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Regulation of attention and response to therapy in dementia by butyrylcholinesterase

Lookup NU author(s): Dr Brian Saxby, Dr Clive Ballard, Professor Gary Ford, Professor John O'Brien, Dr Andrew Fairbairn, Professor Jim Edwardson, Dr Christopher Morris, Professor Ian McKeith

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Abstract

Objectives: To determine the response of patients with different butyrylcholinesterase genotypes to therapy, and the influence of butyrylcholinesterase on cognition. Acetylcholine plays a key role in attention and memory and reduced cortical acetylcholine is associated with the severity of dementia. Inhibitors of the enzyme acetylcholinesterase are an effective dementia treatment, though the role of the related enzyme butyrylcholinesterase is less well understood. Methods: We examined the response of a cohort of dementia patients enrolled in a trial of a cholinesterase inhibitor who had been genotyped at the butyrylcholinesterase locus. Additionally a prospectively assessed cohort of dementia patients was genotyped and rate of cognitive decline examined, along with baseline cognitive performance in a group of elderly non-demented individuals. We identified that the presence of reduced-activity butyrylcholinesterase variants correlates with preserved attentional performance and reduced rate of cognitive decline. During cholinesterase inhibitor therapy, patients with normal butyrylcholinesterase show improved attention, though patients carrying reduced-activity enzyme do not, possibly due to being at ceiling performance. Butyrylcholinesterase did not however affect attentional performance in non-demented individuals with mild cognitive impairment. Conclusions: These findings indicate that the butyrylcholinesterase enzyme is a major regulator of attention especially in cholinergic deficiency states through its ability to hydrolyse acetylcholine. Pharmacologic manipulation of this enzyme may be a viable strategy in dementia treatment and, with butyrylcholinesterase genotyping, may provide pharmacogenomic treatment of dementia. © 2003 Lippincott Williams & Wilkins.


Publication metadata

Author(s): O'Brien KK, Saxby BK, Ballard CG, Grace J, Harrington F, Ford GA, O'Brien JT, Swan AG, Fairbairn AF, Wesnes K, Del Ser T, Edwardson JA, Morris CM, McKeith IG

Publication type: Article

Publication status: Published

Journal: Pharmacogenetics

Year: 2003

Volume: 13

Issue: 4

Pages: 231-239

Print publication date: 01/04/2003

ISSN (print): 0960-314X

ISSN (electronic): 1744-6880

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1097/00008571-200304000-00008

DOI: 10.1097/00008571-200304000-00008

PubMed id: 12668920


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