The first step in treating dementia is attempting to identify any underlying illnesses that may be causing memory impairment and other symptoms of the syndrome. If none is found, or if the symptoms persist after appropriate specific treatment, then several symptomatic treatments are available.
A variety of pharmacological treatments is currently available for Alzheimer's disease.
1- Cholinesterase inhibitors :
One approach to improving memory function has been to enhance cholinergic activity in the brain. Autopsies of patients with Alzheimer's disease have found reduced levels of choline acetyltransferase in the brain, a finding that is consistent with a central cholinergic deficit. Trials of cholinergic agonists have temporarily improved memory in young and old normal volunteers. Trials of several agents'including physostigmine (Antilirium), choline (Mega-B), and lecithin (PhosChol)'have yielded contradictory results (some effects versus no measurable effects on memory in demented patients) or else have not yet been replicated. The U.S. Food and Drug Administration (FDA) has approved for short-term treatment four reversible cholinesterase inhibitors, tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon), and galantamine (Reminyl), which have proven benefits for memory, other aspects of cognition, behavioral disturbances, overall functioning, and even caregiver burden. Tacrine has the disadvantage of causing reversible elevations of serum transaminase levels and is therefore rarely used.
Recent studies point to the importance of early detection and treatment with cholinesterase inhibitor drugs. In randomized, placebo-controlled trials in patients with mild to moderate Alzheimer's disease, these drugs cause significant improvement in cognitive function compared to placebo after 6 months of treatment. During the following 6-month, open-label treatment periods, the patients who were originally treated with placebo were given active drug, and, at 1 year, better cognitive performance was observed in patients who began drug treatment from the beginning of the trial compared to those who had been placebo-delayed for 6 months.
Those drugs deactivate the enzyme which break down the main neurotransmitter active in cognitive functions: acetyl choline. This group of drugs include:
2- N-methyl-d-aspartate receptor antagonist
Memantine (Namenda), a drug used for decades in Europe, was recently approved for treatment of dementia in the United States. Rather than influencing the cholinergic transmitter system, memantine works on the brain's NMDA (N-methyl-D-aspartate) receptors by blocking the brain chemical glutamate, which overstimulates these receptors, allowing too much calcium to enter cells, leading to cell destruction. When taken 20 mg daily, memantine benefits patients with moderate to severe Alzheimer's disease, but many clinicians find that it is effective in milder forms of memory loss as well. Another encouraging observation of memantine is the additional benefit it brings to many patients already taking a cholinesterase inhibitor drug, donepezil, for an average of 6 months. These patients showed additional benefit and slower memory decline when they added memantine to their treatment regimen, compared with those who remained on the donepezil without adding memantine.
5- Other potential cognitive enhancers
Ongoing studies are assessing a variety of other agents that may improve cognitive functioning, including cholesterol-lowering statins, nonsteroidal anti-inflammatory agents, and botanical agents, such as Ginkgo biloba. Unfortunately, any clinical benefit for these various treatments has been inconclusive thus far.
Many of these approaches diminish symptoms and increase quality of life, but none of them can halt the dementing process. Most pharmacological agents that are currently available or are in development target a specific symptom (e.g., agitation or memory loss) and are derived from the known neurobiology of the disease (e.g., a specific neurotransmitter deficit) or hypothesized antidementia approaches (e.g., antiinflammation or antioxidation).
1- Antipsychotics :
Antipsychotic drugs are effective in treating psychotic symptoms and agitation, with the choice of a specific agent depending on its side effect profile. A metaanalysis of controlled trials of antipsychotic treatment in dementia indicated that antipsychotics had a significantly greater effect than did a placebo, but the degree of the effects was small.
High-potency agents, such as haloperidol (Haldol), tend to cause parkinsonian symptoms, whereas low-potency drugs, such as chlorpromazine (Thorazine), cause sedation, postural hypotension, and anticholinergic effects. Less frequently, tardive dyskinesia and neuroleptic malignant syndrome may develop.
Clozapine (Clozaril) can produce anticholinergic effects, as well as agranulocytosis, and thus requires blood-count monitoring, which can be particularly problematic in frail elderly patients. Because of better side effect profiles, the newer atypical antipsychotic drugs, such as quetiapine (Seroquel), risperidone (Risperdal), olanzapine (Zyprexa), and ziprasidone (Geodon), have received greater attention in recent years. Clinical experience and data from controlled trials using these latter medications in older demented patients indicate their usefulness in this patient group.
Clinicians should be aware of the risk of tardive dyskinesia in elderly patients. One study of elderly psychiatric patients showed that the greatest risk is during the first 2 years of antipsychotic treatment. Because of such adverse effects, alternative drugs have been used to treat agitation, including beta-blocking agents and sedating antidepressant drugs, such as trazodone (Desyrel).
