First described in 1961, dementia with Lewy bodies is believed to account for up to 20 percent of dementia cases. The condition is characterized by a progressive decline in cognitive function associated with fluctuation in cognition with pronounced variations in alertness, visual hallucinations, and/or motor parkinsonism (see Table 1). A review by Frank stresses the need for family physicians to recognize dementia with Lewy bodies and to provide specific treatment and management plans for this complex condition.
|Central feature of dementia|
|Progressive decline of cognitive function of sufficient magnitude to impair normal social or occupational function|
|Core features of dementia*|
|Fluctuation in cognition with pronounced variations in alertness and attention|
|Recurrent visual hallucinations|
|Features supportive of DLB diagnosis|
|Transient loss of consciousness|
|Hallucinations in other sensory modalities|
|REM sleep behavior disorder|
Dementia with Lewy bodies is slightly more common in men, and the mean age of onset is between 75 and 80 years. The cognitive changes in this dementia differ from those in Alzheimer's disease. Early in dementia with Lewy bodies, memory loss is not prominent, but poor subscores on the Mini-Mental State Examination in the areas of attention, construction, and clock-drawing (visuospatial and executive functions) are typical. The early clinical picture may be complicated by comorbid depression, apathy, anxiety, and anhedonia.
Fluctuations in cognitive abilities are characteristic of dementia with Lewy bodies. Patients may perform well in new and stimulating situations but have episodes of “blankness” in which awareness of surroundings is decreased. The fluctuations make it difficult for caretakers and physicians to assess the level of cognitive impairment. Assessment can be facilitated by the Clinical Assessment of Fluctuation or the One Day Fluctuation Assessment Scale.
A major clinical distinction between dementia with Lewy bodies and Alzheimer's disease is the occurrence of visual hallucinations. The hallucinations usually are well formed and detailed (often of people or animals coming into the patient's room), but auditory, olfactory, and tactile hallucinations also can occur. Treatment of the hallucinations may not be warranted, because risk for serious adverse reactions to neuroleptic drugs reportedly is increased in patients who have dementia with Lewy bodies.
Motor parkinsonism is another core feature of dementia with Lewy bodies. Patients tend to have prominent rigidity, bradykinesia, mask-like faces, and gait difficulties, but resting tremor is less common than in patients with classic Parkinson's disease. Symptoms of dementia tend to develop within a year of the onset of extrapyramidal signs. In contrast, delayed development of dementia is more typical of parkinsonian dementia. Parkinsonian symptoms in dementia with Lewy bodies can be exacerbated rapidly by neuroleptic drugs. Marked sensitivity to neuroleptic drugs occurs in more than one half of patients, and the effects can be irreversible. In these patients, neuroleptic drug use triples mortality, primarily secondary to severe functional decline.
|Rivastigmine, 1.5 mg twice daily, then increase every two to four weeks to 6 to 12 mg per day||Most common side effects are nausea and vomiting; slow titration (especially with rivastigmine) could minimize this effect.|
|Donepezil, 2.5 or 5 mg per day for one month, then increase to 10 mg per day||Contraindications include sick sinus syndrome, bradyarrhythmias, serious asthma, chronic obstructive pulmonary disease, severe renal failure, and severe liver failure.|
|Galantamine (no published case series or randomized controlled trials), 4 mg twice daily for one month, then increase to 8 mg twice daily||Worsening of motor parkinsonism is a concern; patients should be monitored.|
|Levodopa-carbidopa combination (100 mg/25 mg), one half of a tablet per day, then increase in one-half tablet increments to one tablet three times daily||Short-term side effects include nausea and hypotension; most relevant side effects in patients with DLB are hallucinations, nightmares, and delirium; worsening of hallucinations and cognition has not been noted in small studies.|
|Atypical neuroleptic drugs|
|Risperidone, 0.25 mg twice daily, with cautious titration to maximum of 1 mg twice daily||All atypical agents can cause neuroleptic sensitivity reactions.|
|Olanzapine, 2.5 mg per day, titrated to 5 to 10 mg per day||Close monitoring of motor parkinsonism and cognition is necessary for all agents.|
|Quetiapine, 25 mg twice daily, titrated to 150 mg per day|
The diagnosis of dementia with Lewy bodies is based predominantly on clinical features. Diagnosis can be difficult in patients with mild disease or coexisting Alzheimer's disease. The role of imaging studies is unclear.
Both nonpharmacologic interventions and medications (see Table 2) are used to treat dementia with Lewy bodies. Patients, family members, and caretakers require considerable support and education, especially about the use of neuroleptic drugs. Because cholinergic deficit may be greater in patients with this condition than in those with Alzheimer's disease, cholinesterase inhibitors may play an important role in treatment. To date, studies of rivastigmine have reported improvements in apathy, anxiety, hallucinations, delusions, and cognition, but a high drop-out rate. Reported gains have been significant, with many patients improving by 30 percent or more, but benefits were lost on discontinuation of therapy.
Treatment of motor parkinsonism in dementia with Lewy bodies has not been studied extensively. Patients appear to respond to standard levodopa-carbidopa combinations without a significant increase in side effects, especially hallucinations.
Management of the psychotic features of dementia with Lewy bodies is complicated by the enhanced sensitivity to neuroleptic agents. Benefits and adverse effects have been reported for risperidone therapy; small studies and case reports have noted benefit from other agents such as olanzapine. Cholinesterase inhibitors should be tried first, and neuroleptic drugs should be reserved for situations where psychotic symptoms are causing serious distress, putting the patient or others at risk, or impeding care.