Serum anticholinergic activity and cerebral cholinergic dysfunction: An EEG study in frail elderly with and without delirium

BMC Neuroscience BioMed Central Research article Open Access Serum anticholinergic activity and cerebral cholinergic dysfunction: An EEG study in frail elderly with and without delirium Christine Thomas*1,2, Ute Hestermann3, Juergen Kopitz4, Konstanze Plaschke5, Peter Oster3, Martin Driessen2, Christoph Mundt1 and Matthias Weisbrod1 Address: 1Centre for Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Voßstr. 2, 69115, Heidelberg, Germany, 2Department of Geriatric Psychiatry, Clinic of Psychiatry and Psychotherapy Bethel, Ev. Hospital Bielefeld, Bethesdaweg 12, 33617, Bielefeld, Germany, 3Bethanien-Hospital, Geriatric Centre of the University of Heidelberg, Rohrbacher Str. 149, 69126, Heidelberg, Germany, 4Institute of Molecular Pathology, University of Heidelberg, INF 220, 69120, Heidelberg, Germany and 5Department of Anaesthesiology, Section: ClinicalExperimental Anaesthesiology, University of Heidelberg, INF 110, 69120, Heidelberg, Germany Email: Christine Thomas* - ; Ute Hestermann - ; Juergen Kopitz - ; Konstanze Plaschke - ; Peter Oster - ; Martin Driessen - ; Christoph Mundt - ; Matthias Weisbrod - * Corresponding author Published: 15 September 2008 BMC Neuroscience 2008, 9:86 doi:10.1186/1471-2202-9-86 Received: 1 March 2008 Accepted: 15 September 2008 This article is available from: http://www.biomedcentral.com/1471-2202/9/86 © 2008 Thomas et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Delirium increases morbidity, mortality and healthcare costs especially in the elderly. Serum anticholinergic activity (SAA) is a suggested biomarker for anticholinergic burden and delirium risk, but the association with cerebral cholinergic function remains unclear. To clarify this relationship, we prospectively assessed the correlation of SAA with quantitative electroencephalography (qEEG) power, delirium occurrence, functional and cognitive measures in a cross-sectional sample of acutely hospitalized elderly (> 80 y) with high dementia and delirium prevalence. Methods: 61 consecutively admitted patients over 80 years underwent an extensive clinical and neuropsychological evaluation. SAA was determined by using radio receptor assay as developed by Tune, and standard as well as quantitative EEGs were obtained. Results: 15 patients had dementia with additional delirium (DD) according to expert consensus using DSM-IV criteria, 31 suffered from dementia without delirium (D), 15 were cognitively unimpaired (CU). SAA was clearly detectable in all patients but one (mean 10.9 ± 7.1 pmol/ml), but was not associated with expert-panel approved delirium diagnosis or cognitive functions. Deliriumassociated EEG abnormalities included occipital slowing, peak power and alpha decrease, delta and theta power increase and slow wave ratio increase during active delirious states. EEG measures correlated significantly with cognitive performance and delirium severity, but not with SAA levels. Conclusion: In elderly with acute disease, EEG parameters reliable indicate delirium, but SAA does not seem to reflect cerebral cholinergic function as measured by EEG and is not related to delirium diagnosis. Page 1 of 10 (page number not for citation purposes) BMC Neuroscience 2008, 9:86 Background Additive long lasting anticholinergic side effects of commonly prescribed drugs have recently gained special interest in neuro-geriatric medicine. They are considered one of the main reasons for cognitive decline [1] and delirium in the elderly. Although delirium is a common cause of morbidity and even mortality in the frail elderly and by this has an enormous impact on health economy as well as on individual quality of life, it remains under-diagnosed in elderly patients and especially in concomitant dementia [2]. Multiple causes underlie confusional states, resulting in a common final pathway of probably stress induced neurotransmission imbalances with a predominant cholinergic deficit [2,3]. Frail elderly are especially at risk because of multimorbidity, polypharmacy, accumulated cerebral pathology and physiological age-related changes. The concept of an anticholinergic burden has been established to highlight overall anticholinergic medication effects that could worsen the often impaired cognitive performance in the elderly, and to mark delirium risk The anticholinergic burden has been identified using two different approaches. The first one combines pharmacological knowledge and clinical experience to evaluate the overall central anticholinergic load. [1,4,5] However, mainly peripheral anticholinergic symptoms are screened. The second approach measures the cumulative anticholinergic activity in the peripheral blood utilizing a radio receptor assay developed by Tune in 1980 [6]. This assay detects muscarinic anticholinergic activity in serum samples in comparison to atropine. It has been used to detect global muscarinic anticholinergic properties of various medications [7] and to approve interventions for reducing the anticholinergic burden [8]. Some authors (see [9] for review) found an association of SAA and delirium in various settings, i.e. surgical, ICU- and medical patients [10-12], while some opposing findings exist in oldest old nursing home patients [13]. Cognitive impairment or lower MMSE was associated with higher SAA especially in dementia [9,14,15], depression [16] and community-dwelled elderly [17] but diverging results have also been reported [14,18,19]. It has been presupposed, that this serum assay also reflects the central situation, but this assumption is unproven and has often been questioned [1,20,21]. The CSF-serum-correlation of anticholinergic activity was only reported in two small samples of younger presurgical patients premedicated with central anticholinergics like scopolamine or midazolam [22,23]. The EEG reflects summation potentials of cortical electric activity, modulated by subcortical structures, in an unsur- http://www.biomedcentral.com/1471-2202/9/86 passed high temporal resolution. The basic EEG alpha rhythm is modulated by cholinergic thalamo-cortical pathways responsible for attention, alertness and vigilance regulation. Inactivity of the arousal system causes a rise of slow activity due to glial influences[24]. Centrally acting anticholinergics such as scopolamine result in occipital rhythm slowing, slow wave increase and decrease of fast activity [25-27], a pattern very similar to the EEG findings in delirium. Because of this distinct pattern, the EEG is still regarded as the gold standard of delirium diagnosis. [26,28] Especially quantitative EEG (qEEG) evaluation has the potential to detect disease- and pharmaco-related powerdensity changes (...truncated)