2- Anxiolytics :
Benzodiazepines have also been used to treat the agitation that accompanies dementia. However, they have undesirable adverse effects, including some particularly noxious to the demented elderly patient, such as confusion, memory impairment, disorientation, dysarthria, and agitation complicated by ataxic gait. Short-acting benzodiazepines that do not require oxidative metabolism in the liver and that have no active metabolites are safer than long-acting agents.
Long-acting benzodiazepine agents tend to accumulate in the blood and are best avoided, as are short-acting compounds, which tend to reach high peak levels rapidly. Relatively short-acting benzodiazepines may be useful for treating insomnia, although the clinician should evaluate the specific causes of the insomnia, such as restless legs syndrome, obstructive apnea, urinary frequency caused by prostatic disease, lack of daytime exercise, use of caffeine, and prolonged stays in bed. Moreover, attempts at reducing daytime sleep, avoiding nighttime stimulants, and regulating the timing of meals and activities should be made before using pharmacological agents for sleep.
3- Anti-parkinsonian drugs :
Many patients also use over-the-counter preparations, which should be evaluated routinely. In a trial including more than 300 patients with moderately severe Alzheimer's disease, treatment with vitamin E (alpha-tocopherol) or the selective monoamine oxidase type-B inhibitor selegiline (Carbex) (approved for Parkinson's disease treatment) was found to lower rates of functional decline. These agents, however, did not show evidence of cognitive improvement.
Clinical experience and initial study results suggest the usefulness of anticonvulsant drugs (e.g., carbamazepine [Tegretol] and divalproex sodium [Depakote]) for agitation as well. Psychotherapies aimed at enhancing cognition are ineffective for dementia. Clinical experience also suggests the efficacy of nonpharmacological interventions in minimizing depression and agitation.
5- Beta-adrenergic receptor antagonists:
Available therapies for behaviors associated with dementia (e.g., depression, agitation, psychosis, and anxiety) are often effective. Patients who have dementia with concurrent depression may improve after treatment with antidepressant medications. Antidepressants with minimal anticholinergic effects (e.g., selective serotonin reuptake inhibitors [SSRIs]) are preferred over tricyclic drugs. Lithium (Eskalith) can be an effective antidepressant for geriatric depression and bipolar I disorder. However, patients with underlying neurological diseases have been reported to do poorly with lithium treatment, so it should be used with caution in patients with dementia.
As scientists uncover the basic pathogenetic mechanisms of Alzheimer's disease, additional antidementia treatments, designed to perform functions such as inhibition of amyloid production or accumulation or alteration of apolipoprotein E physiology, will likely emerge. Additional approaches may target other neurotransmitter systems (e.g., noradrenergic) or may use drug combination strategies.
Patients with cognitive losses are sensitive to their surroundings and seem to do best with optimal stimulation. Understimulation may cause withdrawal; overstimulation may cause confusion and agitation. Familiar and constant surroundings maximize the patient's existing cognitive functions. Daily routines often increase a patient's sense of security; memory and orientation can be facilitated by prominent displays of clocks and calendars, a night light, checklists, and diaries. Medication schedules should be simplified, if possible. If moves cannot be avoided, it helps to place familiar objects (e.g., photographs and furniture) in the new environment and to create a home-like atmosphere. The availability of newspapers, radio, and television can be useful in maintaining a patient's contact with and awareness of the outside world.
Psychotherapeutic intervention with family members is a critical aspect of treatment. Education and counseling about the nature of the patient's illness help relatives cope with the anger and puzzlement that they often experience when the demented patient behaves in peculiar, disturbing, and uncharacteristic ways. Relatives may need reassurance that their emotional reactions are common and that talking about them can bring relief. Many relatives also need help in grieving the loss of the patient who now behaves like a stranger rather than the person whom they once knew. The Alzheimer's Association, a national organization of family members with local chapters throughout the United States, has been at the forefront of providing educational and emotional support for family members.
Dementia of the Alzheimer's type has captured the attention of the mass media. Consequently, the public's concern and anxiety have led to a heightened awareness of memory changes and a tendency to overinterpret normal age-related memory impairment as dementia of the Alzheimer's type. Family members of Alzheimer's victims are generally the most anxious about any memory changes that they observe in themselves, given the likelihood of genetic components in the disease.
Sometimes, education and a full physical and neuropsychological evaluation allay, at least temporarily, unfounded anxiety about the disease. At other times, such an evaluation will uncover the early signs of progressive dementia.
In many situations, the elderly person with dementia is the identified patient. However, interpersonal conflicts among the family members require resolution to help the geriatric patient. Moreover, the adult child often makes the initial contact with the geriatric psychiatrist, and considerable skill and sensitivity are necessary to maintain an alliance with the adult child while respecting the elderly parent's autonomy, dignity, and privacy.