Reducing Agitation in People With Dementia: the Customized Activity Trial

Over 5 million Americans have Alzheimer's disease or a related dementia, a progressive and irreversible neurodegenerative condition, affecting also close to 15 million family caregivers (CG). A hallmark of the disease and one of the most significant challenges in dementia care is neuropsychiatric symptoms (NPS) of which agitation is the most disabling and frequently occurring. It is associated with increased health care costs, reduced life quality, heightened caregiver burden, disease acceleration and nursing home placement. Treatment typically involves pharmacologic agents; however, these are at best modestly effective, carry serious risks including mortality, and may not reduce family distress. Recently issued position statements from medical organizations suggest nonpharmacologic strategies as first-line treatment. Nevertheless, nonpharmacological strategies for agitation remain understudied. We propose a Phase III efficacy trial to test a novel 8-session patient-centric intervention, the Customized Activity Program (CAP). We will test CAP using a randomized two-group parallel design of 250 people with dementia (PwD) and their CGs (dyads) who will be randomly assigned to CAP or a control intervention of equivalent in-home attention and social contact. CAP assesses PwDs' preserved capabilities, deficits, previous roles, habits, interests and home environment from which activities are developed to match PwD profiles. Families are trained to implement activities and modify them for future decline. A pilot phase with 60 dyads showed clinically meaningful and statistically significant reductions in agitation, with no adverse effects. Our primary study aim evaluates the effect of CAP at 3 months on agitation (Hypothesis: PwD in TAP will have lower caregiver rated agitation compared to the control intervention condition. Three secondary aims evaluate: 1) 6-month effects of TAP on agitation and quality of life in PwD (Hypothesis: PwD in CAP will manifest lower caregiver rated subscale frequency and severity scores at 6 months and better quality of life compared to PwD in the control intervention); 2) Immediate effects of CAP at 3 and 6 months on CG wellbeing, and time spent providing care (Hypothesis: CGs receiving CAP will report enhanced wellbeing and less time caregiving compared to the control intervention (3 and 6 months); and 3) Cost effectiveness of CAP expressed as an incremental cost outcome achieved in the form of CG burden reductions and willingness to pay for burden reductions (3 and 6 months; Hypothesis: CAP will be cost effective compared to the control intervention at each test occasion). Five exploratory aims will evaluate treatment effects on psychotropic medication use and other troublesome behaviors, if effects differ by cognitive status, if CGs receiving CAP use activities at 6 months and with what frequency, how time gained is spent, and if frequency/duration of treatment and activity use affects outcomes. If proven efficacious and cost effective, CAP has potential to transform clinical practice by offering a proven nonpharmacologic treatment for agitation of PwDs at home. This trial addresses a critical clinical need and public health priority identified by recent legislative activity.

Objectives

Our primary study aim evaluates the immediate effect of CAP on agitation at 3 months. Our hypothesis is that PwD receiving CAP will manifest a lower caregiver rated frequency and severity score on the Neuropsychiatric Inventory-(NPI) subscales of agitation+aggression (21 items), compared to those in the control intervention.

Three secondary aims are to evaluate: 1) effects of CAP at 6 months on agitation and quality of life in patients. Hypothesis: Patients receiving CAP will manifest lower caregiver rated frequency and severity scores on the NPI-C agitation + aggression subscales and better quality of life in comparison to patients receiving the control intervention from baseline to 6 months; 2) effects of CAP at 3 and 6 months on CG wellbeing, (burden, skill acquisition, efficacy using activities), and time spent providing care. Hypothesis: Caregivers receiving CAP will report enhanced wellbeing and less time caregiving compared to those in the control intervention at 3 and at 6 months; and 3) cost effectiveness of CAP expressed as an incremental cost outcome achieved in the form of CG burden reductions and willingness to pay for burden reductions at 3 and 6 months. Hypothesis: CAP will be cost effective compared to the control intervention at each test occasion.

To further understand treatment effects and enhance translation, we propose exploratory aims to evaluate: 1) Impact of CAP on psychotropic medication use in treatment and control conditions at 3 and 6 months by comparing proportion of PwD who require dose increases or incident use of psychotropic medications (negative outcome) and proportion of PwD who reduce or eliminate medication use because agitation improved (positive outcome); 2) Whether treatment effect on agitation differs at 3 and 6 months by cognitive status; 3) Whether CAP reduces total NPI scores as rated by CGs at 3 and 6 months, 4) If at 6-months CGs receiving CAP are using prescribed activities and with what frequency; and how CGs use any personal time gained; and 5) Extent to which treatment receipt and enactment (frequency/duration of sessions and use of activities) affects NPI-C scores. If proven efficacious and cost effective, CAP has potential to transform the current paradigm of dementia care that relies primarily on the pharmacologic management of agitation. It will offer clinicians and families a proven nonpharmacologic approach to enhance quality of life that can be replicated, has reimbursement potential, and resonates with medical treatment guidelines and health care reform efforts aimed at reducing pharmacologic use and helping older adults be cared for at home.