McManus, Kaitlin R.

AbstractBackgroundDelirium and dementia are common causes of cognitive impairment in older adults and frequently co‐exist. Delirium is associated with poor clinical outcomes when comorbid with dementia. Identifying delirium superimposed on dementia (DSD) is clinically challenging given the overlap in symptoms, including inattention, cognitive impairment, and altered level of consciousness, especially in advanced stages of dementia. Recognition of delirium is also critical in ADRD (Alzheimer’s Disease and Related Dementias) clinical trials for both validity and safety reasons. The ECT‐AD study is one such trial investigating the safety and efficacy of electroconvulsive therapy (ECT) for treatment‐refractory agitation and aggression in individuals with advanced ADRD. Herein we review the Confusion Assessment Method (CAM) for identifying delirium in the ECT‐AD study.MethodInclusion criteria for ECT‐AD are hospitalized individuals diagnosed with ADRD (ages 55–89, MMSE ≤ 15) and refractory agitation/aggression, as measured by the Cohen‐Mansfield Agitation Inventory (CMAI). Procedures for detecting baseline and treatment‐emergent delirium involve a 3‐step approach conducted by raters trained in the CAM, which assesses inattention, disorganized thinking, altered levels of consciousness, and fluctuating mental status. Step 1 involves gathering information from nurse informants regarding the patient’s mental status over the past 24 hours. Step 2 involves collecting observational data through informal patient interaction (e.g., brief conversation). Step 3 is an objective assessment of cognitive status using the Severe Impairment Battery – 8 Item (SIB‐8), while also making qualitative observations about delirium features (e.g., level of consciousness). The rater then codes the CAM and determines delirium status based on these 3 steps.ResultOf our 6 consented subjects, 1 experienced delirium detected by the CAM during the Randomization Phase. The subject received three positive CAMs on consecutive treatment days, citing change in mental status, inability to arouse, restlessness, psychomotor agitation, and swearing. ECT/S‐ECT was held each treatment day and the subject was withdrawn from the Randomization Phase.ConclusionIdentifying DSD is challenging due to overlapping symptoms and the fluctuating nature of delirium. The CAM may be useful in this regard by using a multi‐step approach that incorporates observations from reliable informants, direct patient interactions, and structured cognitive assessments.

Objectives Agitation is the most common behavioral symptom of Alzheimer disease (AD) affecting approximately 40% to 60% of the AD population, yet there are no Food and Drug Administration–approved therapies for the myriad of behavioral or psychological symptoms of dementia. There is growing evidence from naturalistic studies that electroconvulsive therapy (ECT) is a safe and effective treatment for agitation in AD patients who are refractory to pharmacotherapy and behavioral interventions. Despite the existing evidence, ECT remains underused because of stigma, lack of education, and concerns regarding adverse cognitive effects. Randomized controlled clinical trials of ECT are an opportunity to provide high-quality evidence of ECT as a safe and efficacious treatment for agitation in the AD population. We describe the methods for the Electroconvulsive Therapy in Alzheimer's Dementia study, which uses a novel, simulated ECT (S-ECT) control group to conduct a single-blind efficacy study of ECT for the treatment of agitation and aggression in individuals with moderate to severe AD. Methods We discuss the rationale, study design, methodology, ethical and practical challenges, and management strategies in using an S-ECT group as the comparator arm in this randomized controlled trial of ECT in AD-related treatment refractory agitation and aggression. Conclusions Validation of the safety and efficacy of ECT in patients with advanced AD with refractory agitation and aggression is necessary. This can be accomplished through creative formulation of S-ECT groups that effectively maintain the blind while providing scientific integrity.