Treatment guidelines for Alzheimer-type dementia

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  • Alzheimer disease
  • Amyloid plaque
  • Neurofibrillary tangle
  • Brain tissue loss
  • Testing and imaging
  • Cognitive therapy

Alzheimer disease

Treatment guidelines for Alzheimer-type dementia
Treatment guidelines for Alzheimer-type dementia

Anticonvulsants. Anticonvulsants can be considered in nonpsychotic, agitated/aggressive patients with AD. Carbamazepine (Carbatrol, Epitol, Equetro, Tegretol) has been shown to be efficacious. Studies of valproate (Depacon) are not yet convincing. Gabapentin (Fanatrex, Gabarone, Neurontin) and lamotrigine (Lamictal) have not been systemically studied. Anticonvulsant doses must be titrated upward, and patients must be closely monitored for side effects.

Benzodiazepines. Earlier studies suggested that benzodiazepines were nearly as efficacious as antipsychotics in comparison trials. The problems associated with this medication class include physical dependence and cognitive worsening, even in the normal elderly population. Benzodiazepines should only be used for short-term crisis management (e.g., lorazepam [Ativan] 0.25 mg-1.0 mg daily or the equivalent).

Depression in patients with AD

Differences in memory performance between patients with major depressive disorder (MDD) and those with mild AD remains problematic.47 Different mechanisms appear to underlie their cognitive deficits. Early AD patients have neuropsychological performance deficits in Delayed-Word-Recall tests,48 verbal learning tasks,49 and language.50 Patients with MDD have impaired neuropsychological performance in attention, concentration, psychomotor skills, and a variety of memory subtest scores, depending on the study.51 Problems that arise in assessment involve symptoms that are common to both depression and AD. These include, but are not limited to, apathy, anhedonia, insomnia, agitation, memory loss, and difficulty concentrating.

Assessment considerations.Ascertain whether the patient has a personal and/or family history of depressive episodes. If so, prior treatment response should be discussed and documented. The history should include questions regarding drug, alcohol, corticosteroid, or sedative use. A depression survey should be administered, and a complete physical, neurologic, and psychiatric evaluation must be done. Lab work—including a complete blood count, comprehensive metabolic panel, B12 level, and thyroid function tests and venereal disease research laboratory test—should be drawn. An MRI should also be performed. Most cases of depression seen in dementia have no specific cause.

Antidepressant treatment in elderly patients with depression and AD.No treatments to date have shown robust effects in reversing the cognitive decline of AD. Several studies have shown mild cognitive improvement in patients with probable AD and concurrent depression (DEP-AD) when depression is effectively treated. These studies indicate a distinction between depression and DEP-AD. Memory is not reversible with remission of depression.52 In contrast, attention, psychomotor, and executive function can be severely impaired during depression and reverse with remission of this disorder.53,54

No difference has been shown between antidepressants and placebo in treating DEP-AD. The evidence of efficacy for selective serotonin reuptake inhibitors (SSRIs) is limited. The evidence of efficacy for most medications is lacking. Many studies featured numerous methodological limitations that resulted in a high placebo response.33

Choosing an antidepressant. History shows that tricyclic antidepressants (TCAs) can be problematic. These drugs are absolutely contraindicated in persons with unstable cardiovascular disease (particularly conduction disease), heart block, and orthostatic hypotension. Patients with sensitivity to anticholinergic side effects may experience increased confusion and impaired cognition.55 In elderly patients with MDD, SSRIs have become particularly popular with PCPs because they are thought to be efficacious with fewer potentially dangerous side effects. Overall, TCAs and SSRIs appear to be effective antidepressants in late-life depression, with both reasonably well tolerated. However, the long-term impact of the side effects of TCAs—specifically increased heart rate and anticholinergic effects—may be deleterious.55

Behavioral treatment/psychotherapy. Behavioral interventions attempt to identify and reduce the antecedents and consequences of problem behaviors. Behavioral treatment has shown modest benefits that do not persist beyond duration of treatment. Systematic data using other types of psychotherapy are just becoming available.56 The behavioral approach has not shown success in improving overall functioning57 but can help reduce such specific problem behaviors as incontinence.58

Emotion-oriented interventions include, but are not limited to, reminiscence therapy, validation therapy, supportive psychotherapy, and sensory integration. Reminiscence therapy involves dialogue about past experiences individually or in a group setting, with the aid of photographs, household items, music and sound recordings, or other familiar items from the past. Validation therapy is based on acceptance of the reality and personal truth of another's experience, while sensory integration is based on exercises aimed to stimulate the senses. Although there are few quality studies on the effectiveness of these therapies, they may be beneficial for cognition and mood.59

Cognition-oriented treatments are aimed at reducing cognitive deficits. Cognitive retraining tries to improve impaired capacities by exercising the patient's mental abilities. This has shown some efficacy in improving cognitive capacities,59 although these effects were shown to be transient in some studies, and such negative effects as frustration have also been reported.2 Sensory integration treatments include music, art, and pet therapies as well as exercise and other types of recreational activities. Despite the lack of significant clinical-effectiveness measurements, the main support for the use of stimulation therapies is the change in the person's routine.2

The role of genetics

Genetic testing for Huntington's disease (HD) was first available through linkage testing, and direct DNA testing has been available since 1993.60 HD has been the model for genetic counseling and testing for AD and other adult-onset diseases. A majority of cases are associated with late-onset familial diseases occurring after age 60 years, whereas early-onset familial AD accounts for less than 5% of all cases.61

While genetic studies have revealed several genes linked to AD, the genotyping has not been found to provide sufficient sensitivity or specificity when used alone as a diagnostic test.62 Although the presence of the epsilon 4 allele of the APOE gene in symptomatic individuals does lead to a small improvement in the predictive value, a consensus statement recommends against diagnostic genotyping.63

The American College of Medical Geneticists and the American Society of Human Genetics do not recommend APOE genotyping for presymptomatic identification of AD: "APOE genotyping in symptomatic people may not be beneficial primarily because the presence of the (epsilon) 4 allele by itself will not alter the medical management of the patient and the APOE genotyping has other implications for family members. Currently, APOE genotyping for presymptomatic individuals with a family history of late-onset AD is not clinically available and is possible only through research studies."64


AD is the most common dementia in the elderly. Accurate diagnosis is of paramount importance. Caregivers play an integral role in the management of patients with AD. Support must be given to the caregivers to prevent role strain and adverse health effects. Consider all therapeutic options before initiating treatment. Monitor patients with AD regularly for presence of target symptoms, underlying comorbidities, medication side effects, and cognitive and functional status. Adhere to standard treatment recommendations and keep abreast of clinical trials. Although the availability of genetic testing for AD is limited, the future is open to possibility of testing for the purpose of targeting specific populations for prevention and treatment. As more effective preventive measures and therapies are identified, it is likely individuals with a family history of AD will seek genetic testing.

Ms. Salamanca is a psychiatric nurse practitioner at Holy Name Medical Center in Teaneck, N.J. The author has no relationships to disclose relating to the content of this article.

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