Clinical Review

Woman, 80, With Hallucinations and Tremors

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References

The diagnosis of DLB is currently based on the presenting clinical symptoms and the exclusion of other medical conditions whose symptoms mimic those of DLB.7 The screening assessment may include a neurologic/psychiatric assessment (MMSE, psychiatric evaluation, and interviews with family members or caretakers), neuroimaging such as MRI to rule out other organic causes, and laboratory evaluation to rule out potentially reversible causes of dementia, including electrolyte imbalance, vitamin deficiency (specifically vitamin B12), anemia, thyroid dysfunction, and kidney or liver impairment.18

The American Psychiatric Assocation1 categorizes DLB under “Dementia Due to Other General Medical Conditions” (294.1x). The World Health Organization19 includes it among “Other specified degenerative diseases of the nervous system” (G31.8).

Treatment
Lewy body dementia is an irreversible neurologic degenerative disorder. Treatment for DLB comprises symptom management, primarily through pharmacology; however, the response to medication is highly individualized. Treatment includes management of the following symptoms:

Cognitive impairment. Cholinesterase inhibitors, such as rivastigmine (3 to 12 mg/d), donepezil (10 mg/d), or galantamine (titrated up to 12 mg bid),20-23 improve attention and behavior and reduce apathy, anxiety, delusions, and hallucinations. As cognitive impairment worsens, memantine (10 mg bid) may be effective.24 The potential for anticholinergic adverse effects requires close monitoring in patients taking these agents.

Parkinsonian symptoms. Medications indicated for Parkinson’s disease and syndrome, such as carbidopa-levodopa (25/100 mg tid), can be effective; dosage may be slowly titrated upward as tolerated and if needed for symptom management.25,26 The dopaminergic effect of antiparkinson medications may intensify the psychotic symptoms and worsen the REM sleep pattern. In this case, a low-dose atypical antipsychotic is suggested27,28 (see below).

Psychotic symptoms. An atypical antipsychotic agent, such as quetiapine (12.5 mg), risperidone (0.25 mg), olanzapine (2.5 mg), ziprasidone (20 mg), aripiprazole (2 mg), or paliperidone (1.5 mg), may be used. Because of the DLB-associated risk of neuroleptic sensitivity, atypical antipsychotic agents should be initiated at a low dose with slow upward titration17,26,29; quetiapine appears less likely than risperidone or olanzapine to cause neuroleptic sensitivity or to trigger EPS.4 For Asian patients, who often respond to lower doses of these medications (and are more easily affected by associated adverse effects), Chen et al30 recommend a starting dose of about one-half the recommended dose.

Depression. An SSRI antidepressant with relatively simple pharmacologic properties and moderate half-life may be used to manage symptoms of depression.26,31,32 Long–half-life SSRIs (eg, fluoxetine) should be avoided in elderly patients; in response to SNRIs (serotonin-norepinephrine reuptake inhibitors), these patients may experience elevated blood pressures and pulses, with subsequent morbidity.33

REM sleep disturbances. Clo­nazepam (0.25 mg), melatonin (3.0 mg), or quetiapine (12.5 mg) may be administered at bedtime.34

Important Lessons
In general, providers should consider the benefits and risks of any pharmacologic treatment and avoid polypharmacy, if possible. Family and caretakers should be included in the treatment planning, with a focus on prioritizing and managing the most debilitating symptoms or dysfunctions that prompt concerns for safety.

For optimal homeostasis, some DLB patients may require joint pharmacologic modalities that appear counterintuitive—for example, an antiparkinsonism (dopaminergic) agent for parkinsonian symptoms or neuroleptic-induced EPS, versus an antipsychotic (eg, a dopamine antagonist) to treat profound hallucinations.26

As the response to treatment for DLB is highly individualized, it is essential to titrate and augment with care.

CONCLUSION
In DLB, as with other dementing illnesses, the onset of symptoms can be gradual and insidious, posing a great challenge to the clinician who seeks to confirm the diagnosis. In the illness’s early stages, the clinician may have to treat targeted symptoms and adjust the treatment plan once signs of the pathologic origins emerge.

It is critical to understand the mechanisms of psychotropic medications and targeted neurotransmitters when evaluating treatment for DLB. Titrating or augmenting these medications in elderly patients requires the clinician to follow a principle of start low and go slow, making only one change at a time.

It is always helpful to include family members in the patient’s care and to gather information on previous history, personality traits, family history, and cultural components. It is also important to communicate with other specialists to implement collaborative care.

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