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Treatment in dementia with Lewy bodies

In this article, Dr Rimona Weil explains the many different options for treating symptoms in people with dementia with Lewy bodies. In DLB, treatment requires particular care as some treatments that improve motor symptoms can worsen cognitive symptoms and some treatments used to improve psychotic symptoms such as hallucinations, can lead to motor symptoms and confusion.

This article is written by Dr Rimona Weil, Clinical Lecturer in Neurology (Department of Molecular Neuroscience, UCL Institute of Neurology).

Although there are currently no specific interventions that change the course of Dementia with Lewy Bodies (DLB), or the related Parkinson’s Disease Dementia (PDD), there are treatments that improve many of the main symptoms. Individuals vary in the spectrum of symptoms and in their response to treatment. It is important to rationalise other medications, where possible stopping those that could worsen confusion. The impact of each symptom should be weighed against the potential side effects of each additional medication. Responses to new treatments should be monitored carefully.

Treatment of cognitive changes

In both DLB and PDD, the function of an important system of neurotransmitters (chemical messengers in the brain) known as the cholinergic system is reduced. Cholinesterase inhibitors are a class of treatments that lower the breakdown of choline, meaning there is more in the brain, and therefore can give improvements in cognition. Rivastigmine (McKeith et al., 2000) and donepezil (Mori et al., 2012), both cholinesterase inhibitors, show benefits in DLB in placebo controlled trials. A recent research study assessing evidence from a number of different trials (known as a meta-analysis) showed that donepezil and rivastigmine improve performance on global evaluation, as well as cognitive function, behavioural symptoms and activities of living and caregiver burden (Wang et al., 2015) (see also (Rolinski et al., 2012)). Adverse effects of these treatments are similar, with nausea and vomiting most frequent. Memantine, a medication that works on a different neurotransmitter system (the glutamatergic system; by blocking N-methyl-D-aspartate receptors) has a positive impact on global impression but not on cognitive function or on other outcomes (Matsunaga et al., 2015; Wang et al., 2015).

Treatment of visual hallucinations

The approach to visual symptoms in DLB and PDD is to address reversible causes and to optimise the visual environment. Early treatment of cataracts and glaucoma is recommended. Medications contributing to hallucinations or confusion should be discontinued. The next step is to gradually reduce parkinsonian drugs where they are being used, in the order of lowest efficacy, starting with anticholinergics. Anticholinergics are sometimes used to treat Parkinson’s disease, but have the opposite effect of cholinesterase inhibitors so may worsen cognitive function and confusion. Following this, amantadine, monoamine oxidase inhibitors, and then dopamine agonists and long-acting L-DOPA preparations may be reduced. In some cases, the L-DOPA dose is reduced ((Connolly and Lang, 2014; Diederich et al., 2009)). Cholinesterase inhibitors, especially rivastigmine, improve hallucinations in some patients (Aarsland et al., 2004). When these measures are not effective, antipsychotic medications may be considered.

Using antipsychotic treatments in Dementia with Lewy Bodies

Particular care is needed when using antipsychotic medications in Dementia with Lewy Bodies due to the risk of severe antipsychotic sensitivity which can present in up to 50% of patients. This causes marked extrapyramidal features (for example muscle spasms, rigidity and tremor), confusion, and instability of the autonomic nervous system (McKeith et al., 1992). General adverse effects include parkinsonism, dystonia, involuntary movements and drowsiness. These are reported with both typical and atypical antipsychotics. However, in some situations, antipsychotic treatment cannot be avoided, due to distressing hallucinations or psychosis. The atypical neuroleptic, clozapine is consistently the most effective medication for DLB-related hallucinations but requires blood monitoring due to the risk of agranulocytosis (a particular change in the composition of blood). For this reason, quetiapine is more frequently prescribed, although double blind trials in Parkinson’s related psychosis have not shown an effect in improving hallucinations (Ferreira et al., 2013). The serotonin2A inverse agonist pimavanserin (a drug that works on another neurotransmitter, serotonin) can be effective for hallucinations in Parkinson’s disease (Meltzer et al., 2010) and may be a future treatment option for hallucinations in DLB.

Motor symptoms

Motor symptoms are an important cause of disability in DLB and can increase the likelihood of falls. L-DOPA (common brands are Madopar and Sinemet) is the preferred treatment. L-DOPA is a precursor to the neurotransmitter dopamine so increases dopamine levels. Another form of medication working on the dopamine system (dopamine agonists) mimic the effects of dopamine. Experience in Parkinson’s disease suggests L-DOPA is slightly less likely than dopamine agonists to induce visual hallucinations (Rascol et al., 2000). Doses should be carefully adjusted to avoid exacerbating confusion and postural hypotension (a head rush or dizzy spell caused by low blood pressure when standing up or stretching). Anticholinergics - another form of treatment for motor symptoms that reduce cholinergic activity - should be avoided as these may worsen confusion (McKeith et al., 2005).

Treatment of other symptoms

Depression is common in people diagnosed with DLB. A class of treatments called selective serotonin reuptake inhibitors are preferred (McKeith et al., 2005) and another form of treatments called tricyclic antidepressants should be avoided as they may worsen confusion due to their anticholinergic effects (Ballard et al., 2011). The sleep disorder associated with DLB responds well to a small dose of clonazepam (a treatment that may also be used for seizures). Restless legs symptoms can improve with low doses of sinemet (L-DOPA), pramipexol (a dopamine agonist) or gabapentin (which has a different mechanism of action). Postural dizziness can be treated with hydration, salt tablets, compression stockings and withdrawing antihypertensives.

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