Emma L. Cunningham

Pain Assessment in Cognitive Impairment

ABSTRACT Pain may adversely affect cognition through its effects on mood and sleep, and chronic pain has been associated with brain atrophy. Studies suggest that chronic pain is undertreated in cognitively impaired people. Pain assessment should involve direct enquiry with the patient; where this is not possible, a proxy history from a caregiver or nurse should be obtained, and observational scales may also be useful. This report is adapted from paineurope 2014; Issue 1, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to health care professionals in Europe. Archival issues can be accessed via the Web site: http://www.paineurope.com, at which European health professionals can register online to receive copies of the quarterly publication.

CSF biomarkers in delirium: A systematic review

In recent years, there has been a blossoming of studies examining cerebrospinal fluid (CSF) as a method of studying the pathophysiology of delirium. We systematically reviewed the literature for CSF studies in delirium and provide here a summary of the implications for our understanding of delirium pathophysiology. We also summarise the methods used for CSF analysis and discuss challenges and implications for future studies.

Drug development in dementia

Dementia is a progressive, irreversible decline in cognition that, by definition, impacts on a patients pre-existing level of functioning. The clinical syndrome of dementia has several aetiologies of which Alzheimers disease (AD) is the most common. Drug development in AD is based on evolving pathophysiological theory. Disease modifying approaches include the targeting of amyloid processing, aggregation of tau, insulin signalling, neuroinflammation and neurotransmitter dysfunction, with efforts thus far yielding abandoned hopes and ongoing promise. Reflecting its dominance on the pathophysiological stage the amyloid cascade is central to many of the emerging drug therapies. The long preclinical phase of the disease requires robust biomarker means of identifying those at risk if timely intervention is to be possible.

Observational cohort study examining apolipoprotein E status and preoperative neuropsychological performance as predictors of post-operative delirium in an older elective arthroplasty population

Introduction delirium following surgery is common and is associated with negative outcomes. Preoperative cognitive impairment has been shown to be a risk factor for post-operative delirium. Often the cognitive tests used are cumbersome. This study tests the hypothesis that the quantification of brain vulnerability, using Apolipoprotein E (ApoE) status and neuropsychological tests, both traditional and more easily administered, can quantify the risk of post-operative delirium following elective primary arthroplasty surgery. Methods this observational cohort study recruited participants aged 65 years or older admitted prior to elective primary hip or knee arthroplasty. Baseline data was collected and participants underwent neuropsychological testing and had blood taken for ApoE genotyping preoperatively. Post-operatively participants were assessed daily for delirium using the Confusion Assessment Method (CAM) and charts were reviewed where possible for reports of delirium. Univariate and multivariate analyses of preoperative factors were undertaken to identify independent predictors of delirium. Results between March 2012 and October 2014, 315 participants completed the study with an overall incidence of post-operative delirium of 40/315 (12.7%). Of these 18 fulfilled the CAM criteria for delirium and 22 were deemed delirious by consensus decision based on chart review. ApoE genotype was not associated with post-operative delirium in this cohort. Time taken to complete Colour Trails 2, errors in mini mental state examination and level of pain preoperatively were independent predictors of post-operative delirium. Conclusions this study challenges the assertion that ApoE4 genotype predicts post-operative delirium. It replicates previous work suggesting cognitive impairment predicts post-operative delirium and shows for the 1st time that simple cognitive tests can be as effective as more detailed tests.

Managing Osteoarthritis Pain in the Older Population

ABSTRACT Challenges to pharmacological management in this patient group include treatment concordance, comorbidity, polypharmacy, and age-related physiological changes affecting pharmacokinetics. Paracetamol (acetaminophen) is generally recommended as a first-choice analgesic in osteoarthritis pain. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) should be considered ahead of oral formulations, and prescribing NSAIDs for older people requires careful consideration. There are some data relating to opioid use for noncancer pain in older people.

Identifying the period of greatest blood loss after lower limb arthroplasty

Background The use of tranexamic acid (TXA) in total hip replacement (THR) typically reduces blood loss by approximately 400 mL, and typical total blood loss is still approximately 1 L. A barrier to harnessing the full potential of TXA is disagreement on the optimum timing of administration. To address this, we aimed to identify the period of greatest blood loss. Methods We analyzed the perioperative data of 870 patients who had undergone THR, total knee replacement, or unicompartmental knee replacement just before the introduction of TXA to our unit. Total blood loss was calculated on postoperative day (POD) 1 and POD2 using an equation based on change in hematocrit. Results Average total blood loss at POD2 was 1505, 1322, and 611 mL for THR, total knee replacement, and unicompartmental knee replacement, respectively. Between 86% and 96% of this blood loss occurred in the period between skin closure and POD1. Intraoperative loss did not correlate with total loss at POD2. Blood transfusion was more likely if the patient was female (odds ratio [OR], 6.8) or if they had preoperative anemia (OR, 8.3) than if there was a high-volume blood loss (OR, 1.6). Conclusions Approximately 90% of blood loss occurs between skin closure and the first postoperative 24 hours. “Intraoperative blood loss” and “transfusion rate” are not reliable markers of total blood loss. The full potential of TXA could be harnessed by using it during the period of greatest blood loss, that is, during the first postoperative 24 hours.

