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Anticholinergic Medications and Cognition in Older Adults

Chew, Marci Lyn (2008) Anticholinergic Medications and Cognition in Older Adults. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

A significant portion of the cognitive decline seen in older adults may be due to anticholinergic medications (i.e., muscarinic receptor antagonists) which are known to cause memory loss, confusion, and delirium. A competitive radioligand binding assay has been used in the research setting to measure the cumulative level of muscarinic receptor binding present in an individual's serum, referred to as serum anticholinergic activity (AA). Serum AA is the measure of binding of all compounds present in a person's serum (e.g., medications, metabolites, and possibly endogenous substances) to muscarinic receptors. Multiples studies have shown that even low serum AA levels are associated with impaired cognitive performance, impaired self-care capacity, and the presence of delirium in nondemented or mildly demented elderly. Serum AA has the potential to be a useful tool for clinicians. However, there are multiple items which first need to be addressed to enhance the reliability and clinical applicability of this assay. One concern is that the muscarinic receptor binding profiles of most medications and their metabolites have never been examined. Thus, even if a clinician decides that a patient is suffering from anticholinergic-induced toxicity, he/she has little guidance on which medication(s) to adjust. To address this issue, we investigated the in vitro AA of 106 commonly used medications and estimated the relationship between dose and AA in older adults. The change in serum AA over time in the absence of medication adjustments is not known. Another limitation is that serum AA is a peripheral measure, while the central anticholinergic effects of a medication are dependent on its distribution into the CNS. An optimal tool to predict medication-induced cognitive impairment would be one which better estimates drug distribution into the CNS. To address these issues, we conducted a pilot study investigating the utility of using centrally mediated pupillary oscillationsin conjunction with serum AA as a possible predictor of cognitive performance. Serum AA levels and ocular response were measured in a double-blind, cross-over study across an 8 hour time period following administration of placebo or the anticholinergic medication, oxybutynin.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Chew, Marci Lynfungifanatic@msn.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairPollock, Bruce G.bruce_pollock@camh.net
Committee CoChairPoloyac, Samuel M.poloyac@pitt.eduPOLOYAC
Committee MemberMulsant, Benoit H.benoit_mulsant@camh.net
Committee MemberSmith, Randall B.smithrb@pitt.eduSMITHRB
Committee MemberBies, Robert R.rrb47@pitt.eduRRB47
Committee MemberSteinhauer, Stuart R.sthauer@pitt.eduSTHAUER
Date: 29 January 2008
Date Type: Completion
Defense Date: 5 October 2007
Approval Date: 29 January 2008
Submission Date: 20 January 2008
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: anticholinergic; cognition; elderly; medications; memory
Other ID: http://etd.library.pitt.edu/ETD/available/etd-01202008-223707/, etd-01202008-223707
Date Deposited: 10 Nov 2011 19:31
Last Modified: 15 Nov 2016 13:36
URI: http://d-scholarship.pitt.edu/id/eprint/6298

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