E X P E R T O P I N I O N Rivastigmine in the treatment of patients with Alzheimer’s disease Thomas Müller Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Germany Correspondence:Thomas Müller Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany Tel +49 234 509 2426 Fax +49 234 509 2414 Email thomas.mueller@ruhr-uni-bochum.de Abstract: Impairment of attention and memory in patients with Alzheimer’s disease (AD) is associated with signiﬁcantly lower levels of acetylcholine. Inhibition of the breakdown of acetylcholine by blocking the enzymes acetylcholinesterase and butyrylcholinesterase with rivastigmine improves this cholinergic depletion. Thus rivastigmine administration provides established, effective, long-term symptomatic treatment in AD and Parkinson’s disease (PD) patients with dementia. A sustained treatment with cholinesterase inhibitors in general may also induce a certain deterioration of ﬁne motor behavior, which may play a crucial role in the treatment of PD patients with dementia. Recent studies show that this altered balance between dopamine and acetylcholine due to cholinesterase inhibition, with its possible negative impact on motion behaviour, does not present a major problem in clinical practice in AD patients and may be compensated for by modiﬁcation of dopaminergic substitution in PD patients with dementia. However, progression of neurodegeneration increases the vulnerability for psychosis in AD and PD patients with dementia in combination with dehydration and often requires additional application of neuroleptics. Since classical neuroleptics increase extrapyramidal symptoms, atypical neuroleptics are used. Out of these, quetiapine shows a distinct lower anticholinergic (muscarinergic) potency with beneﬁcial effects on cognition. This favors its use in combination with rivastigmine. Keywords: neurodegeneration, Alzheimer’s disease, rivastigmine, movement Introduction Alzheimer’s disease (AD) is the commonest cause of dementia affecting older people. Research advances have enabled a detailed understanding of the molecular pathogenesis of the hallmarks of the disease, ie, plaques, composed of amyloid beta, and tangles, composed of hyperphosphorylated tau. The neurodegenerative AD process is histopathologically characterized by nerve cell loss, extracellular deposits of beta amyloid protein, and intraneuronal formation of neuroﬁbrillary tangles. These changes do not exclusively occur in the cerebral cortex but also in several subcortical nuclei. The nucleus basalis of Meynert is most severely affected. Its neurons are cholinergic and project into many cortical areas. Loss of these nerve cells results in a widespread reduction of the cholinergic activity in the cortex. Cholinergic depletion is associated with impairment of attention and memory; therefore the cholinergic deﬁcit in AD presumably contributes to some of the core symptoms. However, as knowledge increases so does also the appreciation for the pathogenic complexity of the disorder. Familial AD is a very rare autosomal dominant disease with early onset, caused by mutations in the amyloid precursor protein and presenilin genes, both linked to amyloid beta metabolism. By contrast with familial disease, sporadic AD is very common with more than 15 million people affected worldwide (Blount et al 2002; Cummings 2005; Alva and Potkin 2003). The cause of the sporadic form of the disease is unknown, Neuropsychiatric Disease and Treatment 2007:3(2) 211–218 © 2007 Dove Medical Press Limited.All rights reserved 211