CEREBROSPINAL FLUID/PLASMA ALBUMIN RATIO PREDICTS POSTOPERATIVE DELIRIUM IN AN OLDER ELECTIVE ORTHOPAEDIC POPULATION

P1-267 CEREBROSPINAL FLUID/PLASMA ALBUMIN RATIO PREDICTS POSTOPERATIVE DELIRIUM IN AN OLDER ELECTIVE ORTHOPAEDIC POPULATION Emma L. Cunningham, Anthony Peter Passmore, Daniel F. McAuley, David Beverland, Tim Mawhinney, Seamus O’Brien, Jamie Toombs, Jonathan M. Schott, Henrik Zetterberg, Michael Lunn, Bernadette McGuinness, Global Brain Health Institute, Dublin, Ireland; Queen’s University Belfast, Belfast, United Kingdom; Queen’s University Belfast, Belfast, United Kingdom; Belfast Trust, Belfast, United Kingdom; UCL Institute of Neurology, London, United Kingdom; Dementia Research Centre, UCL Institute of Neurology, London, United Kingdom; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, M€olndal, Sweden; University College London, London, United Kingdom. Contact e-mail: ecunningham03@qub.ac.uk

CSF Aβ42 CONCENTRATION INDEPENDENTLY PREDICTS POSTOPERATIVE DELIRIUM IN AN ELDERLY ELECTIVE ARTHROPLASTY POPULATION

carried out to assess the association between QoL scores and (i) depression and anxiety and (ii) Florbetapir-PET uptake with voxel-wise analyses (all age and sex adjusted). Results: There were no between group differences in QoL scores except for the physical health sub-score where SCD patients scored lower (p1⁄40.02; see Figure 1A). All QoL scores but the physical health sub-score were related to anxiety, while the physical health subscore was associated with depression (p1⁄40.003). In voxel-wise analyses, only the physical sub-score was associated with FlorbetapirPET uptake, such that worse scores predicted higher uptake in the superior and medial frontal cortex (see Figure 1B). This result remained significant after further correction for the depression score. Conclusions:The physical health sub-score of QoL, which incorporates facets of daily living activities, fatigue, pain and sleep, was affected in the SCD group and associated with Florbetapir-PET uptake in normal older adults and SCD patients independently of subclinical depression. Our results suggest that the assessment of QoL and notably of the self-perception of physical health might be relevant to preclinical AD. P1-348 CSFAb42 CONCENTRATION INDEPENDENTLY PREDICTS POSTOPERATIVE DELIRIUM IN AN ELDERLY ELECTIVE ARTHROPLASTY POPULATION Emma L. Cunningham, Bernadette McGuinness, David Beverland, Daniel F. McAuley, Seamus O’Brien, Tim Mawhinney, Jamie Toombs, Henrik Zetterberg, Jonathan M. Schott, Michael Lunn, Anthony Peter Passmore, Queen’s University Belfast, Belfast, United Kingdom; Belfast Trust, Belfast, United Kingdom; UCL Institute of Neurology, London, United Kingdom; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M€olndal, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; University of Gothenburg, Gothenburg, Sweden; University College London, London, United Kingdom; Dementia Research Centre, Institute of Neurology, University College London, London, United Kingdom. Contact e-mail: ecunningham03@qub.ac.uk

Pisa syndrome due to donepezil: pharmacokinetic interactions to blame?

We report a case of Pisa syndrome (PS) due to the acetylcholinesterase inhibitor donepezil which may have been precipitated by pharmacokinetic interactions with commonly used medications. PS is defined as a reversible lateral bending of the trunk with a tendency to lean to one side. This is a rare but very distressing complication with this commonly used medication which was not initially recognised, leading to increasing disability for the patient and significant carer stress. Cessation of donepezil and modulation of potential interacting medications resulted in complete resolution.

UTILITY OF NEUROPSYCHOLOGICAL TESTS IN PREDICTING POST-OPERATIVE DELIRIUM FOLLOWING ELECTIVE PRIMARY ARTHROPLASTY

Background:Post-operative delirium is common with an estimated incidence of 17% following elective arthroplasty surgery. Pre-operative cognitive impairment has been associated with increased risk of post-operative delirium. Previous studies have incorporated laborious neuropsychological tests undertaken by trained researchers. We aimed to ascertain which component of the neuropsychological assessment had most utility in the prediction of this condition. Methods: In an observational cohort study, participants aged 65 or over, without a diagnosis of dementia, presenting electively for primary hip or knee arthroplasty underwent neuropsychological assessment pre-operatively. Post-operatively participants were assessed daily for delirium using the Confusion Assessment Method. Pre-operative performance in CLOX 1&2, category and letter fluency, Stroop colour-word test, Colour Trails (CT) 1&2, New York University (NYU) paragraph immediate and delayed recall test, total Mini Mental State Examination (MMSE) score and performance in the constituent parts of the MMSE were examined for associations with post-operative delirium on univariate analyses. Those significant at the p1⁄40.1 level were entered into a logistic regression model. Results: Between March 2012 and October 2014 315 participants were recruited. Univariate analyses of pre-operative performance on neuropsychological testing showed significant associations between mean category fluency score, Stroop colour-word score, time taken to complete CT1 &2, NYU Paragraph delayed recall score, total MMSE score, and within the MMSE: any error in 3 item recall, an error in phrase repetition and more than one error on orientation questions and post-operative delirium. On multivariate testing time taken to complete CT2 (p<0.01) and any error on 3-item recall (p1⁄40.02) were independently associated with post-operative delirium. Conclusions: We demonstrated an association between a widely used test of attention (CT2) and delirium. This is also the first study to examine associations between the constituent parts of the MMSE and postoperative delirium and shows that the commonly used 3-item recall test is independently associated with post-operative delirium following elective arthroplasty. The routine inclusion of the 3item recall test in pre-operative assessment could improve perioperative patient counselling and care planning.