Lewy body dementia: therapeutic propositions according to evidence based medicine and practice

Abstract

Lewy body dementia (LBD) may present with two clinical forms: dementia with Lewy bodies (DLB) and Parkinson's disease with dementia. LBD is characterized by a profound deficiency of acetylcholine and a deficiency of dopamine. The cholinergic deficit is implicated in major attention disorders and fluctuations. Acetylcholinesterase inhibitors (donepezil or rivastigmine) were studied in several double-blind placebo-controlled studies. The meta-analyzes show a moderate benefit on the cognitive level and on some psychiatric manifestations including hallucinations. A disabling parkinsonian syndrome can be treated with L-dopa as in Parkinson's disease. However, the results are often limited because the increase in doses is restricted by cognitive and psychobehavioral disorders. Hallucinations may require antipsychotic treatment and the best documented drug is clozapine. Some other antipsychotics were assessed but in few therapeutic trials, and appear less efficacious, and with bad tolerance. Finally, the last of LBD cardinal disorders, REM sleep behavior disorders can be improved by melatonin. Other manifestations of LBD are troublesome. Some therapeutic trials with modafinil were proposed to improve diurnal hypersomnia. Anxiety and depression are often difficult to be treated. For antidepressant drugs, the first choice seems to be selective serotonin receptor inhibitors. Treatment for orthostatic hypotension, constipation, and swallowing dysfunction has also been more or less documented. In each case, non-drug management is considered (cognitive stimulation, physiotherapy, speech therapy, etc.). Finally, a therapeutic strategy is suggested, based on the medical and clinical experience. This strategy underlines the importance to improve cholinergic deficit and sleep disturbances. It also stresses the importance of a careful revision of all drugs administered to the patients with a peculiar attention to the anticholinergic treatment.