symptoms of dementia, thereby improving function and slowing the progression of the disease, which may delay the need for nursing home placement. The effectiveness of the drugs wears off as the disease progresses, as more neurons are destroyed. No evidence suggests that cholinesterase inhibitors alter the disease process or cure the disease. Although these drugs may diminish symptoms, when the medications are stopped, symptoms return, and the patient may soon become as symptomatic as if he had never taken the drug.




Treatment Principles


Standardized Guidelines





Evidence-Based Recommendations




• The evidence is insufficient to compare the effectiveness of different pharmacologic agents for the treatment of dementia.


• An overview of research suggests that donepezil improves cognitive function and global clinical state for up to 2 years in people with mild to severe AD. Quality of life was improved at 24 weeks. Donepezil given to patients with more severe dementia produced improvement in cognitive function at 24 weeks. Research suggests that donepezil delayed the median time to clinically evident functional decline by 5 months.


• Additional studies suggest that galantamine improves cognitive function and global clinical state over 6 months in people with AD or vascular dementia.


• One study in people with AD found no significant difference between donepezil and galantamine in cognitive function or adverse effects at 1 year.


• Ginkgo biloba and memantine are likely to be beneficial.


• Antidepressants given to Alzheimer’s patients with depression appear not to be effective and often cause adverse effects or introduce unwanted drug interactions.

< div class='tao-gold-member'>

Related posts:

  1. Complementary and Alternative Therapies
  2. Design and Implementation of Patient Education
  3. Osteoporosis Treatment
  4. Agents That Act on Blood

Stay updated, free articles. Join our Telegram channel
Tags:
Jul 22, 2016 | Posted by in PHARMACY | Comments Off on Medications for Dementia

Full access? Get Clinical Tree
Get Clinical Tree app for offline access